PMID- 19642139 TI - An intention-to-treat analysis of liver transplantation for hepatocellular carcinoma using organ procurement transplant network data. AB - Single-center studies have shown acceptable long-term outcomes following orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) when tumors are within the Milan criteria. However, the overall survival and waiting list removal rates have not been described at a national level with pooled registry data. To evaluate this, a retrospective cohort of patients listed for OLT with a diagnosis of HCC between January 1998 and March 2006 was identified from Organ Procurement Transplant Network data. Analysis was performed from the time of listing. Adjusted Cox models were used to assess the relative effect of potential confounders on removal from the waiting list as well as survival from the time of wait listing. A total of 4482 patients with HCC were placed on the liver waiting list during the study period. Of these, 65% underwent transplantation, and 18% were removed from the list because of tumor progression or death. The overall 1- and 5-year intent-to-treat survival for all patients listed was 81% and 51%, respectively. The 1- and 5-year survival was 89% and 61% for those listed with tumors meeting the Milan criteria versus 70% and 32% for those exceeding the Milan criteria (P < 0.0001). On multivariate analysis, advanced liver failure manifested by Child-Pugh class B or C increased the risk of death, while age < 55 years, meeting the Milan criteria, and obtaining a liver transplant were associated with better survival. The current criteria for liver transplantation of candidates with HCC lead to acceptable 5-year survival while limiting the dropout rate. Liver Transpl 15:859-868, 2009. (c) 2009 AASLD. PMID- 19642140 TI - Elevated MAL expression is accompanied by promoter hypomethylation and platinum resistance in epithelial ovarian cancer. AB - We previously found that the gene encoding the Myelin and Lymphocyte protein, MAL, was among the most highly expressed genes in serous ovarian cancers from short-term survivors (<3 years) relative to those of long-term survivors (>7 years). In the present study, we have found that this difference in expression is partially attributable to differences in DNA methylation at a specific region within the MAL promoter CpG island. While MAL was largely unmethylated at the transcription start site (Region 1; -48 to +73 bp) in primary serous ovarian cancers, methylation of an upstream region (Region 2; -452 to -266 bp) was inversely correlated with MAL transcription in the primary cancers (R = -0.463) and ovarian cancer cell lines (R = -0.444). Following treatment of the OVCA432 cell line with 5-azacytidine, methylation of Region 2 decreased from 73.3% to 34.7% (p = 0.007) while Region 1 was unaffected. This was accompanied by a 10 fold increase in MAL expression. Since MAL transcripts are elevated in tumors from short-term survivors, all of whom were treated with platinum-based therapy, MAL may have a role in cisplatin response. We therefore determined the 50% growth inhibitory dose of cisplatin in 30 ovarian cancer cell lines and compared this to MAL expression. MAL transcript levels were higher in the resistant ovarian cell lines (p = 0.04). MAL methylation status may therefore serve as a marker of platinum sensitivity while MAL protein may be a target for development of novel therapies aimed at enhancing sensitivity to platinum-based drugs in ovarian cancer. PMID- 19642141 TI - Monocyte chemoattractant protein-1 (MCP-1)/CCL2 secreted by hepatic myofibroblasts promotes migration and invasion of human hepatoma cells. AB - The aim of our study was to investigate whether myofibroblasts and the chemokine monocyte chemoattractant protein-1 (MCP-1)/CCL2 may play a role in hepatocellular carcinoma progression. We observed that hepatic myofibroblast LI90 cells express MCP-1/CCL2 mRNA and secrete this chemokine. Moreover, myofibroblast LI90 cell conditioned medium (LI90-CM) induces human hepatoma Huh7 cell migration and invasion. These effects are strongly reduced when a MCP-1/CCL2-depleted LI90-CM was used. We showed that MCP-1/CCL2 induces Huh7 cell migration and invasion through its G-protein-coupled receptor CCR2 and, to a lesser extent, through CCR1 only at high MCP-1/CCL2 concentrations. MCP-1/CCL2's chemotactic activities rely on tyrosine phosphorylation of focal adhesion components and depend on matrix metalloproteinase (MMP)-2 and MMP-9. Furthermore, we observed that Huh7 cell migration and invasion induced by the chemokine are strongly inhibited by heparin, by beta-D-xyloside treatment of cells and by anti-syndecan-1 and -4 antibodies. Finally, we developed a 3-dimensional coculture model of myofibroblast LI90 and Huh7 cells and demonstrated that MCP-1/CCL2 and its membrane partners, CCR1 and CCR2, may be involved in the formation of mixed hepatoma-myofibroblast spheroids. In conclusion, our data show that human liver myofibroblasts act on hepatoma cells in a paracrine manner to increase their invasiveness and suggest that myofibroblast-derived MCP-1/CCL2 could be involved in the pathogenesis of hepatocellular carcinoma. PMID- 19642142 TI - Cancer incidence among children and adolescents in Brazil: first report of 14 population-based cancer registries. AB - The Brazilian Population-Based Cancer Registry (PBCR) was started in 1967; today there are 20 PBCRs in Brazil. We report the first descriptive analysis of the incidence of childhood cancer based on data from 14 PBCRs, corresponding to 15% of the child and adolescent population in Brazil. Data were obtained from registry databases, including information on population coverage and data quality indicators. The International Classification of Childhood Cancer was used. Age adjusted rates were calculated by world population. Incidence by cancer registry, age, sex, and cancer type were calculated per 1,000,000 children. Age-adjusted rates per 1,000,000 children/adolescents ranged from 92 to 220 among the 14 PBCRs. The principal groups of cancers were leukemia, lymphoma and central nervous tumors. The median incidence rate of childhood cancer in the 14 PBCRs was 154.3 per million; children 1-4 years of age had the highest incidence rates. The Brazilian PBCRs provide important information about pediatric cancer incidence in an emerging country. The observed incidence rates of childhood leukemia were similar to previous reported rates, and the age-specific incidence rates of retinoblastoma (0-4 years of age) were higher than those for developed countries. These data can be used as baseline incidence rates of childhood and adolescent cancer in Brazil in future epidemiological studies. PMID- 19642143 TI - EFNA1 ligand and its receptor EphA2: potential biomarkers for hepatocellular carcinoma. AB - Novel biomarkers are needed for early detection and progression evaluation of hepatocellular carcinoma (HCC). The purpose of this study was to identify useful biomolecular markers for HCC. The 26 genes that encode membrane or secretory proteins were identified from cDNA microarray data. We further examined the expression of EFNA1 and its receptor EphA2 and determined their biological implications during the development and progression of HCC. The EFNA1 mRNA was overexpressed in most HCCs as compared with its expression in corresponding nontumor tissues (36 out of 40 cases, 90%), but EphA2 expression was noted in only half of the HCC tissues (20 of 40 cases, 50%). In most of the hepatoma cell lines, the EFNA1 protein expression was positively associated with alpha fetoprotien (AFP) expression but inversely associated with EphA2 expression. Furthermore, EFNA1 levels were detectable in the supernatant of the cultured hepatoma cells and in the serum of patients with HCC. In contrast, EphA2 expression was prominent in highly invasive hepatoma cells, and its overexpression was significantly correlated with decreased differentiation (r = 0.0248, p < 0.010) and poor survival (p = 0.0453) for HCC patients. EFNA1 and EphA2 may be useful serum markers for the detection of HCC development and progression, respectively. PMID- 19642144 TI - Suppression of ABCG2 inhibits cancer cell proliferation. AB - The ATP-binding cassette efflux transporter, ABCG2, is widely expressed in a variety of normal tissues, stem cells, as well as cancer cells. Existing data suggest that ABCG2 plays an important role in the maintenance of the stem cell phenotype and multidrug resistance of cancer cells. However, the potential role of ABCG2 in other cellular processes remains speculative and poorly understood. Here, we demonstrated that ABCG2 is involved in the proliferation of cancer cells. We used RNA interference approach to efficiently and specifically down regulate ABCG2 protein levels in MCF-7/MX and A549 cells. We showed that knockdown of ABCG2 significantly inhibited the proliferation of these cells. Suppression of ABCG2 reduced the percentage of cells in the S phase of the cell cycle and enhanced G0/G1 accumulation. The G0/G1 growth arrest was associated with down-regulation of cyclin D3 and up-regulation of p21. Furthermore, blocking of ABCG2 function by chemical inhibitor fumitremorgin C also inhibited cell proliferation via the prolonged G0/G1 interval. Taken together, these findings suggest that ABCG2 correlates with cell cycle progression, highlighting a novel function of ABCG2 in cancer cell proliferation. PMID- 19642145 TI - Innovations in medical education: getting closer to our goals. Introduction. PMID- 19642146 TI - Teaching teamwork in medical education. AB - Teamwork has become a major focus in healthcare. In part, this is the result of the Institute of Medicine report entitled To Err Is Human: Building a Safer Health System, which details the high rate of preventable medical errors, many of which are the result of dysfunctional or nonexistent teamwork. It has been proposed that a healthcare system that supports effective teamwork can improve the quality of patient care and reduce workload issues that cause burnout among healthcare professionals. Few clear guidelines exist to help guide the implementation of all these recommendations in healthcare settings. In general, training programs designed to improve team skills are a new concept for medicine, particularly for physicians who are trained largely to be self-sufficient and individually responsible for their actions. Outside of healthcare, research has shown that teams working together in high-risk and high-intensity work environments make fewer mistakes than individuals. This evidence originates from commercial aviation, the military, firefighting, and rapid-response police activities. Commercial aviation, an industry in which mistakes can result in unacceptable loss, has been at the forefront of risk reduction through teamwork training. The importance of teamwork has been recognized by some in the healthcare industry who have begun to develop their own specialty-driven programs. The purpose of this review is to discuss the current literature on teaching about teamwork in undergraduate medical education. We describe the science of teams, analyze the work in team training that has been done in other fields, and assess what work has been done in other fields about the importance of team training (ie, aviation, nonmedical education, and business). Additionally, it is vital to assess what work has already been done in medicine to advance the skills required for effective teamwork. Much of this work has been done in fields in which medical professionals deal with crisis situations (ie, anesthesia, trauma, and labor and delivery). We describe the current programs for teaching medical students these essential skills and what recommendations have been made about the best ways to introduce teaching this skill set into the curriculum. Finally, we include a review on assessing teamwork because one cannot teach team training without implementing an assessment to ensure that the skills are being learned. PMID- 19642147 TI - The utility of simulation in medical education: what is the evidence? AB - Medical schools and residencies are currently facing a shift in their teaching paradigm. The increasing amount of medical information and research makes it difficult for medical education to stay current in its curriculum. As patients become increasingly concerned that students and residents are "practicing" on them, clinical medicine is becoming focused more on patient safety and quality than on bedside teaching and education. Educators have faced these challenges by restructuring curricula, developing small-group sessions, and increasing self directed learning and independent research. Nevertheless, a disconnect still exists between the classroom and the clinical environment. Many students feel that they are inadequately trained in history taking, physical examination, diagnosis, and management. Medical simulation has been proposed as a technique to bridge this educational gap. This article reviews the evidence for the utility of simulation in medical education. We conducted a MEDLINE search of original articles and review articles related to simulation in education with key words such as simulation, mannequin simulator, partial task simulator, graduate medical education, undergraduate medical education, and continuing medical education. Articles, related to undergraduate medical education, graduate medical education, and continuing medical education were used in the review. One hundred thirteen articles were included in this review. Simulation-based training was demonstrated to lead to clinical improvement in 2 areas of simulation research. Residents trained on laparoscopic surgery simulators showed improvement in procedural performance in the operating room. The other study showed that residents trained on simulators were more likely to adhere to the advanced cardiac life support protocol than those who received standard training for cardiac arrest patients. In other areas of medical training, simulation has been demonstrated to lead to improvements in medical knowledge, comfort in procedures, and improvements in performance during retesting in simulated scenarios. Simulation has also been shown to be a reliable tool for assessing learners and for teaching topics such as teamwork and communication. Only a few studies have shown direct improvements in clinical outcomes from the use of simulation for training. Multiple studies have demonstrated the effectiveness of simulation in the teaching of basic science and clinical knowledge, procedural skills, teamwork, and communication as well as assessment at the undergraduate and graduate medical education levels. As simulation becomes increasingly prevalent in medical school and resident education, more studies are needed to see if simulation training improves patient outcomes. PMID- 19642148 TI - Student-run health clinic: novel arena to educate medical students on systems based practice. AB - In recent decades, the United States has experienced substantial growth in the number of student-run clinics for the indigent. Today, over 49 medical schools across the country operate over 110 student-run outreach clinics that provide primary care services to the poor and uninsured. Despite this development, little research has been published on the educational value of such student-led endeavors. Although much has been surmised, no general methodology for categorizing the learning experience in these clinics has been established. This article represents the first literature review of the novel method of educating students through the operation of a clinic for the underserved. It highlights the student-run clinic as a unique enhancement of medical education that may supplant current curricular arenas in teaching students about systems-based practice principles such as cost containment and financing, resource allocation, interdisciplinary collaboration, patient advocacy, and monitoring and delivery of quality care. The novelty of the student-run clinic is that students place themselves at the forefront of problem solving and system navigation to effectively care for severely disadvantaged populations. This article underscores the student-run clinic as a potentially ideal experiential learning method for preparing young physicians to confront a US healthcare system currently facing crises in cost, quality of care, and high rates of uninsurance. The article stresses the need for outcomes research on the long-term effectiveness of the student-run clinic experience in affecting medical student practice behaviors and attitudes in patient care settings that extend beyond the student-run clinic. PMID- 19642149 TI - Closing in on ending the warfarin era for stroke prevention in nonvalvular atrial fibrillation. PMID- 19642150 TI - Direct observation in medical education: a review of the literature and evidence for validity. AB - In 2000, the Accreditation Council for Medical Education introduced a new initiative that substantively changed the method by which residency programs are evaluated. In this new competency-based approach to residency education, assessment of performance became a main area of interest, and direct observation was offered as a tool to assess knowledge and skills. Despite being an inherent part of medical education as faculty and learners work together in clinical experiences, direct observation has traditionally been an informal and underused assessment method across all specialties. Residents and students report rarely being observed during their educational process, even though they value the experience. Reasons for this include a lack of faculty time, a lack of faculty skills, a potential stressful effect on the learner, and a perceived lack of validation of the assessment. This article examines the literature regarding the use of direct observation in medical education with a focus on validity evidence. We performed a PubMed search of articles pertaining to direct observation, using key words such as direct observation, performance observation, clinical observation, students, and residents. A subsequent search was conducted in known articles, focusing on variations of the term observation in the titles of articles and introducing the concept of clinical competence. In conclusion, direct observation is a unique and useful tool in the assessment of medical students and residents. Assessing learners in natural settings offers the opportunity to see beyond what they know and into what they actually do, which is fundamentally essential to training qualified physicians. Although the literature identifies several threats to its validity as an assessment, it also demonstrates methods to minimize those threats. Based on the current recommendations and need for performance assessment in education and with attention paid to the development and design, direct observation can and should be included in medical education curricula. PMID- 19642151 TI - Evaluating the impact of the humanities in medical education. AB - The inclusion of the humanities in medical education may offer significant potential benefits to individual future physicians and to the medical community as a whole. Debate remains, however, about the definition and precise role of the humanities in medical education, whether at the premedical, medical school, or postgraduate level. Recent trends have revealed an increasing presence of the humanities in medical training. This article reviews the literature on the impact of humanities education on the performance of medical students and residents and the challenges posed by the evaluation of the impact of humanities in medical education. Students who major in the humanities as college students perform just as well, if not better, than their peers with science backgrounds during medical school and in residency on objective measures of achievement such as National Board of Medical Examiners scores and academic grades. Although many humanities electives and courses are offered in premedical and medical school curricula, measuring and quantifying their impact has proven challenging because the courses are diverse in content and goals. Many of the published studies involve self selected groups of students and seek to measure subjective outcomes which are difficult to measure, such as increases in empathy, professionalism, and self care. Further research is needed to define the optimal role for humanities education in medical training; in particular, more quantitative studies are needed to examine the impact that it may have on physician performance beyond medical school and residency. Medical educators must consider what potential benefits humanities education can contribute to medical education, how its impact can be measured, and what ultimate outcomes we hope to achieve. PMID- 19642152 TI - Mission-based budgeting for education: ready for prime time? AB - Mission-based budgeting has been touted as the preferred method of assessing and assigning departmental budgets in academic medical centers. Mission-based budgeting in its simplest form is a methodology that allows an institution's finance department to align costs with actual activities (typically clinical care, administration, research, and teaching). Despite its intuitive appeal, a minority of the academic medical centers across the country have embraced it. Mount Sinai School of Medicine was among the first to incorporate this approach, and we have almost a decade of experience with its risks and benefits. This article focuses on the education component of mission-based budgeting. We review all aspects of mission-based budgeting, including (1) the many variables that must be factored into a metric and how those variables differ among institutions, (2) the metric itself and how it reflects institutional philosophy, (3) the impact of mission-based budgeting on faculty and chairs of departments, (4) existing processes that ensure the quality, reliability, and validity of the different mission-based budgeting systems, and (5) a comparative perspective. PMID- 19642153 TI - Introducing INSPIRE, a scholarly component in undergraduate medical education. AB - Individualized learning is a fundamental tenet of the Carnegie Foundation's new recommendations for physician training. A primary goal of Mount Sinai School of Medicine's new curriculum is to train self-directed physicians who have mastered lifelong learning skills. The Individual Scholarly Project and Independent Research Experience (INSPIRE) was created to enable fourth-year students to conduct mentored, independent scholarly projects to develop critical thinking skills and intellectual independence. Four students were accepted into the 2008 12-week pilot. Two did clinical research, 1 conducted medical education research, and 1 continued a basic science project. INSPIRE featured weekly sessions in which students shared their progress, heard about the careers of physician scientists, and participated in presentation skills workshops. Mentors gave feedback using a form based on the program goals. Anonymous evaluations showed that all participants believed their goals were successfully fulfilled, that the likelihood of including research in their careers increased, and that they felt more skilled at writing abstracts and presenting their work orally. Students agreed that INSPIRE was a valuable opportunity for acquiring in-depth knowledge on a topic and building research and presentation skills. Helping students shape an individualized scholarly experience may help to produce doctors who are self directed, are personally fulfilled, are able to serve society with diverse expertise, and have the tools to become leaders in their fields. PMID- 19642154 TI - The risk of upper aero digestive tract cancer associated with smoking, with and without concurrent alcohol consumption. AB - BACKGROUND: Smoking and alcohol are major causal factors for upper aerodigestive tract cancer, but reliable quantification of the combined impact of smoking and alcohol on this cancer and its major subtypes has not been performed. METHODS: A meta-analysis of studies that had published quantitative estimates of smoking and upper aerodigestive tract cancer by January 2007 was performed. Pooled estimates of relative risks were obtained. Publication bias was investigated through funnel plots and corrected if found to be present. RESULTS: Overall, 85 studies with information on 53,940 individuals with upper aerodigestive tract cancer were included. The pooled estimate for the association between smoking and the risk of this cancer was 3.47 (95% confidence interval, 3.06-3.92). The risk remained elevated for a decade after smoking cessation but declined thereafter. Individuals who both smoked and consumed alcohol had double the risk of upper aerodigestive tract cancer in comparison with those who only smoked: the relative risk was 6.93 (95% confidence interval, 4.99-9.62) for the former and 2.56 (95% confidence interval, 2.20-2.97) for the latter (P < 0.001). CONCLUSIONS: Public health interventions that simultaneously discourage smoking and heavy drinking would have greater benefits than would be expected from those that target only one of these risk factors. PMID- 19642155 TI - The management of stage D heart failure. PMID- 19642156 TI - Evidence-based medicine: the accuracy of CT angiography for coronary artery disease. PMID- 19642157 TI - Medical student documentation in the medical record: is it a liability? AB - Medical students have routinely documented patient encounters in both inpatient and outpatient care venues. This hands-on experience has provided a way for students to reflect on patient encounters, learn proper documentation skills, and attain a sense of being actively involved in and responsible for the care of patients. Over the last several years, the practice of student note writing has come into question. Institutional disincentives to student documentation include insurance regulations that restrict student documentation from substantiating billing claims, concerns about the legal status of student notes, and implementation of electronic medical records that do not allow or restrict student access. The increased scrutiny of the medical record from pay-for performance programs and other quality measures will likely add to the pressure to exclude students from writing notes. This trend in limiting medical student documentation may have wide-ranging consequences for student education, from delaying the learning of proper documentation skills to limiting training opportunities. This article reviews the educational value of student note writing, the factors that have made student documentation problematic, and the potential educational impact of limiting student documentation. In addition, it offers some suggestions for future research to guide policy in this area. PMID- 19642158 TI - Percutaneous aortic valvuloplasty: resurrection of something old with something new. PMID- 19642159 TI - Glycosylation status of vitamin D binding protein in cancer patients. AB - On the basis of the results of activity studies, previous reports have suggested that vitamin D binding protein (DBP) is significantly or even completely deglycosylated in cancer patients, eliminating the molecular precursor of the immunologically important Gc macrophage activating factor (GcMAF), a glycosidase derived product of DBP. The purpose of this investigation was to directly determine the relative degree of O-linked trisaccharide glycosylation of serum derived DBP in human breast, colorectal, pancreatic, and prostate cancer patients. Results obtained by electrospray ionization-based mass spectrometric immunoassay showed that there was no significant depletion of DBP trisaccharide glycosylation in the 56 cancer patients examined relative to healthy controls. These results suggest that alternative hypotheses regarding the molecular and/or structural origins of GcMAF must be considered to explain the relative inability of cancer patient serum to activate macrophages. PMID- 19642161 TI - Survival benefit of liver transplantation: one size fits all or fits none? PMID- 19642162 TI - Dropping liver fat droplets. PMID- 19642163 TI - A novel role for human leukocyte antigen-DP in chronic hepatitis B infection: a genomewide association study. PMID- 19642164 TI - Acute cellular rejection and its sequelae developing in a 42-year-old man after liver transplantation. PMID- 19642165 TI - The amazing universe of hepatic microstructure. AB - An informal review is presented by the author of his 50 years of involvement in practice and research in hepatopathology. Some background for the author's attitude and meandering pathway into his professional career serves as introduction to a short discussion of the main topics of his interest and expertise. Histogenesis of liver cancer was the theme of early work for a Ph.D. thesis, the results of which were lost into oblivion due to local rules and circumstances, but were rescued three decades later. His conclusions about the cells of origin of liver cancer remain concordant with the newer concepts in the field after nearly half a century. Studies in the field of chronic hepatitis became a long saga, involving the first classification of this syndrome by "the Gnomes" in 1968, histochemical investigations of viral antigens, lymphocyte subsets and adhesion molecules, and a quarter century later, the creation of a new classification presently in use. Cholestasis was a broadening field in diagnostic entities and involved the study of liver lesions, comprising pathways of bile regurgitation (including reversed secretory polarity of hepatocytes) and so-called ductular reaction. The latter topic has a high importance for the various roles it plays in modulating liver tissue of chronic cholestasis into biliary cirrhosis, and as the territory of hepatic progenitor cells, crucial for liver regeneration in adverse conditions and in development of liver cancer. Study of the embryology of intrahepatic bile ducts helped to clarify the strange appearance of the ducts in "ductal plate configuration" in several conditions, including some forms of biliary atresia with poor prognosis and all varieties of fibrocystic bile duct diseases with "ductal plate malformation" as the basic morphologic lesion. PMID- 19642166 TI - Analysis of pharmaceutical heparins and potential contaminants using (1)H-NMR and PAGE. AB - In 2008, heparin (active pharmaceutical ingredient, API) lots were associated with anaphylactoid-type reactions. Oversulfated chondroitin sulfate (OSCS), a semi-synthetic glycosaminoglycan (GAG), was identified as a contaminant and dermatan sulfate (DS) as an impurity. While DS has no known toxicity, OSCS was toxic leading to patient deaths. Heparins, prepared before these adverse reactions, needed to be screened for impurities and contaminants. Heparins were analyzed using high-field (1)H-NMR spectroscopy. Heparinoids were mixed with a pure heparin and analyzed by (1)H-NMR to assess the utility of (1)H-NMR for screening heparin adulterants. Sensitivity of heparinoids to deaminative cleavage, a method widely used to depolymerize heparin, was evaluated with polyacrylamide gel electrophoresis to detect impurities and contaminants, giving limits of detection (LOD) ranging from 0.1% to 5%. Most pharmaceutical heparins prepared between 1941 and 2008 showed no impurities or contaminants. Some contained DS, CS, and sodium acetate impurities. Heparin prepared in 2008 contained OSCS contaminant. Heparin adulterated with heparinoids showed additional peaks in their high-field (1)H-NMR spectra, clearly supporting NMR for monitoring of heparin API with an LOD of 0.5-10%. Most of these heparinoids were stable to nitrous acid treatment suggesting its utility for evaluating impurities and contaminants in heparin API. PMID- 19642167 TI - Strategies to prevent hepatitis B virus reactivation in patients receiving immunosuppressive therapy. PMID- 19642168 TI - De novo bile salt transporter antibodies as a possible cause of recurrent graft failure after liver transplantation: a novel mechanism of cholestasis. AB - Progressive familial intrahepatic cholestasis type 2 (PFIC-2) is caused by mutations of the bile salt export pump (BSEP [ABCB11]), an ATP-binding cassette (ABC)-transporter exclusively expressed at the canalicular membrane of hepatocytes. An absence of BSEP from the canalicular membrane causes cholestasis and leads to liver cirrhosis, which may necessitate liver transplantation in early childhood. We report on the first case of a child with PFIC-2 suffering from repeated posttransplant recurrence of progressive intrahepatic cholestasis due to autoantibodies against BSEP. These antibodies occurred after transplantation and were detected in the patient's serum and at the canalicular membrane of two consecutive liver transplants. The antibodies were reactive toward the first extracellular loop of BSEP, were of high affinity, and inhibited transport activity of BSEP, thus causing severe cholestasis. The patient had three homozygous, missense changes in the BSEP gene. Their combination resulted in the complete absence of BSEP, which explains the lack of tolerance, a prerequisite of autoantibody formation toward BSEP. The findings illustrate a novel disease mechanism due to a new class of functionally relevant autoantibodies resulting in cholestasis and subsequent liver failure. PMID- 19642170 TI - Increased liver-related mortality to hepatitis C viremia defined on the 20th anniversary of its identification. PMID- 19642171 TI - Rapamycin delays tumor development in murine livers by inhibiting proliferation of hepatocytes with DNA damage. AB - In this study, everolimus (RAD001) was used to determine the role of mammalian target of rapamycin (mTOR) in hepatocarcinogenesis. We show that RAD001 effectively inhibits proliferation of hepatocytes during chronic liver injury. Remarkably, the ability of RAD001 to impair cell cycle progression requires activation of the DNA damage response; loss of p53 significantly attenuates the antiproliferative effects of mTOR inhibition. RAD001 modulates the expression of specific cell cycle-related proteins and the assembly of cyclin-cyclin-dependent kinase complexes to prevent cell cycle progression. Furthermore, RAD001 sustains the apoptosis sensitivity of hepatocytes during chronic liver injury by inhibiting p53-induced p21 expression. Long-term treatment with RAD001 markedly delays DNA damage-induced liver tumor development. CONCLUSION: We provide evidence that mTOR inhibition has a substantial effect on sequential carcinogenesis and may offer an effective strategy to delay liver tumor development in patients at risk. PMID- 19642172 TI - Misconceptions about the diagnosis and treatment of fibromuscular dysplasia. PMID- 19642173 TI - Adenosine diphosphate-ribosylation factor 6 is required for epidermal growth factor-induced glioblastoma cell proliferation. AB - BACKGROUND: : Epidermal growth factor (EGF) signaling plays a pivotal role in gliomagenesis. The authors previously demonstrated that adenosine diphospate ribosylation factor 6 (ARF6), a member of the Ras-related small guanosine-5' triphospate-binding protein family, is required for EFA6A-induced glioma cell migration and invasion. However, the role of ARF6 in EGF signaling is unknown. METHODS: : The authors analyzed messenger RNA (mRNA) levels of ARF6 and EGF receptor (EGFR) in 16 high-grade glioma samples and in 6 low-grade glioma samples by reverse transcriptase-polymerase chain reaction analysis. To determine whether EGF induces ARF6 expression in human glioblastoma U87 cells through transcriptional regulation and EGFR activation, the levels of ARF6 were assayed in EGF-treated U87 cells that were preincubated with a transcriptional inhibitor (actinomycin D) and an EGFR tyrosine kinase inhibitor (PD153035), respectively. The downstream signaling of EGFR-mediated ARF6 up-regulation also was investigated using specific inhibitors of mitogen-activated protein kinase (MEK), phosphatidylinositol 3' kinase (PI3K), and Janus kinase 2. The involvement of SP1 in the downstream signaling was studied by using an SP1 inhibitor (mithramycin A). Small-interfering RNAs (siRNAs) targeting ARF6 were used to investigate the effects of ARF6 on EGF-mediated glioma cell proliferation. RESULTS: : The results demonstrated that ARF6 and EGFR mRNA levels were elevated in glioma tissues. Furthermore, EGF stimulated ARF6 expression in U87 cells in a dose-dependent and time-dependant manner. This stimulation was caused by increased transcription of ARF6 and by activation of the MEK/extracellular signal-regulated kinase 1 and 2 (ERK1/2) and PI3K signaling pathways. It is noteworthy that SP1 was essential for EGF-induced ARF6 up-regulation. Finally, EGF-induced glioblastoma cell proliferation depended on ARF6, because the suppression of ARF6 by siRNA or by a dominant-negative mutant significantly inhibited EGF-induced cell proliferation. CONCLUSIONS: : The results of the current study suggested that EGF-induced ARF6 expression plays a significant role in glioma cell proliferation. Cancer 2009. (c) 2009 American Cancer Society. PMID- 19642174 TI - Alterations in the functional capacity of albumin in patients with decompensated cirrhosis is associated with increased mortality. AB - Albumin concentration is diminished in patients with liver failure. Albumin infusion improves survival of cirrhotic patients with spontaneous bacterial peritonitis, and it is hypothesized that this may be due in part to its detoxifying capabilities. The aim of this study was to perform detailed quantitative and qualitative assessment of albumin function in patients with cirrhosis. Healthy controls and patients with acute deterioration of cirrhosis requiring hospital admission (n = 34) were included. Albumin function was assessed using affinity of the fatty acid binding sites using a spin label (16 doxyl-stearate) titration and electron paramagnetic resonance spectroscopy and ischemia-modified albumin (IMA) was measured. Twenty-two patients developed acute on-chronic liver failure. Twelve were treated with the Molecular Adsorbents Recirculating System (MARS) and 10 with standard medical therapy. For each parameter measured, the patients' albumin had reduced functional ability, which worsened with disease severity. Fifteen patients died, and IMA, expressed as an albumin ratio (IMAR), was significantly higher in nonsurvivors compared with survivors (P < 0.001; area under the receiver operating curve = 0.8). No change in the patients' albumin function was observed following MARS therapy. A significant negative correlation between IMAR and the fatty acid binding coefficients for sites 1 and 2 (P < 0.001 for both) was observed, indicating possible sites of association on the protein. CONCLUSION: The results of this study suggests marked dysfunction of albumin function in advanced cirrhosis and provide further evidence for damage to the circulating albumin, which is not reversed by MARS therapy. IMAR correlates with disease severity and may have prognostic use in acute-on-chronic liver failure. PMID- 19642175 TI - A comparison of outcomes from treating hepatocellular carcinoma by hepatic artery embolization in patients younger or older than 70 years. AB - BACKGROUND: : The objective of this study was to compare the morbidity, mortality, and survival of patients aged <70 years and aged > or =70 years who underwent hepatic arterial embolization (HAE) for the treatment of hepatocellular carcinoma (HCC). METHODS: : Between 1997 and 2007, 386 patients underwent HAE for HCC at a single center. Two hundred patients were aged <70 years (153 men; median age, 60 years), and 186 patients were aged > or =70 years (128 men; median age, 75 years). Patients underwent a total 965 embolization procedures (median, 2 procedures per patient). Patient demographics, morbidity, mortality, length of hospital stay, and survival were analyzed. Complications were categorized using Common Terminology Criteria for Adverse Events, version 3.0 guidelines. Survival was calculated by using the Kaplan-Meier method. RESULTS: : There were no significant differences between younger and older groups in the incidence of infectious, hepatobiliary, renal, vascular, or miscellaneous complications (P > or = .05); complication severity (P = .82); procedural mortality (P = .63); length of hospitalization (P = .55); intensive care unit admission (P = .64); or overall survival (P = .30). There were more cardiopulmonary complications in the older group (P = .04), but the association of age and likelihood of a cardiopulmonary complication lost significance after adjusting for the presence of more cardiovascular comorbidities in the older group (P = .08). CONCLUSIONS: : Survival and mortality outcomes of HAE for the treatment of HCC were similar whether patients were aged <70 years or > or =70 years. Although patients aged > or =70 years with cardiovascular comorbidities more often had a cardiopulmonary complication, other morbidity measures, including complication severity, need for intensive care unit admission, and length of hospitalization, were similar between groups. Cancer 2009. (c) 2009 American Cancer Society. PMID- 19642176 TI - Risk score for outcome after allogeneic hematopoietic stem cell transplantation: a retrospective analysis. AB - BACKGROUND: It was investigated whether the European Group for Blood and Marrow Transplantation risk score, previously established for chronic myeloid leukemia, could be used to predict outcome after allogeneic hematopoietic stem cell transplantation (HSCT) for hematological disease in general. METHODS: Age of patient, disease stage, time interval from diagnosis to transplant, donor type, and donor-recipient sex combination were used to establish a score from 0 to 7 points. Its validity was tested in 56,505 patients, 33,113 (58%) male, 23,392 female, median age 33 years (range, 0.5-77 years), with an allogeneic HSCT for a hematological disorder between 1980 and 2005. RESULTS: Survival probability at 5 years decreased from 71% (95% confidence interval [CI], 69%-73%) for risk score 0 for the whole cohort (75%, 95% CI, 72%-78% for the most recent time cohort) to 24% (95% CI, 21%-27% for risk score 6 and 7; 25%, 95% CI, 22%-29% most recent cohort). Transplant-related mortality increased from 15% (95% CI, 14%-17%) for risk score 0 (11%, 95% CI, 9%-13%, most recent cohort) to 47% with risk score 6 and 7 (95% CI, 44%-50%) for the whole cohort (45%, 95% CI, 42%-48%, most recent cohort). The risk score was predictive in all disease categories, over all time periods, and was not altered by transplant techniques. CONCLUSIONS: Five well defined pretransplant patient and donor characteristics give a reasonable risk estimate of allogeneic HSCT. This risk score can provide a basis for the decision between transplant and nontransplant strategies. PMID- 19642177 TI - Accelerated treatment using intensity-modulated radiation therapy plus concurrent capecitabine for unresectable hepatocellular carcinoma. AB - BACKGROUND: : Patients with unresectable hepatocellular carcinoma (HCC) have limited treatment options. In this study, the authors investigated the feasibility, toxicity, and efficacy associated with intensity-modulated radiation therapy (IMRT) and concurrent, chronomodulated capecitabine in the treatment of unresectable HCC. METHODS: : Twenty patients underwent treatment planning for HCC confined to the liver with helical tomotherapy-based IMRT. Fifty-five percent of patients had Child-Pugh Class A disease, and 45% of patients had Class B disease. Ninety-five percent of patients were prescribed 50 gray (Gy) of radiotherapy to the planning target volume delivered in 20 fractions with concurrent, chronomodulated capecitabine. Transcatheter arterial chemoembolization preceded radiotherapy in 11 patients, and 9 patients received IMRT alone because of portal vein thrombosis, esophageal varices, or tumor size. RESULTS: : The mean greatest tumor dimension was 9 cm (range, 1.3-17.4 cm), the mean dose to normal liver was 22.6 Gy (range, 10-29.2 Gy), and the average volume of liver that received >30 Gy (V30) was 27.2% (range, 12%-43%). Eighteen patients (90%) completed the prescribed treatment of 50 Gy. There was no increase from baseline in acute or late toxicity greater than 2 grades. Partial response or disease stability was achieved at 3 months to 6 months after treatment in 15 of 16 patients (94%). The median survival (+/-standard deviation) for patients who had Child-Pugh Class A and B disease was 22.5 +/- 5.1 months and 8 +/- 3.3 months, respectively. CONCLUSIONS: : In this initial experience with accelerated IMRT plus capecitabine for patients who had large HCC lesions, the results demonstrated acceptable toxicity with promising local control. The relatively low acute and late toxicity observed with this program suggested that dose intensification can be incorporated into the treatment regimen if needed. Cancer 2009. (c) 2009 American Cancer Society. PMID- 19642178 TI - Primary percutaneous coronary intervention decision-making becomes more confusing: where do glycoprotein 2b/3a inhibitors "fit" now? PMID- 19642179 TI - Left main and multivessel coronary artery stenting for patients deemed inoperable A real need for a tandem approach. PMID- 19642180 TI - Two-stent technique: a dead duck or alive and kicking? PMID- 19642181 TI - SES for AMI: moving in the right direction. PMID- 19642182 TI - In-ambulance abciximab administration in STEMI patients prior to primary PCI is associated with smaller infarct size, improved LV function and lower incidence of heart failure: results from the Leiden MISSION! acute myocardial infarction treatment optimization program. AB - OBJECTIVES: Our aim was to evaluate the effects of early abciximab administration in the ambulance on immediate, short, and long term outcomes. BACKGROUND: Early abciximab administration before primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is recommended in practice guidelines. However, optimal timing of administration remains indistinct. METHODS: Within a fixed protocol for PPCI, December 2006 was the cut-off point for this prospective study. A total of 179 consecutive patients with STEMI were enrolled, 90 patients received abciximab bolus in the hospital (in-hospital group), and 89 patients received abciximab bolus in the ambulance (in-ambulance group). RESULTS: The two groups were comparable for baseline and angiographic characteristics. The in-ambulance group received abciximab within the golden period (median 63 min). The infarct related artery (IRA) patency at onset of the PCI was four times higher in the in-ambulance group compared to in-hospital group (odds ratio = 4.9, 95% CI 2.4-10.1). Enzymatic infarct size was smaller in the in ambulance group (cumulative 48-h CK release 8011 vs. 11267 U/L, P = 0.004). This was associated with higher left ventricular ejection fraction (LVEF) at 90 days post-PPCI measured by myocardial scintigraphy (59% vs. 54%, P = 0.01), and lower incidence of heart failure through a median of 210 days of clinical follow-up (3% vs.11%, P = 0.04). CONCLUSION: Early abciximab administration in the ambulance significantly improves early reperfusion in STEMI patients treated with PPCI. Moreover this is associated with a smaller infarct size, improved LV function and a lower risk of heart failure on clinical follow-up. PMID- 19642184 TI - Defining a new standard for IVUS optimized drug-eluting stent implantation--the PRAVIO study: do we know the right technique for stent optimization? PMID- 19642185 TI - Clinical investigation in ACS and PCI: shooting in the dark at a moving target. PMID- 19642186 TI - Treatment of ruptured coronary aneurysm with a novel covered stent. AB - Coronary artery aneurysms are relatively rare but have been diagnosed with increasing frequency since the advent of coronary arteriography. Their reported incidence varies from 1.5% to 5% with male dominance and a predilection for the right coronary artery (RCA), accounting for over 40% of all cases. The most common etiology amongst adults remains atherosclerosis accounting for 50% of coronary aneurysms. We describe the first use of a novel flexible pericardium covered stent for successful treatment of a ruptured coronary aneurysm in 76 year old lady. PMID- 19642187 TI - A horse, a horse, my kingdom for a horse. PMID- 19642189 TI - Transhepatic closure of patent foramen ovale. AB - Transhepatic right heart catheterization is an uncommon procedure for adult interventional cardiologists. We report its successful use for closure of a patent foramen ovale in an elderly patient without femoral vein access. Also described is a novel method of using a vascular plug to achieve hemostasis of the hepatic venous access site. PMID- 19642190 TI - Pulmonary artery growth following arterial duct stenting in congenital heart disease with duct-dependent pulmonary circulation. AB - OBJECTIVES: The aim of this study was to assess the pulmonary artery (PA) growth following arterial duct (AD) stenting in neonates with congenital heart disease (CHD) with duct-dependent pulmonary circulation. BACKGROUND: AD stenting is increasingly deemed as a reliable alternative to surgical shunt in CHD with duct dependent pulmonary circulation. Allowing the stent to conform to the PA anatomy might avoid any unbalance of lung perfusion and promote a uniform growth of the main PAs. METHODS: Of the 47 neonates and infants submitted to AD stenting as palliation of CHD with duct-dependent pulmonary circulation at our Institution, 15 underwent angiographic evaluation of the PA development before surgical repair due to progressive decrease of the systemic oxygen saturation. The Nakata and McGoon indexes as well as the left-to-right PA diameter ratio were considered as being indicative of global and balanced growth. RESULTS: Ductal stabilization was achieved with coronary stents dilated to 3.3 + or - 0.4 mm (range 2.5-4). The control angiography was performed 7 + or - 3 months (range 3-13) after the stenting procedure. At that time, the Nakata and McGoon indexes had significantly increased from 132 + or - 67 to 287 + or - 94 mm/m(2) and from 1.6 + or - 0.3 to 2.1 + or - 0.2 mm/m(2), respectively (P < 0.0001 for both comparisons), due to uniform vascular growth (left PA z-score from -0.7 + or - 1.6 to 1.4 + or - 1.2; right PA from -0.8 + or - 1.4 to 1.4 + or - 1.2, P < 0.0001 for both comparisons; final left-to-right PA ratio 0.9 + or - 0.1). CONCLUSIONS: Percutaneous AD stabilization with highly flexible coronary stents is effective in promoting a significant and balanced growth of the PAs in CHD with duct-dependent pulmonary circulation. PMID- 19642191 TI - Influence of obstructive sleep apnea and treatment with continuous positive airway pressure on fractional flow reserve measurements for coronary lesion assessment. AB - Obstructive sleep apnea (OSA) and sleep-disordered breathing have been implicated in the progression of cardiovascular disease and with increased risk of coronary artery disease, congestive heart failure, and stroke. Fractional flow reserve (FFR) is used to evaluate the physiological significance of coronary artery stenosis, and this technique is largely thought to be independent of systemic hemodynamic changes. Herein, we describe a case of OSA and sleep-disordered breathing cyclically altering FFR measurements from normal to abnormal in a patient with coronary artery disease. More specifically, we show that the abnormal FFR across a coronary lesion in a patient with sleep disordered apnea improves (to a normal threshold) with the initiation of continuous positive airway pressure (CPAP). This finding may have implications for the mechanisms of cardiac dysfunction in patients with OSA. PMID- 19642192 TI - First-in-man case report of the use of an Edwards-Sapien valve to treat a regurgitant CoreValve aortic valve prosthesis. AB - Transcatheter aortic valve implantation is an alternative to conventional aortic valve replacement for patients at high surgical risk, with favorable procedural outcomes. Aortic regurgitation remains an off-label indication. Recent case reports describe the successful use of a second CoreValve inside a malpositioned first CoreValve. In the current case, we report for the first time a valve-in valve procedure for the treatment of a severely insufficient CoreValve prosthesis using the Edwards-Sapien prosthesis. PMID- 19642193 TI - Diastolic transmitral valve pressure gradients in patients with severe calcific aortic stenosis. AB - BACKGROUND: During hemodynamic assessment prior to antegrade balloon aortic valvuloplasty (BAV), unanticipated transmitral valve pressure gradients (MVG) were noted frequently. AIM: To determine the prevalence and significance of a significant MVG in patients with aortic stenosis and no previously diagnosed mitral valve stenosis. METHOD: Retrospective chart review of patients with severe aortic stenosis who underwent antegrade BAV. During antegrade BAV, direct transseptal left atrial (LA) and left ventricular (LV) pressure measurements were obtained allowing for accurate assessment of MVG. Significant MVG is defined as a LA-LV gradient of > or =5 mm Hg. RESULTS: Eighty-two BAV patients were reviewed (mean age 84 +/- 8.9 years, mean additive Euroscore 10.5 +/- 2.2). The mean MVG was 5.0 +/- 3.5 mm Hg (range 0-14 mm Hg). A significant MVG was seen in 54.9% and, compared with no significant MVG, was associated at with significantly higher LA mean pressure (26.0 +/- 6.0 mm Hg vs. 16.8 +/- 6.6 mm Hg, P < 0.001), higher pulmonary arterial systolic pressure (59.3 +/- 14.7 mm Hg vs. 43.1 +/- 16.5 mm Hg, P < 0.001), and higher pulmonary mean systolic pressure (37.7 +/- 10.4 mm Hg vs. 28.0 +/- 11.4 mm Hg, P < 0.001). Statistically significant correlations were seen between MVG and LA mean pressure (r = 0.65, P < 0.001), pulmonary arterial systolic (r = 0.49, P < 0.001) and pulmonary arterial mean pressures (r = 0.41, P < 0.001). There was no association with cardiovascular risk factors, with presence or severity of mitral annular calcification (visually assessed on cine-fluoroscopy) or with the presence of mitral regurgitation. CONCLUSIONS: A significant MVG is commonly seen in patients with severe calcific aortic stenosis and is associated with higher pulmonary arterial and left atrial pressures. PMID- 19642194 TI - Neurodevelopmental consequences of Smn depletion in a mouse model of spinal muscular atrophy. AB - Deletions or mutations in survival of motor neuron 1 (SMN1) cause motor neuron loss and spinal muscular atrophy (SMA), a neuromuscular disorder, with the most severe type manifesting in utero. Whether SMA is a disease of defects in neurodevelopment and/or neuromaintenance remains unclear. We performed an analysis of Smn gene and protein expression during murine embryogenesis. Furthermore, we examined Smn(-/-);SMN2 mice, a model of very severe SMA, for developmental, morphological, and molecular abnormalities. We demonstrate that Smn transcript levels are regulated in a tissue- and developmental stage-specific manner and that the Smn protein expression pattern generally followed that of the Smn mRNA. Cell death and pathological foci were observed in E10.5 Smn-depleted embryos, and this increased in the telencephalon at E14.5. Furthermore, we show an altered morphology of cranial nerves as well as truncated lumbar spinal nerves in a subset of E10.5 Smn(-/-);SMN2 embryos. Finally, we compared the splicing of a subset of genes shown recently to be aberrantly spliced in phenotypic-stage SMA mice. Changes in alternative splicing of the Slc38a5 and Uspl1 genes were detectable in prephenotypic-stage embryos and neonates but became more pronounced with the severity of the phenotype. By comparison, Hif3a alternative splicing was affected only at the end stage of disease. This result suggests that alterations in mRNA splicing in SMA occur, in part, as a result of disease progression. Overall, we conclude that Smn depletion affects developmental processes, which ultimately may also contribute to SMA pathogenesis. PMID- 19642195 TI - Deletion of tau attenuates heat shock-induced injury in cultured cortical neurons. AB - The microtubule-associated protein tau has been implicated in beta-amyloid- and glutamate-induced neurotoxicity. However, the potential role of tau in response to other insults to neurons remains unclear. In this study, we examined whether deletion of tau would change cell injury induced by heat shock in primary cultures of cortical neurons. After 30 min of a 45 degrees C heat shock, lactate dehydrogenase (LDH) release increased, reaching a peak at 6 hr in wild-type (WT) neurons. A significantly lower LDH release, with a peak delayed by 24 hr, was detected in tau knockout (TKO) neurons. After heat shock treatment, MAP-2 and tubulin staining of the processes of WT neurons revealed more dramatic abnormalities than in TKO neurons. Both WT and TKO neurons exhibited a similar elevation of HSP70 level but different time courses of Akt phosphorylation. In contrast to an early, brief response in WT neurons, TKO neurons displayed a late, but long-lasting increase in phosphorylation of Akt and its downstream target, glycogen synthase kinase 3beta. Additionally, inhibition of Akt activity aggravated the cell morbidity caused by heat shock exposure in both WT and TKO neurons, indicating a protective role of Akt against cell injury. In conclusion, our results demonstrate that deletion of tau attenuated heat shock-induced neuronal injury. Enhanced Akt response in the absence of endogenous tau is suggested to represent a compensatory mechanism for regulating cell reactions to stress stimuli. PMID- 19642197 TI - Limitations of angiography for the assessment of renal artery stenosis and treatment implications. AB - Renovascular hypertension due to atherosclerotic renal artery stenosis is the most common cause of secondary hypertension. Percutaneous catheter-based renal artery revascularization has been increasingly utilized for the treatment of renal artery stenosis. Renal artery stenting has a high technical success rate, but the rate of improvement in hypertension is somewhat less than expected with this technique. Misinterpretation of angiographic images may play a role in these unfavorable clinical results. We present a case in which the diagnosis of severe renal artery stenosis was not apparent by angiography. Intravascular ultrasound and translesional pressure gradient measurements during arteriography can help to determine the precise severity of stenosis and may augment the clinical results of percutaneous renal artery stent placement. PMID- 19642196 TI - Down-modulation of programmed death 1 alters regulatory T cells and promotes experimental autoimmune encephalomyelitis. AB - The regulatory role of programmed death 1 (PD-1) was investigated in the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. Typical EAE could be induced by immunization without pertussis toxin (PTX) in PD-1-null but not in wild-type (WT) mice. However, both strains developed a similar EAE phenotype when immunized with PTX or by adoptive transfer of pathogenic T cells. In WT mice that did not develop EAE after immunization without PTX, the frequency of CD4(+)FoxP3(+) Treg cells was boosted in the periphery but not in the thymus. This increase in Treg frequency was abrogated by PD-1 deficiency or inclusion of PTX. In addition, PD-1 expression was critical to in vitro conversion of naive myelin-specific CD4 T cells into Treg cells and was directly related to Treg suppressive activity. Finally, PD-1 was markedly down-modulated in the periphery of WT mice after administration of PTX. Therefore, down-modulation of PD-1 in Treg cells may abrogate Treg-mediated immune suppression, permitting the activation of myelin-reactive T cells and induction of EAE. PMID- 19642198 TI - Passing sheaths and electrode catheters through inferior vena cava filters: safer than we think? AB - Inferior vena cava (IVC) filters are being inserted with increasing frequency for the prevention of pulmonary embolus. Previous case reports have documented the passage of up to three electrode catheters or an individual long sheath through an IVC filter. The current report expands on prior series with regard to the number of devices used. We describe our experience in 10 patients in whom up to five electrode catheters and/or sheaths were placed through an IVC filter using a transfemoral approach under fluoroscopic guidance without routine venography. Devices were successfully introduced and withdrawn in each case without filter dislodgment. Our series illustrates the feasibility and safety of passing multiple electrode catheters and long sheaths through an IVC filter. Evidence is accumulating to suggest that an IVC filter should not be considered an absolute contraindication to performing diagnostic or therapeutic procedures. PMID- 19642199 TI - Telescoping catheter technique for enlarged aortas. AB - Selective coronary angiography in severely dilated ascending aorta is technically challenging and sometimes impossible. The Terumo "five-in-six" system uses an extra long 5Fr guide catheter in a standard 6Fr guide catheter, so that the tip of the 5Fr guide catheter protrudes beyond the tip of the 6Fr catheter allowing an extra reach. This system has been used successfully to advance balloon catheters across chronic total occlusions (Takahashi et al, Catheter Cardiovasc Interv 2004;63:452-456) and stent delivery beyond proximal obstruction point (Mamas et al, Catheter Cardiovasc Interv 2008;71:358-363). We describe the successful use of this system in an atraumatic manner for selective coronary angiography in a patient with a severely dilated ascending aorta. PMID- 19642200 TI - Transcatheter closure of a traumatic VSD in an adult requiring an ASD occluder device. AB - Traumatic ventricular septal defects (VSD) can occur after blunt or penetrating chest trauma or cardiac procedures. There are few publications reporting the safety and efficacy of transcatheter closure of traumatic VSDs. We report a case of a large VSD resulting from penetrating chest trauma that was not repaired at the initial surgical procedure on the disrupted right ventricle. Because of the late identification of the VSD postoperatively, transcatheter closure after the original surgical procedure was recommended and performed requiring an Amplatzer atrial septal defect occluder device because of defect size and configuration. This case describes the technique and postprocedure imaging leading to a cautionary note regarding VSD closure device techniques. PMID- 19642201 TI - Mutant huntingtin and glycogen synthase kinase 3-beta accumulate in neuronal lipid rafts of a presymptomatic knock-in mouse model of Huntington's disease. AB - Patients with Huntington's disease have an expanded polyglutamine tract in huntingtin and suffer severe brain atrophy and neurodegeneration. Because membrane dysfunction can occur in Huntington's disease, we addressed whether mutant huntingtin in brain and primary neurons is present in lipid rafts, which are cholesterol-enriched membrane domains that mediate growth and survival signals. Biochemical analysis of detergent-resistant membranes from brains and primary neurons of wild-type and presymptomatic Huntington's disease knock-in mice showed that wild-type and mutant huntingtin were recovered in lipid raft enriched detergent-resistant membranes. The association with lipid rafts was stronger for mutant huntingtin than wild-type huntingtin. Lipid rafts extracted from Huntington's disease mice had normal levels of lipid raft markers (G(alphaq), Ras, and flotillin) but significantly more glycogen synthase kinase 3 beta. Increases in glycogen synthase kinase 3-beta have been associated with apoptotic cell death. Treating Huntington's disease primary neurons with inhibitors of glycogen synthase kinase 3-beta reduced neuronal death. We speculate that accumulation of mutant huntingtin and glycogen synthase kinase 3 beta in lipid rafts of presymptomatic Huntington's disease mouse neurons contributes to neurodegeneration in Huntington's disease. PMID- 19642202 TI - Memantine lowers amyloid-beta peptide levels in neuronal cultures and in APP/PS1 transgenic mice. AB - Memantine is a moderate-affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist that stabilizes cognitive, functional, and behavioral decline in patients with moderate to severe Alzheimer's disease (AD). In AD, the extracellular deposition of fibrillogenic amyloid-beta peptides (Abeta) occurs as a result of aberrant processing of the full-length Abeta precursor protein (APP). Memantine protects neurons from the neurotoxic effects of Abeta and improves cognition in transgenic mice with high brain levels of Abeta. However, it is unknown how memantine protects cells against neurodegeneration and affects APP processing and Abeta production. We report the effects of memantine in three different systems. In human neuroblastoma cells, memantine, at therapeutically relevant concentrations (1-4 muM), decreased levels of secreted APP and Abeta(1 40). Levels of the potentially amylodogenic Abeta(1-42) were undetectable in these cells. In primary rat cortical neuronal cultures, memantine treatment lowered Abeta(1-42) secretion. At the concentrations used, memantine treatment was not toxic to neuroblastoma or primary cultures and increased cell viability and/or metabolic activity under certain conditions. In APP/presenilin-1 (PS1) transgenic mice exhibiting high brain levels of Abeta(1-42), oral dosing of memantine (20 mg/kg/day for 8 days) produced a plasma drug concentration of 0.96 microM and significantly reduced the cortical levels of soluble Abeta(1-42). The ratio of Abeta(1-40)/Abeta(1-42) increased in treated mice, suggesting effects on the gamma-secretase complex. Thus, memantine reduces the levels of Abeta peptides at therapeutic concentrations and may inhibit the accumulation of fibrillogenic Abeta in mammalian brains. Memantine's ability to preserve neuronal cells against neurodegeneration, to increase metabolic activity, and to lower Abeta level has therapeutic implications for neurodegenerative disorders. PMID- 19642203 TI - Intraarterially delivered human umbilical cord blood-derived mesenchymal stem cells in canine cerebral ischemia. AB - The present study examined the effects of human umbilical cord blood-derived mesenchymal stem cells (HUCB-derived MSCs) delivered through the basilar artery in a canine thromboembolic brain ischemia model. Cerebral ischemia was induced through occlusion of the middle cerebral artery by injecting thrombus emboli into 10 beagles. In the HUCBC group (n = 5), 1 x 10(6) HUCB-derived MSCs were transplanted through the basilar artery 1 day after ischemic induction using an endovascular interventional approach. In the control group (n = 5), phosphate buffered saline (PBS) was injected in the same manner in as the HUCBC group. Upon neurobehavioral examination, earlier recovery was observed in the HUCBC group. The HUCBC group showed a decrease in the infarction volume at 1 week after cerebral ischemic induction, whereas the control group showed an increase in the infarction volume at 1 week, by magnetic resonance image analysis. Transplanted cells had differentiated into neurons and astrocytes and were observed in and around endothelial cells that were positive for von Willebrand factor (vWF). HUCB derived MSCs expressed neuroprotective factors, such as brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF), at 4 weeks after the transplantation. The transplanted cells demonstrated their efficacy by reducing the infarction lesion volume and through earlier recovery from the neurological deficit. These results suggest that intraarterial transplantation of HUCB-derived MSCs could be useful in clinical treatment of cerebral ischemia. PMID- 19642204 TI - Developmental plasticity in fish exposed to a water velocity gradient: a complex response. AB - Developmental plasticity plays a major role in evolution and provides an excellent context for unravelling the ecological implication of variation in abiotic factors to which developing fish are subjected. Water velocity has been known to induce plasticity in salmonids, but the ontogenetic component of these changes is poorly documented. Newly hatched specimens of rainbow trout (Oncorhynchus mykiss) were reared in four constant water velocity treatments (0.4, 0.8, 1.6 and 3.2 cm/sec) for a period of 100 days. Traditional and geometric morphometrics were used complementarily to characterize morphological changes among treatments throughout ontogeny and demonstrated early and complex developmental plasticity in O. mykiss. Certain traits display a constant direction of change, whereas other traits present a break point at 20-25 mm ( approximately 40-60 dph) indicating a modification in the nature of changes between developmental stages. Plasticity in response to water velocity was detected from very early on (15-20 mm; approximately 20-40 dph) and concerned mostly fin-related traits. Body-related traits did not respond conformingly to functional expectations as fishes reared in the fastest velocity treatment show a robust body shape more comparable to that of fish from the slowest treatment than do fish from the intermediate velocity. The noncongruence between treatment and response gradient suggests that different combinations of water velocity have the potential to lead to diverging interpretation of plasticity, both in an ecological and evolutionary context. Overall, the complex shape changes observed in O. mykiss stress the importance of paying better attention to actual functional requirements and adaptations that occur at levels other than hydrodynamics. PMID- 19642205 TI - Characterization of phospholipase A(2) activity in serum of the American alligator (Alligator mississippiensis). AB - PLA(2) is a diverse class of enzymes with a broad spectrum of physiological functions. Secretory PLA(2) isoforms have been reported to exhibit important innate immune function in higher vertebrates. This study was conducted to characterize PLA(2) activity in the serum of the American alligator (Alligator mississippiensis). We used a glycerophospholipid with a fatty acid in the sn-2 position labeled with a fluorescent probe (BODIPY) to detect and quantify alligator serum PLA(2) activity. Incubation of BODIPY-labeled bacteria with different concentrations of alligator serum resulted in a concentration-dependent detection of PLA(2) activity. Kinetic studies showed that product formation was rapid, with substantial activity within 5 min, and maximal activity at approximately 20 min. The alligator PLA(2) activity was temperature-dependent, with activity at lower temperatures (5-10 degrees C) approximately half of that observed at temperatures of 30-40 degrees C. In addition, the generation of fluorescent product was reduced by a specific inhibitor (p-bromophenacyl bromide) of secretory PLA(2) in a concentration-dependent manner, enforcing the idea that the observed activities are due to a secretory PLA(2) enzyme in alligator serum. PMID- 19642206 TI - Nutritional status, body composition, and intestinal parasitism among the Mbya Guarani communities of Misiones, Argentina. AB - Indigenous communities in Argentina represent socially and economically neglected populations. They are living in extreme poverty and environmental degradation conditions. New information about health status and socio-environmental features is urgently needed to be applied in future sanitary policies. Present study describes the nutritional status, body composition, and intestinal parasitism among Mbya-Guarani children from three communities in the Misiones Province. Anthropometric parameters were analyzed for 178 individuals (aged 1-14). Data were transformed to z-scores using NHANES I and II. Stunting showed the greatest prevalence (44.9%). Children were found to have low arm circumference and low arm muscle area, although with tricipital skinfold value near to the reference. They also tend to have shorter than normal lower limbs. Fecal samples and anal brushes (for Enterobius vermicularis) were collected in 45 children (aged 1-13). Ritchie's sedimentation and Willis' flotation techniques were used to determine parasitoses. Ninety five percent of children were infected with at least one species and 81.4% were polyparasitized. The higher prevalences corresponded to Blastocystis hominis, hookworms (Ancylostoma duodenale/Necator americanus), and Entamoeba coli. Associations occurred between hookworms with B. hominis/E. coli and B. hominis with nonpathogenic amoebas. Thirty nine percent of the children with stunting presented B. hominis, Strongyloides, and hookworms. Our results indicate that this indigenous population is subjected to extreme poverty conditions and is one of the most marginalized in this country. Severe growth stunting and parasitic infection are still quite common among Mbya children affecting about half of them along with significant changes in body composition and proportions. PMID- 19642207 TI - Impact of BRCA mutations on female fertility and offspring sex ratio. AB - Positive selection for inherited mutations in breast and ovarian cancer predisposing genes, BRCA1 and BRCA2, may contribute to the high frequency of BRCA mutations among the Ashkenazi Jewish population. Impact of BRCA mutations on fertility has not been generally explored in epidemiologic studies. There are reports of distorted sex ratios in BRCA carrier families but these findings have been attributed to bias. We investigated the effect of BRCA mutations on female fertility and offspring sex ratio in a study of 260 Ashkenazi Jewish women with ovarian cancer and 331 controls, unselected for age or family history of the disease. Pregnancy success was similar for 96 mutation carrier (0.84) and 164 noncarrier cases (0.87) and controls (0.83). After adjusting for covariates, there were no significant differences between BRCA carrier and noncarrier cases and controls with regards to fertility, despite lower pregnancy rates among all cases compared to controls (P = 0.0049). Male/female sex ratios were significantly lower among offspring of carriers (0.71) than offspring of noncarriers (0.95) or those of the controls (0.99). Comparisons among the three groups yielded statistically significant distortion against males among the offspring of known and obligate BRCA carriers compared to noncarriers (OR = 0.74, 95% CI:0.55-0.99) and controls (OR = 0.71, 95% CI:0.54-0.94). In conclusion, we did not find evidence for an effect of BRCA mutations on female fertility. We found a significant excess of females among the offspring of female carriers of BRCA1 and BRCA2 mutations. Potential contribution of observed sex ratio distortions to positive selection for BRCA mutations may warrant further investigation. PMID- 19642208 TI - Diverse modes of 5'-[4-(aminoiminomethyl)phenyl]-[2,2'-bifuran]-5-carboximidamide (DB832) interaction with multi-stranded DNA structures. AB - The modes of binding of 5'-[4-(aminoiminomethyl)phenyl]-[2,2'-Bifuran]-5 carboximidamide (DB832) to multi-stranded DNAs: human telomere quadruplex, monomolecular R-triplex, pyr/pur/pyr triplex consisting of 12 T*(T x A) triplets, and DNA double helical hairpin were studied. The optical adsorption of the ligand was used for monitoring the binding and for determination of the association constants and the numbers of binding sites. CD spectra of DB832 complexes with the oligonucleotides and the data on the energy transfer from DNA bases to the bound DB832 assisted in elucidating the binding modes. The affinity of DB832 to the studied multi-stranded DNAs was found to be greater (K(ass) approximately 10(7)M(-1)) than to the duplex DNA (K(ass) approximately 2 x 10(5)M(-1)). A considerable stabilizing effect of DB832 binding on R-triplex conformation was detected. The nature of the ligand tight binding differed for the studied multi stranded DNA depending on their specific conformational features: recombination type R-triplex demonstrated the highest affinity for DB832 groove binding, while pyr/pur/pyr TTA triplex favored DB832 intercalation at the end stacking contacts and the human telomere quadruplex d[AG(3)(T(2)AG(3))(3)] accommodated the ligand in a capping mode. Additionally, the pyr/pur/pyr TTA triplex and d[AG(3)(T(2)AG(3))(3)] quadruplex bound DB832 into their grooves, though with a markedly lesser affinity. DB832 may be useful for discrimination of the multi sranded DNA conformations and for R-triplex stabilization. PMID- 19642209 TI - Effect of polymer chemistry and fabrication method on protein release and stability from polyanhydride microspheres. AB - The release kinetics and stability of ovalbumin encapsulated into polyanhydride microspheres with varying chemistries were studied. Polymers based on the anhydride monomers sebacic acid (SA), 1,6-bis(p-carboxyphenoxy)hexane (CPH), and 1,8-bis (p-carboxyphenoxy)-3,6-dioxaoctane (CPTEG) were utilized. Microspheres were fabricated using two non-aqueous methods: a solid/oil/oil double emulsion technique and cryogenic atomization. The studies showed that the two fabrication methods did not significantly affect the release kinetics of ovalbumin, even though the burst release of the protein was a function of the fabrication method and the polymer chemistry. Antigenic stability of ovalbumin released from microspheres prepared by cryogenic atomization was studied by western blot analysis. These studies indicate that the amphiphilic CPTEG:CPH polyanhydrides preserved protein structure and enhanced protein stability by preserving the immunological epitopes of released protein. PMID- 19642210 TI - Serum levels of adiponectin in patients with aseptic loosening after total hip replacement. AB - The purpose of this study was to elucidate if the adiponectin level correlates with the survival of joint replacements. Current data indicates that adiponectin regulates lipid and glucose metabolism and acts anti-inflammatory and anti apoptotic. We compared the value of adiponectin in serum taken from patients with early loosening in the first 10 years after implantation with serum from patients with late loosening and from patients without any kind of arthroplasty. Adiponectin was measured using a human Adiponectin ELISA test kit. Serum levels of adiponectin were significantly (p < 0.001) lower in patients with a short hip arthroplasty survivorship of up to 10 years (4.10 mg/microL) in comparison with those from patients undergoing exchange hip arthroplasty later than 10 years after primary surgery (10.86 mg/microL). We speculate that increased adiponectin serum levels may be associated with increased survival of hip replacements by reducing wear particle-induced inflammatory reactions and promoting clearance of apoptotic cell remnants. In conclusion, patients with low levels of adiponectin may have a significantly higher risk for early aseptic loosening when compared with patients with a high level. PMID- 19642211 TI - Spiral-structured, nanofibrous, 3D scaffolds for bone tissue engineering. AB - Polymeric nanofiber matrices have already been widely used in tissue engineering. However, the fabrication of nanofibers into complex three-dimensional (3D) structures is restricted due to current manufacturing techniques. To overcome this limitation, we have incorporated nanofibers onto spiral-structured 3D scaffolds made of poly (epsilon-caprolactone) (PCL). The spiral structure with open geometries, large surface areas, and porosity will be helpful for improving nutrient transport and cell penetration into the scaffolds, which are otherwise limited in conventional tissue-engineered scaffolds for large bone defects repair. To investigate the effect of structure and fiber coating on the performance of the scaffolds, three groups of scaffolds including cylindrical PCL scaffolds, spiral PCL scaffolds (without fiber coating), and spiral-structured fibrous PCL scaffolds (with fiber coating) have been prepared. The morphology, porosity, and mechanical properties of the scaffolds have been characterized. Furthermore, human osteoblast cells are seeded on these scaffolds, and the cell attachment, proliferation, differentiation, and mineralized matrix deposition on the scaffolds are evaluated. The results indicated that the spiral scaffolds possess porosities within the range of human trabecular bone and an appropriate pore structure for cell growth, and significantly lower compressive modulus and strength than cylindrical scaffolds. When compared with the cylindrical scaffolds, the spiral-structured scaffolds demonstrated enhanced cell proliferation, differentiation, and mineralization and allowed better cellular growth and penetration. The incorporation of nanofibers onto spiral scaffolds further enhanced cell attachment, proliferation, and differentiation. These studies suggest that spiral-structured nanofibrous scaffolds may serve as promising alternatives for bone tissue engineering applications. PMID- 19642212 TI - Differential mutagenicity of aflatoxin B1 in the liver of neonatal and adult mice. AB - Children are generally more sensitive to toxicants than adults, including an increased sensitivity to genotoxic carcinogens. We previously demonstrated that neonatal mice are also more sensitive to the mutagenic effects of the direct alkylating agents N-ethyl-N-nitrosoamine and the arylamine 4-aminobiphenyl than adult mice. In this study, we have evaluated the effect of age on the mutagenicity of the fungal toxin and liver carcinogen aflatoxin B(1) (AFB(1)). Neonatal Big Blue transgenic mice were treated with 6 mg/kg AFB(1), a treatment that produces liver tumors, while adult mice were treated with 6 and 60 mg/kg AFB(1), treatments that do not result in tumors. The cII liver mutant frequency (MF) in mice treated with AFB(1) as neonates was 22-fold higher than in control neonatal mice, whereas the treatment of adult mice with either dose of AFB(1) did not significantly increase the liver MF over the controls. In AFB(1)-treated neonatal mice, the frequency of G:C --> T:A transversion, a major type of mutation induced by AFB(1), was about 82-fold higher than for the control and 31 fold higher than for adult mice treated with 60 mg/kg AFB(1). Our mutagenicity findings parallel the relative carcinogenicity of AFB(1) in neonatal and adult mice, and are consistent with previous observations of the lower level of hepatic glutathione S-transferase and higher level of hepatic AFB(1)-DNA adduction in neonatal mice compared to adult mice. PMID- 19642213 TI - Speeding the flow toward personalized therapy in childhood acute leukemia. PMID- 19642214 TI - Five-year longitudinal predictive factors for disordered eating in a population based sample of overweight adolescents: implications for prevention and treatment. AB - OBJECTIVE: The objective of this study is to identify predictors of prevalence and incidence of disordered eating (binge eating and extreme weight control behaviors) among overweight adolescents. METHOD: Five-year longitudinal associations were examined in 412 overweight adolescents who participated in Project EAT-I and II. RESULTS: Among both overweight males and females, risk factors for disordered eating included exposure to weight loss magazine articles, higher weight importance, and unhealthy weight control behaviors, while family connectedness, body satisfaction, and regular meals were protective factors, although there were some differences in predictors of prevalence (total cases) versus incidence (new cases) of disordered eating. Among males, poor eating patterns, including fast food and sweetened beverage intake, increased risk for disordered eating, and the use of healthy weight control behaviors was protective. DISCUSSION: Attention should be directed toward decreasing disordered eating among overweight adolescents. Findings suggest the importance of promoting positive family relationships, psychological health, and regular meals, and steering adolescents away from overemphasizing weight and using unhealthy weight control behaviors. PMID- 19642215 TI - The validity and clinical utility of purging disorder. AB - OBJECTIVE: To review evidence of the validity and clinical utility of Purging Disorder and examine options for the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-V). METHOD: Articles were identified by computerized and manual searches and reviewed to address five questions about Purging Disorder: Is there "ample" literature? Is the syndrome clearly defined? Can it be measured and diagnosed reliably? Can it be differentiated from other eating disorders? Is there evidence of syndrome validity? RESULTS: Although empirical classification and concurrent validity studies provide emerging support for the distinctiveness of Purging Disorder, questions remain about definition, diagnostic reliability in clinical settings, and clinical utility (i.e., prognostic validity). DISCUSSION: We discuss strengths and weaknesses associated with various options for the status of Purging Disorder in the DSM-V ranging from making no changes from DSM-IV to designating Purging Disorder a diagnosis on equal footing with Anorexia Nervosa and Bulimia Nervosa. PMID- 19642216 TI - Regenerating titanium ventricular assist device surfaces after gold/palladium coating for scanning electron microscopy. AB - Titanium is one of the most commonly used materials for implantable devices in humans. Scanning electron microscopy (SEM) serves as an important tool for imaging titanium surfaces and analyzing cells and other organic matter adhering to titanium implants. However, high-vacuum SEM imaging of a nonconductive sample requires a conductive coating on the surface. A gold/palladium coating is commonly used and to date no method has been described to "clean" such gold/palladium covered surfaces for repeated experiments without etching the titanium itself. This constitutes a major problem with titanium-based implantable devices which are very expensive and thus in short supply. Our objective was to devise a protocol to regenerate titaniumsurfaces after SEM analysis. In a series of experiments, titanium samples from implantable cardiac assist devices were coated with fibronectin, seeded with cells and then coated with gold/palladium for SEM analysis. X-ray photoelectron spectroscopy spectra were obtained before and after five different cleaning protocols. Treatment with aqua regia (a 1:3 solution of concentrated nitric and hydrochloric acid), with or without ozonolysis, followed by sonication in soap solution and sonication in deionized water, allowed regenerating titanium surfaces to their original state. Atomic force microscopy confirmed that the established protocol did not alter the titanium microstructure. The protocol described herein is applicable to almost all titanium surfaces used in biomedical sciences and because of its short exposure time to aqua regia, will likely work for many titanium alloys as well. PMID- 19642217 TI - Pregabalin- and gabapentin-associated myoclonus in a patient with chronic renal failure. PMID- 19642219 TI - Increased cortical nitric oxide release after phencyclidine administration. AB - Phencyclidine exerts psychotomimetic effects in humans and is used as a pharmacological animal model for schizophrenia. We, and others, have demonstrated that phencyclidine induces cognitive deficits in rats that are associated with schizophrenia. These cognitive deficits can be normalized by inhibition of nitric oxide synthase. The development of selective microelectrochemical nitric oxide sensors may provide direct evidence for the involvement of nitric oxide in these effects. The aim of the present study was to use LIVE (long term in vivo electrochemistry) to investigate the effect of phencyclidine, alone or in combination with the nitric oxide synthase inhibitor L-NAME, on nitric oxide levels in the medial prefrontal cortex of freely moving rats. Phencyclidine (2 mg kg(-1)) produced an increase in cortical nitric oxide levels and this increase was ameliorated by L-NAME (10 mg kg(-1)). Tentatively, the results from the present study provide a biochemical rationale for the involvement of nitric oxide in the phencyclidine model of schizophrenia. PMID- 19642220 TI - Antioxidants in colostrum and milk of sows and cows. AB - On account of the oxidative stress conditions that may appear during parturition, colostrum should provide with not only nutritional and immunological components but also antioxidative protection of newborn. There is evidence that apart from well-known antioxidative enzymes like glutathione peroxidase, superoxide dismutase, catalase or low molecular antioxidants, proteins like lactoperoxidase (LPO), lactoferrin (LF) and ceruloplasmin (CP) may exert antioxidative properties in colostrum. The aim of present study was to determine and to evaluate LPO, LF and CP activities in colostrum and milk of sows and cows. Samples were collected from 16 healthy cows five times: immediately after parturition, 12, 24 and 48 h, and 7 days postpartum as well as from 14 healthy sows five times: immediately after parturition, 6, 12, 24 and 36 h later. Examined parameters were determined spectrophotometrically at 412, 560 and 540 nm respectively. LPO activity was higher in sows as in cows and increased significantly within examined time. LF ability to inhibit superoxide radical generation was higher in sows as in cows and increased significantly within examined time. CP oxidase activity was higher in cows as in sows and decreased significantly during experimental period. In conclusion, antioxidative defence system in colostrum shows dynamic changes that allow for providing with necessary protection from oxidative stress conditions, which may appear after parturition. PMID- 19642218 TI - GABAA-benzodiazepine receptor availability in smokers and nonsmokers: relationship to subsyndromal anxiety and depression. AB - Many smokers experience subsyndromal anxiety symptoms while smoking and during acute abstinence, which may contribute to relapse. We hypothesized that cortical gamma aminobutyric acid(A)-benzodiazepine receptor (GABA(A)-BZR) availability in smokers and nonsmokers might be related to the expression of subsyndromal anxiety, depressive, and pain symptoms. Cortical GABA(A)-BZRs were imaged in 15 smokers (8 men and 7 women), and 15 healthy age and sex-matched nonsmokers, and 4 abstinent tobacco smokers (3 men; 1 woman) using [(123)I]iomazenil and single photon emission computed tomography (SPECT). Anxiety and depressive symptoms were measured using the Spielberger's State-Trait Anxiety Index (STAI) and the Center for Epidemiology Scale for Depressive Symptoms (CES-D). The cold pressor task was administered to assess pain tolerance and sensitivity. The relationship between cortical GABA(A)-BZR availability, smoking status, and subsyndromal depression and anxiety symptoms, as well as pain tolerance and sensitivity, were evaluated. Surprisingly, there were no statistically significant differences in overall GABA(A)-BZR availability between smokers and nonsmokers or between active and abstinent smokers; however, cortical GABA(A)-BZR availability negatively correlated with subsyndromal state anxiety symptoms in nonsmokers but not in smokers. In nonsmokers, the correlation was seen across many brain areas with state anxiety [parietal (r = -0.47, P = 0.03), frontal (r = -0.46, P = 0.03), anterior cingulate (r = -0.47, P = 0.04), temporal (r = -0.47, P = 0.03), occipital (r = -0.43, P = 0.05) cortices, and cerebellum (r = -0.46, P = 0.04)], trait anxiety [parietal (r = -0.72, P = 0.02), frontal (r = -0.72, P = 0.02), and occipital (r = -0.65, P = 0.04) cortices] and depressive symptoms [parietal (r = 0.68; P = 0.02), frontal (r = -0.65; P = 0.03), anterior cingulate (r = -0.61; P = 0.04), and temporal (r = -0.66; P = 0.02) cortices]. The finding that a similar relationship between GABA(A)-BZR availability and anxiety symptoms was not observed in smokers suggests that there is a difference in GABA(A)-BZR function, but not number, in smokers. Thus, while subsyndromal anxiety and depressive symptoms in nonsmokers may be determined in part by GABA(A)-BZR availability, smoking disrupts this relationship. Aberrant regulation of GABA(A)-BZR function in vulnerable smokers may explain why some smokers experience subsyndromal anxiety and depression. PMID- 19642221 TI - Thrombopoietin and thrombopoietin mimetics in the treatment of thrombocytopenia. AB - Although the thrombopoietin receptor was discovered in 1991 and thrombopoietin (TPO) was purified in 1994, the development of a clinically useful TPO was hampered by the appearance of neutralizing antibodies to some forms of recombinant TPO. However, in 2008 two new drugs that mimic the effect of TPO became available to treat thrombocytopenia. Romiplostim is a TPO peptide mimetic given by subcutaneous injection that activates the TPO receptor by binding to the distal hematopoietic receptor domain just like TPO. Eltrombopag is a TPO nonpeptide mimetic administered orally that activates the TPO receptor by binding to the transmembrane domain. Both increase the platelet count in healthy humans as well as in >80% of patients with immune thrombocytopenic purpura (ITP). Although initially restricted to the second-line treatment of ITP, both agents could help treat many thrombocytopenic disorders. Both agents are well tolerated, with mild headache being the most common complaint. Potential long-term complications include thrombosis, increased bone marrow reticulin, rebound worsening of thrombocytopenia upon discontinuation, and increased blast formation. Ongoing studies should establish the incidence of these complications and determine the efficacy of these new agents in a variety of other thrombocytopenic conditions. PMID- 19642223 TI - Re-modelling the piggery breeding unit may affect the farrowing rate. AB - The objective of this retrospective cohort study was to clarify the effect of re modelling the breeding unit on farrowing rate. The original study population included 63 sow herds that participated in the Finnish herd surveillance system. In these herds, the breeding units were re-modelled between 1995 and 2002. Information about the production system and other herd data for the last year before and the second year after re-modelling were available for 47 herds. The herds had an average of 68.5 (SD 45) sows per herd. Data were collected during one farm visit per herd. Initially, all herds had individual cages in their breeding units. The piggeries had either re-modelled their cages or switched to a group housing system with deep-litter, solid or slatted (partly or totally) floors. Farrowing rates were gathered from the national database, and data were tested with a linear regression model. Re-modelling did not have an effect on farrowing rate if initial reproductive performance of the herd was neglected. However, when farms were stratified according to performance prior to the beginning of study, namely into 'farms with initially high farrowing rate' (HF) and 'farms with initially low farrowing rate' (LF), the re-modelling had a significant effect on farrowing rate. In the HF farms, re-modelling caused a decrease in farrowing rate. Correspondingly, farrowing rate increased after remodelling in the LF farms. Farrowing rate was also influenced by mean parity of sows and by proportion of sows culled because of leg problems. This study could not show a profound impact of the design of the breeding unit on the fertility of the sow in the modern commercial production environment if the farm's reproductive performance before re-modelling was neglected. However, when initial performance was taken into account, re-modelling revealed significant, although varying effects on farrowing rate. PMID- 19642222 TI - Effects of maternal undernutrition on the hypothalamic-pituitary-gonadal axis function in female sheep offspring. AB - A study was conducted to evaluate the effects of maternal undernutrition on the hypothalamic-pituitary-gonadal axis in female sheep offspring. Pregnant ewes were fed to 100% throughout pregnancy (Control) or to 50% from 0 to 30 (R1) or from 31 to 100 days of gestation (R2). Female lambs were selected and fed to appetite throughout the study. At 2, 5.5 and 10 months of age a GnRH challenge was conducted. At the age of 10 months lambs were synchronized and blood samples were collected at 3 h intervals for 72 h following sponge removal. At slaughter (10 months) ovaries were removed and examined macroscopically. Maternal undernutrition did not affect the time of the onset of puberty, defined as the first increase in plasma progesterone concentrations >or=1 ng/ml. The magnitude of the pre-ovulatory gonadotrophin surge and the time to surge were unaffected by treatment. The LH and FSH response to GnRH challenge did not differ between groups at 2 and 5.5 months but at 10 months of age a higher (p < 0.05) FSH response was found in R1 group. Although the total number of visible follicles and corpora lutea did not differ between groups, a significant higher (p < 0.05) number of small (2-3 mm diameter) follicles in R1 group and a significant lower number (p < 0.05) of corpora lutea with diameter 8-11 mm and not even one with diameter >12 mm were detected in the ovaries of R2 lambs. In conclusion, maternal undernutrition during the first month of pregnancy resulted in increased pituitary sensitivity to GnRH and increased number of small follicles in the ovary, while during mid to late gestation resulted in a reduction of large corpora lutea in female offspring. PMID- 19642224 TI - Occupational allergy caused by marigold (Tagetes erecta) flour inhalation. PMID- 19642225 TI - Efficacy of additional ablation of complex fractionated atrial electrograms for catheter ablation of nonparoxysmal atrial fibrillation. AB - BACKGROUND: The efficacy of ablation of complex fractionated atrial electrograms (CFEs) in the single ablation procedure for nonparoxysmal atrial fibrillation (AF) patients is not well demonstrated. The aim of this study was to compare the ablation strategies of pulmonary vein isolation (PVI) plus linear ablation with and without additional ablation ofCFEs in these patients. METHODS: Consecutive 60 patients (49 +/- 11 years old, 50 male, 10 female) with nonparoxysmal AF underwent catheter ablation guided by a NavX mapping system. A stepwise approach included a circumferential PVI and left atrial (LA) linear ablation followed by either the additional ablation of continuous CFEs in the LA/coronary sinus (the first 30 patients) or not (the second 30 patients), detected by an automatic algorithm. RESULTS: There was no difference in the baseline characteristics between the two groups. Complete PVI eliminated some continuous CFEs and altered the distribution of CFEs. Following PVI and linear ablation,the remaining continuous CFEs were identified in 7.9 +/-10% mapping sites of the LA and CS, and were ablated successfully with a procedural AF termination rate of 53%. With a follow-up of 19 +/-11 months, a Kaplan-Meier analysis showed that the patients with additional ablation of the CFEs had a higher rate of sinus rhythm maintenance. Multivariate analysis showed the single procedure success could be predicted by the procedural AF termination and the additional ablation of continuous CFEs in the LA/CS. CONCLUSIONS: Ablation of continuous CFEs after PVI and LA linear ablation had a better long-term efficacy based on the results of single-ablation procedure. PMID- 19642226 TI - Synaptic scaffolding molecule binds to and regulates vasoactive intestinal polypeptide type-1 receptor in epithelial cells. AB - BACKGROUND & AIMS: Vasoactive intestinal polypeptide (VIP) is a principal regulator of fluid and electrolyte secretion in the gastrointestinal system. The VIP type-1 receptor (VPAC1), a class II G-protein-coupled receptor, contains a putative C-terminal PDZ-binding motif. A yeast 2-hybrid screen indicated that the C-terminus of VPAC1 bound to the PDZ domain of synaptic scaffolding molecule (S SCAM, also known as membrane-associated guanylate kinase inverted-2 [MAGI-2]). We analyzed the association between S-SCAM and VPAC1. METHODS: The biochemical properties and physiologic significance of the interaction between VPAC1 and S SCAM were examined in heterologous expression systems, T84 colonic epithelial cells, and human pancreas and colon tissues using an integrated molecular and physiologic approach. RESULTS: The physical interaction between VPAC1 and S-SCAM was confirmed by immunoprecipitation in HEK 293 mammalian cells and human pancreatic and colonic tissues. Immunocytochemical analysis indicated that S-SCAM recruited VPAC1 to the junctional area near the apical end of the lateral membrane in T84 cells. Several lines of evidence revealed that S-SCAM inhibits VPAC1 activation. Overexpression of S-SCAM inhibited VPAC1-mediated cAMP production and agonist-induced VPAC1 internalization in HEK 293 and HeLa cells. In addition, S-SCAM decreased the VPAC1-mediated current through the cystic fibrosis transmembrane conductance regulator in Xenopus oocytes, especially at low concentrations of VIP. Importantly, loss of S-SCAM increased VIP-induced short-circuit currents in T84 monolayers, which endogenously express VPAC1 and S SCAM. CONCLUSIONS: S-SCAM/MAGI-2 interacts with and regulates VPAC1 intracellular localization in epithelial cells and inhibits VPAC1 agonist-induced activation and internalization. PMID- 19642227 TI - Proceedings of the 2008 Red Cell Conference held at the University of Rochester, New York, in memory of Philip Knauf. PMID- 19642228 TI - Patient-at-risk scores. PMID- 19642229 TI - Identifying hidden conditions. PMID- 19642230 TI - RNs are leaders in long-term care. PMID- 19642231 TI - A nurse is NOT a nurse is NOT a nurse. PMID- 19642232 TI - [Intestinal helminthosis in schoolchildren living in rural and urban areas of Tissale, Ivory Coast]. PMID- 19642234 TI - Actinomycosis of the appendix and pelvis. PMID- 19642235 TI - Retraction notice to "Effluent treatment process in molasses-based distillery industries: a review". [J. Hazard. Mater. 152(2) (2008) 453-462]. PMID- 19642236 TI - GlaxoSmithKline, Pfizer to merge HIV drug units in new company. PMID- 19642237 TI - Cepheid unveils fast TB test to aid developing countries. PMID- 19642238 TI - Routine HIV screening, Part 2: beyond testing and referral. PMID- 19642239 TI - CCR5 antagonists in the treatment of HIV-infected persons: is their cancer risk increased, decreased, or unchanged. PMID- 19642240 TI - Images in HIV/AIDS. Unsuspected parvovirus B19 infection in a person with AIDS. PMID- 19642241 TI - Colitis and gastroparesis associated with syphilis in an HIV-infected person with an undetectable viral load. AB - We present a patient with fully controlled HIV disease and a normal CD4 count whose initial treatment for syphilis failed. Biopsy-proven syphilitic colitis and severe gastroparesis developed, requiring the insertion of a temporary percutaneous gastrostomy tube. The patient responded to a course of high-dose aqueous crystalline penicillin followed by doxycycline, and he completely recovered. The occurrence of failure of conventional syphilis treatment in HIV infected patients is discussed. PMID- 19642242 TI - Isolated unilateral acute retinal necrosis syndrome as the initial manifestation of HIV infection. AB - We report a rare case of isolated unilateral acute retinal necrosis syndrome without any history of associated herpes zoster or other conditions attributed to HIV infection as the initial manifestation of HIV infection. A 30-year-old man presented with a history of sudden diminished vision in the right eye with no apparent predisposing factors. Examination revealed right eye acute retinal necrosis. All laboratory test results were normal except the patient tested positive for HIV. This case of an atypical ophthalmic manifestation as initial presentation of HIV infection highlights the need for increased index of suspicion for HIV infection in young patients with acute retinal necrosis syndrome. PMID- 19642243 TI - Acute renal failure in patients with AIDS on tenofovir while receiving prolonged vancomycin course for osteomyelitis. AB - Renal failure developed after a prolonged course of vancomycin therapy in 2 patients who were receiving tenofovir disoproxil fumarate as part of an antiretroviral regimen. Tenofovir has been implicated in the development of Fanconi syndrome and renal insufficiency because of its effects on the proximal renal tubule. Vancomycin nephrotoxicity is infrequent but may result from coadministration with a nephrotoxic agent. Clinicians should be aware that tenofovir may raise the risk of renal failure during prolonged administration of vancomycin. PMID- 19642244 TI - Editorial comment: mixing tenofovir with other nephrotoxins--how safe is this? PMID- 19642245 TI - Position of the American Dietetic Association: Food and water safety. AB - It is the position of the American Dietetic Association that the public has the right to a safe food and water supply. The Association supports collaboration among food and nutrition professionals, academics, representatives of the agricultural and food industries, and appropriate government agencies to ensure the safety of the food and water supply by providing education to the public and industry, promoting technological innovation and applications, and supporting further research. New food and water safety issues evolve as the environment changes. Food and nutrition professionals should collaborate with food and agriculture industries and members of the medical community in a joint effort to address these issues. Recent food- and waterborne illnesses have occurred in new settings and/or unique foods not traditionally associated with foodborne illness outbreaks. New issues associated with food safety and security that have emerged support the need for continued education and research. Government programs have developed powerful tools such as FoodNet and PulseNet to detect food- and waterborne illness outbreaks in the United States. These government programs have provided the data to enhance public policy and educational programs such as FightBac! Mandatory and voluntary adoption of Hazard Analysis Critical Control Points in the foodservice and processing industries have contributed to a decrease in foodborne illness outbreaks from traditional foods and some microorganisms usually associated with foodborne illnesses. Food and nutrition professionals are positioned to provide food and water safety education in community, clinical settings, and foodservice operations and food industries. With an aging population and an increased number of people at risk due to medical conditions for food- and waterborne illness, food and nutrition professionals should be involved in collaborative food and water safety issues in educational, research, and policy agenda settings. As the food and nutrition experts, food and nutrition professionals must assume a major role in food and water safety education and research. PMID- 19642246 TI - American Dietetic Association/Commission on Dietetic Registration code of ethics for the profession of dietetics and process for consideration of ethics issues. PMID- 19642247 TI - American Dietetic Association: Standards of practice and standards of professional performance (generalist, specialty, and advanced) for registered dietitians in pediatric nutrition. PMID- 19642248 TI - Imaging of cardiac masses and myocardial disease: self-assessment module. AB - The educational objectives for this self-assessment module on imaging of cardiac masses and myocardial disease are for the participant to exercise, self-assess, and improve his or her knowledge of imaging and the clinical features of cardiac masses and myocardial disease, with emphasis on CT and MRI. PMID- 19642249 TI - Diagnostic imaging approach to dextrocardia: self-assessment module. AB - The educational objectives for this self-assessment module are for the participant to exercise, self-assess, and improve his or her understanding of the diagnostic imaging approach to dextrocardia. PMID- 19642251 TI - Potential side effects of gadolinium-enhanced MRI . PMID- 19642250 TI - Safe MR practices: self-assessment module. AB - The educational objectives for this self-assessment module on safe MR practices are for the participant to exercise, self-assess, and improve his or her knowledge of hazards to patients, medical personnel, and others in the MR scanner environment, and to exercise, self-assess, and improve his or her knowledge of safe practices in the operation of MR scanners. PMID- 19642252 TI - Information from your family doctor. Obsessive-compulsive disorder. PMID- 19642253 TI - Information from your family doctor. Keloids: prevention and treatment. PMID- 19642254 TI - Imaging of congenital uterine anomalies: review and self-assessment module. AB - OBJECTIVE: The educational objectives of this continuing medical education activity are for the reader to exercise, self-assess, and improve skills in diagnostic radiology with regard to the interpretation of hysterosalpingograms and magnetic resonance imaging (MRI) of the female pelvis in the evaluation of recurrent reproductive failure caused by congenital uterine anomalies. CONCLUSION: This article reviews the common congenital uterine anomalies,characteristic imaging features of each anomaly by hysterosalpingography and MRI, and the clinical importance of diagnosing and properly categorizing each anomaly. PMID- 19642255 TI - 'For the benefit of the people': the Dutch translation of the Fasciculus medicinae, Antwerp 1512. AB - The article deals with the Dutch translation of the Fasciculus medicinae based on the Latin edition, Venice 1495, with the famous woodcuts created in 1494 for the Italian translation of the original Latin edition of 1491. The woodcuts are compared with the Venetian model. New features in the Antwerp edition include the Skeleton and the Zodiac Man, bot originally based on German models. The text also deals with other woodcuts in the Low Countries based on these Venetian illustrations. The Appendices provide a short title catalog of all the editions and translations based on the Venetian edition and a stemma. PMID- 19642256 TI - Imaging popliteal artery disease in young adults with claudication: self assessment module. AB - The educational objectives of this self-assessment module on imaging popliteal artery disease in young adults with intermittent claudication are for the participant to exercise, self-assess, and improve his or her knowledge of the imaging and clinical features of popliteal artery entrapment syndrome, cystic adventitial disease,and masses associated with popliteal artery obstruction. PMID- 19642257 TI - Adults respondent with a problem drinking father were more likely to have been diagnosed with mental health problems relative to other respondents, while those with a problem drinking mother had poor self-perceived health and mental health (SF-12) scores. PMID- 19642258 TI - [EBM (evidence based medicine) and ethics]. PMID- 19642259 TI - [Peracute meningococcal sepsis in a 14-year-old female patient]. PMID- 19642260 TI - Imaging of chronic and exotic sinonasal disease: self-assessment module. AB - Chronic sinusitis is one of the most commonly diagnosed illnesses in the United States. This article focuses on the anatomy, pathophysiology, microbiology, and diagnosis of sinonasal disease, including chronic and fungal sinusitis, juvenile nasopharyngeal angiofibroma, inverted papilloma, and chondrosarcoma. PMID- 19642261 TI - Radiologic diagnosis of cerebral venous thrombosis: self-assessment module. AB - The educational objectives of this self-assessment module are for the participant to exercise, self-assess, and improve his or her understanding of the radiologic diagnosis of cerebral venous thrombosis. PMID- 19642262 TI - A health insurance exchange: prototypes and design issues. AB - Many reform proposals call for the creation of one or more health insurance exchanges, intermediaries that can help individuals or small employers navigate the insurance market. An exchange might be public or private, national or local. It might serve simply as a clearinghouse for plan information or could play an active role in setting benefit packages, choosing high-quality plans, and negotiating premium rates. This paper begins with a summary of recent experience with insurance exchanges and similar systems. It then reviews basic issues in the design of an exchange. PMID- 19642263 TI - Show me the money: the implications of Schedule H. AB - Responding to policymakers' concerns, the Internal Revenue Service (IRS) implemented significant new hospital community benefit reporting under Schedule H of its revised Form 990, the return used by tax-exempt organizations. This issue brief considers the policy implications of the quantitative and qualitative information that hospitals are now mandated to report through Schedule H, including the costs associated with charity care, bad debt, and the unreimbursed costs of Medicaid and Medicare. The paper examines unresolved issues related to the new reporting requirements, such as controversies regarding the scope of Schedule H, and considers the potential for these reports to influence IRS oversight activities, legislative action, and hospital policies and practices. PMID- 19642264 TI - An ORFome assembly approach to metagenomics sequences analysis. AB - Metagenomics is an emerging methodology for the direct genomic analysis of a mixed community of uncultured microorganisms. The current analyses of metagenomics data largely rely on the computational tools originally designed for microbial genomics projects. The challenge of assembling metagenomic sequences arises mainly from the short reads and the high species complexity of the community. Alternatively, individual (short) reads will be searched directly against databases of known genes (or proteins) to identify homologous sequences. The latter approach may have low sensitivity and specificity in identifying homologous sequences, which may further bias the subsequent diversity analysis. In this paper, we present a novel approach to metagenomic data analysis, called Metagenomic ORFome Assembly (MetaORFA). The whole computational framework consists of three steps. Each read from a metagenomics project will first be annotated with putative open reading frames (ORFs) that likely encode proteins. Next, the predicted ORFs are assembled into a collection of peptides using an EULER assembly method. Finally, the assembled peptides (i.e., ORFome) are used for database searching of homologs and subsequent diversity analysis. We applied MetaORFA approach to several metagenomics datasets with low coverage short reads. The results show that MetaORFA can produce long peptides even when the sequence coverage of reads is extremely low. Hence, the ORFome assembly significantly increased the sensitivity of homology searching, and may potentially improve the diversity analysis of the metagenomic data. This improvement is especially useful for the metagenomic projects when the genome assembly does not work because of the low sequence coverage. PMID- 19642265 TI - A probabilistic coding based quantum genetic algorithm for multiple sequence alignment. AB - This paper presents an original Quantum Genetic algorithm for Multiple sequence ALIGNment (QGMALIGN) that combines a genetic algorithm and a quantum algorithm. A quantum probabilistic coding is designed for representing the multiple sequence alignment. A quantum rotation gate as a mutation operator is used to guide the quantum state evolution. Six genetic operators are designed on the coding basis to improve the solution during the evolutionary process. The features of implicit parallelism and state superposition in quantum mechanics and the global search capability of the genetic algorithm are exploited to get efficient computation. A set of well known test cases from BAliBASE2.0 is used as reference to evaluate the efficiency of the QGMALIGN optimization. The QGMALIGN results have been compared with the most popular methods (CLUSTALX, SAGA, DIALIGN, SB_PIMA, and QGMALIGN) results. The QGMALIGN results show that QGMALIGN performs well on the presenting biological data. The addition of genetic operators to the quantum algorithm lowers the cost of overall running time. PMID- 19642266 TI - Scalable computation of kinship and identity coefficients on large pedigrees. AB - With the rapidly expanding field of medical genetics and genetic counseling, genealogy information is becoming increasingly abundant. An important computation on pedigree data is the calculation of identity coefficients, which provide a complete description of the degree of relatedness of a pair of individuals. The areas of application of identity coefficients are numerous and diverse, from genetic counseling to disease tracking, and thus, the computation of identity coefficients merits special attention. However, the computation of identity coefficients is not done directly, but rather as the final step after computing a set of generalized kinship coefficients. In this paper, we first propose a novel Path-Counting Formula for calculating generalized kinship coefficients, which is motivated by Wright's path-counting method for computing the inbreeding coefficient for an individual. We then present an efficient and scalable scheme for calculating generalized kinship coefficients on large pedigrees using NodeCodes, a special encoding scheme for expediting the evaluation of queries on pedigree graph structures. We also perform experiments for evaluating the efficiency of our method, and compare it with the performance of the traditional recursive algorithm for three individuals. Experimental results demonstrate that the resulting scheme is more scalable and efficient than the traditional recursive methods for computing generalized kinship coefficients. PMID- 19642267 TI - Voting algorithms for the motif finding problem. AB - Finding motifs in many sequences is an important problem in computational biology, especially in identification of regulatory motifs in DNA sequences. Let c be a motif sequence. Given a set of sequences, each is planted with a mutated version of c at an unknown position, the motif finding problem is to find these planted motifs and the original c. In this paper, we study the VM model of the planted motif problem, which is proposed by Pevzner and Sze. We give a simple Selecting One Voting algorithm and a more powerful Selecting k Voting algorithm. When the length of motif and the number of input sequences are large enough, we prove that the two algorithms can find the unknown motif consensus with high probability. In the proof, we show why a large number of input sequences is so important for finding motifs, which is believed by most researchers. Experimental results on simulated data also support the claim. Selecting k Voting algorithm is powerful, but computational intensive. To speed up the algorithm, we propose a progressive filtering algorithm, which improves the running time significantly and has good accuracy in finding motifs. Our experimental results show that Selecting k Voting algorithm with progressive filtering performs very well in practice and it outperforms some best known algorithms. AVAILABILITY: The software is available upon request. PMID- 19642268 TI - A max-flow based approach to the identification of protein complexes using protein interaction and microarray data. AB - The emergence of high-throughput technologies leads to abundant protein-protein interaction (PPI) data and microarray gene expression profiles, and provides a great opportunity for the identification of novel protein complexes using computational methods. Although it has been demonstrated in the literature that methods using protein-protein interaction data alone can successfully predict a large number of protein complexes, the incorporation of gene expression profiles could help refine the putative complexes and hence improve the accuracy of the computational methods. By combining protein-protein interaction data and microarray gene expression profiles, we propose a novel Graph Fragmentation Algorithm (GFA) for protein complex identification. Adapted from a classical max flow algorithm for finding the (weighted) densest subgraphs, GFA first finds large (weighted) dense subgraphs in a protein-protein interaction network and then breaks each such subgraph into fragments iteratively by weighting its nodes appropriately in terms of their corresponding log fold changes in the microarray data, until the fragment subgraphs are sufficiently small. Our extensive tests on three widely used protein-protein interaction datasets and comparisons with the latest methods for protein complex identification demonstrate the superior performance of our method in terms of accuracy, efficiency, and capability in predicting novel protein complexes. Given the high specificity (or precision) that our method has achieved, we conjecture that our prediction results imply more than 200 novel protein complexes. PMID- 19642269 TI - MSDash: mass spectrometry database and search. AB - Along with the wide application of mass spectrometry in proteomics, more and more mass spectrometry data are becoming publicly available. Several public mass spectrometry data repositories have been built on the Internet. However, most of these repositories are devoid of effective searching methods. In this paper we describe a new mass spectrometry data library, and a novel method to efficiently index and search in the library for spectra that are similar to a query spectrum. A public online server have been set up and demonstrated outstanding speed and scalability of our methods. Together with the mass spectrometry library, our searching method can improve the protein identification confidence by comparing a spectrum with the ones that are already characterized in the database. The searching method can also be used alone to cluster the similar spectra in a mass spectrometry dataset together, in order to to improve the speed and accuracy of the protein identification or quantification. PMID- 19642270 TI - Estimating support for protein-protein interaction data with applications to function prediction. AB - Almost every cellular process requires the interactions of pairs or larger complexes of proteins. High throughput protein-protein interaction (PPI) data have been generated using techniques such as the yeast two-hybrid systems, mass spectrometry method, and many more. Such data provide us with a new perspective to predict protein functions and to generate protein-protein interaction networks, and many recent algorithms have been developed for this purpose. However, PPI data generated using high throughput techniques contain a large number of false positives. In this paper, we have proposed a novel method to evaluate the support for PPI data based on gene ontology information. If the semantic similarity between genes is computed using gene ontology information and using Resnik's formula, then our results show that we can model the PPI data as a mixture model predicated on the assumption that true protein-protein interactions will have higher support than the false positives in the data. Thus semantic similarity between genes serves as a metric of support for PPI data. Taking it one step further, new function prediction approaches are also being proposed with the help of the proposed metric of the support for the PPI data. These new function prediction approaches outperform their conventional counterparts. New evaluation methods are also proposed. PMID- 19642271 TI - GaborLocal: peak detection in mass spectrum by Gabor filters and Gaussian local maxima. AB - Mass Spectrometry (MS) is increasingly being used to discover disease related proteomic patterns. The peak detection step is one of most important steps in the typical analysis of MS data. Recently, many new algorithms have been proposed to increase true position rate with low false position rate in peak detection. Most of them follow two approaches: one is denoising approach and the other one is decomposing approach. In the previous studies, the decomposition of MS data method shows more potential than the first one. In this paper, we propose a new method named GaborLocal which can detect more true peaks with a very low false position rate. The Gaussian local maxima is employed for peak detection, because it is robust to noise in signals. Moreover, the maximum rank of peaks is defined at the first time to identify peaks instead of using the signal-to-noise ratio and the Gabor filter is used to decompose the raw MS signal. We perform the proposed method on the real SELDI-TOF spectrum with known polypeptide positions. The experimental results demonstrate our method outperforms other common used methods in the receiver operating characteristic (ROC) curve. PMID- 19642272 TI - Optimizing Bayes error for protein structure model selection by stability mutagenesis. AB - Site-directed mutagenesis affects protein stability in a manner dependent on the local structural environment of the mutated residue; e.g., a hydrophobic to polar substitution would behave differently in the core vs. on the surface of the protein. Thus site-directed mutagenesis followed by stability measurement enables evaluation of and selection among predicted structure models, based on consistency between predicted and experimental stability changes (DeltaDeltaGo values). This paper develops a method for planning a set of individual site directed mutations for protein structure model selection, so as to minimize the Bayes error, i.e., the probability of choosing the wrong model. While in general it is hard to calculate exactly the multi-dimensional Bayes error defined by a set of mutations, we leverage the structure of "DeltaDeltaGo space" to develop tight upper and lower bounds. We further develop a lower bound on the Bayes error of any plan that uses a fixed number of mutations from a set of candidates. We use this bound in a branch-and-bound planning algorithm to find optimal and near optimal plans. We demonstrate the significance and effectiveness of this approach in planning mutations for elucidating the structure of the pTfa chaperone protein from bacteriophage lambda. PMID- 19642273 TI - Feedback algorithm and web-server for protein structure alignment. AB - We have developed a feedback algorithm for protein structure alignment between two protein backbones. A web portal implementing this method has been constructed and is freely available for use at http://fpsa.cs.uno.edu/ with a mirror site at http://fpsa.cs.panam.edu/FPSA/. We compare our algorithm with three other, commonly used methods: CE, DaliLite and SSM. The results show that in most cases our algorithm outputs a larger number of aligned positions when the (Calpha) RMSD is comparable. Also, in many cases where the number of aligned positions is larger or comparable, our learning method is able to achieve a smaller (Calpha) RMSD than the other methods tested. This trend of larger number of aligned positions and smaller (Calpha) RMSD is observed more frequently in cases where the similarity between protein structures is weak. PMID- 19642274 TI - Predicting flexible length linear B-cell epitopes. AB - Identifying B-cell epitopes play an important role in vaccine design, immunodiagnostic tests, and antibody production. Therefore, computational tools for reliably predicting B-cell epitopes are highly desirable. We explore two machine learning approaches for predicting flexible length linear B-cell epitopes. The first approach utilizes four sequence kernels for determining a similarity score between any arbitrary pair of variable length sequences. The second approach utilizes four different methods of mapping a variable length sequence into a fixed length feature vector. Based on our empirical comparisons, we propose FBCPred, a novel method for predicting flexible length linear B-cell epitopes using the subsequence kernel. Our results demonstrate that FBCPred significantly outperforms all other classifiers evaluated in this study. An implementation of FBCPred and the datasets used in this study are publicly available through our linear B-cell epitope prediction server, BCPREDS, at: http://ailab.cs.iastate.edu/bcpreds/. PMID- 19642275 TI - Fast and accurate multi-class protein fold recognition with spatial sample kernels. AB - Establishing structural or functional relationship between sequences, for instance to infer the structural class of an unannotated protein, is a key task in biological sequence analysis. Recent computational methods such as profile and neighborhood mismatch kernels have shown very promising results for protein sequence classification, at the cost of high computational complexity. In this study we address the multi-class sequence classification problems using a class of string-based kernels, the sparse spatial sample kernels (SSSK), that are both biologically motivated and efficient to compute. The proposed methods can work with very large databases of protein sequences and show substantial improvements in computing time over the existing methods. Application of the SSSK to the multi class protein prediction problems (fold recognition and remote homology detection) yields significantly better performance than existing state-of-the-art algorithms. PMID- 19642276 TI - Designing secondary structure profiles for fast ncRNA identification. AB - Detecting non-coding RNAs (ncRNAs) in genomic DNA is an important part of annotation. However, the most widely used tool for modeling ncRNA families, the covariance model (CM), incurs a high computational cost when used for search. This cost can be reduced by using a filter to exclude sequence that is unlikely to contain the ncRNA of interest, applying the CM only where it is likely to match strongly. Despite recent advances, designing an efficient filter that can detect nearly all ncRNA instances while excluding most irrelevant sequences remains challenging. This work proposes a systematic procedure to convert a CM for an ncRNA family to a secondary structure profile (SSP), which augments a conservation profile with secondary structure information but can still be efficiently scanned against long sequences. We use dynamic programming to estimate an SSP's sensitivity and FP rate, yielding an efficient, fully automated filter design algorithm. Our experiments demonstrate that designed SSP filters can achieve significant speedup over unfiltered CM search while maintaining high sensitivity for various ncRNA families, including those with and without strong sequence conservation. For highly structured ncRNA families, including secondary structure conservation yields better performance than using primary sequence conservation alone. PMID- 19642277 TI - Matching of structural motifs using hashing on residue labels and geometric filtering for protein function prediction. AB - There is an increasing number of proteins with known structure but unknown function. Determining their function would have a significant impact on understanding diseases and designing new therapeutics. However, experimental protein function determination is expensive and very time-consuming. Computational methods can facilitate function determination by identifying proteins that have high structural and chemical similarity. Our focus is on methods that determine binding site similarity. Although several such methods exist, it still remains a challenging problem to quickly find all functionally related matches for structural motifs in large data sets with high specificity. In this context, a structural motif is a set of 3D points annotated with physicochemical information that characterize a molecular function. We propose a new method called LabelHash that creates hash tables of n-tuples of residues for a set of targets. Using these hash tables, we can quickly look up partial matches to a motif and expand those matches to complete matches. We show that by applying only very mild geometric constraints we can find statistically significant matches with extremely high specificity in very large data sets and for very general structural motifs. We demonstrate that our method requires a reasonable amount of storage when employing a simple geometric filter and further improves on the specificity of our previous work while maintaining very high sensitivity. Our algorithm is evaluated on 20 homolog classes and a non-redundant version of the Protein Data Bank as our background data set. We use cluster analysis to analyze why certain classes of homologs are more difficult to classify than others. The LabelHash algorithm is implemented on a web server at http://kavrakilab.org/labelhash/. PMID- 19642278 TI - A Hausdorff-based NOE assignment algorithm using protein backbone determined from residual dipolar couplings and rotamer patterns. AB - High-throughput structure determination based on solution Nuclear Magnetic Resonance (NMR) spectroscopy plays an important role in structural genomics. One of the main bottlenecks in NMR structure determination is the interpretation of NMR data to obtain a sufficient number of accurate distance restraints by assigning nuclear Overhauser effect (NOE) spectral peaks to pairs of protons. The difficulty in automated NOE assignment mainly lies in the ambiguities arising both from the resonance degeneracy of chemical shifts and from the uncertainty due to experimental errors in NOE peak positions. In this paper we present a novel NOE assignment algorithm, called HAusdorff-based NOE Assignment (HANA), that starts with a high-resolution protein backbone computed using only two residual dipolar couplings (RDCs) per residue, employs a Hausdorff-based pattern matching technique to deduce similarity between experimental and back-computed NOE spectra for each rotamer from a statistically diverse library, and drives the selection of optimal position-specific rotamers for filtering ambiguous NOE assignments. Our algorithm runs in time O(tn3 + tn log t), where t is the maximum number of rotamers per residue and n is the size of the protein. Application of our algorithm on biological NMR data for three proteins, namely, human ubiquitin, the zinc finger domain of the human DNA Y-polymerase Eta (pol eta) and the human Set2-Rpb1 interacting domain (hSRI) demonstrates that our algorithm overcomes spectral noise to achieve more than 90% assignment accuracy. Additionally, the final structures calculated using our automated NOE assignments have backbone RMSD < 1.7 A and all-heavy-atom RMSD < 2.5 A from reference structures that were determined either by X-ray crystallography or traditional NMR approaches. These results show that our NOE assignment algorithm can be successfully applied to protein NMR spectra to obtain high-quality structures. PMID- 19642279 TI - Iterative non-sequential protein structural alignment. AB - Structural similarity between proteins gives us insights on the evolutionary relationship between proteins which have low sequence similarity. In this paper, we present a novel approach called STSA for non-sequential pair-wise structural alignment. Starting from an initial alignment, our approach iterates over a two step process, a superposition step and an alignment step, until convergence. Given two superposed structures, we propose a novel greedy algorithm to construct both sequential and non-sequential alignments. The quality of STSA alignments is evident in the high agreement it has with the reference alignments in the challenging-to-align RPIC set. Moreover, on a dataset of 4410 protein pairs selected from the CATH database, STSA has a high sensitivity and high specificity values and is competitive with state-of-the-art alignment methods and gives longer alignments with lower rmsd. The STSA software along with the data sets will be made available on line at http://www.cs.rpi.edu/-zaki/software/STSA. PMID- 19642280 TI - Combining sequence and structural profiles for protein solvent accessibility prediction. AB - Solvent accessibility is an important structural feature for a protein. We propose a new method for solvent accessibility prediction that uses known structure and sequence information more efficiently. We first estimate the relative solvent accessibility of the query protein using fuzzy mean operator from the solvent accessibilities of known structure fragments that have similar sequences to the query protein. We then integrate the estimated solvent accessibility and the position specific scoring matrix of the query protein using a neural network. We tested our method on a large data set consisting of 3386 non redundant proteins. The comparison with other methods show slightly improved prediction accuracies with our method. The resulting system does need not be re trained when new data is available. We incorporated our method into the MUPRED system, which is available as a web server at http://digbio.missouri.edu/mupred. PMID- 19642281 TI - Extensive exploration of conformational space improves Rosetta results for short protein domains. AB - With some simplifications, computational protein folding can be understood as an optimization problem of a potential energy function on a variable space consisting of all conformation for a given protein molecule. It is well known that realistic energy potentials are very "rough" functions, when expressed in the standard variables, and the folding trajectories can be easily trapped in multiple local minima. We have integrated our variation of Parallel Tempering optimization into the protein folding program Rosetta in order to improve its capability to overcome energy barriers and estimate how such improvement will influence the quality of the folded protein domains. Here we report that (1) Parallel Tempering Rosetta (PTR) is significantly better in the exploration of protein structures than previous implementations of the program; (2) systematic improvements are observed across a large benchmark set in the parameters that are normally followed to estimate robustness of the folding; (3) these improvements are most dramatic in the subset of the shortest domains, where high-quality structures have been obtained for >75% of all tested sequences. Further analysis of the results will improve our understanding of protein conformational space and lead to new improvements in the protein folding methodology, while the current PTR implementation should be very efficient for short (up to approximately 80 a.a.) protein domains and therefore may find practical application in system biology studies. PMID- 19642282 TI - Improving homology models for protein-ligand binding sites. AB - In order to improve the prediction of protein-ligand binding sites through homology modeling, we incorporate knowledge of the binding residues into the modeling framework. Residues are identified as binding or nonbinding based on their true labels as well as labels predicted from structure and sequence. The sequence predictions were made using a support vector machine framework which employs a sophisticated window-based kernel. Binding labels are used with a very sensitive sequence alignment method to align the target and template. Relevant parameters governing the alignment process are searched for optimal values. Based on our results, homology models of the binding site can be improved if a priori knowledge of the binding residues is available. For target-template pairs with low sequence identity and high structural diversity our sequence-based prediction method provided sufficient information to realize this improvement. PMID- 19642283 TI - Using relative importance methods to model high-throughput gene perturbation screens. AB - With the advent of high-throughput gene perturbation screens (e.g., RNAi assays, genome-wide deletion mutants), modeling the complex relationship between genes and phenotypes has become a paramount problem. One broad class of methods uses 'guilt by association' methods to impute phenotypes to genes based on the interactions between the given gene and other genes with known phenotypes. But these methods are inadequate for genes that have no cataloged interactions but which nevertheless are known to result in important phenotypes. In this paper, we present an approach to first model relationships between phenotypes using the notion of 'relative importance' and subsequently use these derived relationships to make phenotype predictions. Besides improved accuracy on S. cerevisiae deletion mutants and C. elegans knock-down datasets, we show how our approach sheds insight into relations between phenotypes. PMID- 19642284 TI - Consistent alignment of metabolic pathways without abstraction. AB - Pathways show how different biochemical entities interact with each other to perform vital functions for the survival of organisms. Similarities between pathways indicate functional similarities that are difficult to identify by comparing the individual entities that make up those pathways. When interacting entities are of single type, the problem of identifying similarities reduces to graph isomorphism problem. However, for pathways with varying types of entities, such as metabolic pathways, alignment problem is more challenging. Existing methods, often, address the metabolic pathway alignment problem by ignoring all the entities except for one type. This kind of abstraction reduces the relevance of the alignment significantly as it causes losses in the information content. In this paper, we develop a method to solve the pairwise alignment problem for metabolic pathways. One distinguishing feature of our method is that it aligns reactions, compounds and enzymes without abstraction of pathways. We pursue the intuition that both pairwise similarities of entities (homology) and their organization (topology) are crucial for metabolic pathway alignment. In our algorithm, we account for both by creating an eigenvalue problem for each entity type. We enforce the consistency by considering the reachability sets of the aligned entities. Our experiments show that, our method finds biologically and statistically significant alignments in the order of seconds for pathways with approximately 100 entities. PMID- 19642285 TI - Detecting pathways transcriptionally correlated with clinical parameters. AB - The recent explosion in the number of clinical studies involving microarray data calls for novel computational methods for their dissection. Human protein interaction networks are rapidly growing and can assist in the extraction of functional modules from microarray data. We describe a novel methodology for extraction of connected network modules with coherent gene expression patterns that are correlated with a specific clinical parameter. Our approach suits both numerical (e.g., age or tumor size) and logical parameters (e.g., gender or mutation status). We demonstrate the method on a large breast cancer dataset, where we identify biologically-relevant modules related to nine clinical parameters including patient age, tumor size, and metastasis-free survival. Our method is capable of detecting disease-relevant pathways that could not be found using other methods. Our results support some previous hypotheses regarding the molecular pathways underlying diversity of breast tumors and suggest novel ones. PMID- 19642286 TI - The effect of massive gene loss following whole genome duplication on the algorithmic reconstruction of the ancestral populus diploid. AB - We improve on guided genome halving algorithms so that several thousand gene sets, each containing two paralogs in the descendant T of the doubling event and their single ortholog from an undoubled reference genome R, can be analyzed to reconstruct the ancestor A of T at the time of doubling. At the same time, large numbers of defective gene sets, either missing one paralog from T or missing their ortholog in R, may be incorporated into the analysis in a consistent way. We apply this genomic rearrangement distance-based approach to the recently sequenced poplar (Populus trichocarpa) and grapevine (Vitis vinifera) genomes, as T and R respectively. PMID- 19642287 TI - Error tolerant sibship reconstruction in wild populations. AB - Kinship analysis using genetic data is important for many biological applications, including many in conservation biology. Wide availability of microsatellites has boosted studies in wild populations that rely on the knowledge of kinship, particularly sibling relationships (sibship). While there exist many methods for reconstructing sibling relationships, almost none account for errors and mutations in microsatellite data, which are prevalent and affect the quality of reconstruction. We present an error-tolerant method for reconstructing sibling relationships based on the concept of consensus methods. We test our approach on both real and simulated data, with both pre-existing and introduced errors. Our method is highly accurate on almost all simulations, giving over 90% accuracy in most cases. Ours is the first method designed to tolerate errors while making no assumptions about the population or the sampling. PMID- 19642288 TI - On the accurate construction of consensus genetic maps. AB - We study the problem of merging genetic maps, when the individual genetic maps are given as directed acyclic graphs. The problem is to build a consensus map, which includes and is consistent with all (or, the vast majority of) the markers in the individual maps. When markers in the input maps have ordering conflicts, the resulting consensus map will contain cycles. We formulate the problem of resolving cycles in a combinatorial optimization framework, which in turn is expressed as an integer linear program. A faster approximation algorithm is proposed, and an additional speed-up heuristic is developed. According to an extensive set of experimental results, our tool is consistently better than JOINMAP, both in terms of accuracy and running time. PMID- 19642289 TI - Efficient haplotype inference from pedigrees with missing data using linear systems with disjoint-set data structures. AB - We study the haplotype inference problem from pedigree data under the zero recombination assumption, which is well supported by real data for tightly linked markers (i.e., single nucleotide polymorphisms (SNPs)) over a relatively large chromosome segment. We solve the problem in a rigorous mathematical manner by formulating genotype constraints as a linear system of inheritance variables. We then utilize disjoint-set structures to encode connectivity information among individuals, to detect constraints from genotypes, and to check consistency of constraints. On a tree pedigree without missing data, our algorithm can output a general solution as well as the number of total specific solutions in a nearly linear time O (mn x alpha(n)), where m is the number of loci, n is the number of individuals and alpha is the inverse Ackermann function, which is a further improvement over existing ones. We also extend the idea to looped pedigrees and pedigrees with missing data by considering existing (partial) constraints on inheritance variables. The algorithm has been implemented in C++ and will be incorporated into our PedPhase package. Experimental results show that it can correctly identify all 0-recombinant solutions with great efficiency. Comparisons with other two popular algorithms show that the proposed algorithm achieves 10 to 10(5)-fold improvements over a variety of parameter settings. The experimental study also provides empirical evidences on the complexity bounds suggested by theoretical analysis. PMID- 19642290 TI - Knowledge representation and data mining for biological imaging. AB - Biological and pharmaceutical research relies heavily on microscopically imaging cell populations for understanding their structure and function. Much work has been done on automated analysis of biological images, but image analysis tools are generally focused only on extracting quantitative information for validating a particular hypothesis. Images contain much more information than is normally required for testing individual hypotheses. The lack of symbolic knowledge representation schemes for representing semantic image information and the absence of knowledge mining tools are the biggest obstacles in utilizing the full information content of these images. In this paper we first present a graph-based scheme for integrated representation of semantic biological knowledge contained in cellular images acquired in spatial, spectral, and temporal dimensions. We then present a spatio-temporal knowledge mining framework for extracting non trivial and previously unknown association rules from image data sets. This mechanism can change the role of biological imaging from a tool used to validate hypotheses to one used for automatically generating new hypotheses. Results for an apoptosis screen are also presented. PMID- 19642291 TI - Fast multisegment alignments for temporal expression profiles. AB - We present two heuristics for speeding up a time series alignment algorithm that is related to dynamic time warping (DTW). In previous work, we developed our multisegment alignment algorithm to answer similarity queries for toxicogenomic time-series data. Our multisegment algorithm returns more accurate alignments than DTW at the cost of time complexity; the multisegment algorithm is O(n(5)) whereas DTW is O(n(2)). The first heuristic we present speeds up our algorithm by a constant factor by restricting alignments to a cone shape in alignment space. The second heuristic restricts the alignments considered to those near one returned by a DTW-like method. This heuristic adjusts the time complexity to O(n(3)). Importantly, neither heuristic results in a loss in accuracy. PMID- 19642292 TI - Graph wavelet alignment kernels for drug virtual screening. AB - In this paper we introduce a novel graph classification algorithm and demonstrate its efficacy in drug design. In our method, we use graphs to model chemical structures and apply a wavelet analysis of graphs to create features capturing graph local topology. We design a novel graph kernel function to utilize the created feature to build predictive models for chemicals. We call the new graph kernel a graph wavelet-alignment kernel. We have evaluated the efficacy of the wavelet-alignment kernel using a set of chemical structure-activity prediction benchmarks. Our results indicate that the use of the kernel function yields performance profiles comparable to, and sometimes exceeding that of the existing state-of-the-art chemical classification approaches. In addition, our results also show that the use of wavelet functions significantly decreases the computational costs for graph kernel computation with more than 10 fold speed up. PMID- 19642293 TI - [The use of personalized genomic comprehensions]. PMID- 19642294 TI - [Human genome sequencing--next generation technology or will the routine sequencing of human genome be possible?]. AB - DNA sequencing has become a standard method widely used in molecular genetic analysis of biological materials. Its use in medicine is widespread, especially in diagnostics of inherited disorders and cancer related diseases. Development of DNA diagnostics has been strongly accelerated by publication of the human genome sequence in 2001. During the last few years one can observe rapid development of novel sequencing technologies, which have led to the introduction of so called "New Generation Sequencing". These new technologies based on principles of massive parallel sequencing (e.g. Roche/454, Illumina Genome Analyzer IIx, Life Technologies SOLiD 3 and others) enable a massive increase of sequencing capacity and in parallel also a fundamental decrease of costs. This major technological breakthrough allowed development of the whole-genome sequencing including analyses of individual human genomes. It also started the era of personal genomics. The first sequenced individual human genomes belonged to famous geneticists J. C. Venter (2007) and J. D. Watson (2008), but they were rapidly followed by sequencing analyses of other individuals from various ethnic groups. These studies brought substantial information about interpersonal differences in genome structure (through characterization of nucleotide polymorphisms, DNA deletions and amplifications etc.). Sequencing of cancer cell genomes, e.g. acute myeloid leukemia has already brought first important clinically relevant results. Although currently we are still unable to interpret the relevance of all detected genome variants, it is obvious, that the possibility to sequence individual human genomes represents a fundamental breakthrough not only in DNA diagnostics but also in clinical medicine. PMID- 19642295 TI - [Review of patients with musculoskeletal injury treated during winter months in a highland hospital]. AB - BACKGROUND: The authors examined the incidence of musculoskeletal injuries according to their type and location in the period of winter at a highland hospital, which also functions as a regional hospital for a few winter sport resorts. METHODS AND RESULTS: . In the sample there were 1644 patients (696 women, 948 men) treated for primary musculoskeletal injuries from 1.1. to 31.3.2008. This was a retrospective study; the data were collected from medical reports. It included: age, sex, mechanism of injury, diagnosis and whether the patient had to be hospitalised or not. Age of the patients ranged from 1 to 95 years with an average of 29 years (31 for women and 28 for men). Younger age groups dominated among men. After 70 years of age there was a prevalence of women. Fractures were the most common cause of injury (653, 39.7%), followed by injuries to the joints' ligamentary apparatus by mechanism of distortion (379, 23.1%). Next in incidence were soft tissue injuries caused by contusion (325, 19.7%) and open wounds (241, 14.7%). The least common were luxated joints (43, 2.6%) and closed injury to muscles and tendons (3, 0.1%). The most frequent site of injury was the hand (404, 24.6%), while the least frequent place was the thigh (17, 1.0%). CONCLUSIONS: In conclusion the study confirmed that other than the age, gender and the season, the geographic location also influences the spectrum of musculoskeletal injuries. The study also showed that the most common type of injuries was that of the upper extremity. The study did not confirm the expected prevalence of fractures among women. The prevalence of men was probably because of the prevalence of winter sport activities as a leading cause of injury (mostly skiing and snowboarding). PMID- 19642296 TI - [Features of metabolic syndrome in patients with depressive disorder]. AB - BACKGROUND: Depressive disorder is a serious illness with a high incidence, proxime accessit after anxiety disorders among the psychiatric diseases. It is accompanied by an increased risk of development of type 2 diabetes mellitus, cardiovascular disease, and by increased all-cause mortality. Recently published data have suggested that factors connected with the insulin resistance are at the background of this association. METHODS AND RESULTS: In this pilot study we have investigated parameters of lipid metabolism and glucose homeostasis in consecutively admitted patients suffering from depressive disorder (DD) (group of 42 people), in 57 patients with the metabolic syndrome (MetS) and in a control group of 49 apparently healthy persons (CON). Depressive patients did not differ from the control group by age or body mass index (BMI) value, but they had statistically significantly higher concentrations of serum insulin, C-peptide, glucose, triglycerides (TG), conjugated dienes in LDL particles (CD-LDL), higher value of microalbuminuria and of insulin resistance (HOMA-IR) index. They simultaneously had significantly lower value of the insulin sensitivity (QUICKI) index. In comparison with the MetS group the depressive patients were characterized by significantly lower both systolic and diastolic blood pressure, BMI , serum TG, apolipoprotein B, uric acid, C-peptide and by higher concentrations of apolipoprotein A-I and HDL-cholesterol. On the contrary, we have not found statistically significant differences between the DD and MetS groups in the concentrations of serum insulin, glucose, HOMA and QUICKI indices, in CD-LDL and MAU. CONCLUSIONS: In this pilot study, we have found in patients with depressive disorder certain features of metabolic syndrome, especially insulin resistance and oxidative stress. PMID- 19642297 TI - [The comparison of serum levels of selected biomarkers in monoclonal gammopathy of undetermined significance and multiple myeloma]. AB - BACKGROUND: The aim of the study was the evaluation of serum levels of 12 selected biomarkers in monoclonal gammopathy of undetermined significance (MGUS) and in initial, asyptomatic phase of multiple myeloma, especially from the view of potential differentiation of these conditions in clinical practice. METHODS AND RESULTS: Analyzed group of 268 individuals consisted of 89 individuals with MGUS and 179 patients with MM examined in time of diagnosis before treatment initiation. For evaluation of serum levels were used following methods: radioenzymatic method (thymidinekinase), enzymatic immunoassay (beta2-M, IL-6R, ICAM-1, VCAM-1, ICTP, PINP and OPG) and quantitative sandwich enzymatic immunoassay (HGF, VEGF, syndecan-1/CD138 and Fas). Pearson's chi2-test and test according to Mann-Whitney were used for statistical evaluation (p < 0.05). Wide statistic differences in serum levels of analyzed markers in MGUS vs. MM were detected in case of beta2-M, TK, ICTP, OPG, HGF and syndecan-1 (p < 0.0001), lower differences in case of VCAM-1, PINP and VEGF (p = 0.003, 0.001 and 0.04), and without difference in case of Fas. Except for thymidinekinase (p = 0.014) and syndecan-1 (p = 0.001) was not detected statistically important contrast of measured values in MGUS individuals and in patients with initial, asymptomatic phase of MM (stage 1), but these markers cannot be used in clinical practice due to significant overlap of serum values. Continuous downgrade of serum values of VEGF due to degree of MM progression (stages 1-3 according to Durie-Salmon) was unexpected. RESULTS: Although the significant differences in 9 of 12 evaluated serum levels of selected biomarkers in groups of MGUS and MM were seen, the results revealed that these markers are unprofitable to bring discriminatory potential capable of being used to distinguish between MGUS and initial, asymptomatic phase of MM. PMID- 19642298 TI - [Bilateral spontaneous pneumothorax--wrong therapies]. AB - In spite of being a relatively rare disorder, synchronous bilateral spontaneous pneumothorax requires proper attention because of its consequences that essentially constitute an acute life-threatening chest cavity event. Standard of care is stabilization of the patient's condition with emergency drainage of both pleural cavities that should be followed by early surgical revision, preferably using miniinvasive approach involving intervention of the lung, or pleura. The case report uses the example of a 19-year-old patient to alert to possible errors in the process of therapy of this disorder, presenting, at the same time, the correct alternative of the process. PMID- 19642299 TI - [The curative effect of carotid endarterectomy]. AB - The preventive effect of carotid endarterectomy in the reduction of ischemic stroke was reliably confirmed. Carotid endarterectomy may also be a curative method, but it has not been confirmed yet. In our case report we illustrate the curative effect of carotid endarterectomy in a patient after a combined embolic and hemodynamic stroke. The administration of intravenous thrombolysis did not have the expected clinical response. Neuroimaging showed ischemia and homolateral hypoperfusion of the brain hemisphere caused by critical internal carotid artery stenosis. On the 8th day after thrombolysis a carotid endarterectomy was performed with beneficial effect. Normalization of hemodynamic in the altered hemisphere was demonstrated by perfusion examination along with the clinical improvement. A curative effect of endarterectomy appears more probable in a hemodynamic ischemic stroke. For the improvement of a neuronal function the existence of penumbra is a condition. While a positive influence of hemodynamic by carotid endarterectomy is confirmed, the possibility of an increase in neuronal activity after repair of vasomotor activity is not documented. The curative effect and it's connection to the timing of the carotid endarterectomy require testing in the further studies. PMID- 19642300 TI - [On human ageing and longevity--2. Internal determinants]. AB - Longevity as a result of prolonged or postponed ageing is substantially influenced by genetic determinants. Most of them were analyzed by studying different progeria syndromes and their genetic control. From this point of view the use of experimental animals, because it enables to identify genes involved in shortening or prolongation of life-span by changing experimental conditions, has been also very effective. Expression of ageing processes at cellular as well on organism level as a biological unit revealed sets of genetic pathways involved in longevity. Several theories which elicit different aspects have been constructed to explain the ageing process. PMID- 19642301 TI - [Addictive diseases and finances--relevant relationships]. AB - Alcohol, other addictive substances and gambling are economically clearly disadvantageous. The financial losses caused by addictive problems should be more compensated by taxation. There are also compelling health reasons for higher taxation. Uncontrolled and accessible financial resources and also poverty represent the risk factors especially for adolescents. Poverty also limits the affordability of psychotherapeutic and medical services for the large segments of population. Material and financial aspects often motivate people to seek treatment for their addictive problems. We also mention the fact that the treatment and especially prevention are economically profitable for individuals, families and societies. PMID- 19642302 TI - [Czech model for decrease of maternal mortality in Uganda]. AB - High maternal and perinatal mortality is the leading problem of the health care in developing countries of Sub-Saharan Africa, including Uganda. The main condition for decrease of maternal mortality is availability of an emergency obstetrical care in hospital accompanied by skilled team of specialists (gynaecologist, anaesthesiologist, paediatrician), which are able to treat all obstetrical complications and provide an intensive care to risk newborns. The Czech Hospital and School for midwives in Uganda was founded and build with the aim to accomplish a grant project for the decrease of maternal, perinatal and child mortality. Our project to connect emergency obstetrical care in hospital to villages and traditional delivery attendants by mobile phones shows a simple and original model, which can help to decrease maternal mortality in Uganda and in the other countries of Sub-Saharan Africa as well. The Czech-Uganda Hospital started its work on 19th February 2007 with a team of Slovak doctors; however, till now, after 2 years of work, it doesn't fulfil its role of a specialised obstetrical department, which would be able to join its partners in villages and start the grant project for decrease of maternal and perinatal mortality. PMID- 19642303 TI - [Joshua Lederberg (1925-2008)]. PMID- 19642304 TI - [From ethicotherapy to modern psychiatry]. AB - The author introduces the reader to the work of the founder of "ethics therapy" Ctibor Bezdek, M.D. She explains the conception and the practice of his therapeutic method and evaluates it from the point of view of the contemporary psychotherapy. In spite of the fact, that some of his ideas and ways of his phrasing are out of date and in spite of the fact, that she does not share some of his views and procedures, she appreciates many of his ideas as well as some of the renowned persons from our medical, psychological and theological professional life. In this connection the autor comments on the contemporary situation in Czech hospitals concerning the provision of the spiritual health care and she refers to the activities being followed through for the sake of its improvement. PMID- 19642305 TI - [Celiac disease and its relation to bone metabolism]. AB - Celiac disease (nontropical sprue) is autoimmune disorder of the intestinal mucose, which usually develops in humans hypersensitive to gluten. The disease can occur at any age, with the greatest occurrence in early adulthood. Besides intestinal symptomatology--abdominal pain, diarrhoea and weight loss--celiac disease is often accompanied by extra-intestinal complications including osteopenia or osteoporosis and osteomalacia. Overproduction of cytokines IL-1 alpha, IL-1 beta and TNF-alpha increases bone resorption, which is further accelerated by hyperparathyroidism connected with malabsorption of calcium and vitamin D. Interaction of both these mechanisms activated bone loss. Similarly as the classic (symptomatic) celiac disease, the occult form, commonly seen in the elderly, may be associated with a risk of osteoporosis or osteomalacia related fractures. Diagnosis is based on positivity of IgA and IgG antigliadin and endomysial antibodies and characteristic endoscopic detection of inflammation and atrophy of duodenal mucose. Areal screening of celiac disease in osteoporotic patients is very dubious. However, a methodical examination should be performed in all patients with unexplainable hyperparathyroidism or in those with various autoimmune diseases (type 1 diabetes, thyroiditis chronica), or in premenopausal women and men, who did not reach the appropriate peak bone mass. On the other hand, detailed analysis of calcium metabolism, including markers of bone remodlling and X-ray densitometry (DXA), are recommended in all patients with verified celiac disease. The effectiveness of a gluten-free diet and substitution with vitamin D and calcium, or treatment with bisphosphonates are discussed. The promising therapy appears to be new molecules with reparative effect on intestinal mucose such as AT-1001. PMID- 19642306 TI - Confocal laser endomicroscopy in experimental pigs. Methods of ex vivo imaging. AB - BACKGROUND: Confocal laser scanning endomicroscopy (CLSE) enables online in vivo cellular surface and subsurface imaging of normal and pathological tissue at high resolution and magnification. The aim of this study was to work out a method of ex vivo in vitro CLSE in experimental pigs and to compare CLSE images with those of "classic" histology. MATERIAL AND METHODS: Five mature female pigs entered the study. CLSE on an ex vivo in vitro basis was started 10 minutes after pharmacological euthanasia and carried out for 30 minutes. Fluorescein was administrated i.v. as a fluorescence substance. RESULTS: CLSE was successful in all tissue samples of all animals (the oesophagus, stomach, small intestine, large bowel). We have succeeded to obtain high quality images within the first 30 minutes that means 40 minutes after the euthanasia of experimental animals. CLSE images corresponded well with those of haematoxylin-eosin staining. CONCLUSIONS: CLSE on an ex vivo in vitro basis in experimental pigs is feasible. PMID- 19642307 TI - [Child abuse in common family population--a longitudinal study]. AB - BACKGROUND: Dunovsky, Dytrych, Matejcek et al. have published their experience from their consulting and interventional activities, alongside with an analysis of the paediatric, psychological, psychiatric and social components of the child's development in the family and outside it, in a fundamental and still up to-date paper (1, 2). In this elaborate they emphasized the necessity to map the occurrence, in our country, of pathological phenomena included in the CAN notion- a child that is abused and neglected. The background of the presented study lays in a retrospective investigation in an adult population. The subject of the study are men--the near future fathers of the investigated children, who have among other information specified within an extensive personal history if and how they were maltreated in their childhood. THE GOAL OF THE STUDY: A group of men maltreated in childhood is compared to a group which was not maltreated and the investigating team searched for indications as to how different were their natal families, their parents and their own selves and if any identifiable differences occurred later in their own families, relationships, conduct and health. METHODS: A comparative study was conducted in the group of fathers based on three consecutive questionnaire investigations, between those maltreated in childhood and those who were not maltreated (control). Fathers maltreated in childhood were identified based on the response variants (1-often, 2-sometimes, 3-never) to three questionnaire inquiries filled in before the birth of their children who are included in the ELSPAC (European Longitudinal Study of Pregnancy and Childhood) study. The data was provided by men whose wives with permanent residence in Brno gave birth from March 1st 1991 till June 30th 1992. RESULTS: According to three types of test it was found out that from the parents of the studied children 57.9% of the 3580 fathers and 48.3% of the 3848 mothers were physically or psychologically maltreated during childhood: boys were maltreated more often. Maltreated fathers as compared to control: a) were more often born prematurely (p < 0.05), in the childhood and adulthood they were ill more often (p < 0.01) and they were less resistant psychologically (p < 0.001); b) more often had parents with impaired health (p < 0.001) and worse partner relationships (p < 0.001); c) came from families which didn't differ according to the father's education or employment status. The mothers had secondary education more often (p < 0.01); d) had more often wives and children with worse health (p < 0.01); e) in their own families manifested more violence towards their own wives and children (p < 0.001), they maltreated them more often physically (p < 0.01) and psychologically (p < 0.01); f) manifested more often extra-family asocial behavior (p < 0.001); g) they felt less satisfied with their financial situation (p < 0.001), with their family life (p < 0.01) and life in general (p < 0.001). CONCLUSIONS: Men maltreated in childhood resembled their parents in the social and health aspect and in the partner relationships. Towards their children they acted similarly like their parents used to--violent behavior aimed at children and between partners transferred from one generation to the next. PMID- 19642308 TI - [On human longevity--1. external influences]. AB - Human life-span is controlled by many factors, both internal (genomic) and external. In this paper only impact of external conditions is to be discussed. External factors are very variable, sometimes difficult to ascertain, but their control is relatively easier to address than the internal ones. The effect of human activities on human lifespan can be positive or negative. Experimental results have shown that one of the ways leading to prolongation of life-span is caloric restriction (CR). There are, of course, many other factors, not only of nurture character, inflicting on quality and length of human life. Some of them are human products including stress with different levels of inherited ability to resist it, but also possibility to improve individual capacity to control its effect due to hormesis. Prolongation of life expectancy--ageing of the population has become an economic burden in many countries, especially for social and health services. PMID- 19642309 TI - [DESIDENT CaviCide a new disinfectant]. AB - The properties of the new disinfection agent DESIDENT CaviCide, such as characteristics, disinfection efficiency, biological degradability and ecotoxicity are described. Also areas and forms of usage this biocidal agent are mentioned. PMID- 19642310 TI - [Family based prevention--relevant information for parents]. AB - Czech children and adolescents are at risk of substance related problems more than the majority of their European peers. We review some possibilities how to prevent alcohol and drug related problems in family and how to cope with these problems. The availability of alcohol and illegal drugs in the Czech Republic considerably increased in past 20 years and this topic is thus very important. PMID- 19642311 TI - [Prevention of influenza by use of intradermal vaccination]. AB - Intradermal vaccination against influenza represents a new method of protection against the heavy incidence disease. For its very good immunity response, intradermal injections are frequently used for many types of vaccines. Results of clinical studies are presented and the system of intradermal microinjections for vaccine administration is introduced. Sensitive vaccination can increase the prevalence of vaccinated persons and thus decrease morbidity and mortality of influenza. PMID- 19642312 TI - [Minimally invasive thyroidectomy]. AB - The past several decades have seen rapid developments in videolaparoscopic surgery. Minimally invasive methods can now be used even for endocrine surgeries. Minimally invasive thyroid procedures can be broken down into three groups: endoscopic access from a small lateral incision in the neck, video assisted methods using a central incision-MIVAT and a range of endoscopic methods. Indications for minimally invasive procedures are precisely defined and, MIVAT consequently represents a safe method that involve minimal tissue trauma, a short period of hospitalisation and that offers significant cosmetic benefits for the patient. PMID- 19642313 TI - [Tuberculosis in Czech Republic in the year 2007]. AB - BACKGROUND: The number of notified tuberculosis cases in the Czech Republic decreased in the year 2007. 871 new tuberculosis cases and relapses were reported in the year 2007 (8.4/100 000 inhabitants). METHODS AND RESULTS: 744 cases were pulmonary tuberculosis (7.2/100 000) and from them 506 were definite pulmonary cases (4.9/100 000). In 2007 266 smear-positive cases of pulmonary tuberculosis were diagnosed. The decreasing trend in tuberculosis incidence reported since 1998 has continued. Only 14.7% of new cases of pulmonary tuberculosis were discovered by active case-finding. CONCLUSIONS: Next targets of tuberculosis control in the Czech Republic must be an active case-finding in high-risk groups and monitoring of latent tuberculosis infection. PMID- 19642314 TI - [Quality of life of Crohn's disease patients]. AB - BACKGROUND: The assessment of the quality of life in chronic diseases has started to move from clinical studies to practice. The main goal of the project was to assess the quality of life of Crohn's disease patients from two Czech centres by means of Czech versions of the general World Health Organization Quality of Life- BREF and specific Inflammatory Bowel Disease Questionnaire, to compare the quality of life of patients with an active disease and those in remission and to compare the quality of life with the general Czech population. METHODS AND RESULTS: 103 patients with Crohn's disease underwent a survey performed by means of two Czech versions of quality of life questionnaire. The dataset consisted of 53 men and 50 women; the average age of patients was 42 years. Increased activity was observed in 45 patients; 58 patients were in remission. By means of WHOQOL BREF, we found the average global score of quality of life and satisfaction with health in our group to be 3.5 (Czech standard 3.8) and 2.8 (Czech standard 3.7), respectively. The results were compared to the Czech standards. A negative influence of disease activity was statistically significant (p < 0.001) in all domains using either of the two questionnaires. Clinical factors such as the use of corticosteroids or immunosuppressives, and the history of surgery influenced some domains. CONCLUSIONS: The results from our study indicate that the disease activity may have a significant impact on the quality of life in Crohn's disease patients. A combination of the general and specific questionnaire may identify factors that would otherwise remain unappreciated properly. The quality of life of patients in remission was comparable to that of the general Czech population. PMID- 19642315 TI - [Contemporary clinical medicine--assurances and uncertainties]. AB - Selected topics in the contemporary clinical medicine are reflected. The main fields of interest and characteristic features unifying theory and praxis are outlined; specificities of clinical thinking and decision making, and conception of clinical medicine as a scientific discipline are presented. Author deals with assurances, various forms of irresolution in clinical medicine and with problems resulting from the scientific progress. PMID- 19642316 TI - [What is spirituality and how it helps]. AB - In 2006 we reviewed the medical aspects of spirituality in this journal (1). Since the end of 2006 till March 27th 2009 the number of papers dealing with spirituality in the database of U. S. National Library of Medicine increased from 2805 to 3948. We present brief updated review what spirituality is, what its medical consequences are and how it can be developed. PMID- 19642317 TI - [100 years of Miles' surgery--W. Ernest Miles 1869-1947]. AB - Just 100 years ago Ernest Miles published his method of performing abdomino perineal excision for rectal cancer in Lancet. According to detail anatomic studies he recognized the directions of lymphatic spread of this cancer. Based on these observations he suggested the surgery excising not only involved rectum, but also pelvic mesentery. The method is still current. E. Miles was excellent surgeon of peculiar personality; some of his statements and opinion are mentioned. PMID- 19642318 TI - [Population screeining of colorectal carcinoma in the Czech Republic]. PMID- 19642319 TI - [Epidemiology and treatment of colorectal carcinoma--Czech population data]. AB - The analysis of therapeutic load and evaluation of quality of care require data collected on a long-term basis. The Czech Society for Oncology develops a comprehensive information system that combines data from population-based and clinical registries and that covers all key aspects of health care assessment: monitoring of population risks and associated therapeutic burden, predictions of number of patients to be treated, evaluation of results of diagnostics and of cancer care outcomes. Accessible data proves high cancer burden in the Czech population, colorectal carcinoma being a typical example. Czech population reveals one of the highest incidence of colorectal cancer in the world. Regardless of steadily increasing incidence of colorectal carcinoma, Czech cancer care has managed to stabilize mortality of this disease and also probability of 5 yr relative survival was significantly improved in last 15 years. Developed data base allows to assess burden and results of all therapeutic modalities, including surgery. This work is aimed to present Czech data platform that can be employed in any relevant health care assessment. To keep its position in current financially limited health care system, modern surgery must effectively use all accessible data sources. PMID- 19642320 TI - [Chemotherapy and biological treatment in the complex management of large intestinal and rectal carcinomas. When, why, how?]. AB - The colorectal cancer treatment has significantly changed in last few years. Use of new drugs such as oxaliplatin, irinotecan, or capecitabine improved long term survival of patient with this disease. Research of biologic and genetic behavior of CRC has brought new ways in therapy called "biologic therapy". Standard today's treatment consist of three drugs: bevacizumab (antiVEGF antibody), cetuximab and panitumimab (anti EGFR antibodies). Biology therapy should be used simultaneously with chemotherapy only and after genetic examination of the cancer (K ras mutation). For patients with stage III the adjuvant therapy with combination of FOLFOX (oxaliplatin, fluorouracil, and leukovorin) is recommended to reduce the probability of recurrence and improve survival. In stage IIB there is a clear need to determine further risks which classify the high risk patients who should be enrolled in adjuvant chemotherapy. In palliative treatment of colorectal cancer there are several chemotherapy combinations (FUFA, FOLFOX, FOLFIRI, XELOX, XELIRI) used with biologic therapy. International recommendation for the biologic therapy is in the first line treatment bevacizumab and cetuximab or panitumumab in the second line is recommended. The new discoveries in biology of colorectal cancer show the need of tailoring. PMID- 19642321 TI - Complications after colorectal surgery. PMID- 19642322 TI - [Endoscopic diagnostics and treatment of flat intestinal lesions]. AB - The aim of the article is to provide information on current options for endoscopic diagnostics and treatment of flat tumor intestinal lesions. These neoplasms are frequently and inaccurately described as sessile polyps, which have different genetic and diagnostic features, different prognosis and therapy. Although until recently, the lesions have been managed using surgery, the current approach is predominantly endoscopic. PMID- 19642323 TI - [Vertical rectus abdominis myocutaneous flap for the closure of perineal wound after abdominoperineal resection of the rectum]. AB - INTRODUCTION: A major source of morbidity after abdominoperineal resection (APR) after neoadjuvant external beam pelvic radiation are perineal wound complications. Wound complications are common for 25-66% of patients overall. There are many of procedures provided to reconstruct the perineal defect after APR e.g. primary closure, secondary closure, superior gluteal artery flap and vertical rectus abdominus myocutaneous (VRAM) flap. Our purpose was to describe the effect of VRAM flap on reconstruction of perineal wound. VRAM flaps are ideally suited to bring nonirradiated tissue into defect associated with radical surgical extirpation procedures and irradiated fields. This flap, distally based in the deep inferior epigastric vessels, provides several distinct advantages. It is well perfused by the robust dominant pedicle and the deep inferior epigastric artery and vein. In addition, this flap provides adequate muscle bulk to obliterate pelvic dead space. The skin island can be used for resurfacing the perineal region, including the vaginal wall, and provides versatility for all patterns of resection. CONCLUSION: VRAM flap provides very good aesthetic and functional results, is technically relatively simple and radically decreases wound complications rate. The additional possibility is pull-through the flap transpelvically intraabdominally instead of pull-through via subcutaneous channel, especially with females. PMID- 19642324 TI - [Rectal lymphoma--indication for surgery?]. AB - Malignant lymphoma in colorectal location represents a rare involvement and very exceptional reason for elective surgery. The case of mantle cell lymphoma--mantle cell lymphoma-MCL, even with caecal and rectal involvement has been described and progressed on despite several previous chemotherapy regiments. Rectal lesion caused rectal syndrome and was the reason for surgery. All intestinal symptoms disappeared at once after resection of rectum (and right colectomy). The case report reminds of important aspects of multimodal treatment and stress the role of surgery in special cases. PMID- 19642325 TI - [Sexual dysfunction in men after surgery of colorectal carcinoma. New developments in prevention and therapy]. AB - Current procedures in the treatment of rectal carcinoma respect preservation quality of life. Development of sexual dysfunction (SD) in men after iatrogenic damage to neurovascular structures has been reported in 21-38% and significantly decreases quality of life. The author summarizes new developments in the area of surgical anatomy of Denonvilliers' fascia, occurrence of accessory pudendal arteries (APA), and neural anatomy. Introduction of robotic nerve-sparing surgery along with application of new diagnostic perioperative methods such as Doppler diagnostics and Optical Coherence Tomography will allow precise perioperative identification of neurovascular structures. New approaches in the treatment of erectile dysfunction prevent cavernosal hypoxia after neurovascular damage. Decrease of pO2 leads to fibrosis of penile structures and development of venous leak. Early administration of phosfodiesterasis-5 (PDE5) inhibitors forms the basis of treatment. Besides inducing erection in spite of decreased pO2, inhibitors PDE5 also have protective effect on the smooth muscles and endothelia of the penis. Combination with intracavernously applied prostaglandin PGE1 or with statins (Atorvastatin) increases efficacy. Currently, there is no standardized procedure in penile rehabilitation. Early start of therapy is recommended. In case of permanent medication support, the dosage for achieving erection is lower than in non-rehabilitated patients. Complex sexologiceal care is essential. It is necessary to initiate educational campaign of sexologists, surgeons, oncologists and patients themselves. Patients must be well informed and referred to a sexologist prior the treatment of carcinoma. Late start of rehabilitation leads to irreversible structural changes that require increased doses of drug therapy. PMID- 19642326 TI - [Incidence and prognostic significance of mesorectal extranodal tumor deposits in patients with rectal carcinoma following neoadjuvant therapy]. AB - BACKGROUND: Extranodal mesorectal deposits (ENDs) occur frequently in advanced rectal tumors. It is supposed they are related to a higher incidence of local recurrence and a poor prognosis. AIM: To discover both occurrence and impact of ENDs in patients with advanced rectal cancer after neoadjuvant therapy and surgery. PATIENTS, METHOD: 325 patients meeting following criteria were enrolled: rectal adenocarcinoma, neoadjuvant therapy, anterior or AP rectal resection, complete check up information. Both fresh and archive specimens were examined using standard histopathologic methods. RESULTS: ENDs were discovered in 45 from 325 cases. The occurrence of ENDs was significantly higher in increasing stage of tumor (p < 0.001) and in increasing tumor grade (p < 0.001). Positive correlation between number of involved lymph nodes and occurrence of ENDs (p = 0.005) was proved. The 5-year survival rates were border significantly decreased in patients with ENDs (p = 0.052). CONCLUSION: ENDs are the form of metastatic spreading of primary rectal cancer and have negative prognostic impact in 5 year survival and increase local recurrence of cancer. PMID- 19642327 TI - [Antibiotic prophylaxis in colorectal surgery]. AB - OBJECTIVE: Antibiotic (ATB) prophylaxis is generaly recommended in surgery. There is an important role in colorectal surgery especially. Colorectal surgery is associated with a particularly high risk of post-operative infection because of contamination of the wound with faecal bacteria. ATB prophylaxis decreases surgical wound infection, morbidity and mortality as well. Morbidity and mortality are associated with longer hospital stays and increased costs of care. METHOD: At surgical department of Faculty hospital Brno, during March-June 2008 an 88 patients were operated because of different diagnoses in colorectum. Both an emergent and schedule operations were made. Type of ATBs, time of application before operation, reapplication after operation and surgical site infection (SSI), in - hospital stay were followed up prospectively. SSI were divided into superficial, deep and intraabdominal. Data were analyse statistically. RESULTS: The most used combination of ATBs, almost in 91%, were Cefazoline and Metronidazole. In 50% were time of application till 20 minutes before incision. Only in 17% were time of application in interval 20-30 minutes before incision, which is recommended. We noticed 25 SSI. We prove that patients with SSI has almost two-times longer in-hospital stay. Enterococcus and enterobacterias were the most common etiological agents. CONCLUSION: ATB prophylaxis is indicated in colorectal surgery. It has to be applied in correct dose and right time before operation to decrease SSI. PMID- 19642328 TI - [Enteral fistula as a postoperative complication--a case report]. AB - Enteral fistula is a serious postoperative complication. A therapeutical approach must be individual with regard to the character of the fistula and especially with regard to the entire state of the patient. With our patient the fistula occurred as a further complication after the reconstruction operation after the preceding Hartmann resection for the perforated diverticulitis. The serious catabolic state did not make possible an immediate operational revision. It was necessary to improve first the nutritional parameters by TPN and bring about anabolism. Only then the surgical intervention with the abolishment of the fistula was possible. PMID- 19642329 TI - [Use of local hemostyptic drugs in liver resections]. AB - INTRODUCTION: Bleeding during and following liver resection continues to be an object of surgeon's attention and a potential source of significant morbidity. Topical hemostatic agents are used during surgical intervention when conventional methods are not sufficient because of the site of surgery or degree of bleeding. A variety of agents with different effects is now available. AIM: To verify the efficacy and safety of cellulose based local hemostat during liver resections. METHODS: In 67 cases of liver resection the surface was covered by Traumacel TAF net which was left in place. RESULTS AND CONCLUSION: There were no postoperative bleeding in this group of patients. No other serious complication has been observed. Traumacel is a safe and effective local hemostat during liver resections. PMID- 19642330 TI - Management of infected tibial fractures and chronic tibial osteomyelitis by muscle flap transfer: a comparison of two series of patients. AB - OBJECTIVE: The goal of this work is to compare therapeutic results of two groups of patients with an infected fracture or chronic osteomyelitis of the lower leg and ankle joint treated by the method of radical debridement followed by free flap transfer or muscle transposition. PATIENTS: In the period between 1 January 2002 and 30 September 2007 the authors used this method in the treatment of 52 patients (10 females and 42 males) with the average age of 44 years (ages ranged from 10 to 67). The observed group of patients was divided into retrospective and prospective subgroups. METHODS: The difference between the retrospective and prospective parts of the study was how radical the debridement and necrectomy of the soft tissues was. A comparison of therapeutic results in both subgroups was made by evaluation of the amounts of postoperative complications, number of follow-up surgeries and the actual weight-bearing ability of the treated extremity. RESULTS: The difference in the number of postsurgical complications (7 versus 2) was not significant (p=0.123), and neither was the difference in the number of follow-up surgeries (20 versus 17, p=0.706). The difference in the number of patients with fully weightbearing extremities (21 versus 22) was also not significant (p=0.670). CONCLUSION: The authors feel that analysis of complications showed somewhat better results in the prospective part of the study, despite the lack of statistical proof. Therefore the authors regard the method of extensive debridement with the following coverage of the soft tissue defect by muscle flap as suitable for the treatment of infected fractures in the area of the lower leg and ankle joint and the treatment of osteomyelitis of the tibia. PMID- 19642331 TI - Preservation of venous outflow improves transverse rectus abdominis musculocutaneous flap survival following vascular delay. AB - BACKGROUND: The rat abdominal island model has proved to be a reliable and reproducible model for the study of surgical delay procedures. It has been customary to simultaneously divide both the artery and the accompanying vein to obtain maximum survival of the rat TRAM flap undergoing delay procedure. This study evaluates the effect of selective arterial interruption compared to standard vascular delay on flap survival in the rat TRAM flap model. METHODS: Thirty-six Wistar rats were randomly assigned to three groups (n=12), depending on the vascular ligation selected for the initial experimental delay stage. In group A (control group) no vessels were ligated. In group B the right deep inferior epigastric vessels were preserved and the right superior and left inferior and superior deep vessels were ligated. In group C the right inferior epigastric vessels and the left inferior epigastric vein were preserved while superior epigastric vessels and the left inferior epigastric artery were ligated. For the second stage one week later, TRAM flaps were elevated based on the right deep inferior epigastric vessels, re-inset in their original position and digitally photographed. Skin island viability was determined 96 hours later using digital photography and image-analysis software SigmaScan (SPSS, Inc., Chicago, IL). RESULTS: The percentage of flap survival in control group A was 50+/-6%, in group B 60+/-4% and in group C 85+/-4%. The occlusion of the three vascular pairs in group B improved the survival percentage in comparison to the control group A, but this did not achieve statistical significance. In contrast, the percentage of flap survival in control group C was statistically significant compared to groups A and B (p<0.05, ANOVA). Zone IV exhibited no necrosis in any group C animals. CONCLUSIONS: This indicates that delay with preservation of the venous outflow of zone IV results in increased blood supply. PMID- 19642332 TI - The efficacy of magnesium sulfate on resolving surgically provoked vasospasm of the flap pedicle in an experiment. AB - BACKGROUND: Vasospasm frequently accompanies manipulation of small vessels during free flap surgeries and replantations. The purpose of this experimental study was to evaluate the effect of magnesium sulphate on vasospasm provoked by surgical manipulation (axial tension) on the flap pedicle. This kind of surgical manipulation of the vessel cannot be studied in a clinical environment without putting flap viability into risk. MATERIAL AND METHODS: Forty male Wistar rats weighing around 300 g each were classified in two experimental groups (n=20 in each). In the treatment group (group A) Magnesium Sulphuricum 10% (Biotika, Czech Republic) was applied; the second group (group B) served as a control. The vasopasm was provoked by pulling the pedicle of the right groin flap of the rat. The peripheral blood perfusion of the flap was continuously measured using laser Doppler recording. In the study group, magnesium sulphate was applied topically on the flap pedicle to relieve vasospasm, and duration of the vasospasm was compared to the control group. RESULTS: A statistically significant difference (p=0.01) between the groups was found. The duration of vasospasm was significantly shorter in the treatment group A. CONCLUSIONS: We conclude that in an experimental environment magnesium sulphate is effective in relieving surgically provoked vasospasm of the flap pedicle. This finding is in accordance with our clinical observations. PMID- 19642333 TI - Award of the G. Whitaker International Burns Prize for 2009 Palermo, Italy. PMID- 19642334 TI - The effect of blood around a flap pedicle on flap perfusion in an experimental rodent model. AB - BACKGROUND: The vasospasm has been studied to a considerable extent in the neurosurgical literature. Little experimental and basic scientific literature about vasospasm of flap pedicle is available in the field of reconstructive microsurgery. The purpose of the study was to investigate the effect of presence of blood around the pedicle on a flap perfusion. MATERIAL AND METHODS: Blood flow through a right groin flap was continuously measured using Laser Doppler flowmetry on 40 male Wistar rats. A segment of the flap's pedicle was surgically cleared of adventitia and bathed in blood. The blood used was either collected from the tail of the rat (group A) or from the bleeding branch of the pedicle itself (group B). The differences between the signal amplitudes before and after exposure of the pedicle to blood were recorded. RESULTS: The presence of blood around the pedicle resulted in a significant decrease in perfusion of the flap in both groups. However, no significant differences in the duration of impaired blood flow between the groups were observed. CONCLUSIONS: In conclusion, the presence of blood around the vascular pedicle may cause a significant decrease in the perfusion of a flap, while the origin of the blood does not appear to be an important factor. PMID- 19642336 TI - [Czech thoracic surgery]. PMID- 19642335 TI - Use of piezoelectric bone scalpel in hand and reconstructive microsurgery. AB - Performing osteotomies with piezoelectric bone scalpel is also possible with bones of larger diameter/thickness. At the same time, adjacent soft tissues are not in danger from cutting or thermal damage, reducing the risk of damaging neurovascular structures - which is of primary importance in hand and reconstructive microsurgery. These features contribute to the safety and easy execution of the procedure. The resulting bony cut is precise and permits immediate and safe bone fixation. Osteotomy of bones of >1 cm thickness takes 20 30% longer than when using a conventional oscillating saw, though the increased safety of the procedure more than compensates for this. Three cases are presented, illustrating of the use of Genera Ultrasonic for cutting bones of major thickness (metacarpal, fibula and rib) without any complication. Because of its selectivity for bony tissue, precision and ability to protect soft tissues we also advocate the use of the Genera piezoelectric bone scalpel in hand and reconstructive microsurgery. PMID- 19642337 TI - [Malignant mediastinal teratoma--a case review]. AB - In this case report the authors present a case of mediastinal malignant teratoma of a 23 years old patient, who suddenly suffers form chest pain as the only symptom. During examination is a huge mediastinal tumor diagnosed. After histological diagnosis is a radical surgery performed. According to the definitive histology is an adjutant oncological treatment indicated. The aim of our report is to think always about the mediastinal tumors as one of the possible cause of thoracic pain. PMID- 19642338 TI - [Impact of neoadjuvant chemotherapy on postoperative complications following pneumonectomy]. AB - BACKGROUND: The risks of complications in patients undergoing pneumonectomy after preoperative chemotherapy for nonsmall cell lung cancer remain controversial. We reviewed a consecutive series of patients having undergone pneumonectomy in a single centre. MATERIAL AND METHODS: This retrospective study included 292 patients operated from January 1, 1998 through December 31, 2008. Group 1 included patients those who received preoperative chemotherapy and pneumonectmy (57 patients, 19%), and group 2 included patients who underwent pneumonectomy alone (235 patients, 81%). The main objectives were 30-day and 90-day mortality rates, and major postoperative complications. RESULTS: There was no statistically significant difference in patients' age, gender, cardiovascular co morbidity, histology and side of pneumonectomy between these two groups. Overall 30-days and 90-days mortality rates were 5.5 % and 8.6%, respectively. Postoperative mortality at 30 days was 5.2% in group 1 and 5.6 % in group 2 (p = 0.16), and 10.5% for group 1 and 8.1% in group 2 at 90 days (p = 0.8). Incidence of empyema was 5.2% in group 1 and 3.0% in group 2 (p = 0.12); incidence of bronchopleural fistula was 3.5 % in group 1 and 3.0% in group 2 (p = 0.10); incidence of postoperative respiratory failure was 3.4% in group 1 and 3.0% in group 2 (p = 0.75). CONCLUSION: Preoperative chemotherapy does not significantly increase postoperative morbidity and early mortality after pneumonectomy in our experience. PMID- 19642339 TI - [Open pleural window at treatment of the advanced thoracic empyema: 20 high-risk patients' treatment experience]. AB - The aim of the retrospective clinical study was the analysis of the 20 high-risk patients operated in our department within years 2000-2008 by the modified Eloesser procedure for the serious thoracic empyema. MATERIAL AND METHODS: We have analyzed the data of the 17 men and 3 women. The most important objectives were the cause of the disease, type of procedure, perioperative mortality, length of stay and subsequent procedures. The underlying disease was the malignant intrathoracic disease in 40%, diabetes mellitus was found in 25%. The cause of empyema was pleuropneumonia in 45%, postresectional empyema occurred in 35%. RESULTS: There were two perioperative deaths (10%), remaining patients were all dismissed in a stabilized condition the 22nd postoperative day at average. Six subsequent reconstructive procedures were performed. There was no early death for the postpneumonectomy empyema. CONCLUSION: In case of the serious pleural empyema in a high-risk patient is the modified Eloesser procedure safe and life saving surgical operation. The timing of the procedure and correct indication for surgery are essential. PMID- 19642340 TI - [Disadvantages of unilateral videothoracoscopic thymectomy]. AB - The authors highlight disadvantages of the unilateral videothoracic approach in thymectomy procedures. They present a case-review of a young female patient, indicated for the procedure for myastenia gravis. In these patients, the primary objective is to remove all the thymus tissue and the surrounding adipose tissue within the anterior mediastinum, which, using the above approach cannot always be guaranteed. Considering the number of patients indicated for the procedure based on the above diagnosis, it is inevitable to perform the procedures in specialized centres, experienced with these conditions. PMID- 19642341 TI - [Pulmonary segmentectomy for tumour]. AB - BACKGROUND: An analysis of outcome data of pulmonary segmentectomy focused on local efficacy in primary non small cell lung cancer and true or seeming lung metastasis. PATIENTS AND METHODS: Miscellaneous series of twenty patients treated with classical open procedure involving individuals with primary or metachronous non small cell lung cancer, solitary pulmonary metastasis of extrapulmonary cancer and/or benign pulmonary lesions, lung metastasis mimicing. Thirteen patients after segmentectomy because of malignancy are separated into a group of 7 cases with NSCLC up to 20 mm in diameter, and a group of 6 persons with solitary pulmonary opacity up to 38 mm treated previously surgically for extrapulmonary cancer. Both without enlargement of hilar and/or mediastinal lymphatics proven on preoperative CT imaging. Third part of the group collects benign pulmonary lesions: chondrohamartoma, pneumonitis and pulmonary infarct. Persons involved through a ten years period are followed up at 3 (4)-months intervals. RESULTS: No perioperative and thirty day mortality was registered. Six cases of distant recurrence were recorded, three in NSCLC and three in extrapulmonary cancer patients. Five patients died within the follow-up period, three of them through the general progression of the oncological disease. Two deaths were non-cancer related. One R1 disease was discovered in a patient with primary lung adenocarcinoma. No local recurrence was recorded in both cancer series with median age of 63 yrs (range 45-79 yrs) and median duration of follow up 35 months. CONCLUSION: Lung segmentectomy seems to accomplish local control of early stage non small cell lung cancer and pulmonary metastasis of extrapulmonary cancer in selected patients. PMID- 19642342 TI - [Use of the KLS Martin Nd:YAG laser MY 40 13 in lung parenchyma surgery]. AB - INTRODUCTION: Nd:YAG laser MY 40 1.3 has been developed to be employed in lung tumor resections. The method's principle is based on tissue absorption of light energy and its transformation into heat. The light beam wavelength is 1318 nm and its output power is 40 W. The beam even penetrates fluid media up to the depth of 6mm, and its hemostatic effect is much larger than in other models (obstruction of arteries of up to 2 mm in diameter, veins of up to 3 mm in diameter). The laser beam application to the lung parenchyma is continuous and non-contact. AIM: Analysis of our initial experience with the use of the instrument in surgical management of primary and secondary lung tumors. METHODOLOGY: From March 2008 to December 2008, the authors operated 12 male and 5 female patients, the average age was 60.7 years. In 12 subjects, lung metastases of malignant tumors were detected, 3 subjects suffered from primary lung carcinoma and two from benign lung lesions. 7 operated subjects had multiple secondary lung tumors in various lobes of a single lung or both lungs, in 5 subjects, the secondary tumors were solitary. Most commonly--in 7 cases, the subjects suffered from colorectal carcinoma metastases. All the above surgical procedures were performed under general anesthesia with selective lung ventilation via posterolateral thoracotomy. RESULTS: In the all 12 patients, the lung metastases were radically removed using parenchyma-saving laser metastasectomy. In 3 subjects with primary pulmonary carcinoma, the laser was used to perform limited resection for intraoperative biopsy purposes, which was followed by standard radical pulmonary resection. The two benign lesions were managed in a similar way. Perioperative morbidity and mortality was nil, no significant air leak was recorded in the subjects during the postoperative period. CONCLUSION: Nd:YAG laser MY 40 1.3 facilitates radical removals of secondary pulmonary neoplasms, in particular of the multiple and deeply located ones, with no need for extensive lung parenchyma resections and with minimum intraoperative morbidity and mortality rates. Furthermore, it can be successfully used in a numer of other surgical procedures, such as management of pleural adhesions, lung biopsies, resections of emphysematous bullae, resections of benign lung tumors, dissections of inerlobal fissures, etc., where the method can fully replace staplers. It has potential for its further application in miniinvasive pulmonary surgery in the near future. PMID- 19642343 TI - [Acute mediastinitis--optimum diagnostic and therapeutic measures]. AB - The term of acute purulent mediastinitis (APM) is understood as a bacterial inflammatory process involving mediastinal tissue and organs. It is a group of clinical disorders originated primary or secondary as a complications another disease of different etiology. The definitive clinical picture is a combination of both pathologies. APM having obviously purulent character develops usually extremly fast and is objectively harming patient's life. In case of Descending Necrotizing Mediastinitis (DNM) the mortality is up to 25-40%. The only perfect and early stated diagnosis and choosen effective therapy mode can lead to patient life salvage and survival. The surgery share on therapy is substantional. During years 2004-2008 we have taken experience in this field by treatment of 18 patients with APM. Our conclusions after that most important condition for effective therapy is early and enough wide dissection of the involved area, mainly thoracocervical and mediastinal, their drainage and installation of the continual rinsing, eventually. There is no exception we indicate an operative repeated revision including rethoracotomy, if necessary. PMID- 19642344 TI - [Mediastinal lymphadenectomy in surgery of pulmonary metastasis]. AB - The effect of lymphadenectomy in pulmonary metastasectomy is unceratain. Good indication and right radicality of resection are to-days surgery possibilities to manage the best patient survival. Next possibility is performance of systematic mediastinal lymphdenecomy for currative effect and increasing of staging quality for indication of adjuvant therapy by metatatic lymphnode involvement. The answer about performance of mediastinal lyphadenectomy and its kind was seeked by authors in retrospective study in years 1999-2008. Hundred and six patient underwent pulmonary metastasectomy, 34% patients were of sarcomatous origin. Mediastinal lymhadenectomy was made in 31% patients. There were found the lyphnode involvement in five cases. The group of own patiens is non homogenous for exact conclusion of impact mediastinal lymphadenectomy on survival after pulmonary metastasectomy. The comparison of patient survival with diferent kind of lymphadenectomy isn't acceptable because sampling of lymphonodes may be false negative. For exact comparison of mediastinal lymphadenectomy importance is necessary to do systematic mediastinal lymphadenectomy in prospective multicentric study. PMID- 19642345 TI - [Late diagnosed rupture of the diaphragm --a case review]. AB - The authors describe a case of the patient with late diagnosis of the diaphragmatic rupture. There was a bowel obstruction found in X-ray scan. After endotracheal intubation was complicated of tension pneumotorax. Laparotomy was found rupture of the diaphragm. PMID- 19642346 TI - [Intraoperative neuromonitoring, neuroprotection and preventive carotid endarterectomy in patients with increased risk for development of cerebral ischemia indicated for cardiosurgery]. AB - AIM OF STUDY: To demonstrate the benefit of peroperative electrophysiological monitoring and neuroprotection in cardiac surgery that makes use a cardiopulmonary bypass in patients with a high risk of stroke and to analyze the importance of prophylactic carotid endarterectomy. BACKGROUND: Cerebral ischemia is the most dreaded complication of cardiovascular operations that make use of a cardiopulmonary bypass. It is necessary to select an approach that minimalizes neurological complications. In our treatment strategy we use preoperative electrophysiological monitoring and neuroprotection. Prophylactic carotid endarterectomy performed as part of a combined operation we performed in patients with a high risk of hemodynamic stroke. METHOD: We retrospectively evaluated 86 patients (2004-2008) after cardiac surgery that made use of a cardiopulmonary bypass and synchronous electrophysiological neuromonitoring. After any decrease in neuronal function neuroprotection was used. Combined carotid and cardiac operations were performed under one general anestesia in ten patients with a high risk of hemodynamic stroke. RESULTS: A peroperative decline in electrophysiological responses was noted in 76.5%, of these 54.5% were insignificant alterations, 42.4% significant and in two cases there was a total deletion. After administration of neuroprotection electrophysiological responses partially normalized in 14%, totally normalized in 60% and did not change in 26%. Only one permanent stroke and four temporary encephalopathy were identified after surgery. No morbidity/mortality were detected after combined operations. CONCLUSION: Peroperative electrophysiological neuromonitoring combined with neuroprotection eliminate cerebral ischemic complications in cardiac surgery that makes use of a cardiopulmonary bypass. Selected patients with high risk of hemodynamic stroke profit from carotid endarterectomy. PMID- 19642347 TI - [GIST as an acute abdomen]. AB - Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive tract. The authors present the rare common case localisation tumor in hepatal flexure of colon, witch presented as acute abdominal situation. PMID- 19642348 TI - [Another modified approach in laparoscopic cholecystectomy]. AB - The author presents his own experience with an alternative, modified insertion of throcars in elective laparoscopic cholecystectomies. The approach results in a lower number of surgical entrance points, reduced down to two incision holes. However, the procedure is suitable for certain, selected patients only. In order to be safe, the procedure is only recommended for experienced surgical teams, performing laparoscopic procedures on a routine basis. PMID- 19642349 TI - [Endovenous laser therapy of low extremity varices]. PMID- 19642350 TI - [Haemothorax after blunt thoracic trauma]. AB - BACKGROUND: Haemothorax is frequent consequence of blunt and penetrating thoracic trauma and is usually associated with pneumothorax. The occurence of haemothorax in blunt thoracic trauma patients is estimated between 25-75%. The reason of bleeding is impairment of intercostal arteries or lung parenchyma after trauma of the ribs. Uncontrolled bleeding is the main cause of the death. The article is focused on the treatment of this injury. MATERIAL AND METHODS: There were enrolled 238 patients with thoracic trauma, who were admitted into our department, into the study. The average age of the patients was 42.5 years. The ISS > or = 16 were in 101 patients. Forty two patients were artefitially ventilated. Conservative treatment prevails, almost in 65%. Special care was indicated in patients with haemothorax (fluidotoraxem). RESULTS: Clinically and based on other screening methods the presence of the fluid in thoracic cavity was in 131 patients. Surgical treatment (punction, drainage, videothoracoscopy and thoracotomy) was necessary in 47 (35.0%). Thoracotomy for the bleeding was indicated in seven cases (5.3 %). CONCLUSION: In diagnostics and in treatment of the bleeding in thoracic trauma patients the most important factor is clinical status of the patient. Indication for thoracotomy must be unambigous. Massive haemotorax leads to restrictive ventilation disorder with decreased preload and can be activator of the haemocolaguation disorders. This fact decreases chance for the survival of the patient. PMID- 19642351 TI - [Inflammatory diseases of the thorax]. AB - Inflammatory diseases of the thorax can affect its own lungs, pleural cavity, mediastinum or chest wall. They often complicate the treatment of traumatic injury of the thorax. Even infectious complication after intrathoracic surgery are not rare. The early removal of infectious substance (tissue, fluid) and relevant antibiotics therapy are basis of surgical treatment. This article deal about infection of the thorax in surgery and posibilities of treatment options. Contribution of well-timed surgical intervention is demonstrated on case report of patient with infectious complication after traumatic thorax injury. PMID- 19642352 TI - [Examination of the acute central retinal artery occlusion (CRAO) by means of optical coherence tomography (OCT3)]. AB - PURPOSE: Ischemic edema of the retina develops after CRAO and a regressive phase follows usually without any possibility of objectification. The aim of the study is to determine dynamics of edematous changes in the central retina using the OCT (Optical Coherence Tomography). SETTING: Department of Ophthalmology, Regional Hospital in Pardubice, Czech Republic, E.U. METHODS: During the period between June 2004 and January 2005, ten patients with the diagnosis of CRAO were examined by means of Stratus OCT3 (Zeiss). A protocol designed for analysis of the thickness and volume of the macula (Fast Macular Thickness Map) was used for the evaluation. Obtained readings were compared with the healthy eye. Examinations were performed on the 1st up to the 5th day after the CRAO onset and 2, 5, and 10 weeks thereafter. RESULTS: The average volume of the macula (Average Total Macula Volume) of the affected eye was (mean +/- SD; mm3): at the day of diagnosis (the initial examination) 9.196 +/- 1.376 (range, 10.315-7.301), the 2nd week 7.313 +/ 1.209 (range, 9.441-5.854), the 5th week 5.970 +/- 0.688 (range, 7.401-4.971), and the 10th week 5.091 +/- 0.558 (range, 5.768-3.989). The average volume of the most swollen macular quadrate was (mean +/- SD; mm3): at the day of diagnosis (the initial examination) 0.695 +/- 0.319 (range, 1.526-0.359), the 2nd week 0.607 +/- 0.206 (range, 1.118-0.416), the 5th week 0.520 +/- 0.220 (range, 1.070 0.334), and the 10th week 0.409 +/- 0.195 (range 0.948-0.282). In some patients, the onset of macular atrophy was found 5 weeks after the CRAO. No edema in the macular area was confirmed in any patient 10 weeks after the CRAO. CONCLUSION: On the average, we proved the regression phase of the retinal edema 5 weeks after the CRAO appearance. The OCT examination appears to be a suitable method for the determination of the dynamics of the edematous changes in the macular area after the CRAO. PMID- 19642353 TI - [Drainage implants in surgical management of pediatric glaucoma]. AB - PURPOSE: To evaluate the effectiveness and safety of glaucoma drainage implants (Molteno and Baerveldt devices) in primary and secondary childhood glaucomas refractory to conventional surgical treatments and medical therapy. PATIENTS AND METHODS: Retrospective study included 76 children (76 eyes) younger than 18 years who underwent glaucoma drainage device (GDD) implantation in our clinic between 1990 and 2004. The mean age at time of surgery was 6.9 5.3 years (range: 4months to 17.5 years). Intraocular pressure (IOP), visual acuity, corneal diameter, axial length, intraoperative and postoperative complications and number of glaucoma medications were evaluated. Criteria for success were defined as IOP between 7 and 22 mmHg with or without glaucoma medications, no further glaucoma surgery, and the absence of visually threatening complications, no loss of light perception. Results were compared for children with primary and secondary glaucomas. The mean follow-up was 7.1 6.5 years (range: 1.6 to 15.2 years). RESULTS: Mean preoperative and postoperative IOP was 33.6 11.4 mmHg and 17.1 6.5 mmHg (p 0.001), respectively. Kaplan-Meier survival analysis showed cumulative probability of success: 93% at 6 months, 91% at 1 year, 82% at 2 years, 76% at 3 years, 71% at 4 years, 67% at 5 years and 65% at six years. There was no difference between primary (n = 31 eyes) and secondary glaucoma (n = 45 eyes) patients in terms of cumulative success (p = 0.186), final IOP, number of medications, or length of follow-up. On average, the GDI surgery was successful for a mean period of 6.7 years. Fourteen eyes of 76 (18.4%) failed with these causes: 10 eyes with uncontrolled IOP, 2 eyes of retinal detachment and 2 eyes with no light perception. Statistical regression model did not show influence of gender and previous surgery. Lower age at the time of surgery was found to be associated with higher probability of treatment failure. CONCLUSION: Molteno and Baerveldt glaucoma drainage implants surgery seems to be safe and effective treatment for primary and secondary pediatric glaucoma refractive to the initial surgical procedure and medical therapy. PMID- 19642354 TI - [Changes in the retinal nerve fiber layer in non-arteritic anterior ischemic optic neuropathy revealed by means of the optical coherence tomography]. AB - Aim of this study was to reveal the contribution of the Optical Coherence Tomography (OCT) to the diagnosis and the follow-up of the non-arteritic form of the anterior ischemic optic neuropathy (AION) and to establish quantitative changes of the thickness of the retinal nerve fiber layer (RNFL) in the peripapillar and the macular regions. In a group of 12 eyes with non-arteritic AION the authors performed the measurements of the average RNFL thickness by means of OCT. The measurements were taken peripapillary and in the macular region. The measurements were taken in the acute phase of the disease and at least three months after the beginning of the disease during a follow-up control. At the time of both examinations, the static perimetry was performed as well. All findings were compared to each other. During the follow-up period, the authors proved statistically significant decrease of the thickness of the RNFL. The mean thickness in the acute phase (mean +/- SD) was 219.26 +/- 61.02 microm, decreased at the follow-up control to 69.44 +/- 20.40 microm. This value corresponds to the postischemic atrophy and was always lower than the measurement in the other, healthy eye. The damages were in strong correlation to the perimetry changes. PMID- 19642355 TI - [Analysis of prognostic factors of anatomical and functional results of idiopathic macular hole surgery]. AB - PURPOSE: Analysis of preoperative prognostic factors in idiopathic macular hole surgery and determination of their significance for the final postoperative visual functions. METHODS: Ninety-one patients with idiopathic macular hole were enrolled into this study. The best-corrected visual acuity, macular hole staging according to Gass classification and duration of macular hole symptoms were evaluated preoperatively. Pars plana vitrectomy with internal limiting membrane peeling and expanding gas (C3F8) tamponade was subsequently performed in all patients. Macular hole closure rate--anatomical success of the surgery--and visual acuity (functional results) were postoperatively assessed. RESULTS: Positive correlation between the duration of the macular hole symptoms and the final postoperative visual functions (Kruskal-Wallis; P = 0.003) as well as between the duration of the macular hole symptoms and the postoperative macular hole closure rate (Man-Whitney; P = 0.001) were found in patients with idiopathic macular holes. Postoperative significant improvement of visual acuity depends on the preoperative macular hole stage according to Gass classification (Pearsovov xhi2; P = 0.05). CONCLUSION: Macular hole symptoms duration and preoperative macular hole stage are the two significant prognostic factors for postoperative functional and anatomical results. PMID- 19642356 TI - [Awareness and quality of life in patients with glaucoma]. AB - PURPOSE: To test the Czech version of a validated questionnaire in assessing health-related quality of life in patients with glaucoma and also determine the level of understanding of their disease. METHODS: Quality of life was assessed using the NEI-VFQ 25 (National Eye Institute - Visual Function Questionnaire) in 20 patients with open-angle glaucoma. Results of the questionnaire were processed by standardized methods and a score between 0 and 100 was assigned to each of the 12 subscales, where 100 represents the best possible score on the scale and 0 represents the worst. The awareness of patients about glaucoma was elicited by 9 questions concerning the origin, course, diagnostic methods and prognosis of glaucoma. RESULTS: The lowest scores in our study group were associated with the subscales of general vision (61.4 +/- 19.7), mental health (61.4 +/- 17.4), role limitations (72.1 +/- 26.7), and dependency (58.3 +/- 23). Our knowledge inquiry revealed poor level of knowledge about glaucoma in our study group. CONCLUSIONS: in our study, the NEI-VFQ 25 proved to be useful and the scores comparable to the results published abroad. The results of our knowledge inquiry suggest that there is an urgent need for patients to receive more information. Patients who are more knowledgeable of their condition are more likely to be adherent to treatment. PMID- 19642357 TI - [Chlamydia pneumoniae in the etiology of the keratoconjunctivitis sicca in adult patients (a pilot study)]. AB - AIM: In the pilot study the authors refer to the possible connection between the appearance of keratoconjunctivitis sicca (KCS) and Chlamydia pneumoniae (CP) infection. MATERIALS AND METHODS: At the Department of Ophthalmology, 10 adult patients older than 45 years were followed up during the period of 5.5-7 years, where in the chronic folicular conjunctivitis caused by CP, the KCS was revealed as the same time. METHODS: The chlamydial infection diagnosis was established due to the positivity to the familiar (anti-LPS) and species (anti-CP) immunoglobulins (IgG, IgM, and IgA) and to the conjunctival impression specimen, using the indirect immunofluorescence of specific monoclonal antibodies. The patients were treated by means of systemically administered macrolide antibiotics Azithromycine. After the termination of the treatment, the signs of the clinical inflammation of the conjunctival inflammation subsided but the KCS problems remained. After 6 years, the control examinations of the familiar and species antibodies of the CP were performed and the clinical findings of the KCS and its treatment were evaluated. RESULTS: The decrease of the antibody levels was proved and objective findings and subjective symptoms of KCS in all patients subsided. Altogether 7 patients were without clinical signs of the KCS and without regular application of local artificial tears treatment. At the same time, in two thirds of the patients, the levels of the antibodies decreased or remained unchanged. In the last three patients, the signs of the dry eye decreased, but they didn't disappeared permanently. These patients had to apply artificial tears several times a day. The suspect signs of this serologically active infection persisted despite the antibodies levels' decrease. CONCLUSION: This pilot study until now didn't confirm the direct dependence between the KCS and CP, but it didn't exclude it as well. PMID- 19642358 TI - [Ranibizumab (Lucentis) in the treatment of age-related macular degeneration]. PMID- 19642359 TI - [Clinical study on the fibrinolytic activity in patients with acute promyelocytic leukemia]. AB - OBJECTIVE: To study the fibrinolytic activity in patients with acute promyelocytic leukemia (APL) and its alteration in all-trans retinoic acid (ATRA) and/or arsenic trioxide (ATO) treatment. METHODS: Plasma fibrinogen concentration was determined with the conventional method, and the levels of fibrin degradation products (FDP) and D-dimer were quantified with ELISA. Plasminogen was measured by chromogenic assay. Cell surface expression of Annexin II and u-PAR and their mRNA levels were measured by flow cytometry and real time-PCR, respectively. RESULTS: The levels of FDP and D-dimer in APL were remarkably higher in APL patients than that in normal controls, while fibrinogen and plasminogen were lower. Both Annexin II and u-PAR were highly expressed on APL cells, which declined after treatment with ATRA and/or ATO, but remained higher than those on normal bone marrow mononuclear cells. CONCLUSION: Abnormally high levels of Annexin II and u-PAR expression on APL cells may contribute to the increased production of plasmin, leading to primary hyperfibrinolysis in APL. ATRA and ATO therapy induces down-regulation of Annexin II and u-PAR expression, which may be contribute, at least in part, to the relief of the hemorrhagic complications in APL. PMID- 19642360 TI - [Intron 1 and 22 inversions in factor VIII gene in patients with haemophilia A]. AB - OBJECTIVE: To analyze intron 1 and 22 inversions in factor VIII (FVIII) gene in hemophilia A (HA) patients and and their families and to investigate the correlation between intron inversion and FVIII antibody. METHODS: All patients were detected FVIII: C and FVIII antibody. In addition, 81 unrelated HA patients were directly detected by multiplex PCR and long-distance PCR for intron 1 and 22 inversions in FVIII gene. Pedigree investigation for some patients were conducted. RESULTS: In 81 unrelated HA patients, 3 severe cases were found intron 1 inversion which accounted for 4.6% of total 65 severe cases. Of the 3 cases, one was FVIII antibody positive. Two female family members of a intron 1 inversion patient were identified as one carrier and one non-carrier. Twenty five of 65 (38.5%) severe cases were found intron 22 inversion. Of the 25 cases 1 was FVIII antibody positive. Nine female members in 5 HA families which had patients with intron 22 inversion were identified as 7 carries and 2 non-carriers. CONCLUSION: Besides intron 22 inversion, intron 1 inversion was another important molecular defect in resulting in severe HA. Intron inversion analysis can also be used for deviation rectification of experiment grouping in HA patients. Intron 1 and 22 inversions may be one of the higher risk factors for resulting in FVIII antibodies. PMID- 19642361 TI - [Development of a monoclonal antibody to factor VIII C2 domain and its functional study]. AB - OBJECTIVE: To develop a monoclonal antibody (mAb) directed to FVIII C2 domain and investigate its effect on FVIII activity. METHODS: FVIII C2 protein was expressed in E. coli and purified. A murine antihuman FVIII C2 domain mAb SZ-132 was developed by standard hybridoma technology and characterized. In coagulation assays, different concentrations of SZ-132 were incubated with freshly collected pooled human plasma and the residual activity of FVIII and activated partial thromboplastin time (APTT) were determined. The effects of SZ-132 on rhFVIII binding to purified human vWF, phosphatidylserine (PS) and platelets were assessed by enzyme linked immunosorbent assays (ELISA). RESULTS: SZ-132 could inhibit FVIII procoagulant activity in a dose-dependent manner within the concentrations of 0-25 microg/ml and the FVIII activity was completely inhibited on above 25 microg/ml. It could also prevent rhFVIII from binding to vWF, PS and platelets. CONCLUSIONS: SZ-132 is a neutralizing mAb against FVIII C2 domain and can inhibit FVIII procoagulant activity by preventing FVIII from binding to vWF and PS. PMID- 19642362 TI - [Identification of Arg77Cys and Arg174stop double heterozygous mutation in a Chinese family with inherited FXIII deficiency]. AB - OBJECTIVE: To identify the gene mutation type of an inherited coagulation factor XIII (FXIII) deficiency pedigree. METHODS: PCR and DNA sequencing were used to identify the mutations in the 15 exons and the flank sequence of FXIII gene in the proband. The identified mutations were validated by allele specific PCR, PCR restriction fragment length polymorphism technique or DNA sequencing in the family members and 100 healthy volunteers. RESULTS: Arg77Cys and Argl74stop double heterozygous mutations were discovered in the proband. The pedigree analysis showed that Arg77Cys missense mutation inherited from her father, and Arg174stop from her mother. The Arg77Cys missense mutation in exon 3 was not found in her husband and the other 100 healthy volunteers. CONCLUSION: A novel Arg174stop nonsense mutation was discovered in human FXIII gene. A simple DNA assay based on PCR for detection of this mutation was developed. The congenital FXIII deficiency in the proband might be caused by the coinheritance of the Arg77Cys missense mutation in exon 3 and the Arg174stop nonsense mutation in exon 4. PMID- 19642363 TI - [Effect of alpha-galactosidase A deficiency on FV leiden fibrin deposition and thrombosis in mice]. AB - OBJECTIVE: To evaluate the effect of alpha-galactosidase A (Gla) deficiency on FV Leiden (FVL) associated thrombosis in vivo. METHODS: To generate the mice carrying mutations in Gla and FVL and analyze the tissue fibrin deposition in organs and thrombosis. RESULTS: In the presence of FVL, Gla deficiency greatly increased tissue fibrin deposition compared with that in wild-type [Gla(-/0) FV(Q/Q) vs. Gla(+/0) FV(Q/Q) = (0.24 +/- 0.07)% vs. (0.086 +/- 0.049)%, P < 0.0001; Gla(-/-) FV(Q/Q) vs. Gla(+/+) FV(Q/Q) = (0.32 +/- 0.03)% vs. (0.06 +/- 0.005)%, P < 0.05]. With Gla deficiency, the number of thrombi on organ sections in FVL mice was significantly increased [(Gla(-/-) FV(Q/Q) and Gla(-/0) FV(Q/Q)) vs. (Gla(+/+) FV(Q/Q) and Gla(+/0) FV(Q/Q)) = 1.9 +/- 0.7 vs. 0.3 +/- 0.1, P < 0.05]. CONCLUSIONS: Gla deficiency could be an important genetic modifier for the enhanced thrombosis associated with FVL. PMID- 19642364 TI - [Establishment of a high expressing system of human coagulant factor VIII in vitro]. AB - OBJECTIVE: To construct a recombinant lentiviral vector (pXZ208-BDDhFVIII) mediating B-domain-deleted human coagulation factor VIII (BDDhFVIII) gene and investigate its expression in HLF, Chang-Liver and MSC cells. METHODS: BDDhFVIII gene fragment was separated by endonuclease digestion and was cloned into the multiple cloning sites of pXZ208 to construct a recombinant lentiviral vector pXZ208-BDDhFVIII. Viral particles were prepared by means of three-plasmid cotransfection of 293T package cells by calcium phosphate precipitation. After infection, the coagulant activity of human FVIII in the culture medium of 293T, HLF, Chang-Liver and MSC cells was assayed by one-stage method. The gene transduction efficiency was assayed by flow cytometry (FCM). Furthermore, PCR was performed to test the integration of BDDhFVIII. RESULTS: The infection rates of HLF, Chang-Liver and MSC were (74.52 +/- 7.57)%, (27.24 +/- 6.53)% and (42.34 +/- 5.84)% respectively. The activities of FVIII in supernatants of HLF, Chang-Liver and MSC were (54.1 +/- 5.6)%, (22.5 +/- 2.9)% and (12.5 +/- 2.7)% respectively. BDDhFVIII gene integration was detected in all the infected cells. CONCLUSION: The recombinant lentiviral vector pXZ208-BDDhFVIII was successfully constructed and efficiently integrated into target cells to express human FVIII activity in vitro. PMID- 19642365 TI - [Inhibition of protein kinase A leads to cleavage of platelet GP I balpha and downregulation of GP I b-dependent platelet aggregation]. AB - OBJECTIVE: To explore the regulatory role of protein kinase A (PKA) in platelet surface glycoprotein (GP) I balpha expression. METHODS: Washed platelets from healthy volunteers were incubated with PKA inhibitor. The N-terminal fragment of GP I balpha (glycocalicin, GC) in the supernatant of platelet suspensions was detected by Western blot and GP I balpha surface expression by flow cytometry. Calpain activity was determined by cytoskeletal proteins proteolysis and calpain surface expression by flow cytometry. The effect of PKA inhibitor on ristocetin induced platelet aggregation was measured by platelet aggregometer. RESULTS: After PKA was inhibited in washed platelets, GP I balpha was cleaved and released to the supernatant, which significantly decreased the surface expression of GP I balpha (P < 0.05). The event was suppressed by pre-treatment with various calpain inhibitors, indicating that PKA inhibitor-mediated shedding was calpain dependent. The actin-binding protein (ABP) and talin proteolysis demonstrated that calpain was activated by PKA inhibitor and expressed on the platelet membrane. Ristocetin-induced aggregation was inhibited by PKA inhibitor. CONCLUSION: PKA inhibition results in calpain-dependent GP I balpha shedding, which thus reduces GP I balpha surface expression and GP I balpha-dependent platelet aggregation. These results might provide a view to develop new drugs for thrombotic diseases. PMID- 19642366 TI - [Noninvasive prenatal diagnosis of Hb Bart's hydrops fetus using cell-free fetal DNA in maternal plasma]. AB - OBJECTIVE: To explore a new noninvasive method for Hb Bart' s hydrops fetus by using PCR amplification efficiency discrimination between cell-free fetal DNA (cffDNA) and cell-free maternal DNA in maternal plasma. METHODS: CffDNA samples from pregnant women bearing possible Hb Bart's hydrops fetus were collected. Fluorescent PCR and capillary electrophoresis (CE) were performed. Hb Bart's hydrops fetus was conclusively identified by different peak area ratio of products. RESULTS: The peak area ratio of 30 cffDNA samples from Hb Bart' s hydrops fetus was much less than 1. However, the ratio of cffDNA sample from hydrops fetus due to other reasons was approximately equal to 1. CONCLUSION: By using cffDNA fluorescent PCR and CE, a prenatal screening method for Hb Bart' s hydrops fetus was developed. PMID- 19642367 TI - [The clinical and laboratory characteristics of T cell large granular lymphocyte leukemia]. AB - OBJECTIVE: To analyze the characteristics of T-cell large granular lymphocyte leukemia (T-LGLL). METHODS: Retrospectively analyze the clinical and laboratory data of 27 patients with T-LGLL diagnosed between 1999 and 2007 in our hospital. RESULTS: The median age at diagnosis was 48 years. All patients were symptomatic, mainly complaining of fatigue. Of the 27 patients, 14 (51.9%) had splenomegaly, and 4(14.8%) hepatomegaly. Rheumatoid arthritis was not present in any patients. The most frequent hematological abnormality was anemia (24 patients, 88.9%) with a median Hb level of 57.5 g/L. Pure red cell aplasia was found in 18 patients (66.67%). The median WBC count was 4.24 x 10(9)/L and 19 cases were neutropenia (ANC < 1.5 x 10(9)/L). The median LGL count in peripheral blood was 1.45 x 10(9)/L and most of them (77.8%) were less than 2.0 x 10(9)/L. Twenty-two patients (81.5%) showed the CD3+ CD8+ CD57+ CD56(-) LGL phenotype. With immunosuppressive therapy, 91.3% of patients responded and complete hematological remission rate was 65.2%. CONCLUSION: T-LGLL mainly presented with anemia and complete hematological remission rate was 65.2%. Pure red cell aplasia was commonly associated with the disease. The patients had a good response to immunosuppressive therapy. PMID- 19642368 TI - [Effect of zoledronic acid on the growth and CD138 expression of myeloma cell line KM3]. AB - OBJECTIVE: To study the inhibitory effect of zoledronic acid (ZA) on the growth and CD138 expression of myeloma cell line KM3. METHODS: KM3 cells were treated with different concentrations of ZA The growth of KM3 cells was measured by trypan blue dye exclusion, and the changes of apoptosis rate, cell cycle and expression of CD138 induced by ZA by flow cytometry. RESULTS: Within the concentration of 10(-5)-10(-3) mol/L, ZA obviously inhibited the growth of KM3 cells in a dose dependent manner. IBN at 10(-5)-10(-4) moL/L increased Annexin V positive rate, blocked cells at the S/G2 boundary, reduced the expression of CD138 and its fluorescence intensity. CONCLUSION: ZA can inhibit the growth of KM3 cells in a dose-dependent manner and inhibited CD138 expression. The mechanism is probably related to induction cell cycle accumulation in S phase and apoptosis. PMID- 19642369 TI - [Long term outcome of acute myeloid leukemia with t(8;21)]. AB - OBJECTIVE: To investigate the influence factors on survival and outcome of acute myeloid leukemia (AML) patients with t(8;21). METHODS: Eighty seven AML patients with t(8;21) after long-term follow-up were enrolled in the analysis of clinical feature, immunophenotype, chromosome karyotype, treatment regimen, as well as the overall survival (OS) and relapse-free survival (RFS). RESULTS: The overall complete remission (CR) rate was 95.3%. CR rate after first course therapy was 69.8%, after first course therapy containing medium dose Ara-C was 86.2%, and after first course of therapy containing standard-dose Ara-C was 60.3%. The median OS duration was 16.4 months, median RFS 11.7 months, 3 year OS rate 42%, 5 year OS rate 39%, 3 year RFS rate 55% and 5 year RFS rate 55%. Male gender chromosome 9q(-) had statistical significance for shorter OS and poor outcome, 2 courses of post-remission therapy with intermediate dose Ara-C, induction therapy with intermediate-dose Ara-C and post-remission with 4 courses consolidation therapy had statistically longer OS and RFS. CONCLUSION: Sex, chromosome karyotype, induction and consolidation therapy were important influence factors on OS and RFS. Application of intermediate dose Ara-C to induction and consolidation therapy leads to a higher CR rate, prolong OS and RFS. PMID- 19642370 TI - [The relationship between body mass index, waist circumference, waist-to-hip ratio, waist-to-height ratio and hyperglycemia: a three-year follow-up study in Nanjing]. AB - OBJECTIVE: To explore whether the increase of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) can predict a higher risk of developing hyperglycemia. METHODS: A population based cross-sectional study was conducted on local residents above 35 years of age in three urban districts and one rural county in July 2004. The subjects who were non-hyperglycemia in the baseline survey were selected to follow the survey in July 2007. Multivariable logistic regression analysis and area under curve (AUC) of receiver-operating characteristics (ROC) were used to evaluate the predictive value of BMI, WC, WHR and WHtR. RESULTS: Of 3727 subjects without hyperglycemia who had completed in the baseline survey, 3031 of them participated in the follow-up survey, with a follow-up rate of 81.3%. The Three-year cumulative incidence of hyperglycemia was 6.7%, with male 6.3% and female 7.0%. By multiple linear regression, on average, an increase in BMI, WC, WHR, WHtR of 1 unit was associated with a 0.015 mmol/L, 0.023 mmol/L, 1.923 mmol/L, 2.382 mmol/L increase in fasting plasma glucose, respectively. The risk of developing hyperglycemia increased along with the increase of all the four indexes. When compared with other three indexes, the group which WHtR was more than 0.5, had the highest risk (male OR = 1.998, 95% CI: 1.231-3.212, female OR = 1.832, 95% CI: 1.157-2.902) of developing hyperglycemia. Data from ROC curve analysis showed that the AUC of WHtR was the highest in both males and females. CONCLUSION: The increase of BMI, WC, WHR and WHtR could predict the higher risk causing the development of hyperglycemia. WHtR might serve as a simple but most effective index of hyperglycemia. PMID- 19642371 TI - [Clinical predictability of the waist-to-hip ratio in assessing the risk factors of cardiovascular disease among public servants in Shijiazhuang city]. AB - OBJECTIVE: To assess the clinical predictability of waist-to-hip ratio (WHR) among female civil servants who had experienced risk factors of cardiovascular disease. METHODS: Data was gathered from 4153 female civil servants aged 21-91 y working at universities who were enrolled in health screening centre at the Second Hospital Attached to Hebei Medical University, in 2006. WHR quartiles were determined., as: < 0.80, 0.80- < 0.84, 0.84- < 0.90 and > or = 0.90. Subjects were placed into high-risk categories for cardiovascular disease on the basis of national health reference on range norms of protocol including hypertension, diabetes mellitus and dyslipidemia. RESULTS: Participants had an increased likelihood of hypertension (systolic blood pressure), dyslipidemia (elevated triacylglycerol and descending HDL-C) and diabetes mellitus at WHR > or = 0.84. All aforementioned variables had a significant odds ratio at WHR > or = 0.84. This trend was further persisted after adjustment had been made on smoking, age, and BMI. Descended HDL-C was observed at the 0.80 < or = WHR < 0.84 when compared with WHR < 0.80. CONCLUSION: These data indicated an upward shift in the critical threshold for WHR to > or = 0.84. Above which point, there was an elevation of risk factors on cardiovascular diseases among all the female civil servants. The trend persisted regardless of smoking, BMI < or > or = 28 and at what age group, among the civil servants population. PMID- 19642372 TI - [Using three different screening methods to study overweight and simple obesity among children under age 7 in Ningbo city]. AB - OBJECTIVE: To investigate the occurrence of simple obesity among children under age 7 in Ningbo and to analyze the data regarding body mass index (BMI) from overweight screening under different standards. METHODS: Randomized cluster sampling was adopted and 64 038 children under 7 years old in Ningbo were chosen and their length/height and weight were measured but pathological and secondary obesity cases were excluded. According to the Standardized Height and Weight set by WHO, more than 10% referring to overweight and more than 20% referring to obesity. Moreover, results of this study were compared with growth standards with WHO's 2006 and IOTF standards. RESULTS: According to the Standardized Height and Weight set by WHO, the prevalence rates of overweight and obesity of children under age 7 were 4.25% and 2.88%. The ratio for boys were 4.45% and 3.01%, while for girls as 3.86% and 2.56%, with significant difference (P < 0.01). Data showed that the rates for overweight and obesity increased along with age, reaching 11.84% and 9.68% for boys and 10.14% and 9.46% for girls at the age of 6. The ratios of overweight/obesity among different age groups and sex were 1.15-1.94:1. The critical value for P85, P95 were lower than the standards set by WHO and IOTF. The rates for overweight and obesity for latter were 9.72%, 2.83% and 6.11%, 0.55% respectively. CONCLUSION: Early childhood is the key period for obesity prevention, with boys in particular. Prevention and control for childhood obesity should be included in the programs for children's health. Value of classification standards for the BMI screening of overweight and obesity for children under age 7 should be established in no time. PMID- 19642373 TI - ['Life satisfaction' as a moderator or mediator of accommodation category and loneliness for rural school students]. AB - OBJECTIVE: To examine life satisfaction as a moderator or mediator of accommodation category and loneliness for elementary and middle school students in rural areas so as to provide evidence for psychological health intervention among said students. METHODS: All participants were asked to complete an anonymous questionnaire battery which including an 18-item General Health Questionnaire, Children's Loneliness Scale and Multidimensional Students' Life Satisfaction. RESULTS: The average score of loneliness scale (35.0 +/- 9.5) among boarding-school students was significantly higher than those students living at home (33.1 +/- 10.1) (P < 0.01). The average scores on school-satisfaction (33.5 +/- 6.3), friend-satisfaction (42.1 +/- 6.2) and self-satisfaction (32.4 +/- 5.0) of boarding-school students were significantly higher than those students living at home (35.9 +/- 6.6, 42.9 +/- 6.6, 32.9 +/- 5.3) (P < 0.05). The association between accommodation category and loneliness was fully mediated by school satisfaction (the standardized coefficients of loneliness was reduced from 0.043 (P < 0.05) to 0.021 (P > 0.05) and partly mediated by self-satisfaction and friend-satisfaction. Data through Moderation analyses indicated that self satisfaction, school-satisfaction and friend-satisfaction did not serve as moderators. CONCLUSION: Accommodation category, life satisfaction seemed to be good predictors on loneliness among elementary and middle school students and the fully mediated effect of school-satisfaction between accommodation category and loneliness was significant, suggesting that intervention of loneliness should focus on these variables. PMID- 19642374 TI - [Risk factors on anemia among rural elderly women aged 50-75 y in Xinning county, Anhui province, China]. AB - OBJECTIVE: To study the risk factors on anemia among elderly women in rural areas of Xiuning county, Anhui province, China. METHODS: Xiuning county was selected as working field and elderly women aged 50-75 y were selected as subjects. Finger hemoglobin (Hb) was measured and basic health survey was face-to-face interviewed. 220 elderly women with anemia entered into the case group; and matched by age, another 220 women with normal Hb concentration entered the control group. Survey on diet, questionnaire regarding health and lifestyle and related blood indexes were studied and tested. RESULTS: When comparing the data from both case and control groups, weight was (49.4 +/- 7.3) kg vs. (52.5 +/- 8.4) kg (t = 3.97, P < 0.01), waist circumference was (75.8 +/- 7.8) cm vs. (79.1 +/- 9.3) cm (t = 3.85, P < 0.01), BMI was (21.8 +/- 2.6) kg/m2 vs. (22.9 +/- 3.2) kg/m2 (t = 3.775, P < 0.01), respectively. The total protein was (76.4 +/- 5.0) g/L vs. (78.4 +/- 5.6)g/L (t = 3.83, P < 0.01), albumin was (45.7 +/- 3.1) g/L vs. (47.3 +/- 2.9)g/L (t = 5.24, P < 0.01), serum iron was ( 10.3 +/- 4.1) micromol/L vs. (12.7 +/- 4.6) micromol/L (t = 5.48, P < 0.01), and saturation of transferrin was (19.0 +/- 7.6)% vs. (23.1 +/- 9.1) % (t = 4.90, P < 0.01), respectively. Results from multifactor conditioned logistic regression analysis showed that the odd ratios (OR) for anemia with staple food, BMI and vitamin A were 1.54, 1.89, 1.69, and the OR for anemia with BMI, staple food, animal food, carbohydrate and vitamin A were 2.0, 1.6, 1.6, 1.4, 1.6, with their confidence intervals (CI) as 1.3-2.9, 1.1-2.3, 1.0-2.3, 1.0-2.1, 1.1-2.4, respectively. CONCLUSION: The quality of diet, health status and related blood indexes on anemia among elderly women were lower than that in control group. Lower BMI, less staple food and animal food, less carbohydrate and vitamin A intake appeared to be risk factors of anemia. PMID- 19642375 TI - [Studies on HIV-1 strains in Henan province]. AB - OBJECTIVE: To study the epidemic status of human immunodeficiency virus type 1 (HIV-1) subtypes and sequence variation in Henan thus to explore the characteristics and sources of transmission. METHODS: HIV-1 env and gag gene were amplified by nested PCR from uncultured peripheral blood mononuclear cells (PBMCs) obtained from 1287 HIV-1 carriers confirmed in Henan from 2006 to 2007. 1287 env and gag genes were obtained from the patients. RESULTS: Among 1287 samples, there were 4 HIV-1 strains including subtype B', C and recombinant subtype BC and AE, accounting for 95.882% (1234/ 1287), 0.466% (6/1287), 2.875% (37/1287), 0.777% (10/1287) respectively. In comparison with the sequence of the international strains of RL42, C.95in21068, 07-BC.CN.97.C54A, 01AE.TH.90.CM240, the genetic divergence was 9.327% +/- 0.245%, 5.214% +/- 0.183%, 6.278% +/- 0.194% and 5.332% +/- 0.158%, respectively. CONCLUSION: There were 4 HIV-1 strains including subtype B', C and recombinant subtype BC and AE in Henan with main dominant subtype as subtype B' which was closely related to HIV-1 strains of Thailand B'. The major transmit route in subtype B' was through blood donation in the past years while with BC, it was through sexual transmission. The major transmit routes in subtype AE were sexual transmission and blood donation. The major route of transmission in subtype C was through sexual contact. PMID- 19642376 TI - [Distributions of pathogenic capsular types and in vitro antimicrobial susceptibility of different serotypes of Streptococcus suis isolated from clinically healthy sows from 10 provinces in China]. AB - OBJECTIVE: To determine the distributions of major pathogenic capsular types and in vitro antimicrobial susceptibility of different serotypes of Streptococcus suis isolated from clinically healthy sows in China. METHODS: Tonsil specimens of clinically healthy sows from 10 different provinces in China were collected, a total of 421 S. suis were isolated. Capsular types of S. suis were decided using the sera agglutination reaction. Antimicrobial susceptibility testing was performed using a broth microdilution method and the differences between serotypes were decided statistically. RESULTS: The prevalent capsular types of S. suis isolated from clinically healthy sows were 9 (26.6%), 3 (23.5%) and 7 (15.7%) types, respectively. 7.4% of isolates were confirmed to be S. suis type 2. Overall, differences in antimicrobial susceptibility among serotypes of S. suis were found. By comparison, lower resistance was observed for S. suis type 2 from clinically healthy sows. CONCLUSION: The prevalence of pathogenic S. suis serotypes from clinically healthy sows again indicates S. suis is a conditional pathogenic bacterium. Differential prevention and treatment regimes should be considered according to antimicrobial susceptibility of different serotypes of S. suis. PMID- 19642377 TI - [Survey on host animal and molecular epidemiology of hantavirus in Chuxiong prefecture, Yunnan province]. AB - OBJECTIVE: To determine the hosts of hantavirus (HV) and its molecular epidemiological characteristics, to provide evidence for prevention and control on hemorrhagic fever with renal syndrome (HFRS). METHODS: Rodents were captured by a special trap within the residential area. The antigens of HV in lung tissues were detected by direct immuno-fluorescence assay (DFA). Nucleotide sequences of HV were amplified by RT-PCR with HV genotype-specific primer. The amplified genes were then sequenced. Phylogenetic tree were built on nucleotide sequence with ClustalX 1.83 software. RESULTS: 1421 rodents were captured and classified into 8 species of 4 Genera in the epidemic area within 10 counties of Chuxiong prefecture, Yunnan province, between 2005 and 2006. Out of the 1421 rodents, 1056 (74.31% ) of them were Rattus norvegicus and 280 (19.70%) belonged to Rattus flavipectus. The antigens of HV were detected by DFA in lung tissues and the total positive rate of HV was 5.15% (53/ 1029). After applying the sequencing nucleotide method to the 53 positive specimens, data showed that 21 specimens were positive and all of them belonged to Seoul type (15 samples were from Rattus norvegicus, 4 samples Rattus flavipectus, 2 samples Rattus nitidus). The partial S segments from 12 specimens were sequenced which appeared homologic with R22, L99 and HLD65 from GenBank in relatively high level (87.1% -99.7%). When compared to 76-118 strain of Hantaan type, their homologic degree was only 64.4%-69.1%. Results from Phylogenetic analysis showed that 12 specimens belonged to Seoul type. As for their homology, they were significantly similar to Seoul type and could be tentatively divided into two subtypes S1 and S3. CONCLUSION: It was confirmed that the Seoul type virus, as HFRS's pathogenetic agent mainly carried by rats, prevailed widely in Chuxiong prefecture. Owing to the local ecological environment, we also noticed the characteristics of different HV subtypes among Seoul type. PMID- 19642378 TI - [An eight-year study on maternal and child health service utility in Sichuan province]. AB - OBJECTIVE: To evaluate the effect of intervention on factors influencing the health service utility regarding Maternal and Child Health (MCH) under the 'Qinba Health Project' in Sichuan province. METHODS: 15 towns in 5 programmed counties were selected, using the method of 'random layer sampling' to be the trial group. With similar MCH status and comparable to the trial group, another 9 towns in 3 non-programmed counties were chosen as the control group, using the same sampling method. Indicators on MCH service utility were compared with that in the control group, and the influencing factors of MCH service utility analyzed by logistic model. RESULTS: The main characteristics of the two groups were quite similar at the baseline study, with the average annual family incomes and MCH service per 1000 people. Annual input on MCH services from the government had an distinct increase. The average annual rates of increase regarding the indicators as clean delivery, hospitalized delivery, systematic care on maternal and children, maternal and infant mortality rates were: 1.95%, 9.34%, 4.82%, 3.04%, -2.67%, 13.84% (P < 0.02) through chi2 trend tests. In the trial group, the changes seen in the 6 indicators were better in the control group than in the control group (P < 0.05). Data from the logistic regression model showed that the major influencing factors on the use of hospitalized delivery service were: age of the pregnant woman, average annual income of the family, health insurance status, number of pre-delivery visits, whether on poverty alleviate program, and on knowledge of MCH. CONCLUSION: The intervention project in this programmed area seemed effective and better than the non-programmed area, through an eight-year observation. PMID- 19642379 TI - [Study on hearing impairment among elderly population in the community of Taiyuan city, Shanxi province]. AB - OBJECTIVE: To study the characteristics and influencing factors on hearing impairment among elderly population in the community of Taiyuan city. METHODS: 384 ageing people above 60 years old were selected from Chaoyang and Guandi community in Taiyuan city by multi-stage sampling. Data on influencing factors of hearing impairment were collected by questionnaire. 5 ml fasting blood samples were drawn to detect the level of glucose, triglyceride and cholesterin in the blood samples. All the objects were tested with binaural hearing. The level of binaural hearing threshold at 0.5 kHz, 1 kHz, 2 kHz, 3 kHz, 4 kHz, 8 kHz were measured by GVSLN-TC-GK2000 hearing-assistant evaluative apparatus. The level of 3 kHz, 4 kHz, average hearing threshold from ear with better audition was chosen as dependent variable. Socio-demographic data, environmental factors and biochemical indicator were chosen as independent variables, t test, ANOVA and accumulative logistic regression were performed to analyze the influencing factors on hearing impairment by software SPSS 13.0. RESULTS: The prevalence of hearing impairment among elderly population was 90.9%. The hearing disorder was 78.6% with 1.3% of them using hearing-assistant apparatus. Results from single factor analysis showed that the average levels of 3 kHz, 4 kHz, 8 kHz hearing thresholds were significantly different among elderly with different age, sex, education background and the levels of glucose and cholesterin (P < 0.01). Results of accumulative logistics regression showed that except glucose in which was the only one included in regression model of lower median frequency group, all the others were included in regression model of frequency group. Being male, older age and with higher level of glucose and cholesterin in blood were risk factors causing hearing impairment. Higher education level seemed to be a preventive factor. CONCLUSION: Hearing impairment appeared in higher prevalence among the elderly population, suggesting that proper measures should be taken. It is beneficial for abating hearing impairment to decrease the level of glucose and cholesterin in blood. PMID- 19642380 TI - [Epidemiological and etiological characteristics of typhoid and paratyphoid fever in Ningbo during 1988 - 2007]. AB - OBJECTIVE: To study the epidemiological and etiological characteristics of typhoid and paratyphoid fever in high epidemic areas. METHODS: Reported data on typhoid and paratyphoid fever during 1988-2007 in Ningbo were analyzed epidemiologically. Shellfish from the market was collected for laboratory testing and Salmonella typhi strains collected from the patients were also studied. RESULTS: Number of reported cases on both typhoid and paratyphoid fever was 19 404 with 7 deaths, from 1988 to 2007. The annual mean incidence was 17.68 per one hundred thousand with the fatality rate as 0.36 per thousand. Most cases were among adults aged 20-50 years and an obvious regional distribution was observed with high incidence seen in winter and spring. Since 1990s, the advantage strain had changed from Salmonella typhi to Salmonella paratyphi A. Etiologic studies showed that raw Anadara subcrenata and oyster were the main risk factors. One Salmonella paratyphi A strain was detected in both Anadara subcrenata and oysters collected from the market, which contained TEM-1 drug resistance gene. PFGE genotyping showed that PFGE-X2 was the strain which causing pandemic in Ningbo. CONCLUSION: Eating contaminated raw shellfish like oysters and hairy clams was the primary risk factor, responsible for the outbreaks. Salmonella paratyphi A was the advantages pandemic strain in Ningbo. Strategies as supervision on personal hygiene and health education should be strengthened. PMID- 19642381 TI - [Analysis on maternal mortality in China, 2000 - 2005]. AB - OBJECTIVE: To analyzes the characteristics, the trend and the leading causes of maternal deaths in China between 2000 and 2005. METHODS: Data under analysis were those from a population-based epidemiological survey conducted by the national maternal mortality surveillance network which covered a total population of about 80 000 000 in China. RESULTS: Maternal mortality ratio (MMR) was both higher in the countryside than that in the city and in the remote area than that in the inland and in the coastal region. From 2000 to 2005, the overall MMR in China dropped from 53.0/100 000 livebirths to 47.6/100 000 livebirths, from 67.2/100 000 livebirths to 59.2/100 000 livebirths in rural area, from 28.8/100 000 livebirths to 27.6/100 000 livebirths in urban area. The descending ranges of maternal mortality were 10.2%, 11.9%, 4.2%, respectively. The top three leading causes of maternal deaths in China were obstetric hemorrhage, pregnancy induced hypertension and amniotic fluid embolism in 2000, but minor changes in the ranking of top three leading causes: hemorrhage, cardiac disorders and pregnancy induced hypertension in 2005. The main causes led to hemorrhage were retention of placenta, uterine inertia and rupture of uterine. CONCLUSION: MMR in China appeared a trend less change during 2000- 2005. The number one cause of maternal deaths was obstetric hemorrhage. Reducing MMR in rural area and improving the skill of treating obstetric hemorrhage were essential to achieve the goal of reducing maternal death in the Outline of Chinese Women's Development (2000 2010). PMID- 19642382 TI - [Study on the health status and affecting factors among people living in the surveillance sites of three Gorges Reservoir Areas, in 2007]. AB - OBJECTIVE: To understand the health status and potential impact resulted in the second stage of Three Gorges Reservoir Areas sluicing. METHODS: Data were collected on deaths, prevalence rates of infectious and endemic diseases, as well as on vector surveillance through the project entitled 'Three Gorges Population Health Survey System'. RESULTS: The main causes of death in the population living in the Three Gorges Reservoir Areas would include: circulatory system diseases, tumors, respiratory system diseases, injuries/poison and digestive system diseases. The number of deaths caused by the above said five kind of diseases accounted for 90.94% of the total number of deaths. The prevalence rates on Water born diseases related to the sluicing of reservoir and zoonosis-borne diseases related to the changes of vectors were still low. The indoor and outdoor densities of rodents were 3.11% and 3.16%, both were higher than that in 2006 but lower than the average numbers in the five years prior to the sluicing. The constituent ratio of Apodemus agrarius had constantly risen since 2006. The density of mosquitoes found in livestock barns and human households was higher than that in 2006 but lower than the average number of the five-year studies prior to the sluicing. CONCLUSION: Environment change after the sluicing of the Three Gorges Reservoir Areas did not seem to have obvious impact on the health status of the people living in the areas. However, to strengthen the surveillance on the biological features of the vectors which might have related to the transmission of diseases would be highly recommended. PMID- 19642383 TI - [Study on the timeliness of detection and reporting on public health emergency events in China]. AB - OBJECTIVE: To analyze the timeliness of detection and reporting on public health emergency events, and to explore the effective strategies for improving the relative capacity on those issues. METHODS: We conducted a retrospective survey on 3275 emergency events reported through Public Health Emergency Events Surveillance System from 2005 to the first half of 2006. Developed by county Centers for Disease Control and Prevention, a uniformed self-administrated questionnaire was used to collect data, which would include information on the detection, reporting of the events. RESULTS: For communicable diseases events, the median of time interval between the occurrence of first case and the detection of event was 6 days (P25 = 2, P75 = 13). For food poisoning events and clusters of disease with unknown origin, the medians were 3 hours (P25, P75 = 16) and 1 days (P25 = 0, P75 = 5). 71.54% of the events were reported by the discoverers within 2 hours after the detection. CONCLUSION: In general, the ranges of time intervals between the occurrence, detection or reporting of the events were different, according to the categories of events. The timeliness of detection and reporting of events could have been improved dramatically if the definition of events, according to their characteristics, had been more reasonable and accessible, as well as the improvement of training program for healthcare staff and teachers. PMID- 19642384 TI - [Study on carbapenemase and 16S rRNA methylase of imipenem-resistant Acinetobacter baumannii]. AB - OBJECTIVE: To investigate the prevalence of 16S rRNA methylases gene in imipenem resistant Acinetobacter baumannii isolates from China. METHODS: A total of 342 imipenem-resistant A. baumannii isolates were collected between December 2004 and December 2005, from 25 hospitals of China. Agar dilution was used to determinate the minimal inhibitory concentration (MIC) of these isolates. The homology of these isolates was analyzed by pulse-field gel electrophoresis (PFGE). Several 16S rRNA methylase genes and carbapenemase genes were detected by PCR-based assays and PCR products were sequenced. RESULTS: The rates of resistance to ampicillin-sulbactam, cefoperazone-sulbactam, tobramycin, and minocycline were 68.0%, 54.2%, 87.4%, and 75.9%, respectively. The rate of resistance to polymyxin E was 10.8%, the lowest among the tested agents. The rates of resistance to all other tested antimicrobial agents were more than 90%. The A. baumannii isolates belonged to 29 distinct clones. Among them, 6 clones were dominant, consisting of 303 isolates in total. All isolates contained the blaOXA-51-like gene (blaOXA-66) and 322 isolates contained the blaOXA-23-like gene. PCR with the ISAba1-OXA-23 like primers generated a PCR product in 314 isolates, and PCR with the ISAba1-OXA 51-like primers generated a PCR product in 13 strains. 221 armA-positive isolates were identified. CONCLUSION: Most of the imipenem-resistant A. baumannii contained blaOXA-23, with ISAbal upstream of the gene. 16S rRNA methylase gene armA was widely distributed in these isolates. The results suggested that the spread of clones played an important role in the outbreak of imipenem-resistant A. baumannii in China. PMID- 19642385 TI - [Evaluation of BED-CEIA assay with dried blood spot specimens in China]. AB - OBJECTIVE; To study the feasibility of using dried blood spot (DBS) specimens in BED-CEIA assay and to estimate the HIV-1 incidence with DBS in China. METHODS: 10 313 participants from 27 voluntary counseling and testing (VCT) sites were enrolled in this study. Both plasma and DBS specimens were collected. 349 eligible pairs of HIV-1 positive specimens confirmed by Western Blot were available for BED-CEIA and the results compared. Negative control, low positive control, high positive control and calibrator in DBS were used to evaluate the stability and repeatability of the detection results of DBS specimens. RESULTS: Of the total HIV positives, 294 and 53 participants were tested as long-term or recent HIV infections by both DBS and plasma specimens. Two participants showed different results from DBS and plasma specimens, but their final An values were close to the cutoff value of BED-CEIA assay. The concordance rate between the two types of specimens was 99.43% and the R2 linear of the stability and repeatability results of DBS specimens reached 0.9551 and 0.95, respectively. CONCLUSION: Although some individual specimens showed different results, the incidence rates calculated from both types of specimen were equivalent. DBS specimens were suitable for estimating the HIV incidence and could be popularized in China. However, further studies regarding window period and adjustment coefficients of BED-CEIA assay are needed. PMID- 19642386 TI - [Development and evaluation of TaqMan-based one-step reverse transcription polymerase chain reaction assay for the detection of Japanese encephalitis virus]. AB - OBJECTIVE: To establish a TaqMan based real-time reverse transcription-polymerase chain reaction (RT-PCR) assay for the detection of Japanese encephalitis virus. METHODS: The gene sequences of Japanese encephalitis virus downloaded from the GenBank was aligned, using the biologic software. Specific primers and probes were designed in the conserved region of the C gene for Japanese encephalitis virus. The real-time RT-PCR reactive condition was optimized and the sensitivity, specificity and the stability of the assay were evaluated. Mosquitoes collected from Zhejiang province were detected by this assay. RESULTS: Mg2+, primer and probe were optimized at 5 mmol/L, 0.2 micromol/L and 0.1 micromol/L respectively. The specificity of the assay was high and there were no cross reactions with dengue virus, rabies virus, seoul virus or hantan virus. The detection limits of the assay was 0.1 TCID50. Results from preliminary application showed that TaqMan RT-PCR for Japanese encephalitis virus was sensitive, easier and faster to perform the process of traditional virus isolation and identification. It took only three hours to extract viral RNA and perform the real-time RT-PCR. CONCLUSION: This TaqMan-based one-step RT-PCR assay was a quick, sensitive and specific tool for molecular diagnosis of Japanese encephalitis virus. PMID- 19642387 TI - [DNA repair gene xeroderma pigmentosum group D 751 polymorphism and the risk on esophageal cancer: a meta-analysis]. AB - OBJECTIVE: To explore the association between XPD codon 751 polymorphism and esophageal cancer (EC) by systematically reviewing the risk of the original studies. METHODS: A comprehensive search was conducted to identify all case control studies of XPD codon 751 polymorphism and EC risk. Meta-analysis was applied with Rev Man 4.2 software for calculation of pooled OR value (with 95% CI) of EC, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). RESULTS: Of the 12 case-control studies selected for this Meta-analysis, a total of 2558 EC cases and 5122 controls were included. Compared with the wild-type homozygote Lys/Lys, the pooled Odds Ratios (with 95% CI) of Lys/Gln, Gln/Gln, (Lys/Gln + Gln/Gln) genotypes of XPD codon 751 polymorphism for EC risk were 1.19 (1.05, 1.34), 1.22 (0.86, 1.74), 1.20 (1.01, 1.42), respectively. In a stratified analysis, a total of 1417 ESCC cases and 2312 controls were included, and individuals carrying Lys/Gln genotype or (Lys/Gln + Gln/Gln) had 1.22-fold or 1.24-fold excess risks for ESCC compared with those carrying Lys/Lys genotype. A total of 935 EAC cases and 2604 controls were included, and none of the genotype of XPD codon 751 genetic polymorphism was found to be related to EAC. CONCLUSION: Both heterozygote Lys/Gln and (Lys/Gln + Gln/Gln) for XPD codon 751 genetic polymorphism were associated with an increased risk of developing esophageal cancer. Furthermore, heterozygote Lys/Gln and (Lys/Gln + Gln/Gln) for XPD codon 751 genetic polymorphism might have increased the risk of ESCC, but have no association with EAC. PMID- 19642388 TI - [Study on liver damage caused by anti-TB drug intermittent treatment on patients with HBV-TB co-infection]. AB - OBJECTIVE: To study the features of liver damage caused by anti-TB medicines among patients with TB-HBV co-infection, in order to complement and improve the implementation of DOTs strategy in the region. METHODS: A historical cohort study was conducted including the process of reviewing and analyzing files of the 781 naive TB patients hospitalized from June 2004 to October 2005. Cases were divided into HBsAg (+) group and HBsAg (-) group. RESULTS: The overall damage rate among the 781 investigation cases was 20.74%, including 121 cases (74.69%) in HBsAg (+) group and 41 cases (25.31%) in HBsAg (-) group. Data showed that liver damage rate and average value of ALT and AST of HBsAg (+) group were higher than those in HBsAg (-) group. First case with liver damage in HBsAg (+) group happened on the 7th day of the treatment, while the first liver damage case happened in HBsAg (-) group was on the 16th day. The average onset in HBsAg (+) group was earlier than HBsAg (-) group for 18.09 days. The average time of liver function recovery in HBsAg (+) group was 57.02 days and in HBsAg (-) group it was 27.56 days while the appearance among HBsAg (+) group was 29.46 days later than in HBsAg (-) group. CONCLUSION: The incidence rate of liver damage caused by anti-TB medicines was higher among HBV positive patients than those HBV negative patients. Patients co-infected with HBV infection appeared to be more serious, with higher incidence on liver damage and earlier onset, as well as with the degree of damage to the liver. PMID- 19642389 TI - [Application of Monte Carlo techniques in designing compensatory scheme of new cooperative medical system]. AB - To design a workable compensatory scheme of new cooperative medical system (NCMS) in rural China, 'Monte Carlo Simulation Techniques' is developed based on the data of a multistage random sampling survey. The total compensation rate, the decreased percentages of poverty caused by diseases and the deficit ratio of fund a 0.3782, 0.6540 and -0.0794 respectively, when the main strategy of inpatient reimbursement is recognized as 'serious illness'. The deficit ratios of funding appeared to be 0.4840, 0.4091 and -0.3789 when the main strategy of outpatient reimbursement is recognized on minor diseases. Compensation for minor diseases is more important than that of serious diseases. Considering the further impact of minor diseases on peasants, we should incorporate compensation for minor diseases into the compensatory scheme of NCMS. PMID- 19642390 TI - [Development of methods for estimation and prediction on epidemic situation of HIV/AIDS]. PMID- 19642391 TI - [Relationship between environmental changes and schistosomiasis transmission]. PMID- 19642392 TI - [Serological survey on antibodies to influenza A viruses subtype H1, H3, H5 and H9 of population in Shanghai]. PMID- 19642393 TI - [Study on the infection condition and resistance genes of type b of Hemophilus influenza isolated in children with community acquired pneumonia in Shenzhen]. PMID- 19642394 TI - [Phylogeny for NS1 proteins of influenza B virus]. PMID- 19642395 TI - [Drug resistance characterization on Beijing family of Mycobacterium tuberculosis]. PMID- 19642396 TI - [Epidemiological investigation on Helicobacter pylori infection in Dongcheng region of Dongguan city]. PMID- 19642397 TI - [Immunogenicity and safety of influenza split vaccine]. PMID- 19642398 TI - [Thalassemia screening in 4976 pairs rural couples of child bearing age in Nanning Guangxi and follow-up of high-risk pregnant women]. PMID- 19642399 TI - Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise. AB - REASON FOR PERFORMING STUDY: Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. OBJECTIVES: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. METHODS: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatography-mass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. RESULTS: Median back-extrapolated time zero plasma concentration was significantly lower and median plasma half-life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. CONCLUSIONS AND POTENTIAL RELEVANCE: Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect. PMID- 19642400 TI - The effect of rising and sitting trot on back movements and head-neck position of the horse. AB - REASON FOR PERFORMING STUDY: During trot, the rider can either rise from the saddle during every stride or remain seated. Rising trot is used frequently because it is widely assumed that it decreases the loading of the equine back. This has, however, not been demonstrated in an objective study. OBJECTIVE: To determine the effects of rising and sitting trot on the movements of the horse. HYPOTHESIS: Sitting trot has more extending effect on the horse's back than rising trot and also results in a higher head and neck position. METHODS: Twelve horses and one rider were used. Kinematic data were captured at trot during over ground locomotion under 3 conditions: unloaded, rising trot and sitting trot. Back movements were calculated using a previously described method with a correction for trunk position. Head-neck position was xpressed as extension and flexion of C1, C3 and C6, and vertical displacement of C1 and the bit. RESULTS: Sitting trot had an overall extending effect on the back of horses when compared to the unloaded situation. In rising trot: the maximal flexion of the back was similar to the unloaded situation, while the maximal extension was similar to sitting trot; lateral bending of the back was larger than during the unloaded situation and sitting trot; and the horses held their heads lower than in the other conditions. The angle of C6 was more flexed in rising than in sitting trot. CONCLUSIONS AND CLINICAL RELEVANCE: The back movement during rising trot showed characteristics of both sitting trot and the unloaded condition. As the same maximal extension of the back is reached during rising and sitting trot, there is no reason to believe that rising trot was less challenging for the back. PMID- 19642401 TI - Stability of common biochemistry analytes in equine blood stored at room temperature. AB - REASONS FOR PERFORMING STUDY: Time delays between collection of blood samples and biochemical analysis of equine blood are unavoidably common in equine practice. The effect that delays may have on the accuracy of results of blood biochemical analyses is not well established. HYPOTHESIS: Delays in processing of blood of up to 72 h results in alterations in measured levels of common biochemical analytes that are of potential clinical relevance. Separation of serum prior to storage is protective against the effects of time delays. METHODS: Samples of clotted blood, separated serum and oxalate fluoride plasma from 20 horses were stored and analysed at 0, 24, 48 and 72 h. Graphical exploration of each analyte was undertaken. General linear models with fixed effects were fitted for the whole blood data. The mean bias and 95% limits of agreement were calculated, using bootstrapped data, to assess agreement between pairs of samples analysed at 0 h and other time points. Bland-Altman plots were used to explore general trends in the data. Paired t tests were used to compare the results from whole blood and separated serum. RESULTS: Delays in processing equine blood resulted in significant increases in measured concentrations of aspartate aminotransferase, creatine kinase, lactate dehydrogenase, total bile acids and magnesium. A significant decrease in concentration was identified for glucose (serum and oxalate fluoride preserved plasma). Separation of serum immediately following clot formation resulted in nonsignificant increases in accuracy for some analytes. CONCLUSIONS AND PRACTICAL SIGNIFICANCE: Delays in processing of blood samples may result in biochemical changes of clinical relevance in individual cases; however, in the majority of cases, where delays are only a few days and a number of analytes are assessed concurrently, delays are unlikely to have an effect on the interpretation of results. Separation of serum following clot formation is of limited benefit. Clinical samples in which a delay in processing has occurred may be interpreted with reference to the data presented. PMID- 19642402 TI - Two- and three-dimensional computed tomographic anatomy of the enamel, infundibulae and pulp of 126 equine cheek teeth. Part 1: Findings in teeth without macroscopic occlusal or computed tomographic lesions. AB - REASONS FOR PERFORMING STUDY: Dental disorders are of major clinical importance in equine practice; however, the knowledge of normal dental anatomy, especially that of the pulp remains incomplete. Computed tomography (CT) is being used increasingly in the diagnosis of dental disease, although the normal 2- (2D) and 3-dimensional (3D) CT anatomy has not yet been fully described. OBJECTIVE: To describe the 2D and 3D CT appearance of the enamel, infundibulae and pulp of normal equine cheek teeth. METHODS: One-hundred-and-twenty-six cadaveric cheek teeth with eruption ages of 0.5-19 years were evaluated; CT scans of each tooth were performed after occlusal surface examination with a dental probe. Three dimensional reconstructions of the enamel, infundibulae and pulp were created from the CT scans using greyscale thresholding and subsequent polynomial meshing. Each tooth was sectioned coronally or axially into serial slices using a band saw and the sections compared to the corresponding CT images. RESULTS: The CT reconstructions enabled the systematic description of the pulpar anatomy of the mandibular and maxillary cheek teeth in 3D, which has not been described in detail previously. The number of interpulpar communications between pulp horns and the pulpar volume of each tooth was shown to decrease with increasing age. The interpulpar communications of the maxillary cheek teeth were found to be of greater complexity and variety in comparison to their mandibular counterparts. Mandibular and maxillary cheek teeth showed different, but consistent patterns in their pulpar and enamel morphology. CONCLUSIONS AND POTENTIAL RELEVANCE: The detailed description of the normal 2D and 3D CT appearance of equine cheek teeth provides a reference basis for the diagnosis of dental disease with CT. Additionally, in depth knowledge of the pulpar anatomy of the equine cheek teeth is an essential prerequisite if endodontic therapy is to develop further in the future. PMID- 19642403 TI - Two- and three-dimensional computed tomographic anatomy of the enamel, infundibulae and pulp of 126 equine cheek teeth. Part 2: Findings in teeth with macroscopic occlusal or computed tomographic lesions. AB - REASONS FOR PERFORMING STUDY: Dental disease often presents a diagnostic challenge in the horse. Computed tomography (CT) is increasingly used in the evaluation of head related disease in the horse, but the CT appearance of the most common dental diseases of horses has not yet been fully described. OBJECTIVE: To describe the CT appearance of the peripheral enamel, pulp, infundibular enamel and cement in equine cheek teeth with macroscopic occlusal or CT lesions. METHODS: In this study, 126 cadaveric cheek teeth with eruption ages of between 05 and 19 years were evaluated for lesions of their infundibulae, pulp and enamel using occlusal surface morphology, 2- (2D) and 3-dimensional (3D) CT and anatomical sectioning. Variations in teeth with no macroscopic lesions have been described in a previous study. The infundibular lesions were categorised further into one of 6 classifications. RESULTS: Infundibular lesions were identified on CT in 90% (115/128) of infundibulae. Of these, 65% (83/128) had infundibular lesions on occlusal surface examination. The extent of infundibular lesions observed varied with age group. All infundibulae over 6 years post eruption had detectable lesions. Peripheral enamel hypoplasia and enamel prolapses, were observed in 10% (12/126) and 1.6% (2/126) of teeth, respectively. The CT appearance of teeth with pulp infections was seen to vary with differing pathologies. CONCLUSIONS AND POTENTIAL RELEVANCE: The high prevalence of infundibular lesions should encourage consideration of their clinical significance, in addition to the role of infundibulae in dental disease of the horse. Two-dimensional and 3D CT proved to be highly valuable imaging modalities for dental disease, enabling lesions within the enamel, infundibulae and pulp of equine cheek teeth to be easily detected. The results of this study will facilitate the use of 2D and 3D CT as clinical diagnostic tools for dental disease and aid in the selection of the most appropriate treatment protocol. PMID- 19642404 TI - Ultrasonographic assessment of the superficial digital flexor tendons of National Hunt racehorses in training over two racing seasons. AB - REASONS FOR PERFORMING STUDY: It is important to ascertain the prevalence of superficial digital flexor tendon (SDFT) injuries and to improve methods of predicting injury in National Hunt (NH) racehorses. OBJECTIVES: To establish: 1) the prevalence of SDFT tendinopathy in NH horses; 2) whether routine ultrasonography can be used to predict SDFT injuries; 3) whether previous tendinopathy predisposes to reinjury; 4) a normal range for the SDFT cross sectional area (CSA); and 5) the effects of gender, age, background (ex-flat or ex-store), limb, training and rest periods on SDFT CSA. METHODS: Routine ultrasound assessment of the palmar metacarpal soft tissues of 263 NH racehorses was performed on up to 6 occasions over 2 NH racing seasons. RESULTS: The prevalence of SDFT pathology detected using ultrasonography was 24% (n = 148), with a nonsignificant variation between yards of 10-40%. No changes in SDFT CSA or ultrasonographic appearance were detected prior to injury. Older horses had a significantly higher prevalence of SDFT pathology compared to younger horses, and horses with tendinopathy were more likely to suffer an acute injury compared to horses with no evidence of pathology. A reference range for normal CSA measurements was established as 77-139 mm2 at level 4, from 142 horses with no ultrasonographic evidence of SDFT pathology. The CSA of normal horses did not vary significantly with age, limb or over 2 racing seasons, but did with sex and background. CONCLUSIONS: The study confirms that SDFT tendinopathy is common in NH horses, with substantial variation between training yards. Ultrasonography at 3 month intervals did not seem to predict acute SDFT injuries. POTENTIAL RELEVANCE: Variation in the prevalence of tendinopathy between yards suggests that training methods may influence injury rate. It was not possible to predict injury using routine ultrasonography and therefore other methods must be identified. A normal reference range for SDFT CSA is provided. PMID- 19642405 TI - Crib-biting in US horses: breed predispositions and owner perceptions of aetiology. AB - REASONS FOR PERFORMING STUDY: Crib-biting is an equine stereotype that may result in diseases such as colic. Certain breeds and management factors have been associated. OBJECTIVES: To determine: breed prevalence of crib-biting in US horses; the likelihood that one horse learns to crib-bite from another; and owner perceptions of causal factors. METHODS: An initial postal survey queried the number and breed of crib-biting horses and if a horse began after being exposed to a horse with this habit. In a follow-up survey, a volunteer subset of owners was asked the number of affected and nonaffected horses of each breed and the extent of conspecific contact. The likelihood of crib-biting given breed and extent of contact was quantified using odds ratio (OR) and significance of the association was assessed using the Chi-squared test. RESULTS: Overall prevalence was 4.4%. Thoroughbreds were the breed most affected (133%). Approximately half of owners believed environmental factors predominantly cause the condition (54.4%) and crib-biting is learned by observation (48.8%). However, only 1.0% of horses became affected after being exposed to a crib-biter. The majority (86%) of horses was turned out in the same pasture with other horses and extent of contact with conspecifics was not statistically related to risk. CONCLUSION: This is the first study to report breed prevalence for crib-biting in US horses. Thoroughbreds were the breed more likely to be affected. More owners believed either environmental conditions were a predominant cause or a combination of genetic and environmental factors contributes to the behaviour. Only a small number of horses reportedly began to crib-bite after being exposed to an affected individual, but approximately half of owners considered it to be a learned behaviour; most owners did not isolate affected horses. POTENTIAL RELEVANCE: Genetic predisposition, not just intensive management conditions and surroundings, may be a factor in the high crib-biting prevalence in some breeds, and warrants further investigation. Little evidence exists to suggest horses learn the behaviour from other horses, and isolation may cause unnecessary stress. PMID- 19642406 TI - Short-term outcome of equine emergency admissions at a university referral hospital. AB - REASONS FOR PERFORMING STUDY: Obtaining data on emergency admission survival rates is important to provide clients with an estimate of prognosis and to identify areas in which improvements in case management can be achieved. OBJECTIVE: To determine the short-term outcome of equine emergency admissions to a university referral hospital during a 12 month period. METHODS: Short-term outcome was defined as survival to discharge or died/euthanasia during hospitalisation. The overall death (euthanasia) rate was calculated; and rate for horses with different categories of: age; admission month, day and time; presenting complaint (PC); duration of clinical signs prior to presentation; clinical pathology abnormalities; and therapy/therapeutic-related procedures performed was recorded. RESULTS: There were 918 admissions. The overall death rate was 24%. Foals (34%) and geriatric (40%) subjects had a death rate that was higher than that for mature horses (21%, referent). The death rate was highest in March (37%). Horses with a PC categorised as neurological (46%) or neonatal (41%) had the highest and as ophthalmological (5%) or trauma/skin (13%) the lowest death rates. There was no difference in death rate between different admission days or times or the duration of clinical signs prior to presentation. The death rates for horses with abnormal peritoneal fluid (71%), coagulopathy (63%), acid base abnormalities (52%), hypoproteinaemia (47%), dehydration (43%), hypoxia/hypercapnia (48%), leucopenia (44%), electrolyte abnormalities (39%), hyperlactataemia (39%) or azotaemia (35%) were high. The death rate for horses treated with intranasal oxygen (57%), plasma (34%) or polymixin B (35%) was high and for horses undergoing laceration repair/joint (0%) or synovial cavity lavage (4%) was low. CONCLUSIONS: Age and critical illness were important contributing factors to a higher death rate. POTENTIAL RELEVANCE: Improving the understanding of disease processes in and developing treatment strategies for neonatal and geriatric patients as well as critically ill patients is required. PMID- 19642407 TI - Surgical management of complete diaphyseal third metacarpal and metatarsal bone fractures: clinical outcome in 10 mature horses and 11 foals. AB - REASONS FOR PERFORMING STUDY: Osteosynthesis of third metacarpal (McIII) and third metatarsal (MtIII) bone fractures in horses is a surgical challenge and complications surrounding the repair are common. Retrospective studies evaluating surgical repair, complications and outcome are necessary to increase knowledge and improve success of long bone fracture repair in the horse. OBJECTIVES: To evaluate clinical findings, surgical repair, post operative complications and outcome of 10 mature horses and 11 foals with McIII or MtIII fractures that were treated with open reduction and internal fixation (ORIF). METHODS: Medical records were reviewed and follow-up information obtained by means of radiographs and/or telephone questionnaire. RESULTS: Survival was achieved in 62% of the horses (3 mature/10 foals). On long-term evaluation (> 6 months) 11 horses (2 mature/9 foals) were fit for their intended activity, one mature horse had a chronic low grade lameness, and one foal was lost to follow-up because it was sold. The main fracture types were simple transverse (333%) or simple oblique (28.6%) and 71.4% of the fractures were open, 3 Type I (one mature/2 foals) and 12 type II (7 mature/5 foals). The preoperative assessment revealed inadequate emergency treatment in 10 horses (5 mature/5 foals; 47.6%). Survival rate of horses with open fractures was 12.5% (1/8) in mature and 85.7% (6/7) in foals. Post operative incisional infection (4 mature, 3 foals) was only managed successfully in 2 foals. Fracture instability related to inadequate fracture fixation technique occurred in 4 horses (all mature) and was always associated with unsuccessful outcome. CONCLUSIONS: Age, bodyweight and infection are strongly associated with outcome in treatment of complete McIII/MtIII fractures. CLINICAL RELEVANCE: Rigid fixation using plates and screws can be successful in treatment of closed or open, complete diaphyseal McIII/MtIII fractures in mature horses and foals. Instable fixation, infection and a bodyweight > 320 kg are major risk factors for unsuccessful outcome. PMID- 19642408 TI - The range and prevalence of pathological abnormalities associated with lameness in working horses from developing countries. AB - REASONS FOR PERFORMING STUDY: Lameness is highly prevalent in working horses, but published reports on the associated pathological abnormalities are lacking. With over 42 million horses in developing countries and the majority used for work, lameness has major welfare implications. OBJECTIVES: To describe the range and prevalence of pathological abnormalities associated with lameness in working horses. METHODS: A standard lameness assessment was adapted for field use in working equids. Data on pathological abnormalities and pain responses in the feet, limbs and spine were collected through observation, palpation, manipulations and gait assessment in working horses from India (n = 110) and Pakistan (n = 117). Lameness at the walk was scored on a scale of 0-4 (sound nonweightbearing). RESULTS: All horses examined were lame. Overall, 98% showed a gait abnormality in all 4 limbs and 87% had at least one limb scoring 3 or 4 on the lameness scale. Multiple pathological abnormalities within each limb were associated with lameness, with similar results in both countries. Chronic foot pathology was seen in every horse; 94% horses showed signs of chronic joint disease; 83% had digital flexor tendonitis in at least one limb. Lameness and pathological abnormalities were associated with specific pain responses in the feet, limbs and spine. CONCLUSIONS: The extremely high prevalence of multilimb lameness and its association with pain is of great concern. The multiple pathological abnormalities present in working horses makes lameness complex to address. POTENTIAL RELEVANCE: The results of this detailed study of lameness should facilitate the identification of risk factors and the implementation of interventions to reduce the prevalence of lameness in working equids. PMID- 19642409 TI - Initial investigation of mortality rates and prognostic indicators in horses with colic in Israel: a retrospective study. AB - REASONS FOR PERFORMING STUDY: Initial assessment of the mortality rates and prognostic indicators in horses with colic presented to a referral hospital in Israel. OBJECTIVES: To determine mortality rates and to identify potential prognostic indicators in horses undergoing treatment for colic. METHODS: The medical records of 208 colic cases were reviewed and mortality rates calculated including 95% confidence intervals. Mortality rates in surgical cases were calculated separately for strangulating and nonstrangulating lesions as well as for lesions of the large and small intestines. Potential prognostic indicators were identified and evaluated by Student's t test or chi2 test, where appropriate. Those found to be significant (P < 0.05) were evaluated in 2 logistic regression models; one including all horses with colic and one for surgical cases only. RESULTS: The overall mortality rate was 51/208 (25%); 5/72 (7%) in medically treated cases, 46/136 (34%) in surgical cases, 30/50 (60%) in strangulating lesions and 15/85 (18%) in nonstrangulating lesions, 17/27 (63%) in cases involving small intestinal lesions and 28/108 (26%) in cases with large intestinal lesions. Clinical parameters found to be significantly associated with death by univariate analysis were medical/surgical treatment, location of lesion, severity of lesion, mucous membrane colour (MM), capillary refill time (CRT) and heart rate. Using a multivariate logistic regression model, including all cases, medical/surgical treatment, CRT and MM were found to be prognostic indicators and when using the surgical cases alone, only CRT and lesion severity remained related to mortality. CONCLUSIONS: Mortality rates were similar or better than those previously reported in most cases, however, studies from the USA and the UK published better success rates for small intestinal surgeries. Cultural attitudes toward euthanasia may be associated with mortality rates. POTENTIAL RELEVANCE: These results assist clinicians in providing an immediate prognosis based on clinical findings at presentation and contribute to an international database that may aid future research in improving treatment of colic. PMID- 19642410 TI - Effects of different forms of exercise on post inhibitory rebound and unwanted behaviour in stabled horses. AB - REASONS FOR PERFORMING STUDY: It is unknown if different locomotor activities are equally effective at meeting the stabled horse's need for exercise and if they attenuate unwanted behaviour. HYPOTHESIS: Alternative forms of exercise influence the intensity of locomotor activities during a period of turn-out (the so-called rebound effect) and the occurrence of unwanted or undesirable activities during standard handling situations. METHOD: Twenty-four horses kept in stables were randomly assigned to one of 4 exercise regimes (walker, treadmill, turn-out and riding) for 4 consecutive days. Because these forms of exercise provide additional environmental stimulation, beyond that provided by exercise, each horse served as its own control in 4 corresponding (no exercise) control treatments presented in a balanced order. Unwanted behaviour was tested by taking horses to weighing scales and loading and unloading them onto a 4-horse float by an experienced handler and the rebound effect was tested by releasing them into a large arena for a period of 15 min at the end of the exercise and control treatments. RESULTS: Locomotor activities made up a large part of behaviour in the large arena following control treatments and all exercise regimes were sufficient to reduce the intensity of walking (P < 0.05), trotting (P < 0.01) and cantering (P < 0.001) on release into a large arena. Exercise regime reduced the number of bucks (P < 0.01) and rolling (P < 0.05) during rebound tests suggesting that turn-out was having a stronger effect than the other 3 exercise regimes. Exercise regimes significantly reduced the amount of unwanted behaviour and the number of commands given by the handler during weighing (P < 0.05) but had no effect on these behaviours during loading onto a float. CONCLUSION: Providing stabled horses with one hour/day of exercise on a walker, treadmill, turn-out or by being ridden are all effective at allowing expression of locomotor activities in stabled horses. POTENTIAL RELEVANCE: Providing stabled horses with regular exercise is likely to provide positive effects on horse welfare, training ability and handler safety. PMID- 19642411 TI - The effect of training on stride parameters in a cohort of National Hunt racing Thoroughbreds: a preliminary study. AB - REASONS FOR PERFORMING STUDY: The influence of training on stride parameters is controversial and to date there is no information on how training influences stride parameters during high-speed locomotion in the field. OBJECTIVE: To determine the influence of training on stride variables during high-speed locomotion in Thoroughbred racehorses. METHODS: Speed, stride frequency, stance and protraction times were quantified in 8 Thoroughbreds with foot mounted accelerometers and GPS sensors during their first week of canter after the summer break and 6 months into training. RESULTS: At a speed of 11 m/s, stride frequency was (mean +/- s.d.) 2.160 +/- 0.120 strides/s pre- and 2.167 +/- 0.083 strides/s post training; mean stance time was 125.3 +/- 9 ms pre- and 125.9 +/- 7 ms post training; protraction time was 340.7 +/-20.4 ms pre- and 337.2 +/- 14.3 ms post training. The increase in stride frequency and the decrease in protraction time after training were significant. There was no statistically significant difference in the maximum speed reached by each horse pre- and post training. CONCLUSIONS: Stance time stayed constant throughout the training season in the tested horses. A significant decrease in protraction time and a corresponding significant increase in stride frequency were observed after training. POTENTIAL RELEVANCE: Training of racehorses could be adapted to maximise the effect on modifiable parameters and reduce the risk of training-induced pathologies. Further research will be conducted to investigate the effect of different training protocols on a large number of horses. PMID- 19642412 TI - Influence of the position of the foot on MRI signal in the deep digital flexor tendon and collateral ligaments of the distal interphalangeal joint in the standing horse. AB - REASONS FOR PERFORMING STUDY: Hyperintense signal is sometimes observed in ligaments and tendons of the equine foot on standing magnetic resonance examination without associated changes in size and shape. In such cases, the presence of a true lesion or an artifact should be considered. A change in position of a ligament or tendon relative to the magnetic field can induce increased signal intensity due to the magic angle effect. OBJECTIVES: To assess if positional rotation of the foot in the solar plane could be responsible for artifactual changes in signal intensity in the collateral ligaments of the distal interphalangeal joint and in the deep digital flexor tendon. METHODS: Six isolated equine feet were imaged with a standing equine magnetic resonance system in 9 different positions with different degrees of rotation in the solar plane. RESULTS: Rotation of the limb induced a linear hyperintense signal on all feet at the palmar aspect of one of the lobes of the deep digital flexor tendon and at the dorsal aspect of the other lobe. Changes in signal intensity in the collateral ligaments of the distal interphalangeal joint occurred with rotation of the limb only in those feet where mediolateral hoof imbalance was present. CONCLUSIONS: The position and conformation of the foot influence the signal intensity in the deep digital flexor tendon and in the collateral ligaments of the distal interphalangeal joint. POTENTIAL RELEVANCE: The significance of increased signal intensity in the deep digital flexor tendon and in the collateral ligaments of the distal interphalangeal joint should be interpreted with regard to the position and the conformation of the foot. PMID- 19642413 TI - Workshop report. Third International Workshop on Equine Osteochondrosis, Stockhom, 29-30th May 2008. PMID- 19642414 TI - Neurectomy of the deep branch of the lateral plantar nerve can cause neurogenic atrophy of the muscle fibres in the proximal part of the suspensory ligament (M. interosseous III). AB - Neurectomy of the deep branch of the right lateral plantar nerve was performed on a single healthy mature horse. Six weeks after surgery, the horse was subjected to euthanasia and both hind suspensory ligaments harvested. The cross sectional area of the muscular part of the proximal part of the suspensory ligament was measured and assessed for morphological abnormalities in a blinded fashion. There was a clear difference in cross sectional area of the muscular part between treated and control ligament and there was profound neurogenic atrophy of the muscular fibres in the treated ligament. PMID- 19642415 TI - Inspired by nature. Interview by Elizabeth Davies. PMID- 19642416 TI - Food for thought. PMID- 19642418 TI - Rediscovering the bioactivity and ecological role of 1,4-benzoxazinones. AB - Compounds of the (2H)-1,4-benzoxazin-3(4H)-one class have attracted the attention of phytochemists since the first isolation of 2,4-dihydroxy-2H-1,4-benzoxazin 3(4H)-one (DIBOA) and 2,4-dihydroxy-7-methoxy-(2H)-1,4-benzoxazin-3(4H)-one (DIMBOA). Extensive research has been carried out on the isolation and synthesis of these materials as well as on the dynamics of their degradation in different systems. This has led to the discovery of a wide variety of compounds that are of high interest from the point of view of phytotoxic, antifungal, antimicrobial, and antifeedant effects among others. The potential application of benzoxazinones and their derivatives as leads for natural herbicide models is a topic of current interest. Furthermore, the importance of degradation on the ecological behaviour of benzoxazinone-producing plants is also being realised, and proposals concerning the role of the degradation products in chemical defence mechanisms have been put forward. There is also increasing interest in the improvement of analytical methodologies, and ecotoxicologic effects, toxicity on target and non target organisms, and degradation kinetics are also being addressed. The development of new phytotoxicity bioassay techniques represents one of the most important breakthroughs in this respect. Moreover, benzoxazinones and some of their derivatives have been employed in the development of pharmaceuticals. The versatility of the benzoxazinone skeleton, in addition to its relative chemical simplicity and accessibility, makes these chemicals amongst the most promising sources of bioactive compounds that are natural in origin. PMID- 19642419 TI - Biosynthesis of insect spiroacetals. AB - The volatile secretions of numerous species of Coleoptera (beetles), Hymenoptera (wasps, bees) and Diptera (true flies) contain complex blends of spiroacetals. In several species, a certain number of them appear to function as sex pheromones. The structure of insect-derived spiroacetals will be summarised and the techniques useful for their identification and the investigation of their biogenesis will be discussed. Progress in the study and delineation of likely biosynthetic pathways to these spiroacetals in Dipteran (Bactrocera) and Hymenopteran (Megarhyssa) species will be reviewed, and the validity of these pathways as a general paradigm for spiroacetal generation in the wider insect world will be assessed. PMID- 19642417 TI - The isolation, total synthesis and structure elucidation of chlorofusin, a natural product inhibitor of the p53-mDM2 protein-protein interaction. AB - Inhibitors of key protein-protein interactions are emerging as exciting therapeutic targets for the treatment of cancer. One such interaction between MDM2 (HDM2) and p53, that silences the tumour suppression activities of p53, was found to be inhibited by the recently isolated natural product chlorofusin. Synthetic studies on this complex natural product summarized herein have served to reassign its chromophore relative stereochemistry, assign its absolute stereochemistry, and provided access to a series of key analogues and partial structures for biological evaluation. PMID- 19642420 TI - Conotoxins: natural product drug leads. AB - Venomous marine cone snails harbour a variety of small disulfide-rich peptides called conotoxins, which target a broad range of ion channels, membrane receptors, and transporters. More than 700 species of Conus are thought to exist, each expressing a wide array of different peptides. Within this large repertoire of toxins, individual conotoxins are able to discriminate between different subtypes and isoforms of ion channels, making them valuable pharmacological probes or leads for drug design. This review gives a brief background to the discovery of conotoxins and describes their sequences, biological activities, and applications in drug design. PMID- 19642422 TI - Challenges in the synthesis of a unique mono-carboxylic acid antibiotic, (+) zincophorin. AB - (+)-Zincophorin, also referred to as M144255 or griseocholin, is a polyoxygenated ionophoric antibiotic that was isolated from Streptomyces griseus in 1984. It possesses strong in vivo activity against Gram-positive bacteria and Clostridium coelchii. Its methyl ester was reported in a patent as having strong inhibitory properties against influenza WSN/virus with reduced toxicity for the host cell. Its ability to strongly bind with Zn2+, which is also present in its X-ray structure, is the basis for its name. Over the last two decades, (+)-zincophorin has attracted an impressive array of synthetic efforts including Danishefsky's first total synthesis, along with two recent elegant total syntheses reported by Cossy and Miyashita as well as our own formal total synthesis. This review provides a comparison of the different synthetic efforts on this novel mono carboxylic acid antibiotic and documents its interesting isolation, structure determination, and biological activities. PMID- 19642423 TI - Sterilizing filtration of liquids. Technical report no. 26 (revised 2008). PMID- 19642424 TI - [Influenza A: the calm before the storm?]. PMID- 19642425 TI - [The role of palliative care and end of life support in the French health care system: examples of action]. PMID- 19642426 TI - [Thevenard's disease]. PMID- 19642427 TI - [Malignant mesothelioma]. AB - Malignant pleural mesothelioma (MPM) is an agressive and rare tumour, but with increasing incidence linked to previous exposure to asbestos fibers, its main etiological factor. The interest for this cancer has been stimulated by recent improvements in the diagnosis and in the treatment of mesothelioma, including new cytotoxic drugs and multimodal treatment, associating chemotherapy, radical surgery and radiotherapy in prospective, randomised and multicentric trials. The management of MPM is now better defined by the guidelines from the experts Conference of the Societe de Pneumologie de Langue Francaise in 2005, actualised this year by the European Respiratory Society. PMID- 19642428 TI - [Diffuse alveolar hemorrhage in a cannabis smoker]. PMID- 19642421 TI - Ribosomal peptide natural products: bridging the ribosomal and nonribosomal worlds. AB - Ribosomally synthesized bacterial natural products rival the nonribosomal peptides in their structural and functional diversity. The last decade has seen substantial progress in the identification and characterization of biosynthetic pathways leading to ribosomal peptide natural products with new and unusual structural motifs. In some of these cases, the motifs are similar to those found in nonribosomal peptides, and many are constructed by convergent or even paralogous enzymes. Here, we summarize the major structural and biosynthetic categories of ribosomally synthesized bacterial natural products and, where applicable, compare them to their homologs from nonribosomal biosynthesis. PMID- 19642429 TI - [Role of palliative approach in medical and nursing care practice]. PMID- 19642430 TI - [April 22nd, 2005 law of patients' rights and end of life: not a well-known law due to poor communication]. AB - The law number 2005-370 of April 22, 2005, or "Leonetti law", is a very important law for patients' rights and management of the end of life. In spite of its importance, it seems to remain largely unknown to ordinary citizen and even health professionals. In this study, we evaluated the knowledge of this law among general practitioners from Isere (France), and looked at the best communication mode to channel information about the law. The analysis of the content of the 581 answers out of 1050 sent questionnaires (55,3%) confirms the poor knowledge about the law. General practitioners went through a self-evaluation about their knowledge: they estimate they had a rather low knowledge, with a median at 2 over 10. 23% had never heard about the law. Paradoxically, the objective evaluation of their knowledge gives more positive results (below 56,3% per question). However, their mistakes deal with important points of the law: traceability of decisions, trusted person, value of advanced directives, and collegial medical procedure. In addition to accompanying the patient and his family, the role of the general practitioner in respect to this law lies more specifically in helping patients who want to draft early directives or to designate a trusted person. In primary care, tough decisions concerning withholding or withdrawal of treatments should be made collaboratively. PMID- 19642431 TI - [When does palliative care begin and who decides?]. AB - Contrary to a widespread approach, palliative care does not begin when curative care stops. Care is a single entity and an ongoing process which sometimes leads the person not to recovery but to progression of the illness and death. The proportion of treatments intended for recovery and treatments intended for palliative care thus changes over time and over the course of the illness. The sick person, who is most directly concerned, but also sometimes the doctor, may find themselves in denial of the palliative phase; this leads them to "dismiss" entering into acknowledgement of uncertainty and finiteness, and towards a form of stubbornness. PMID- 19642432 TI - [Continuity in palliative care]. PMID- 19642433 TI - [Major organ deficiencies in palliative care]. AB - The development of one or more life-threatening deficiencies in the course of a serious disease progression is an indicator of the terminal stage. Management aims at relieving symptoms reported by the patient as being particularly painful, and not treating causes of such deficiencies. Repeated clinical examinations help to adapt treatments and care to ensure their adequacy to the situation. The patient's level of consciousness should be determined to assess their distress while preserving, wherever possible, their communication capacities. During agony, explanations are provided to families to support them in these moments, sometimes experienced as being distressing. PMID- 19642434 TI - [Symptomatic treatments (pain management excluded) for adults in palliative care]. AB - Patients with evolutive and terminal desease often present 4 to 5 annoying symptoms, linked to the desease and implying a rigorous assessment as well as a treatment of the cause whenever possible. When all etiologic treatments have been used, the symptomatic treatments often allow to relieve the patient. This demands allying care and medication as well as mastering the available therapeutics so as to adapt the prescriptions at best. The present work essentially approaches the etiologies and symptomatic treatments of nausea and vomiting, hiccup, constipation, bowel obstruction, dyspnoea, congestion and death rattle and neuropsychic disfunctionning, in particular anxiety, depression and delirium. For the situations where the oral, transdermic and intravenous routes become difficult or impossible, medication to be administrated through subcutaneous routes are listed, with prudence, for not regulated. PMID- 19642435 TI - [Pain management for adult patients relative to palliative care]. AB - Pain management for a patient in palliative care requires a multi-functional approach that entails the physical, psychological, social and spiritual dimensions. It is based on a deep understanding of the pain physiopatology and its accurate assessment to optimize the treatment. This article provides guidelines to manage nociceptive and neuropathic pains, along with tips in case of refractory pains. It gives detailed instructions relative to the use of strong opiods taking advantage of the availability of new types of galenics. It proposes a decision tree relative to neuropatic pain management. PMID- 19642436 TI - [Supporting palliative care patients]. AB - Since the early days of the discipline, the fundamental principles of palliative care have been focusing on recognizing patient "overall suffering" and the necessity for caregivers to work as a team. Besides curative medicine, it becomes necessary to acknowledge a caring medicine which, based on the relationship to the sick one, aims at establishing with the latter a real life project until their very last days. To the patient, considered as a "subject of care", a man or a woman living up to the very last breath, the team will offer supportive care, quality of life, individualized care, in a climate of real confidence, an essential component of any relationship. In palliative supportive care, techniques, therapies and specific, effective and quality knowledge are indispensable. Moreover, palliative and supportive care cannot be separated from doubt and questioning, nor limited to a fulfilled and completed mission, since the other's life is and will remain, from their own personal assessment, that of the dying patient who sometimes, in my role of caregiver and witness, I have the privilege to meet. PMID- 19642437 TI - [Care networks, mobile palliative and supportive teams. What benefits are there for patients, natural caregivers and general practitioners in patient homes?]. AB - Civil society at large and all caregivers, whether at home or within institutions, are involved in palliative care However, procedures may vary considerably, excluding a single approach. So as to best adapt their responses, the authors recorded everyone's expectations. Such a participatory methodology is, sine 1990, behind the establishment of local networks providing assistance, support and training to physicians non-specialized in palliative care (general practitioners, specialists, students or residents facing specific aspects of this medical management, as well as other health and social workers). PMID- 19642438 TI - [Cocaine: from recreational use to dependence]. AB - Cocaine has become an essential part of the French drug scene and is the most commonly abused stimulant worldwide. The principal routes of cocaine administration are intranasal ("snorting"), intravenous ("injecting"), and inhalation ("smoking" freebase or crack cocaine). Distinct classes of primary cocaine users were identified in the literature. Cocaine dependence is a multifactorial disorder, variable in its manifestations, and heritable. It comprises distinct clinical phenomena that drive a cycle of addiction: cocaine induced euphoria, acute withdrawal, cue-induced craving (people, places, things), loss of control with poor decision making, cocaine seeking behaviour with multiple risks taken and cocaine administration. PMID- 19642440 TI - [Therapeutic approaches to cocaine addiction]. AB - Recent advances in neurobiology, genetics, neuropsychology and brain imaging research have identified various physiopathological mechanisms implicated in cocaine addiction and suggested several promising pharmacological approaches. Clinical targets of the pharmacological treatments are cocaine-induced euphoria and craving. Currently, there is no specific pharmacological therapy with established efficacy for the treatment of cocaine dependence, nor is any medication approved by regulatory authorities for such treatment. However, recent controlled clinical trials have highlighted the promise of several medications, especially N-acetylcysteine, modafinil, topiramate, GABAergic agents, disulfiram, agonist replacement therapy (methylphenidate LP, d-amphetamine). Partial agonists at the dopamine D2 receptor and anticocaine vaccines are other promising treatment approaches. It is important to clearly differentiate the detoxification treatment and the relapse prevention treatment phases. PMID- 19642439 TI - [Complications of cocaine addiction]. AB - Addiction is a chronic relapsing disorder characterized by repetitive and compulsive drug-seeking behavior and drug abuse despite negative health or social consequences. Cocaine addiction is a significant worldwide public health problem, which has somatic, psychological, psychiatric, socio-economic and judicial complications. Some of the most frequent complications are cardiovascular effects (acute coronary syndrome, cardiac arrhythmias, increased blood pressure); respiratory effects (fibrosis, interstitial pneumonitis, pulmonary hypertension, alveolar haemorrhage, asthma exacerbation; emphysema), neurological effects (strokes, aneurysms, seizures, headaches); risk for contracting HIV/AIDS, hepatitis B and C, sexual transmitted disease and otolaryngologic effects. Other complications are not discussed here. The vast majority of studies indicate that there are cognitive deficits induced by cocaine addiction. Attention, visual and working memories, executive functioning are affected in cocaine users. Psychiatric complications found in clinical practice are major depressive disorders, cocaine-induced paranoia, cocaine-induced compulsive foraging and panic attacks. PMID- 19642441 TI - [A reform]. PMID- 19642442 TI - [Polycystic kidneys]. PMID- 19642443 TI - [Peripheral neuropathies]. PMID- 19642444 TI - [Psychomotor development of infants and children]. PMID- 19642445 TI - [Acute abdominal pain in the pregnant woman]. PMID- 19642446 TI - [Vaginal hemorrhage]. PMID- 19642447 TI - [Otalgia and otitis in children and adults]. PMID- 19642448 TI - [Glomerular disease]. PMID- 19642449 TI - [From cadaver to stiff: symbolic learning of medical students]. PMID- 19642450 TI - [Therapeutic monoclonal antibodies]. PMID- 19642451 TI - [Basic immunological knowledge for understanding monoclonal antibodies]. AB - Antibodies (Ab) are molecules with dual functions: on the one hand, they bind to antigens (Ag) through their variable regions (Fab, "Fragment antigen binding"), located at one of their extremities; on the other hand, they recruit cells of the immune system, via the other extremity, the constant region or Fc region, which results in a selective destruction of cells that have the corresponding Ag. The capacity of recognition of Ag by Ab is unique. Ag generally have several different epitopes that all are binding sites for Ab. Ab may be classified according to their ability to recognize one single epitope or several epitopes. They are called monoclonal Ab (mAb) or polyclonal Ab, respectively. MAbs recognize the same epitope because they are issued from one single line of plasmocytes, originating from one single cell. It is the reason why they are so selective. MAbs exert complex, but unique mechanisms of action: they inhibit or activate signal transduction, and they specifically drive the immune system against target cells, such as tumoral cells. After their extensive use in fundamental and in applied research as wells as diagnostic tools, mAbs are now largely exploited in therapeutics. PMID- 19642452 TI - [International classification of various types of monoclonal antibodies]. AB - Significant advances in the development of monoclonal antibodies ("mabs") have been acknowledged during the last two decades. Successive developments led to the marketing of murine antibodies ("o-mab" first, followed by chimeric antibodies ("xi-mab"), humanised antibodies ("zu-mab") and, finally, human monoclonal antibodies ("u-mab"). In order to facilitate the distinction between the various monoclonal antibodies used in clinical practice, an international nomenclature has been proposed with the use of a specific suffix corresponding to the origine/source of "mabs" preceded by an infix referring to the medicine's target. The efforts in developing new types of monoclonal antibodies aimed at improving their pharmacokinetics (longer half-life), pharmacodynamics (better efficacy because of stronger affinity to human receptor), and safety profile (less antigenic and immunogenic reactions). These progresses could be obtained thanks to the remarkable development of molecular biotechnology. PMID- 19642453 TI - [Production of monoclonal antibodies]. AB - In contrast to a polyclonal antiserum, a monoclonal antibody is specific to a single epitope on the surface of a complex antigen. In 1975, Kohler and Milstein produced the first monoclonal antibodies by using a method which rapidly became a key technology in immunology. By fusing activated antibody-forming cells (B cells) with myeloma cells, they obtained hybrid cells--the so-called hydridomas- which combine the ability of the activated B cells to secrete a single species of antibody and the immortality of the myeloma cell. The selected hybridomas proliferate continuously, their clonal progeny providing an unending supply of antibody with a single specificity. These antibodies have found many applications in basic research and in vitro diagnosis. In the clinical laboratory, monoclonal antibodies are used as reagents in immunoassays, often replacing traditional antisera. Many years of development and innovation were needed to humanize monoclonal antibodies in order to make them usable in human therapy. PMID- 19642454 TI - [New advances in therapeutic use of monoclonal antibodies]. AB - New major advances may be expected in a near future regarding the use of monoclonal antibodies (mAb), mainly thanks to the remarkable progress in biotechnology and the better knowledge of cellular homeostasis. The concept of antibody-targeted drugs relies upon the use of mAbs as vectors capable of specifically delivering at targeted cells (i.e. tumours) other active agents that could exert locally a cytotoxic effect (radioisotope, toxin, enzyme, drug). Other approaches will also be concidered such as the development and use of bispecific mAbs, intracellular mAbs or fragments of mAbs. These novel original approaches open promising therapeutic prospects. However, in many cases, their real interest in terms of "efficacy-safety-cost" ratio remains to be demonstrated as compared to other classical therapeutic approaches. PMID- 19642455 TI - [Interest of monoclonal antibodies in biomedical laboratory analysis]. AB - Immunoassays, or assays with antibodies as reagents, are widely used in medical laboratories. These assays are used to identify and quantify various substances in biological fluids, such as specific proteins (various tissue markers, markers of inflammation, hormones, coagulation factors...) or immunoglobulins (viral or bacterial antibodies, auto-antibodies...) and even both viral antigens and antibodies (HIV virology). The use of monoclonal antibodies allowed, through their specificity for a single epitope of the target molecule, the development of increasingly sophisticated immunoassays. In particular, the use of monoclonal antibodies with microarrays permits the simultaneous determination of various proteins (inflammatory profile, cardiac profile, specifics IgE...) quickly and accurately. Very important tools in the clinical laboratory, immunoassays techniques are, however, subject to various analytical interferences which may be responsible for significant changes in the test results. PMID- 19642456 TI - [Therapeutic monoclonal antibodies in hemato-oncology]. AB - For many years, chemotherapy, hormonotherapy and immunotherapy were the mainstay of cancer treatment. Recent advances in our knowledge of cell biology and particularly of cancer cell transformation, growth and metastasis have led to the identification of specific pathways playing a role in the pathophysiology of cancer. New drugs specifically developed to control these targets are collectively named "targeted therapies". Two types of targeted therapies are available: kinase (mainly tyrosine kinase) inhibitors (suffix -nib) are small molecules binding directly to the intracellular kinase domain and acting as competitive inhibitor of ATP binding and monoclonal antibodies (suffix -mab) directed towards specific cell surface receptors or their ligands to prevent receptor activation. This paper will only review monoclonal antibodies (mabs). Thirty years after their discovery mAbs have become efficient therapeutic tools. Progress in molecular engineering as well as improved knowledge of cell signalling pathways together with a better selection of the targets turned them into valuable treatments. Several mAbs are currently licensed for the treatment of hematological or solid malignancies and many others are expected in the near future. PMID- 19642457 TI - [Monoclonal antibodies in hematology in 2009]. AB - Directed against the CD20 antigen on B lymphocytes, rituximab (MabThera) is now incorporated in the first line therapy of symptomatic follicular as well as diffuse large B cell non-Hodgkin's lymphoma and offers superior response and survival rates. 90Y ibritumomab tiuxetan (Zevalin) combines the specificity of rituximab for the CD20 antigen and the therapeutic effect of beta irradiation. Given in monotherapy, it constitutes an interesting alternative therapy for follicular lymphomas in second relapse. Alemtuzumab (MabCampath) recognizes the CD52 antigen and offers encouraging results in chronic lymphocytic leukemia resistant to classical chemotherapy. PMID- 19642458 TI - [Monoclonal antibodies therapies for colorectal cancer: cetuximab, panitumumab and bevacizumab]. AB - Colorectal cancer is the third most common form of cancer in Europe, Its prognosis is poor, since median survival time for metastatic patients is about 20 months. Progresses in molecular biology have lead to significant improvement in the management of metastatic colorectal cancer with targeted therapies. The monoclonal antibodies anti-EGFR and anti-VEGFR improve the overall and the progression-free survival. The anti-EGFR antibodies (cetuximab and panitumumab) have been marketed in Belgium, as monotherapy or in association with chemotherapy (FOLFIRI) for third line use in patients with wild type K-ras. The anti-VEGFR bevacizumab is the standard first line treatment in metastatic colorectal cancer with irinotecan based chemotherapy. For the future, the place of monoclonal antibodies therapies in adjuvant or in first line settings and the value of combining targeted therapies have to be further defined. PMID- 19642459 TI - [Monoclonal antibodies and breast cancer. Current therapeutic progress]. AB - About 9,500 new breast cancers are diagnosed in Belgium every year. Improvement of our knowledge of altered molecular events leading to the proliferation of tumor cells has resulted in the development of targeted therapies in subgroups of cancers. One of the first validation of targeted therapy is the anti-HER-2 monoclonal antibody trastuzumab (Herceptin) in patients with overexpression of human epidermal growth factor receptor type 2 (HER2) occurring in 20 to 25% of invasive breast carcinoma. Trastuzumab binds the extracellular juxtamembrane domain and is only active in tumor with HER2 gene amplification detected by fluorescence in situ hybridization (FISH). The results from randomized trials have rapidly lead to the approvement of the drug in the metastatic and then in the adjuvant setting. Another targeted therapy, also approved in the treatment of breast cancer, is the monoclonal antibody bevacizumab with an anti-VEGF (Vascular Endothelial Growth Factor) activity. We will review the benefit of these targeted therapies in breast cancer and their role in the treatment of breast cancer. PMID- 19642460 TI - [Monoclonal antibodies for the treatment of head and neck cancer]. AB - Monoclonal antibodies are now part of the armamentarium available for the treatment of head and neck cancer. Cetuximab, a monoclonal antibody targeting EGFR, improves overall survival as compared with radiotherapy alone as radical treatment of locally advanced head and neck cancer. It is now reimbursed in Belgium after multidisciplinary discussion if cisplatin is contra-indicated. In the metastatic setting adding cetuximab to platinum based chemotherapy improves overall survival as compared with chemotherapy alone, a first-time event over a 30-year period, unfortunately not yet accessible to the Belgian patients. Other monoclonal antibodies targeting EGFR or VEGF are also currently under investigation while cetuximab is being explored in the induction, the maintenance or the post-operative radiotherapy settings. PMID- 19642461 TI - [Monoclonal antibodies in renal transplantation]. AB - Renal transplantation is the best treatment for end-stage renal disease, but requires efficient immunosuppressive therapy. The latter has evolved over recent years with the development of more powerful drugs and of monoclonal antibodies with very specific target. The first monoclonal antibodies, acting against the interleukin 2 receptor, named basiliximab and daclizumab, have showed an excellent tolerance profile and efficacy to reduce acute graft rejection. However, in spite of these properties, the development of delayed graft function or the graft and patient survivals at 1 year were not modified by the use of such specific treatment. One potential advantage could yet be a decreasing need for corticosteroids and sometimes calcineurin inhibitors which could provide some long term benefits for the renal graft, but also the patient. Alemtuzumab, another monoclonal antibody, aimed at the membrane glycoprotein CD52, can also decrease the incidence of acute rejection and the depth of the required immunosuppressive therapy. Other antibodies are still in development with some interesting preliminary results which however demand confirmation in larger studies. PMID- 19642462 TI - [Biological therapies in rheumatology]. AB - Biological therapies consisting of monoclonal antibodies and soluble receptors have revolutionized the care of rheumatologic patients. These therapies ensued from a better understanding of the physiopathology of rheumatologic disorders. Most of the latter have been concerned: rheumatoid arthritis (for about 10 years), psoriatic arthritis and ankylosing spondilitys (for more or less five years). Rheumatology was among the first disciplines to make use of these advances; it continues to benefit from the results of intense research efforts. These developments request from clinicians an increased expertise in immunology. PMID- 19642463 TI - [Biologic therapies in chronic inflammatory bowel diseases]. AB - Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases which can be difficult to control with conventional therapies. Thanks to a better knowledge of their physiopathology, new therapies aimed at specific targets of the inflammatory cascade were developed. Three monoclonal anti-TNF antibodies were produced. Infliximab and adalimumab, currently widely used, can induce sustained remission in Crohn's disease. Infliximab is also efficacious in UC. Certolizumab pegol provides good short term results; its long term efficacy, however, remains to be assessed by further clinical trials. Therapies targeting leucocyte trafficking (anti-integrine) have also been provided and are associated with good clinical responses in Crohn's disease. Natalizumab (anti-alpha4) is responsible for significant side effects and is no longer in use in gasrtoenterology in Europe whereas MLN02 (anti-alpha417) has a good profile in terms of efficacy and safety. Monoclonal anti bodies targeting other cytokines are under development, mainly ustekinumab which inhibits IL12 and IL23. Ustekinumab generates favourable clinical responses in Crohn's disease. The development of biologic therapies in inflammatory bowel disease has dramatically altered the course and management of these disorders. PMID- 19642464 TI - [Monoclonal antibodies in neurology]. AB - Since their inception in the 1970's, monoclonal antibody therapies became increasingly efficient and common in numerous medical conditions and their use in neurology has been boosted during the last couple of years with the rise of natalizumab (Tysabri). Furthermore, if most monoclonal antibodies currently assessed in neurologic conditions remain considered as experimental, they may soon become first-line approved treatments in a broad range of neuromuscular and demyelinating diseases. Since the introduction of new therapies is likely to unravel specific adverse events and sui generis iatrogenic disorders, it is important to be able to recognize the side-effects of monoclonal antibodies delivered for neurological or non-neurological diseases. PMID- 19642465 TI - [Monoclonal antibodies in cardiology]. AB - Clinical efficacy of antiplatelet agents administration to reduce ischemic complications has supported the concept of atherothrombosis and plaque rupture. Specifically, administration of monoclonal antibody against platelet membrane receptor glycoprotein IIb/IIa was shown to be highly effective whenever percutaneous intervention is performed in the setting of unstable coronary syndrome. The in-hospital use of glycoprotein IIb/IIIa is unanimously recommended in these situations. PMID- 19642466 TI - [Omralizumab (Xolair) in severe persistent allergic asthma]. AB - Asthma is a chronic inflammatory airways disease. The inflammatory process is in many patients driven by an immunoglobulin E (IgE)-dependent process. Patients with severe asthma are at high risk of serious exacerbations and death and have few therapeutic options available. Omalizumab is a humanized monoclonal antibody that acts by binding to and inhibiting the effects of IgE, thereby interfering with one aspect of the asthma cascade. In addition to decreasing exacerbations, it has a steroid sparing role and many beneficial effects in asthma. As suggested by the new asthma GINA 2006 guidelines, this biological agent is indicated in severe persistent allergic asthma. PMID- 19642467 TI - [Practical pediatric aspects of palivizumab]. AB - Palivizumab (Synagis) is a monoclonal antibody directed against the respiratory syncytial virus (RSV), for reducing mortality and morbidity in infants at risk of cardio-respiratory impairement due to bronchiolitis: 1. prematurity less than 28 weeks and less than 1 year of age; 2. between 28 and 32 weeks plus mechanical ventilation and less than 6 months of age; 3. chronic lung deficiency and less than 2 years of age; 4. congenital cardiopathy with either desaturation, pulmonary hypertension or cardiac failure. Another group of infants is those having a severe imnnunodeficiency. These infants are listed in a hospital recognized to have a competence in neonatal intensive care or a cardio-thoracic care program. The specialist in those disciplines prescribe the palivizumab which is delivered by the pharmacy of the competent hospital. The infant receives it by IM route at a dose of 15 mg/kg, monthly between October or November and February or March. Reduction of mortality and morbidity have been observed in the infants at risk. However, this costly pharmacological preventive approach needs to come after other simple preventive measures such as avoiding contact with potential carriers of nasal viruses and passive smoking, for bronchiolitis is not solely due to RSV. PMID- 19642468 TI - [VEGF inhibitors in ophthalmology]. AB - The exsudative form of age-related macular degeneration (AMD) is characterized by the development of choroidal neovascularization (CNV) under the retina driven in part by the vascular endothelial growth factor. Several VEGF inhibitors have recently been produced for ocular administration. This review will focus on ranibizumab which is a specific antibody neutralizing all VEGF isoforms. The development, pharmacokinetics, clinical efficacy, current and future indications of ranibizumab are discussed. PMID- 19642469 TI - [Monoclonal antibodies in diabetes: almost approaching the dream?]. AB - Type 1 diabetes is characterized by the autoimmune-mediated destruction of the insulin-producing beta cells of the pancreatic islets of Langerhans. Several cells are potentially implicated in the selective destruction of beta cells, including the beta cells themselves, and T-lymphocytes and B-lymphocytes that are working as antigen-presenting cells. Both types of lymphocytes play also a role in the progressive loss of graft function after islet transplantation. Therefore, immunotherapy may represent a great opportunity to prevent, treat or even cure type 1 diabetes, and the input of monoclonal antibodies (mAb) appears crucial in such a strategy. The concept has first been validated in various animal models, especially the classical one of the NOD mouse. During recent years, promising results of a few clinical trials have been published with the administration of anti-CD3 mAbs targeting T lymphocytes at the time of diagnosis of type 1 diabetes. Results showed a more sustained residual insulin secretion during the following months associated with a reduction in insulin needs. Interesting results may also be expected from the use of anti-CD20 mAbs targeting B lymphocytes. Finally, when considering immunosuppressive therapies after beta cell transplantation, mAbs, especially those blocking interleukin-2, are already used in clinical practice, but new trials are expected with mAbs targeting T or B lymphocytes. Thus, mAbs might be efficacious in a near future in the prevention (when administered early in the natural course of the disease, in high risk patients) and the treatment of type 1 diabetes, and therefore could avoid, or at least minimize, the constraints of intensive subcutaneous insulin therapy. PMID- 19642470 TI - [A range of targeted treatments using monoclonal antibodies in dermatology. Current and future practice]. AB - Targeted therapies are focused on one or a few molecules particularly involved in specific diseases. Some inflammatory dermatoses and cutaneous neoplasia potentially benefit from these approaches. Nine monoclonal antibodies of interest in dermatology are presented according to the disorders where they have proven their efficacy. Biotherapies extend beyond monoclonal antibodies. A given effect, such as TNF-alpha antagonism, is indeed obtained by distinct drug classes. The interindividual differences in the therapeutic responses remain unpredictable, and there is no criteria of selection of patients who could benefit the most from these targeted medications. PMID- 19642471 TI - [Cutaneous adverse reactions to monoclonal antibody treatments]. AB - A number of adverse skin reactions can occur during some treatments using monoclonal antibodies. Some of the reactions are specifically linked to the pharmacological effect of the drug. Others are the expression of more common drug reactions. Their early recognition and their adequate management are important to consider in order to avoid a morbidity severely altering the quality of life and even the life prognosis. PMID- 19642472 TI - [Cutaneous adverse effects predicting the efficacy of targeted antineoplastic therapies]. AB - A series of medical disciplines benefit from the emergence of diverse targeted therapies using monoclonal antibodies. Skin is affected by adverse events of such therapies primarily targeting internal cancers. As a unique event in medicine, some of the skin adverse effects are predictive markers of the therapeutic antineoplastic activity. This fact concerns the paroxismal acneiform eruption and the inflammatory flare-up of actinic keratoses. Such a situation is linked to the fact that these specific "unwanted" effects are not really side effects but rather represent the direct pharmacological consequence of the activity directed to the EGF receptors which are particularly abundant in the follicular ostium and in precursor lesions to skin carcinomas. PMID- 19642473 TI - [Nurses moving towards deep thinking?]. PMID- 19642474 TI - [An analysis of professional practice as a means to enhance one's skills: theoretical basis, actual process and associated limitations]. AB - With the advent of skill-based approaches in the training of health professionals, trainers have been encouraged to make use of a methodology which analyses actual practice. This paper's main objective is to take a deeper look, from a theoretical perspective, at the process of analysing professional practice. This particular training method, which has been in use for a considerable amount of time in certain professional circles, has two "historical" sources: Balint Groups and Schon's Reflective Practice. I intend to concentrate on the latter, Reflective Practice approaches. These involve a group of peers working with a facilitator, whose objective is to consider the various work contexts associated with the participants. As a result, they are involved with a "hindsight approach", so that real work situations, the way in which practitioners have carried out a contextual analysis, how this has been interpreted and the strategies which have been put in place can be understood. So, what process do these approaches enable as regards developing professional skills? How does this evaluation of practice challenge knowledge, experience and representations? Finally, if this approach indeed facilitates a change in practice, what are the constraints? PMID- 19642475 TI - [An interprofessional or an interdisciplinary problem? Distinctions to develop an analytical scheme of interdisciplinarity based on the case of a long-term care hospital]. AB - This communication distinguishes interdisciplinary problems from other neighbouring difficulties, such as difficulties related to work organization. The conceptual proximity between discipline and profession can in fact cause difficulties experienced in the interprofessionnal space to mistakenly incriminate interdisciplinarity. For the analyst, this proximity blurs his insight and, in effect, inhibits the development of adequate solutions to the encountered problem. Hence, this article, based on an ethnographic study of interdisciplinary relations in a small long-term care hospital, aims to alleviate the ambiguity surrounding this issue. In order to do so, this article will begin by recalling the parameters of the theoretical field of interdisciplinarity. Subsequently, the difficulties observed in the long-term care hospital's setting, as they were conceived in the light of interdisciplinarity theory, will be exposed. This article will notably highlight how the nursing staffs contribute to the maintenance of a philosophy of care favourable to the long term deployment of interdisciplinarity. PMID- 19642476 TI - [Emotional labour of nursing care: an evolutionary concept analysis]. AB - Caring is considered as the essence of nursing. Underpinning caring, the internal regulation of emotions or the emotional labour of nurses is invisible. The concept of emotional labour is relatively underdeveloped in nursing. DATA SOURCES: A literature search using keywords 'emotional labour', 'emotional work' and 'emotions' was performed in CINAHL, psycINFO and REPERE from 1990 to January 2008. We analysed 72 papers whose main focus of inquiry was on emotional labour. REVIEW METHODS: We followed Rodgers' evolutionary method of concept analysis. RESULTS: Emotional labour is a process whereby nurse adopt a 'work persona' to express their autonomous, surface or deep emotions during patient encounters. Antecedents to this adoption of a work persona are events occurring during patient-nurse encounters, and which consist of three elements : organization (i.e.social norms, social support), nurse (i.e.role identification, professional commitment, work experience and interpersonal skills) and job (i.e.autonomy, task routine, degree of emotional demand, interaction frequency and work complexity). The attributes of emotional labour have two dimensions : nurses' autonomous response and their work persona strategies (i.e. surface or deep acts). The consequences of emotional labour include organizational (i.e.productivity, 'cheerful environment') and nurse aspects (i.e. negative or positive) CONCLUSION: the concept of emotional labour should be introduced into preregistration programmes. Nurses also need to have time and a supportive environment to reflect, understand and discuss their emotional labour in caring for 'difficult' patients to deflate the dominant discourse about 'problem' patients. PMID- 19642477 TI - [Mixed methods: promising strategies for the evaluation of nursing interventions]. AB - Based on a survey of the literature in human and nursing sciences and illustrated with concrete research examples, we will identify promising research directions for mixed-methods studies and present strategies for applying this type of research design to the evaluation of nursing interventions. This article provides three examples of mixed-methods design that utilize schematic representation about evaluation of nursing interventions. Based on examples, the issues discussed are: (1) sufficient significance for research program to invest the required human and material resources, (2) reason for using qualitative and quantitative data simultaneously or sequentially, (3) integration of qualitative and quantitative data when the participants are from different target populations; (4) presentation of the findings. PMID- 19642478 TI - [Validation of a tool for family caregivers]. AB - The purpose of this transcultural study was to translate and adapt for the province of Quebec (Canada) a tool for assessing the support needs of family caregivers of aging persons, as well as to validate the relevance and feasibility of its utilization in Quebec homecare services. Developed jointly in the United Kingdom and Sweden and based on a caregiver-service provider partnership process, the Carers Outcome Agreement Tool (COAT) is presently the focus of a large-scale implementation study in Sweden. Following parallel back-translation and adaptation, the tool, entitled Entente sur le Soutien aux Proches-Aidants (ESPA) in French, was validated in terms of relevance and feasibility via focus groups with service providers and interviews with family caregivers. Results show the ESPA to be a culturally sensitive tool that systematically identifies the support needs of caregivers and indicates the type of help best suited to meet these needs. As with other European studies, the results suggest that the caregiver role comprises a common core of needs and highlights the tool's potential for transfer to the cultural context of French-speaking Europe. PMID- 19642479 TI - [Validation of the French version of "Self Appraisal of Illness Questionnaire"]. AB - Poor insight into mental illness is associated with treatment non-compliance, relapse and re-hospitalization. Measuring insight becomes therefore important in assessing risk of non-compliance. A few reliable insight instruments are available in English. Self Appraisal of Illness Questionnaire (SAIQ) (Marks & al., 2000) was translated in French and validation analysis was performed. The 17 items French version is called Questionnaire d'autoevaluation de l'introspection (QAI). Cronbach's alpha showed 0.78 for internal consistency (N = 124). Factor analysis generated three factors explaining 49.8 % of the variance. They were: Need for treatment (Awareness of), Worry and Presence/Outcome of mental disorder. Concurrent validity analysis of QAI and Insight Scale (IS) (Markova & al., 2003) resulted in a coefficient of 0.37. QAI demonstrated solid psychometric properties and should be further reassessed in research and clinical practice. It is well adapted for use in hospital and clinical setti PMID- 19642480 TI - [Assessment strategies of the impact of healing touch in nursing care]. AB - New care methods have emerged in the last few years. Healing Touch is relaxing and as such, helps prepare the patient for the medical act, the pain of which he may often feel anxious about As they foster confidence between the patient and the medical practitioner, such practices create better conditions for the medical care act to be performed. Even if there is no doubt about its impact on the patient, the effect of Healing Touch has never been scientifically assessed, and the only available references are rather scarce. This is the reason why we wished to assess the impact of this care in a number of clinical situations through a randomised clinical experiment. The object of this paper is to assert the efficacy of such care on the patient, especially on pain relief and the decrease of anxiety. To this end, authenticated assessment scales were used, such as the visual analog pain scale or Spielberg's test anxiety inventory. A prospective multicentre randomised study was carried out to create a control group to be compared to the group treated with Healing Touch. Only willing patients who were prescribed healing touch were included in the experiment. Patients with cognitive problems - be they temporary (linked to a temporary clinical conditions) or not - or those suffering from some disabilities preventing them from using assessment scales and questionnaires are excluded. The recruitment of a 784-patient panel was needed to set out the 8 situations in which a Healing Touch indication may be effective. PMID- 19642481 TI - [Evaluation of the impact of nursing care touch--statistical results of a multicenter, prospective and randomized study]. PMID- 19642482 TI - [Perceived stigma at the end of hospitalization and mentally ill subjects' social reinsertion]. AB - This paper deals with a study carried out in the framework of a course in a medium-term pavilion and in a psychiatric admissions unit. The aim of that study was to look at the effect of psychiatric institutionalization on the way subjects with mental illness perceive the stigmatization they are subjected to in society. The findings permit us to evoke, in that paper, the social reinsertion of these subjects who have sometimes been hospitalized for more than five years. PMID- 19642483 TI - [Suffering and complaints in the adult sickle cell anemia patient in a painful crisis]. PMID- 19642484 TI - [Contribution of the upper health cadre to nursing recruitment in geriatrics]. PMID- 19642485 TI - [Impact of the mode of arrival in the emergency department for patients with a STEMI and the clinical outcomes in terms of ejection fraction and survival]. AB - Emergency Medical Services (EMSs) play a key role in the recognition and treatment of ST-segment elevation myocardial infarction (STEMI). This study evaluates patient outcome according to his mode of arrival in the care unit dealing with acute coronary syndromes. METHODS: Retrospective analysis of STEMI infarctions registered by the Belgian Interdisciplinary Working Group on Acute Cardiology (BIWAC) at Saint-Pierre University Hospital, Brussels (C.H.U. Saint Pierre), between 01/01/2005 and 31/12/2006. Comparison of two groups according to their arrival in the care system: group 1: brought in following an emergency call by mobile medical team (SMUR) or normal ambulance ; group 2: arrived at the hospital by their own means and classic admission to Emergency Service. STUDIED PARAMETERS: descriptive patient characteristics, localisation of the infarction and survival to the end of hospitalization, to six months and to one year. RESULTS: Among 136 patients, 56.6 % arrived by EMS and 43.4 % by their own means. Patients who arrived by EMS were older (p = 0.008) and had a higher Killip score (p < 0.05). Pain-to-Angiography and Door-to-Angiography intervals were shorter in patients who arrived by EMS (222 vs 416 mins, p < 0.0001 and 62.6 vs 147 mins, p < 0.0001, respectively). There were no differences in the left ventricular ejection fraction (LVEF) and survival. However, for patients suffering an IVA attack, survival to six months and one year was better in the EMS group (88.9% vs 78.3%, p < 0.05 and 80.5 % vs 69.6 %, p = 0.05). In conclusion, dealing with STEMI infarctions is quicker by EMS admission. The infarctions admitted by this way are more serious. Wherever STEMI infarctions were localised, no improvement of LV function and survival was observed according to the mode of arrival, contrary to the subgroup with an IVA attack where survival is better at six months and one year by EMS admission. PMID- 19642486 TI - [The erythrocyte phenotype in ABO and Rh blood groups in blood donors and blood recipients in a hospital setting of Cameroon: adapting supply to demand]. AB - The administration of ABO and Rh compatible blood products is primordial for the immulogic safety of blood during blood transfusion, more so in resource limited settings where blood grouping is confined to ABO and Rh testing only. Thus, from an immunological perspective, the frequency of blood phenotypes and the qualitative balance between supply and demand of blood products in a Cameroonian hospital were analyzed. All blood collected was phenotypically typed and compared to the phenotypes of all transfusion recipients during the same period. A total of 1007 units of blood and 1013 recipients were typed. Our results showed that in the donor group, the frequencies of phenotypes A, B, AB, O, and RH1 were respectively 24.2 %, 18.8 %, 5.7 %, 51.3 % and 97.6 %. In the recipient group, the respective frequencies were 40 %, 12.4 %, 3.4 %, 44.2 % and 96.9 %. The supply for blood phenotypes O, B and AB was higher than the demand, and the reverse was true for phenotype A and RH-1. Further sensitization of phenotype A and RH-1 donors may enhance meeting these needs. PMID- 19642487 TI - [A prospective longitudinal study of coma in the intensive care unit in an African setting: case of Dakar, Senegal]. AB - Little is known on coma in neurological intensive care unit (NICU) in the setting of developing country in Sub-Saharan Africa. The aim of this study was to determine the morbi-mortality and survival of coma in the NICU of Dakar, Senegal. We carried out a prospective longitudinal study in the NICU of the teaching hospital of Fann in Dakar during a period of 15 months (with 12 months of inclusion) on comatose patients. Were included all patients presenting with a Glasgow score inferior to 9. Standard biological analyses were prescribed for each patient while CT scan was performed if indicated. Daily evaluation was done and complications recorded. Each patient was followed for at least 3 months. Survival was determined by the Kaplan Meier method. 345 patients were admitted in the NICU and 169 were included (48,99 %). The mean age of the patients was 58.04 +/- 17.55 years with a sex ration of 0.92. The mean time from installation of disorders and initial consultation was 47.30 +/- 138.34 hours. Etiologies were vascular disease (71 %), status epilepticus (9.47 %), meningoencephalitis (8.88 %) and metabolic disorders (8.88 %). The mean duration of hospitalization was 8.89 +/- 9.53 days associated with a mortality rate of 82.25 % for the same period. Survival at day 90 was 10.65 %. Mortality was related to infectious condition (28.4 %), renal failure (14.78 %), cardiovascular failure (13.61 %), cerebral engagement (12.43 %), multivisceral failure (11.24 %), pulmonary embolism (1.18 %) and unknown cause (18.34 %). In conclusion, coma is associated with a high mortality rate in our context and suggests that early consultation, a good control of vascular risk factors and better management of infectious condition should reduce this impact. PMID- 19642488 TI - [Hodgkin's disease, fertility and pregnancy]. AB - Hodgkin's disease, the most common cancer between 15 and 24 years, raises two problems in women in reproductive age: the preservation of fertility and the care during pregnancy. Chemotherapy and radiotherapy can destroy gonads and subsequently lead to a loss of fertility and premature ovarian failure. Many options are available today to maintain fertility in female patients treated for Hodgkin's disease, thanks to advances in assisted-reproduction technology. Chemotherapy and radiotherapy during the first trimester are associated with increased risk of congenital malformations and this risk diminishes as pregnancy advances. The management of this disease during pregnancy must be examined case by case. PMID- 19642489 TI - [Colorectal cancer screening: an absolute necessity and an imminent reality in the French community]. AB - Colorectal cancer is a true problematic of public health. The screening is an absolute necessity. An ambitious program of screening is launched in French Community. Faecal occult blood test (FOBT) will be proposed to average risk patients in general population. A total colonoscopy will be performed if FOBT will be positive. First step colonoscopy will be proposed to high or very high risk patients. General practitioners are in the core of the multidisciplinary program. PMID- 19642490 TI - [Maxillary cementoblastoma. A case report]. AB - Cementoblastoma is a rare benign odontogenic neoplasm. Its cause is unknown. It represents less 6 % of all odontogenic tumors. The aim of our work is to present a rare case of maxillary cementoblastoma involving an included central incisor. A 32-year old man consulted for a left maxillary swelling to projection under nostril. A panoramic radiographic examination revealed an included tooth 21 with a radiopaque lesion around its root. The computed tomography revealed the included tooth 21 with a process around its root. This process is well-defined, high-dense and is surrounded by a radiolucent halo. The treatment should consist of complete removal of the lesion with the tooth 21. Histological examination concluded to the diagnosis of a cementoblastoma. The cementoblastoma occurs most frequently in young persons and predominantly among men. The mandibular premolar and molar are the more frequently reached. The maxillary localization remains rare. This tumor occurs around the roots of the posterior and lower teeth. Radiographically, the lesion is well-defined and attached to the root of the tooth, radiopaque dense and surrounded by a radiolucent halo. The cementoblastoma evolves slowly and has the tendency to blow the cortical. The prognosis is good. PMID- 19642491 TI - [A huge inguino-scrotal hernia]. AB - We report herein a case of a 76 year-old-man, who presented a huge left inguino scrotal hernia. Laparoscopic reduction of the hernia contents and hernia repair through an inguinal approach were performed. No recurrence was observed two years and a half postoperatively. Reconstructive surgical approach and important postoperative complications were discussed. PMID- 19642492 TI - [Fever after a stay in the tropics]. AB - We report the case of a patient suffering from dengue fever after returning from Guadeloupe. The differential diagnosis of fever after a stay in the tropics is discussed and attention is drawn on the emergence and diagnosis pitfalls of dengue fever. PMID- 19642493 TI - [Cor triatriatum in the adult]. AB - A 18-year old girl suffering from effort dyspnea presented to our hospital. She had no previous medical history. The first investigations revealed a linear structure traversing the left atrium. A transoesophageal echocardiogram demonstrated a thin mobile membrane in the atrium. Many investigations were realized to describe better this structure and its contribution to the symptoms. Cor triatrium is a rare congenital disease and its discovery is rare in adulthood. So, there are no guidelines for the optimal management. PMID- 19642494 TI - [Staphylococcus aureus bacteremia and epidural mass in a patient with tophaceous gout]. AB - We present a case of Staphylococcus aureus septicaemia complicated with endocarditis and spondylodiscitis C2-C3 with compressive epidural mass in a 74 year old patient with a history of gouty arthritis and aortic prosthetic valve. Tophaceous material has been found when surgical decompression of the abscess has been performed. Staphylococcus aureus bacteremia is a serious and common infection with high mortality and complication rate. Amongst those complications, endocarditis is more likely to develop if cardiac prosthetic valve is present. The probability of a metastatic infection may be evaluated by several factors, such as: the time to positivity of blood culture, a community-acquired Staphylococcus aureus bacteremia and the presence of Osler nodes. All were present in our case. In fact, spondylodiscitis C2-C3 with compressive epidural mass was discovered, which was suspected to be an epidural abscess. Epidural abscess is a rare but potentially life-threatening disease that remains often underdiagnosed. Diagnosis is made by imaging and anatomopathological findings. In the case of our patient the finding of tophaceous material raises the issue of the nature of the epidural lesion. Spinal involvement with gout has been described. It can mimic epidural abscesses, most often in an infectious context as it was the case of our patient. PMID- 19642495 TI - [A blow to the larynx]. PMID- 19642496 TI - [The end of numerus clausus: a false bit of good news? A reflexion in defense of education]. PMID- 19642497 TI - [Is it serious, Doctor? ]. PMID- 19642498 TI - [Early nutrition: the role of genetics and epigenetics]. AB - Many adult diseases seem to be associated with early nutrition and the subsequent growth pattern. Epidemiological studies hypotized that babies with intrauterine and/or neonatal growth retardation may be at greater risk of metabolic syndrome later in life. According to the Barker's "thrifty phenotype hypotesis" early malnutrition, whereas inducing physiological compensation by the promotion of early survival, appears to confer greater susceptibility to adults diseases. Epigenetics, that is the interindividual variation in DNA methylation patterns and chromatin remodelling, provide a potential explanation for how environmental factors can modify the risk for development of many common diseases. Beginning from animal models, many studies concerning early nutrition, epigenetic modifications and genes expression have been carried out. Maternal undernutrition during pregnancy, especially in the peri-implantation period, not only causes a prolonged growth retardation but also modifies the programming of biochemical mechanisms related to endocrine-metabolic control. Human studies have demonstrated the role played by IGF-1 as indicator of nutritional status and fetal/postnatal growth retardation. It has been reported that alterations in IGF axis, which predispose to adults diseases, may be due to an alterated epigenetic regulation that can modify IGF expression. Despite the critical inter-relation between early nutrition, growth, development, and subsequent health, there are few data on the influence of early nutrition on the modifications of the epigenetic gear. Furthermore it is hoped for a bigger attention to the early nutrition to prevent the development of diseases later in life. PMID- 19642499 TI - [Fetal and neonatal outcomes in infants of mothers with TSH receptor antibody positivity in pregnancy]. AB - OBJECTIVES: To know the mother's frequency with TRAb (TSH receptor antibodies) positivity during pregnancy in the population afferent to Agostino Gemelli Hospital in the five years 2002-2007 and the itself antibodies's role determining fetal and neonatal symptoms. MATERIALS AND METHODS: We performed a prospective analysis with maternal and neonatal variables detection in 16 couples mother newborn with TRAb positivity during the pregnancy. The method to dose neonatal TRAb is ELISA (enzyme linked immunosorbant assay). RESULTS: The prevalence of newborns of mothers with TRAb positivity during pregancy results 0.1 per thousand (16/16783). The prevalence of neonatal hyperthyroidism, clinical and biochemical, in the studied population results especially elevated equal to about 30% (5/16). The 5 newborns are born to mothers with Basedow disease with TRAb serum levels greater than TRAb levels of newborn without hyperthyroidism: 2 are showed the symptoms of clinical hyperthyroidism and 3 a transient biochemical hyperthirodism. 3 newborns with hyperthyroidism among 5 are born to mother undergo thyroidectomy with L-tiroxina teraphy during the pregnancy. Then the newborns of thyroidectomized mothers also many years before the pregnancy must be considered high risk of developing neonatal hyperthyroidism because of long lasting persistence of mother's TRAb. The neonatal hyperthyroidism, clinical and biochemical, appears later in newborns of mothers using antithyroid drugs. The pharmacological treatment of neonatal hyperthyroidism was difficult to standardize and highly individualized. CONCLUSIONS: Although the neonatal hyperthyroidism is a very rare disease it is essential to apply specific protocol assistance, both during pregnancy and the neonatal period, in the presence of maternal TRAb positive for the risk of serious cardiovascular complications. PMID- 19642500 TI - [Therapeutic proposal for ingestion of button battery in pediatric age: our cases and review of the literature]. PMID- 19642501 TI - [Potential of three-dimensional brain ultrasonography in newborn: description of 3 case reports]. AB - Three neonates with enlargement of the lateral ventricle were evaluated with sonography. Two out of 3 patients had hydrocephalus and 1 an ischemic stroke. 3D US improved accuracy in diagnosing and following up hydrocephalus, while the diagnosis of arterial ischemic stroke was immediate. 3D US has the potential to become a valuable additional imaging tool for the evaluation of the paediatric neonatal brain, enabling an earlier diagnosis. PMID- 19642502 TI - [Efficacy of meloxicam in juvenile polyposis syndrome. A case report]. AB - The Authors present a case of a 11 year-old patient with a history of Juvenile Polyposis Syndrome (JPS), a condition characterized by the occurrence of multiple hamartomatous polyps in the gastrointestinal tract. Patients with JPS are traditionally treated by repeated endoscopic polypectomies and elective surgery. Recent studies reported up-regulation of cyclo-ossigenase 2 (COX-2) in colorectal polyps. Specific COX-2 inhibitors have been withdrown from the market for tromboembolic side effects. However efficacy and safety of preferential selective COX-2 inhibitor has been reported as antiinflammatory drugs also in children. In this patient meloxicam treatment, a preferential selective COX-2 inhibitor, leaded to a significant reduction in the number of colorectal polyps during 3 years follow up. PMID- 19642503 TI - [Thyroid disease in pregnancy]. PMID- 19642504 TI - Concepts and developments in peripheral nerve surgery. AB - Nerve injuries may result in sensory and motor deficits when not treated appropriately. Especially the surgical management of nerve defects still represents a challenge for the surgeon. In these cases the grafting of autologous nerves represents the only reasonable approach. Due to the side effects associated with this method (sacrifice of donor nerves, neuroma formation in the harvesting area, limited availability of donor nerves, etc.), numerous alternatives were proposed in order to avoid the transplantation of autologous tissue. This review provides a general view on the state of the art of how to supply gaping injuries in the peripheral nerve. Furthermore new approaches emphasizing tubulization techniques for the reconstruction of lost nerve tissue are described with a special focus on various materials with their advantages and disadvantages. PMID- 19642505 TI - Neuropathological changes in the peripheral nervous system and spinal cord in a transgenic mouse model of Niemann-Pick disease type A. AB - OBJECTIVE: Type A Niemann-Pick is a severe neurological disease, caused by a mutation of the gene of acid sphingomyelinase (ASM) and reduced enzyme activity. Some studies reported neuropathological changes occurring in the central nervous system of ASM deficient transgenic (ASMKO) mice, while a detailed study on the peripheral nervous system (PNS) at different ages is currently lacking. The aim of our study was to examine the pathological changes occurring in the PNS and in the spinal cord in an AMSKO model of Niemann-Pick disease (NPD) Type A. MATERIAL AND METHOD: Dorsal root ganglia (DRG), peripheral nerves and spinal cord specimens were obtained from ASMKO mice and age-matched wild type animals (age range = 1-7 months). They were observed at the light and electron microscope. Behavioral testing was performed to assess motor coordination and reactivity. Fluoro-Jade B was used as a high affinity fluorescent marker for degenerating neurons. RESULTS: Typical NPD cytoplasmic inclusions were observed in DRG neurons and satellite cells, in peripheral nerve Schwann cells, in spinal cord neurons and in endothelial cells. All these inclusions were present from the age of 1 month and increased with aging. By Fluoro-Jade B staining we demonstrated the occurrence of neuronal degeneration starting from 5 months of age. CONCLUSION: Despite the fact that a definite diagnosis of NPD Type A depends on enzymatic assays and/or molecular analysis, morphological investigation remains an important diagnostic procedure. Well-defined and complete neuropathological information about the ASMKO mouse model, inclusive of PNS examination, may be crucial in the pre-clinical evaluation of new therapies. PMID- 19642506 TI - Dementia in a retired world boxing champion: case report and literature review. AB - OBJECTIVE: Dementia in retired boxers, also referred to as "dementia pugilistica" (DP), is usually attributed to repeated concussive and subconcussive blows to the head. We report the case of a former world boxing champion whose progressive cognitive decline could be ascribed to DP, cerebral infarcts and Wernicke Korsakoff syndrome. This case demonstrates that dementia in retired boxers may be caused and/or exacerbated by etiologic factors other than DP. MATERIALS AND METHODS: We correlated the clinical features with the histochemical and immunohistochemical changes observed on autopsy brain material from a retired boxer, reviewed the literature on boxing-related dementia, and compared our findings with previous reports on DP. RESULTS: Neuropathologic examination revealed numerous neurofibrillary tangles (NFTs), rare neuritic plaques (NPs), multiple cerebral infarcts, fenestrated septum pellucidum, atrophic and gliotic mamillary bodies, and pale substantia nigra and locus ceruleus. CONCLUSIONS: Our neuropathologic data confirmed the notion that dementia in retired boxers could be due to several factors such as DP, multiple cerebral infarcts and Wernicke Korsakoff syndrome. Our findings illustrate the need to comprehensively examine former boxers with dementia as well as carefully evaluate the neuropathologic changes that may cause or contribute to the patient's cognitive and behavioral symptoms. Such an approach is crucial in order to provide prompt and more definitive therapies. PMID- 19642507 TI - Meningioma of the cavernous sinus in a child: case report and review of the literature. AB - Meningiomas infrequently develop in children, and their clinical picture is somewhat different than in adults. We describe here a case of a meningioma in a 9 year-old girl unusual in two aspects. Firstly, it arose from the cavernous sinus what is exceptional in children. Secondly, despite the big tumor mass the child was almost asymptomatic. The only symptoms at presentation were a slight facial asymmetry and minimal laterodeviation of her mandible. Those symptoms had not been noticed by her parents and were detected during careful routine dental examination. The clinical course was quite aggressive and several neurosurgical interventions were necessary. This case underlines the importance of careful medical and dental examination during routine checkup consultations and undertaking necessary diagnostic procedures aimed at elucidating of all detected, even minimal abnormalities. PMID- 19642508 TI - Papillary glioneuronal tumor--prognostic value of the extension of surgical resection. AB - OBJECTIVE: Papillary glioneuronal tumors (PGNT) is well-recognized in the literature, although reports usually have not attempted a critical analysis of their characteristics. We report two PGNT and perform a comprehensive review of the published cases, aiming to clarify their clinical, imaging and histopathological features. MATERIAL AND METHODS: We have reviewed all glioneuronal tumors diagnosed in our laboratory over the last 10 years and found 2 cases PGNTs along with their clinical, imaging and surgical data. We have processed material for light microscopy, and for immunohistochemistry study, we have used antisera against glial fibrillary acidic protein, Olig-2C, neurofilament protein, synaptophysin and Ki-67. We searched Medline (1966 through October 2007) for original articles or previous reviews. RESULTS: Case 1, a 19 year-old girl with a left, partially cystic, occipital tumor, totally removed, with no signs of recurrence 32 months after surgery, Case 2, a 9-year-old girl with a right, cystic with a solid nodule, temporal tumor, totally removed, with no signs of recurrence 19 months after surgery. Histopathology and immunohistochemistry studies favored a diagnosis of PGNT. A survey of 38 reported PGNT cases together with our two disclosed the following typical profile: young adulthood predominance, temporal lobe location, presence of cystic components: a close association with the lateral ventricles, a few anaplastic tumors, and gross total resections were usually possible with no recurrences the extent of surgical removal being the main prognostic factor. CONCLUSIONS: Although histopathology is usually characteristic, imaging features may also be important in the presurgical evaluation of PGNTs. Gross total resections are usually possible and seem to govern prognosis. However, longer follow-up data are required. PMID- 19642509 TI - Papillary tumor of the pineal region--a recently described entity: a report of three cases and review of the literature. AB - BACKGROUND: The papillary tumor of the pineal region (PTPR) is a distinct clinicopathologic entity, the exact biological behavior of which is not known. FINDING: In the present report we describe 3 additional cases of PTPR because of its rarity. During a study period of 4 years (between January 2003 and December 2006), we diagnosed three cases of papillary tumor of the pineal region (PTPR). Clinico-radio-pathologic examination was done and follow-up was assessed. Microscopically, all 3 cases showed uniform morphology and consisted of papillary and solid areas. Immunohistochemistry showed strong and diffuse positivity for synaptophysin, NSE, chromogranin A, S-100 protein, MAP-2 and cytokeratin. CONCLUSION: PTPR is a distinct entity and needs to be differentiated from other tumors of the pineal region as the biological behavior of this tumor is not fully understood. Radiologically this tumor can sometimes be misdiagnosed as tectal glioma. PMID- 19642510 TI - Rapidly recurring folliculostellate cell tumor of the adenohypophysis with the morphology of a spindle cell oncocytoma: case report with electron microscopic studies. AB - We report a rapidly recurring folliculostellate cell tumor of the adenohypophysis in a 63-year-old woman. Morphologically the tumor had the typical appearance of a spindle cell oncocytoma of the adenohypophysis. It recurred within 5 months of selective transsphenoidal resection, requiring a second transsphenoidal operation followed by radiation therapy. The spindle cell oncocytoma (SCO) of the adenohypophysis is a relatively recently described entity and a new addition to the fourth edition of the WHO Classification of Tumors of the Central Nervous System. In our case, the ultrastructural features were significantly different from those so far described in SCO, in that tumor cells formed a network of structures indistinguishable from pituitary follicles. In addition, a minority of tumor cells exhibited endocrine differentiation. PMID- 19642511 TI - Evidence for a progenitor cell population in the human pituitary. AB - The ability to isolate and propagate adult stem/progenitor cells from the human brain opens novel avenues for cell replacement therapy. This will also apply to the pituitary gland, i.e., following tumor induced endocrine deficiency. Herein, we examine autopsy derived pituitaries to unravel a putative stem/progenitor cell population in humans. In tissue sections of the anterior lobe nestin immunoreactive cells co-expressing smooth muscle actin (SMA) were identified in the perivascular space, indicating a pericytic differentiation. Under clonal conditions, this particular cell population generated primary and secondary cell aggregates (spheres). Pituitary cell cultures maintained a stable cell cycle length with a doubling time of 10 days for over eight months. Forskolin treatment induced a prolactin-expressing phenotype in the majority of cell progenies as well as few betaIII-tubulin (Tuj1) expressing cells of putative neuronal lineage. The presence of sphere-forming, nestin-immunoreactive cells and their ability to generate differentiated cell lineages indicates the existence of a progenitor cell population persisting in the adult human pituitary. Further studies are needed to characterize this cell population in more detail and to clarify their potential to initiate neoplastic transformation for example in the cellular pathogenesis of pituitary adenoma. PMID- 19642512 TI - Anthropometric reference data for children and adults: United States, 1988-1994. AB - OBJECTIVE: This report presents national anthropometric reference data for the U.S. population aged 3 months and older in 1988-1994. METHODS: Data in this report are from the Third National Health and Nutrition Examination Survey (NHANES III), which was conducted on a complex, stratified, multistage probability sample of the civilian, noninstitutionalized U.S. population. A total of 31,241 persons were examined. The anthropometric measurements taken included weight, height, recumbent length, circumferences, limb lengths, joint breadths, and skinfold thicknesses. Body mass index values were computed from measured height and weight values. RESULTS: The tables in this report include weighted population means, standard errors of the means, and selected percentiles of body measurement values. Because measurements varied by sex and age (and by race and ethnicity in adults), results are reported by these subgroups. CONCLUSIONS: These data add to the knowledge about trends in child growth and development and are useful in monitoring overweight and obesity in the U.S. population. PMID- 19642513 TI - [Proteomics and biomarkers for detection of ovarian cancer]. AB - OBJECTIVE: The purpose of this study was to focuse on recent developments on the evolving field of biomarker discovery and validation techniques using proteomics platforms for ovarian cancer. DESIGN: Review. SETTING: Department of Obstetrics and Gynecology Medical Faculty Charles University Hradec Kralove. Institute of Molecular Pathology. Faculty of Military Health Sciences, University of Defense, Hradec Kralove. METHODS: The last decade has seen major changes in the technologies used to identify markers for diagnosing early stages of ovarian cancer. Currently the major developments were made in three distinct areas: protein profilig, highthroughput validation techniques and solid and liquid phase protein microarray platforms for analyzing candidate markers across stages hold significant of ovarian cancer. These new technologies hold significant promise in identifying more robust markers for ovarian cancer. CONCLUSION: The present review summarizes the results of clinical and experimental research on biomarkers of ovarian cancer. PMID- 19642514 TI - [Paraneoplastic syndromes in oncogynecology]. AB - OBJECTIVE: Informations about paraneoplastic syndromes occurring in gynecological malignancies. DESIGN: Literature review with case reports. SETTING: Department of Gynaecology and Obstetrics, Faculty of Medicine, Masaryk's University and Faculty Hospital, Brno. METHODS: Literature review about paraneoplastic syndromes in gynecological malignancies with illustrative case reports. CONCLUSION: As paraneoplastic syndromes known symptoms that accompany cancer, but not linked directly with the progression of primary bearings or creation distant metastases. These symptoms require attention especially because in some cases may be manifestations of primary tumor, which has not yet been diagnosed. The paraneoplastic syndromes that have occurred in the malignancy, which are of interest to oncogynecologists include fever tumor origin, anorexia and weight loss, paraneoplastic syndromes endocrine, neurological, musculosceletal, haematological and skin. As part of the diagnosis is necessary interdisciplinary cooperation involving the participation of not only oncogynecologist, but also dermatologist, neurologist, rheumatologist, hematologist and other specialists according to the current state and the dominant issue patiens. PMID- 19642515 TI - [New diagnostic approach to different hydatidiform mole types, hydropic abortions and relevant clinical management]. AB - OBJECTIVE: To describe new diagnostic approach to complete hydatidiform mole, immature complete hydatidiform mole, partial hydatidiform mole, proliferative mole and hydropic abortion. TYPE OF STUDY: Original research. SETTING: Trophoblastic Disease Center in the Czech Republic (TDC-CZ), Institute for the Care of Mother and Child, Prague. METHODS: Our study consists of 1321 partial hydatidiform moles, 805 complete hydatidiform moles, 524 proliferative moles, and over 2500 hydropic abortuses diagnosed and treated at theTDC-CZ, besides which 2896 of these lesions were examined at the TDC-CZ by referral. The material was examined by routine histopathological methods, which in selected cases was supplemented by immunohistological examination and correlated with cytogenetic and molecular genetic results and clinical features. RESULTS: The study describes the diagnostic procedures enabling the differential diagnosis between mature complete hydatidiform mole, immature complete hydatidiform mole, partial hydatidiform mole, proliferative mole and hydropic abortion. Fourteen histological parameters have been defined which are most common, individually or in combination, in various types of hydatidiform moles and hydropic abortions. Warning is given to errors in histological diagnosis correlated with cytogenetic and molecular genetic results. Proposed reliable method of eliminating the influence of these errors on the possible development of trophoblastic disease. CONCLUSION: The study describes differential diagnosis of complete hydatidiform mole, immature complete hydatidiform mole, partial hydatidiform mole, proliferative mole, hydropic abortion and relevant clinical management. PMID- 19642516 TI - [Current options of prenatal diagnosis in congential diaphragmatic hernia]. AB - OBJECTIVE: The aim of this article is to review the current options of prenatal diagnosis in congential diaphragmatic hernia (CDH). SUBJECT: Systematic review. SETTING: Institute for the Care of Mother and Child, 3rd Medical Faculty, Prague. SUBJECT AND METHOD: Review of recent published data. CONCLUSION: The basic method for prenatal diagnosis of congenital diaphragmatic hernia is 2D ultrasonography: measurement of lung-to-head ratio (LHR), observed to expected lung to head ratio (observed to expected LHR - O/E LHR), localization of diaphragmatic defect, assessment of liver position and presence of associated anomalies (negative prognostic factors). Prenatal diagnosis can be supplied with 3D ultrasonography and magnetic resonace (imaging methods for valid measurement of fetal lung volume and/or presence of associated congenital defects confirmation). The reactivity of intrapulmonary arteries are evaluated by hyperoxygenation test and measurement of arterial Doppler parameters. Isolated diaphragmatic hernia is not an indication for invasive prenatal diagnostic methods. Important part of succesful prenatal diagnosis and therapy of CDH is concentration of cases in specialized centre. PMID- 19642517 TI - [IgG antibodies against laminin-1 in serum and in peritoneal fluid in patients with decreased fertility]. AB - OBJECTIVE: To study of IgG antibodies against laminin-1 (IgG-a-Ln-1) in patients with decreased fertility, especially with endometriosis and with diagnosis of polycystic ovaries. DESIGN: Prospective study. SETTING: Special Consultation for Immunology of Reproduction and Research Laboratories for Reproductive Immunology, Department of Gynaecology and Obstetrics, Medical School of Charles University and Faculty Hospital, Pilsen. METHODS: Commercial ELISA kits for detection of IgG antibodies against laminin-1 in serum (S) and peritoneal fluid (PF) in 120 patients after diagnostic laparoscopy, and in serum in 277 patients after 2-3 in vitro fertilizations and with diagnosed endometriosis. RESULTS: Only 16 positive results in IgG-a-Ln-1 antibodies (more than 15 IU/ml) were detected in sera and peritoneal fluids in the group of 120 women after laparoscopy. We have not detected any serum IgG-a-Ln-1 positivity in the group of 277 patients after 2-3 unsuccesfull IVF and with anamnestical date about endometriosis together. CONCLUSION: Increased levels of IgG-a-Ln are in particular found in endometriosis II-III and in diagnosis of polycystic ovaries, in female diseases also related to autoimmune process. PMID- 19642518 TI - [Disorders of sex differentiation: genes responsible for development of genital system and final phenotype]. AB - OBJECTIVE: The study summarizes data on genes responsible for development of gonads and subsequently of additional structures of genital system in humans. It comprises the effect of gene defects on clinical phenotype. SUBJECT: Review article. SETTING: Department of Pediatrics, University Hospital Motol and 2nd Faculty of Medicine, Charles University in Prague. SUBJECT AND METHOD: We present the overview of genes that contribute to development of genital system. Special emphasis is given on patient's phenotype related with various genetic disorders. Data were mainly found on Pubmed or OMIM web-sites according to key words "sex development" and "sex determination". We focused on ten genes with known relation to gonadal development--SRY, SOX9, SF1, DAX1, WNT4, WT1, DMRT1, DHH, RSPO1, ATRX. CONCLUSION: Sex development is a complex process orchestrated by numerous genes. Here we collect information on gene defect (gene mutations or defective number of gene copies) that cause gonadal maldevelopment with effects on final phenotype. Currently, genetic background of numerous disorders can be detected. That allows not only to verify the diagnosis but also to predict the future sexual development and genetic risk for other family members. PMID- 19642519 TI - [Common variable immunodeficiency in pregnancy (set of case reports)]. AB - Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency, which is characterized by impaired antibody responses. It's manifestation includes mainly severe and recurrent bacterial infections affecting predominantly upper and lower respiratory tract. Because of the improved standard of hypogammaglobulinemic patients many affected females become pregnant. When a woman treated for CVID gets pregnant the adequate treatment is necessary not only to protect patient from infections, but also to allow suffitient transfer of IgG through the placenta to supply the fetus and consequently the newborn. Regular periodic replacement therapy with intravenous immunoglobulins (IVIG) is applied in pregnant women as well as in other hypogammaglobulinemic patients. Regimen of IVIG administration must be modified in order to reach satisfactory IgG levels in the newborns' blood. Here we present a set of case reports of five pregnant women with CVID treated by immunoglobulins during pregnancy. In all cases labor was induced in term after the last IVIG infusion. The mode of delivery depended on the obstetric indication. All pregnancies resulted in healthy newborns. PMID- 19642520 TI - [Isolation and immunology identification of spermagglutinating antibodies from human serum]. AB - OBJECTIVE: Isolation of spermagglutinating antibodies and their assesment. DESIGN: Retrospective study. SETTING: Special consulting for reptoduction immunology, Department of Obstetrics and Gynecology, Charles University and Faculty Hospital, Plzen. METHODS: Fractionation of serum samples by liquid exclusion chromatography, examination of full sera and their chromatographic fractions by Friberg teste (Tray Agglutination Test--TAT), indirect antiimmunoglobulin reaction test (i-MAR test) and by supplementar radial immunodiffusiona (RID). RESULTS: Isolation of spermagglutinating fractions of antisperm antibodies positive sera preserved spermagglutinating aktivity and confirmed great spermagglutinating potential of IgM. CONCLUSION: According to assesment of the presence of IgG and IgG we reported possible states of immunisation: actual immunisation with IgM activity, perpetual stimulation (IgG and IgM) and, finaly, anamnestic titres in IgG. These findings can help us to choose an optimal way of treatment. Excluding gel chromatography is suitable method for serum proteins fractionation, but not their identification--presence of antisperm antibodies does not affect the chromatographic spectrum, nor the RID patterns. PMID- 19642521 TI - [Contraceptive methods used by women in the period before and after giving birth]. AB - GOAL OF THE STUDY: To provide information on the knowledge and practices involving the use of the contraceptive methods employed by women of a fertile age, especially in the period of lactation. DESIGN: A cross-section, descriptive study. SETTING: Institute for the Care of Mother and Child, Prague; Department of Gynaecology and Obstetrics at the Institute of Postgraduate Education in Healthcare, Prague; Cegedim Strategic Data CZ s.r.o., Prague. METHODOLOGY: The method involved a written questionnaire in a structured form. The investigation was undertaken in two phases; the first round took place directly after giving birth, while the second took place 6 months after giving birth. The group consisted of 4535 women who gave birth at the Institute for the Care of Mother and Child in the period between 15. 11. 2006 - 15. 11. 2007. RESULTS: 2540 women (56.0%) answered the questions in the first round; 85% of them were in the 26-35 age group, 44.3% were secondary school graduates and 36.7% were university graduates. 61.3% were first-time mothers, 32.3% were second-time mothers and 5.4% were third-time mothers. Contraception used before current gravidity: (n=2540) oral hormonal contraception 59.7%, a condom 11.1%, intrauterine contraception 1.0% and 20.6% of the women used no contraceptive method. The users of oral hormonal contraception (n=1517) were most frequently prescribed (12.8% of the women) a preparation containing 20 microg ethinylestradiol and 150 eLg desogestrel (Mercilon). The contraception used during the course of lactation after a birth in the group of mothers of more than one child (n=982): oral hormonal contraception 19.6%, a condom 17.1%, intrauterine contraception 1.3%, no contraceptive method 54.5%. Breastfeeding users of oral hormonal contraception (n=192) were most frequently prescribed (20.3% of women) a preparation containing 500 microg lynestrenol (Exluton) and a preparation containing 75 microg desogestrel (Cerazette) (16.1% of women). The contraceptive methods planned by women after birth (n=2540): oral hormonal contraceptive 36.5%, a condom 18.8%, intrauterine contraception 18.8%, no method 20.1%. 1440 women (56.7%) answered the questions in the second round; 83.5% of them were in the 26-35 age group, 45.0% were secondary school graduates and 37.0% were university graduates. 64.4% were first-time mothers, 30.6% were second time mothers and 4.2% were third-time mothers. 74.6% of women were still breastfeeding 6 months after giving birth. Contraception used by breastfeeding women (n=1074): oral hormone contraception 27.6%, a condom 21.8%, an intrauterine system with levonorgestrel 2.8%, intrauterine contraception 2.4%, no method 39.5%. Contraception used by non breastfeeding women (n=366): oral hormonal contraception 42.1%, a condom 15.0%, an intrauterine system with levonorgestrel 2.7%, intrauterine contraception 2.7%, no method 31.4%. In both groups of women, the users of oral hormonal contraception were most frequently prescribed a preparation containing 75 pg desogestrel (Cerazette); this accounted for 99.3% of the breastfeeding women and 18.8% of those not breastfeeding. 40.0% of breastfeeding and 48.4% of non breastfeeding women are planning to use hormonal contraception in the coming period. The self-evaluation of the knowledge of contraception methods (n=2540): 61.6% of women evaluated their knowledge as good, but 77.6% of women did not know a suitable hormonal contraceptive for the period of lactation. According to 80.7% of the women, their main source of expert information in the area of family planning is their gynaecologist. CONCLUSION: The prevalence of breastfeeding women 6 months after giving birth is high in the monitored group. Oral hormonal contraceptives are the most frequently used contraceptive method in general, including during the lactation period when women prefer a preparation containing 75 microg desogestrel regardless of whether or not they are breastfeeding. The women's knowledge of suitable methods of contraception during the period of lactation is unsatisfactory and represents a challenge for healthcare providers to improve the amount of information available to women in this area PMID- 19642522 TI - [Corelation between hyperviscosity of the ejaculate and physical-morphological and biochemical parameters]. AB - OBJECTIVE: The aim of our study was to investigate the corelation between hyperviscosity and physical-morphological and biochemical parameters of the ejaculate and potential influence of local infections on spermatic plasma viscosity and observed parameters. DESIGN: Retrospective analysis. SETTING: Associated Tissue Bank of P. J. Safarik University of Faculty of Medicine and L. Pasteur Faculty Hospital, Kosice, Slovak Republic. METHODS: The study was based on semen samples showing increased viscosity obtained from 100 consecutive men undergoing fertility assessment (median 35 years, range 27-49 years) in Associated Tissue Bank between years 1996 and 2006. The ejaculates were obtained by masturbation after 2-7 days of sexual abstinence (median 5 days). RESULTS: Increased viscosity correlated with lower motility and increased pathology (95% and 91%, respectively). Within the diagnosis of asthenozoospermia there was a correlation between PMN (polymorphonuclear granulocytes) (95%), higher seminal fluid pH (94%), decreased sperm vitality (100%), decreased total seminal plasma fructose (100%) and positive microbiology (95%). There was significant positive correlation between high visco-elasticity and positive microbiology (85%), although a leukocytospermia (>1 x 106/mL) was present just in 10% of the semen samples. CONCLUSION: Hyper-visco-elasticity is simple but important parameter of men fertility assessment and is associated with the diagnosis of asthenoteratozoospermia. It is suggested from our patient data that decrease of the leukocytospermia cutoff criteria could detect a chronic and/or latent infection of the urogenital tract. Furthermore, combination of the diagnoses of viscopathy and asthenoteratozoospermia seems as potential marker and indication, respectively, for microbiology examination. PMID- 19642523 TI - [Comparison of prenatal ultrasound examination, post-mortem magnetic resonance imaging and autopsy (a case report--schizencephaly)]. AB - OBJECTIVE: To improve prenatal diagnostic with a feedback of autopsy, complemented by post mortem magnetic resonance imaging (MRI). MRI is important for malformations of CNS, where autopsy can be insufficient. SUBJECT: Case report. SETTING: MR unit of the Department of radiology, Department of obstetrics and gynaecology and Department of pathology, 1st medical school, Charles University in Prague, General Teaching Hospital. SUBJECT AND METHOD: To compare prenatal ultrasound, post mortem MRI and autopsy. CONCLUSION: Case report documented complementarity of all three method; full agreement in brain malformation type was found. PMID- 19642524 TI - [Unwanted children]. AB - OBJECTIVE: Aim of the study is review of knowledges about psychosocial aspects of unwanted pregnancy for child. DESIGN: Literary review. SETTING: Department of psychology, Faculty of psychology, Charles University Prague. SUBJECT AND METHODS: In our review article we give results of studies which evaluate physical, psychological and social aspects of beeing unwanted baby. Especially we show unique results of Prague study. CONCLUSION: The majority of studies confirm that unwanted children are significantly discriminated against wanted children. Unwanted children have more diseases, worse school result with identical inteligence quotient, higher frequency of nervous and psychosomatic disables and worse social adaptibility. Results of studies confirm order to find for every women safe and effective method for familly planning. PMID- 19642525 TI - [Uterine torsion--the rare compliation of pregnancy]. AB - OBJECTIVE: To give attention to the rare compliation of pregnancy. DESIGN: Case strory. SETTING: Dept. of Obstetrics and Gynecology, 1st Faculty of Medicine, Charles University and General Faculty Hospital Prague. SUBJECT AND METHOD: We ilustrate risks and resolvings of the uterine torsion during labor on own unrecognized case. It induced the caesarean section delivery. We review possible diagnostic signs and management of this rare complication from literature. CONCLUSION: Uterine torsion is the rare complication of pregnancy. Uterine torsion could be cause of dystokia. The solution is based on caesarean section. PMID- 19642526 TI - [Rectal duplication cyst--case report]. AB - OBJECTIVE: The authors demonstrate a rare case of duplication anomaly of the rectum. DESIGN: Case report. SETTING: Institute for the Care of Mother and Child, Prague. SUBJECT AND METHOD: We present a rare case of cystic rectal duplication in adult, completely removed and histologically confirmed. A literature review was summarized. CONCLUSION: The case was complicated by delay in diagnosis, multiple operations, and by the association with endometriosis, as well. Mentioned anomaly is published in the Czech literature for the very first time. PMID- 19642527 TI - [Knowledge of Czech and Romanian women about STIs. Representative survey]. AB - OBJECTIVE: Survey of knowledge of Czech and Romanian women about STIs and their perception of sources of the information. DESIGN: Representative survey. METHODS: Anonymous questionnare survey of the sample of 1011 Czech and 1001 Romanian women aged 15 to 50. RESULTS: The doctor or the psychologist is considered to be the most reliable source of information about STIs, the Czech women prefer information from books and papers, Romanian women consider the close persons to be more better source of information than Czech women. The Czech women know better the realy effective methods of STI prevention and situations which are risky from the possible HIV/AIDS infection, Romanian ones more often believe in non effective methods of prevention and more often are afraid of situations, which are not dangerous and more often were not able to answer the questions at all. CONCLUSION: Romanian women have worse konwledge in the area of STIs than Czech ones. They are also more credulous to information from different sources, especially to those provided by experts or by close persons. PMID- 19642528 TI - [ISKRA guidelines on antimicrobial treatment and prophylaxis of urinary tract infections--Croatian national guidelines]. AB - These guidelines refer to diagnosis, antimicrobial treatment and prophylaxis of urinary tract infections in adults and children older than 12 years of age and cover lower urinary tract in females, uncomplicated pyelonephritis, complicated UTI with or without pyelonephritis, asymptomatic bacteriuria and recurrent UTI. These guidelines do not cover sexually transmitted diseases. The guidelines are primarily intended for use by general practitioners and specialists working in primary health care and hospitals. The members of the Working Group for the development of guidelines on antimicrobial treatment and prophylaxis of urinary tract infections were appointed by the Croatian Ministry of Health and Social Welfare. The project was financially supported by the Dutch government and professional assistance was provided by international consultants. The evidence for this guidelines is based on a systematic review of the literature, local antibiotic resistance data, the existing clinical protocols on the treatment and prophylaxis of UTIs, as well as suggestions and comments made by colleagues physicians during more than 50 continuous medical education courses held in the last three years on antimicrobial treatment and prophylaxis of UTIs. Draft version of the guidelines was available for comments on the web site http://iskra.bfm.hr and during the two-month piloting period the guidelines were widely presented to general practitioners, specialists working in primary care and hospitals--urologists, gynecologists, infectious disease specialists, nephrologists. The final version of the guidelines was approved by the Intersectoral Coordination Mechanism for the Control of Antimicrobial Resistance (ISKRA) Board. PMID- 19642529 TI - [The influence of fibrinolytic and heparin therapy in acute myocardial infarction upon gastrointestinal bleeding in patients with asymptomatic ulcerous disease]. AB - AIM: To determine in patients with asymptomatic ulcerous disease frequency of hemathemesis and melena (H/M) as complications of fibrinolytic and heparin therapy in acute ST-elevation myocardial infarction (STEMI). METHODS: According to heparin and streptokinase therapy, STEMI patients were divided into two groups. Each group consisted of case study subgroup with patients who had asymptomatic ulcerous disease and a control study subgroup with patients who did not have ulcerous disease. RESULTS: In heparin therapy there was no significant increase of H/M in patients with and without ulcerous disease (3.4% vs 2.8%, n.s.) as well as in fibrinolytic therapy (5.9% vs 6.8%, n.s.). Fibrinolytic therapy causes more H/M in relation to heparin therapy in patients with ulcerous disease (5.9 vs 3.4%; chi2=6.389; p=0.011) as well as in patients without ulcerous disease (6.8 vs 2.8%; chi2=616; p=0.013). In patients with H/M there were insignificantly more women than men (42.4% vs 57.6%, n.s.). CONCLUSION: Patients with asymptomatic ulcerous disease can be exposed to fibrinolytic and heparin therapy when treating STEMI without a significant risk to H/M occurrence in relation to patients without ulcerous disease. PMID- 19642530 TI - [Neuroradiologic diagnostics in patients hospitalized in Vrapce Psychiatric Hospital]. AB - The authors discuss the frequency of indication for and the results of CT and MRI brain scans in patients hospitalized in Vrapce Psychiatric Hospital. They wanted to contribute to the solving of the dilemma whether neuroradiologic tests should be a part of a routine diagnostic procedure in all psychiatric patients. Retrospectively, on the basis of case histories, the patients were analyzed in the first nine months of 2006. In this period 90 CT brain scans and two MRI brain scans were done, most often in the patients who were treated under the diagnoses of endogeneous psychoses, psychoorganic syndrome (dementia), affective disorders and epilepsy. Most CT findings (59%) and both MRI findings were normal. Abnormal findings were most often described as various forms of brain atrophy. Only one brain tumor was found. Electroencephalographic findings quite more often differed significantly from normal in the patients with abnormal CT findings compared with the patients with normal CT findings. The conclusion is that very small number of positive findings, except the brain atrophy, does not give good reason for routine CT and MRI brain scan in all hospitalized psychiatric patients. Indication must be made selectively on the basis of clinical psychiatric neurologic evaluation. EEG, with limitations, can be of help in this matter. PMID- 19642531 TI - [Necrotizing fasciitis of the upper leg--case report and review of the literature]. AB - Necrotizing fasciitis is an uncommon but serious infection of skin, subcutaneous fat and fascia, characterised by rapidly spreading inflammation and associated with considerable morbidity and mortality. A 42-year-old man, with necrotizing fasciitis of the right upper leg, was hospitalized and treated by surgical debridement, along with intravenous administration of antibiotics, fluid resuscitation, correction of acidosis and electrolyte abnormalities. Four debridements were performed over four days. The patient developed septic shock with early stage of multiple organ failure, requiring one week in intensive care unit (ICU). Split-thickness skin grafts were placed on the fourth day after admission to the hospital. The patient was released to home care on the 21st day after admission, fully recovered. Necrotizing fasciitis is a life threatening infectious entity that requires rapid diagnosis, urgent extensive surgical debridement and tissue coverage as soon as possible to prevent secondary infections. ICU measures including intravenous antibiotics are often necessary, along with surgical treatment. PMID- 19642532 TI - [Duplication of the pituitary gland]. AB - Duplication of the pituitary gland is a rare malformation. To the best of our knowledge, only 40 cases throughout the world have been reported previously. Due to associated severe developmental anomalies lots of these cases were diagnosed at autopsy. Only 7 patients survived beyond puberty, however, it is important to stress that none of them had major brain anomalies. We present the case of a girl with duplication of the pituitary gland (DPG), central precocious puberty and associated midline defects. Among fenestration of basilar artery, previously described in the literature, we also found, for the first time, a duplication of the M1-segment of the left median cerebral artery. Our patient is one of the 4 DPG patients with associated precocious puberty treated with gonadotropine releasing hormone agonists (GnRH), but the only one in whom this treatment was finished successfully. PMID- 19642533 TI - [The role of taxanes in breast cancer chemotherapy: what's new 15 years after?]. AB - Taxanes were established as leading drugs in chemotherapy of breast cancer. In the first line chemotherapy of advanced disease taxanes were combined with other cytostatics. Taxane-based combinations in comparison with taxanes in sequential use were observed. There was insufficient evidence to discriminate in favour of taxane-based combinations. In randomized studies several oftaxane-based combinations were tested: taxanes with anthracyclines, capecitabine and gemcitabine. There is no evidence data to prefer any taxane combination to another. Taxanes became fundamental in the adjuvant setting of node positive breast cancer patients. The results of recent meta-analysis were not influenced by the number of axillary metastases or by estrogen receptor expression. At this time there is no data to support the superiority of any particular taxane. Paclitaxel is treatment schedule dependent, because its weekly administration setting may result in better treatment outcome. Docetaxel may be more effective if given every 3 weeks rather than weekly. Targeted therapy in combination with taxanes improves survival rate in adjuvant setting as in advanced disease. PMID- 19642534 TI - [Diabetic nephropathy and primary glomarular diseases]. AB - The primary glomerular disease in patients with diabetes mellitus is rare. Several reports have shown that primary glomerular diseases can be superimposed on diabetic nephropathy. The recognition of nondiabetic glomerular diseases in diabetic patients is of utmost importance since they might be successfully treated. This would positively affect the otherwise poor prognosis of renal disease in diabetic patients. The suspicion on nondiabetic renal disease is raised by the appearance of urinary abnormalities such as hematuria, massive nephrotic proteinuria or deterioration in renal function in patients with diabetes mellitus but without coexisting diabetic retinopathy. We report on diabetic patients who underwent renal biopsy because of the massive nephrotic proteinuria and non-nephrotic proteinuria without diabetic retinopathy, hematuria, and because of the deterioration of renal function. On pathohistological examination different types of primary glomerular diseases were found. The diagnosis and the treatement of glomerular diseases improved the renal prognosis in some of these patients. PMID- 19642535 TI - [Salt--hidden poison in everyday meal]. AB - A large number of epidemiologic, evolutionary and clinical studies have confirmed that table salt is a significant factor in determining the blood pressure (BP) level, and thereby in the prevalence of arterial hypertension (AH). It has been observed in epidemiologic studies that BP increases with age only if accompanied by excessive table salt intake. In addition to affecting BP, increased salt intake independently contributes to target organ damage. Correlation has also been observed between coronary artery disease, left ventricular hypertrophy, cerebrovascular insult, microalbuminuria. Table salt, i.e. NaCl, is directly involved in the process of atherothrombogenesis by changing the relation between vasoactive factors in the blood vessel wall, by affecting the expression of receptor for angiotensin II and, which is particularly important, by elevating platelet aggregability. From clinical and public health aspects, the data obtained in interventional studies are particularly important, as well as those that apparently confirm the benefit of restricting NaCl intake. This benefit is manifested not only in decreased BP and reduction in cardiovascular morbidity and mortality, but also in improved total health as it is known that excessive table salt intake is also a risk factor for osteoporosis, nephrolithiasis, gastric and nasopharyngeal carcinoma, etc. Although there were some studies that raised doubt about the fact that reduced table salt intake could be harmful due to activation of counter-regulative mechanisms, a substantially higher number of authors demonstrated that moderate intake reduction was not associated with the increased risk but rather the contrary. Table salt intake restriction should be performed as part of other lifestyle changes, primarily weight loss and increased physical activity. During NaCl intake reduction, it is necessary to pay attention to other electrolytes and microelements that are also important stones in the mosaic of healthy living. Gooverment authorities and food manufacturers bear heavy responsibility as ready or half-cooked food accounts for over 70% of NaCl intake into the body. PMID- 19642536 TI - [First female physicians in Bjelovar: obstetrician and surgeons]. AB - An obstetrician and two surgeons were the first three female physicians in Bjelovar. Francisca Szumerthinn (Ringelhorn), was the first obstetrician and physician in Bjelovar, according to records on the 1803-1814 period. She was a MS in Obstetrics and Durdevac Regiment doctor (Artis Obstetritiae Magistra et Reg. Szentvariensis Medicinae Doctoria). After more than a century, Regina Atijas, MD, was employed at Bjelovar Hospital, at first at the Department of Surgery and Gynecology, where she worked from 1930 until 1935. The third woman physician was Ljubica Bosner, MD, a surgeon, working at the Department of Surgery and Gynecology during the 1935-1942 period. PMID- 19642537 TI - [Table salt and hypertension--silent killers. Inform yourself and live longer. World day of hypertension 2009 in Croatia]. PMID- 19642538 TI - [Obesity and osteoarthritis of the knee]. PMID- 19642539 TI - [Stent or a Croatian term: is there any place for doubt?]. PMID- 19642540 TI - [Less salt--more health]. PMID- 19642541 TI - [Cholesterol in oncology--what is its significance?]. PMID- 19642542 TI - [Chromosomal translocation t(8,21) in acute myeloid leukemia of children: prognostic value of additional karyotype abnormalities]. AB - Prognostic significance of additional karyotype abnormalities was studied in 73 children with t(8,21) acute myeloid leukemia (AML). Additional chromosomal aberrations were documented in 61 cases (83.6%). The loss of sex chromosomes and/or deletion of the long arm of chromosome 9 (9q-) were predominant abnormalities, in agreement with the literature data. Other additional abnormalities detected in 14 cases were tentatively designated as "atypical". Comparison of pretreatment cytogenetic data and those obtained during relapses revealed the previously unknown rise in the frequency of atypical abnormalities in AML relapses (to 63.6% vs 19.2% at the first presentation, p < 0.005). It is supposed that atypical additional abnormalities reflect relatively late stages of leukemia, and their presence before therapy predicts poor prognosis. In fact, general, relapse-free, and uneventful survival rates in patients with atypical abnormalities were significantly lower that in the remaining patients with t(8;21) AML. Poor survival was associated not only with early relapses but also with high mortality from fatal infections soon after onset of treatment. The incidence of fatal infections in this group was significantly higher than in patients without atypical abnormalities (p = 0.027). Atypical additional abnormalities are rather variable and each variant should to be specifically characterized to estimate its prognostic significance. Our results need to be verified in a larger-scale multicentre study. PMID- 19642543 TI - [Assessment of carcinogenic activity of industrial toxicants in occupational epidemiological surveys]. AB - Evaluation of cancer morbidity and mortality from workplace exposure to industrial toxicants is a main avenue of research aimed to identify causes of human cancer. Many chemicals classified as carcinogens by International Agency for Cancer Research were first identified at workplaces. However, the value of these findings for the study of carcinogens in the occupational environment was compromised for a variety of reasons. A major methodological problem is to elucidate the cause-and effect relationship between inhomogeneous exposure to industrial pollution and cancer morbidity/mortality rates in different categories of workers. Another important problem in occupational epidemiology is the deficiency of data on the exposure level in women because reproductive organs are specific targets of certain chemicals and their carcinogenic effects are especially well apparent as gynecological diseases. Moreover gender-specific differences account for different risks and outcomes of apparently similar environmental exposure. PMID- 19642544 TI - [Peculiarities of adaptive hemodynamic processes during high-frequency jet lung ventilation]. AB - This study concerns poorly known features of adaptive hemodynamic reactions of the heart pump function during traditional and high-frequency jet lung ventilation. Spectral analysis of slow-wave oscillations of stroke volume and left ventricular diastolic filling wave in 36 patients with craniocerebral injury and acute cerebral insufficiency showed that beneficial adaptive reactions were realized through a rise in the general spectrum power and entropy. High-frequency jet lung ventilation ensured better effect on the adaptive processes than the traditional technique. PMID- 19642545 TI - [Efficiency of combined endoscopic hemostasis in patients with peptic ulcer complicated by hemorrhage]. AB - Results of endoscopic application of collagenous preparation thrombocol to the ulcer are presented. It is maintained that combined treatment of patients with peptic ulcer complicated by hemorrhage including endoscopic hemostasis (EH) and eradication therapy improves its outcome. Specifically, combined EH (adrenalin injection and subsequent application of thrombocol to the ulcer) reduces the frequency of recurrent hemorrhage and the need in urgent surgical intervention in patients with active hemorrhage (F Ia, Ib). Preventive EH with thrombocol in patients with active hemorrhage and high probability of its relapse (F IIa, IIb) reduces the frequency of recurrent hemorrhage and the necessity of emergency surgical treatment. In patients with active hemorrhage (F IIa, IIb, IIc) thrombocol promotes healing of the ulcer and decreases duration of hospitalization. PMID- 19642546 TI - [Diagnostic significance of podography in patients with gonarthrosis]. AB - Results of podography in 48 women aged 24-62 (46.6 +/- 2) years with bilateral gonarthrosis of metabolic/dystrophic etiology (grade I, II, III by N.S. Kosinskaya's osteoarthrosis classification) were analysed using a DIASLED-SCAN computed system (Sankt-Peterburg). Qualitative and quantitative changes detected by podography proved to be typical of different stages of female knee osteoarthrosis. A summary table illustrating dynamics of quantitative podogram characteristics as a function of severity of the disease is presented. PMID- 19642547 TI - [Possible role of sarcoplasmatic reticulum in anti-arrhythmic effects of the class III agent amiodarone]. AB - The study was designed to evaluate changes in functional activity of cardiomyocyte sarcoplasmic reticulum under effect of amiodarone (1 mM). It was shown that post-rest potentiation significantly increased after perfusion of cardiomyocytes with amiodarone or calcium (3 mM). The stimulatory action of amiodarone was more pronounced than that of calcium. Treatment with amiodarone solution containing high concentration of calcium had a lower potentiating effect compared with that of perfusion with either of them. Moreover, amiodarone in combination with calcium significantly extended the period of relaxation without affecting the contraction rate. It is concluded that amiodarone improves activity of sarcoplasmic reticulum. PMID- 19642548 TI - [Impact of ambient air pollution by a pulp-and-paper mill on the cytological status of the nasal and oral mucosa in children]. AB - The cytological state of nasal and oral mucosae in the children and adolescents living in the town of Koryazhma was evaluated at the schools located differently from the Kotlas pulp-and-paper mill (PPM). All the Kozyazhma children under examination were found to have an increased epithelocytic alteration index, which is likely to suggest cytotoxic exposure, which was shown to a greater extent with the duration of residence at the school more adjacent to the PPM. The first-form pupils from the school locates more closely to the PPM were found to showed a higher index of natural microflora colonization with buccal epitheliocytes and a trend for an increase in the epitheliocytic differentiation coefficient characterizing the high incidence of diseases. PMID- 19642549 TI - [Influence of ambient air pollution on children's health in Krivoi Rog]. AB - The degree and nature of surface air pollution with man-made chemicals were studied in Krivoy Rog in 1996 to 2005. The priorities of pollutants were established in the area with different forms of technogenic emissions and residential areas. Immunological parameters were studied in healthy neonates and 7-10-year-old children. There was a reduction in the major immunological parameters in both healthy neonatal infants and 7-10-year-old children and a rise in pediatric morbidity. PMID- 19642550 TI - [Prenosological diagnosis of the upper airway mucosa]. AB - The paper analyzes the results of microbiological, immunological, and cytological studies of the upper airway in apparently healthy individuals exposed to toxic agents. The upper airway endoenvironmental changes have been found at the prenosological level, which may lead to the development of clinical pathology. The informative indicators of prenosological diagnosis have been determined, which make it possible to detect early changes in microbiocenoses, the body's resistance, and mucosal cytological status. PMID- 19642551 TI - [Carcinogenic hazard of chloroform and other drinking water chlorination by products]. AB - The paper presents the results of studying the carcinogenic effect of chloroform and its combination with carbon tetrachloride, 1,2-dichloroethane, trichloroethylene during chronic oral administration to F1(CBAxC57Bl6) mice. There is a relationship between the manifestation of carcinogenesis to the dose of chloroform and a combination of chemicals, as well as its enhancement upon exposure to the combination as compared with acute administration of chloroform. Exposure to a combination of substances at the level of their maximum permissible concentrations does not affect carcinogenesis. The possible mechanisms of the specific features of carcinogenesis in this experiment are discussed. PMID- 19642552 TI - [Evaluation of the toxicity of returned and natural waters by biotesting techniques]. AB - The background of the development of a new procedure for calculating the value of water toxicity, by using the test object--Paramecium caudatum infusoria is successively set forth. A series of experiments analyzing the toxic effect of water on the infusoria have been carried out by nongraphic method using the probit analysis. The high coefficient of a correlation between the unified toxicity values obtained by an example of various test objects allows adequate comparison of these results, which is the basis for the systems analysis of environmental factors. PMID- 19642553 TI - [New wording of sanitary regulations and standards 2.2.1/2.1.1.120-03 "Control Areas and Sanitary Classification of Enterprises, Erections, and Other Projects"]. AB - The paper gives the SanPiN requirements 2.2.1/2.1.1.120-03 "Control Areas and Sanitary Classification of Enterprises, Erections, and Other Objects" (a new wording), with emphasis on the new provisions concerning the problems associated with the determination of the size of a control area of both individual industrial projects and a group of industrial projects (industrial zones). Requirements for the evaluation of the efficiency of an established control area, by assessing the risk to human health have been first established. PMID- 19642554 TI - [Assessment of the use of chlorine-containing solid disinfectants in case of avian influenza pandemic]. AB - The paper gives an economic assessment of the present market of monochlorine containing disinfectants. It analyzes the consumption of disinfectants in g per m2 for disinfection measures in case of avian influenza epidemic. PMID- 19642555 TI - [Integrated estimation of carcinogenic load on the population in the town of Aktobe]. AB - Identification of carcinogens from the results of monitoring various environmental objects in an industrial town (Actobe) could single out 8 priority trace elements, which might cause their human accumulation. A carcinogenic risk was found to be formed due to the high ambient chromium pollution in the residential areas, to the accumulation of the elements in the deposited media and human body. Drinking water is a minor source of the identified carcinogens; therefore it may be borne in mind in the further analysis of a carcinogenic risk. PMID- 19642556 TI - [Childhood allergic morbidity in a town with developed petrochemical industry]. AB - The degree of ambient pollution was studied in a town with developed petrochemical industry and allergic morbidity in its pediatric population. The specific features of the pattern and course of allergic diseases were revealed in children in relation to the qualitative and quantitative characteristics of ambient pollution. The findings permit elaboration of practical measures aimed at lowering the influence of environmental factors and to improve the health status in children. PMID- 19642558 TI - [Assessment of human health in the areas adjacent to a large industrial center]. AB - The paper presents data on morbidity in the population living in the suburban area of an industrial center (the city of Ryazan), by taking into account gross ambient emission from the stationary sources, ambient pollution levels, and a sanitary assessment of the quality of life. Differences were found only in the extent of specific emission (per km2 and per capita). The studies in the 1991 2006 changes in the health status of the children living in the suburban areas indicated that the average many years' morbidity rates were significantly less than those in the city (other than diseases of blood and blood organs), but these were at the level of the average regional rates. The comparison of childhood morbidity in the suburban areas versus a control area revealed a significant rise in morbidity with the diagnosis first established as a whole and by individual classes of diseases. Morbidity and correlation analysis in the rural areas adjacent to the industrial center suggest that ambient emission of chemicals from the stationary sources has a great impact on these parameters. PMID- 19642557 TI - [Analysis of the mutagenic activity of aqueous and buffer extracts from oil polluted soil samples]. AB - The Ames test on Salmonella typhimurium TA 100 and TA 98 strains were used to study the mutagenic activity of aqueous (pH 7.4) and buffer (pH 4.5) extracts from soil samples containing different oil levels (from 16 to 3526 mg per kg soil), which had been taken from different areas of a town, and buffer extracts from model soil samples added by crude West-Siberian oil (160-15625 mg/kg). The extracts from all soil samples showed no mutagenic activity. The buffer soil sample extract containing oil in the amount of 12290 mg/kg and oil and coal combustion products had a mutagenic effect with metabolic activation on the TA 98 strain. It is suggested that the mutagenic effect of this sample is associated with oil and coal combustion products. PMID- 19642559 TI - [Rapid analysis of the radionuclides plutonium and americium-241 in soils]. AB - The paper shows it possible to perform a rapid analysis of the isotopes of plutomium and americium-241. The basis of the developed rapid analysis is X spectrometric determination of the amount of plutonium isotopes and gamma spectrometric determination of the radionuclide 241AM. PMID- 19642560 TI - [The problems of individual respiratory protection in medical workers]. AB - The paper discusses a problem of high occupational and occupation-induced overall morbidity in medical workers and shows that a discrepancy between the existing system for individual protection of the personnel and specific working conditions and hazardous factors is one of the causes. The authors have developed regional guidelines "Enhancing the efficiency of individual respiratory protection in the workers of health care facilities" which provide evidence-based guidelines for the usage of certified, ergonomically acceptable respiratory protective means at the health care facilities. The main task of medical recommendations is to change the established stereotype in using lowly effective gauze bandages and surgical protective facial masks as respiratory protective means at the therapeutic-and prophylactic institutions for the personnel. PMID- 19642561 TI - [Cytochemical parameters in nasal mucosal and peripheral blood cells in beryllium production workers]. AB - Nasal mucosal and peripheral blood cells from beryllium production workers underwent cytochemical tests for catecholamines and phospholipids and the activity of esterase and lysosomal cationic proteins. The established peripheral blood metabolic changes reflect reduced cell resistance in response to poor occupational factors and may be used in the rapid hygienic assessment of cytotoxicity of toxic substances. PMID- 19642562 TI - [Hygienic characteristics of children's educational establishments]. AB - The improved procedure for an integrated assessment of the state-of-the-art of preschool educational establishments was appraised. This procedure provides the qualitative and quantitative characteristics of each factor, the degree of its incompliance to the hygienic standards, reveals risk factors, and allows one to take operative decisions to manage a risk, which are aimed at promoting the health status in infants, and expands a sociohygienic monitoring methodology, by increasing the number of accountable objects of the vital activity medium. PMID- 19642563 TI - [Hygienic education in pupils from general educational establishments]. AB - The high prevalence of the major behavioral factors of a risk to health: violation of the study leisure regimen, violation of dietary pattern and quality, low motor activity, smoking, frequent alcohol abuse, drug taste, and deteriorated family microclimate, was revealed in middle and senior schoolchildren from Moscow, Kaliningrad, and Murmansk. Proposals are given to mold healthy lifestyle in adolescents and to optimize their hygienic education at general educational establishments. PMID- 19642564 TI - [Morphofunctional parameters in the students of Tyva State University]. AB - The paper provides a comparative analysis of some morphofunctional parameters and their trends during education of the students at the Tyva State University. The antropometric studies of the total body sizes and their relative parameters have revealed that the Tuva students show a lower absolute stature, force parameters of dynamometry and the respiratory system. The morphofunctional parameters have a wide range of variability that is determined by not only age-gender-related features, but also regional features. PMID- 19642565 TI - [Prediction of the major tuberculosis epidemiological parameters among the children of the Udmurt Republic]. AB - The tuberculosis epidemiological situation was studied among the children of the Udmurt Republic and the tuberculosis morbidity rates in children, the risk of primary infection, and the infection rates were predicted by the Bayes procedure. To study the impact of chemoprophylaxis on the incidence of tuberculosis in children, the risk of its primary infection, and the infection rates, the authors used the multivariate statistical method--hypotheses theorem (the Bayes formula). The application of the hypotheses theorem has shown that if the cohort of children who had chemoprophylaxis in 2007, they should receive it at the same rate as in 2002, which is 30% greater, the morbidity rates in children should show a 1.1-fold reduction. PMID- 19642566 TI - [Marketing as an effective tool to overcome systems problems in the organization of antituberculous care to the pediatric population]. AB - The paper analyzes the efficiency of vaccination and tuberculin diagnosis in the megapolis on the basis of official reporting forms Nos. 8 and 33 approved by the 11 November, 2005 Resolution of the Russian Statistics Agency and the Moscow tuberculosis monitoring system. It is concluded that refusals to undergo vaccination and tuberculin diagnosis may result in the system crisis of antituberculous care to the pediatric population. For the optimum solution of reducing the rate of refusals to take the drugs prescribed by a physician, the authors propose to use in pediatric antituberculous care the marketing methods that level off the responsibility of the parties in taking a decision whether a medical service is expedient. Under the marketing conditions of medical services, combating the foci of tuberculous infection should be a main line to reduce the prevalence of tuberculosis. Prevention of tuberculosis is most effective with the active interaction of medical services (pediatric phthisiological and primary pediatric care services) and society and with the needs being molded in it (as a market medical service) in the population. PMID- 19642567 TI - [The clinical features of tuberculosis in children and adolescents excreting drug resistant Mycobacterium tuberculosis strains]. PMID- 19642568 TI - [Tuberculosis in children of various ages: vaccination, chemoprophylaxis, the specific features of detection, and clinical course]. AB - Examination of 296 cases of active forms of tuberculosis in children showed various age-dependent antituberculous measures. 14.8% of the children less than 3 years of age had not been vaccinated against tuberculosis; 19.8% had earlier received chemoprophylaxis; and contact with patients with tuberculosis was detected more frequently (70.4%). Against this background, tuberculosis in infancy was more commonly identified from complaints (48.1%) and less frequently at mass tuberculin diagnosis (19.8%); the generalized forms of the disease and complicated tuberculosis of intrathoracic lymph nodes were more frequently found (16% and 24.7%), a fatal outcome was oftener observed (7.4%). The secondary forms of tuberculosis were revealed in 23.8% of schoolchildren. Overall, the mean size of a papule emerging from the Mantoux test was 12.8 +/- 0.37 mm at the detection of tuberculosis. PMID- 19642569 TI - [In vitro interferon-gamma induction in whole blood samples is a test for tuberculous infection in children and adolescents]. AB - By applying the interferon-gamma (IFN-gamma) induction technique in the whole blood samples exposed to short-term (22-24-hour) incubation in the presence of Mycobacterium tuberculosis antigens--PPD tuberculin and specific recombinant ESAT 6 lacking in the cells of vaccine BCG and other non-tuberculous mycobacteria, the authors studied the groups of children and adolescents with a negative Mantoux test (n = 31), with postvaccine BCG allergy (n = 40), as well as patients with primary tuberculous infection (n = 84) and those with pulmonary tuberculosis (n = 44). Patients with primary tuberculous infection and a high sensitivity (94%) and a high specificity (97%) may be differentiated from children and adolescents with postvaccinal allergy when the recombinant ESAT-6 antigen and the critical IFN gamma level (greater than 70 pg/ml) detectable in the plasma samples after incubation with the antigen. It has been also shown that in adolescents with local forms of pulmonary tuberculosis specific IFN-gamma induction may be suppressed in number of cases, which is ascribed to decreased specific immunity. PMID- 19642570 TI - [Estimation of the clinical and pharmacoeconomic efficiency of treatment in patients with community-acquired pneumonia with third-generation cephalosporins]. AB - The clinical and pharmacoeconomic effectiveness of the third-generation cephalosporin Ceftriabol versus the original drug Claforan in the treatment of varying community-acquired pneumonia was studied in 60 and 58 patients, respectively. The Russian third-generation cephalosporin Ceftriabol was shown to be as effective as Claforan in treating patients with community-acquired pneumonia. However, in addition to the main--therapeutic effect, Ceftriabol produces a certain economic gain. PMID- 19642571 TI - [Role of social factors in the formation of life quality indices in patients with chronic obstructive pulmonary diseases]. AB - The indices of life quality were estimated by the Seattle questionnaire in 140 patients aged 19 to 79 years who had chronic obstructive pulmonary diseases (COPD). The results of the study determined the lower life quality indices in patients with COPD according to a number of social factors: domicile, occupation, number of family members, living conditions, and medical care. PMID- 19642572 TI - [Improving the activity of the inpatient departments of tuberculosis facilities]. AB - The state-of-the-art of care given in the inpatient departments of tuberculosis facilities (TF) in the Kemerovo Region is analyzed. Large municipal TFs have been reorganized as interregional ones with their adjacent areas being assigned. Indications for hospitalization have been formulated. Continuous supply with antituberculous drugs (ATDs) is ensured. Strict monitoring of the use of each dose of ATDs has been made. Schools for tuberculosis patients have been set up. The posts of a psychologist and a social worker have been introduced. Compulsory hospitalization of bacteria-excreting patients is used by the decision of the court. As a result of the work done, queue to be admitted to the TFs of the Kemerovo Region has been eliminated; the treatment time has been optimized. The informative value of simple sputum smear microscopy against acid-resistant mycobacteria has significantly increased. The rate of premature treatment discontinuity has reduced. The efficiency of inpatient treatment has enhanced. PMID- 19642573 TI - [Role of material incentives of medical workers in the early detection and effective treatment of new cases of pulmonary tuberculosis in the Republic of Dagestan]. AB - The authors studied the efficiency of material incentives in the amount of 300 rubles for each case to medical workers of the general health care network for early detection and to those of tuberculosis facilities for effective treatment us in 2001-2007. Due to the tuberculosis-controlling measures made in these years with the mechanism of material incentives to medical workers being introduced, the tuberculosis situation stabilized and the major epidemiological indices, such as morbidity, mortality, and prevalence, decreased by 1.3, 2.2, and 1.7 times, respectively. The higher fluorographic coverage of the population and the introduction of microscopy at the general health care facilities resulted in that the number of new cases of fibrocavernous tuberculosis from 5.6 to 0.7% and, on the contrary, the proportion of bacteria-excreting subjected among the new cases of pulmonary tuberculosis increased from 18.4% in 2000 to 45.2% in 2007 or by 2.5 times (p < 0.001). The results of treatment of the new cases became better. Thus, there were increases in the rate of bacterial discharging cessation from 67% in 2000 to 84.5% in 2007 (p < 0.001), that of cavity closure from 59% in 2000 to 75.2% in 2007 (p < 0.001), and that of transfer to diagnostic registration group III from 23.1% in 2000 to 32.4% in 2007 (p < 0.01). Thus, introduction of the material incentives to the medical workers of the general health care network and tuberculosis facilities had a positive impact on the quality of diagnosis and the efficiency of treatment in patients with tuberculosis. PMID- 19642574 TI - [Clinical and immunological features of concomitant HIV/tuberculosis infection and HIV infection without tuberculosis]. AB - The clinical and hematological manifestations and functional state of the immune system were comparatively evaluated in patients with concomitant HIV/tuberculosis (TB) infection (n = 84) and in those with HIV infection without tuberculosis (n = 106). The course of concomitant HIV-TB infection was ascertained to differ from HIV monoinfection in a diversity of additional exposures that aggravated the patients' general condition. These included: the parameters of a long proceeding inflammatory process, which were accompanied by the signs of the infection-toxic syndrome, inflammatory changes in the hemogram, by a sharp stimulation of the nonspecific link of immunity. So the comparative analysis of the trend in HIV infection in combination with active tuberculosis and HIV monoinfection revealed a prompter progression of the disease in the former case. PMID- 19642575 TI - [A case of brain cavernous tuberculosis]. PMID- 19642576 TI - [Use of nitric oxide in the complex treatment of patients with pulmonary tuberculosis]. PMID- 19642577 TI - [Treatment of children and adolescents with latent tuberculous infection]. PMID- 19642578 TI - [The activity of metalloproteinases and concentration of C-reactive protein in the blood of patients with coronary heart disease during the administration of statins and coronary artery bypass surgery]. PMID- 19642579 TI - [Laboratory evaluation of endothelial function in term neonatal infants born to mothers with gestosis]. PMID- 19642580 TI - [Porphyrin metabolic disorders in the genesis of fetoplacental insufficiency in hyperandrogenism]. AB - The association of a ratio of blood porphyrin fraction concentrations in pregnant women with hyperandrogenism (HA) with the osmoresistance of red blood cells and the microviscosity of their membranes was studied. A cohort examination was made in parallel groups of 64 pregnant women aged 20 to 30 years at 28-36 weeks gestation. The levels of dehydroepiandrosterone sulfate (DHEAS) and testosterone were measured. External cardiotocography, ultrasonography, and Doppler study were conducted. The blood concentrations of endogenous protoporphyrin (PP) and coproporphyrin (CP) were estimated by the spectral fluorescence technique. Erythrocytic membrane microviscosity was determined from the degree of pyrene eximeration, by measuring the fluorescence spectra; erythrocytic osmoresistance was ascertained by the procedure developed by N. L. Vasilevskaya. The pregnant women with placental insufficiency in the presence of HA were found to have an altered ratio of the concentrations of erythrocytic porphyrin fractions, which enhanced the microviscosity and resistance of red blood cell membranes, causing worse microcirculation. There was an inverse correlation between the level of DHEAS and the ratio of the concentrations of endogenous PP to CP. It is concluded that the development of placental insufficiency in pregnant women with HA is attended by the decreased ratio of PP to CP along with the higher microviscous characteristics of erythrocytic membranes and the lower amplitude of their osmoresistance, by increasing the lower osmoresistance range. PMID- 19642581 TI - [The state of enzymatic redox system of glutathione in the blood of patients with lymphosarcoma (non-Hodgkin's lymphoma]. AB - Lipid peroxidation (LPO) processes are enhanced and metabolism is disturbed in patients with lymphosarcoma (LS) (non-Hodgkin's lymphoma). The blood enzymatic redox system was analyzed in patients with LS of two types: lymphoblastic LS (LB LS) and prolymphocytic LS (PL LS). The activities of glutathione reductase (GR), glutathione peroxidase (GP), glutathione dehydroascorbate reductase (GDAR), gamma glutamyl transpeptidase (GGT), and glucose-6-phosphate dehydrogenase (G6PDH) were spectrophotometrically (Humalyzer 2000, DE) determined in the peripheral plasma, white blood cells, lymphocytes, and red blood cells of 32 aged 42-57 years who had LS and 25 healthy individuals. Peripheral blood lymphocytes and leukocytes were obtained by the method developed by A. Boyum. A search for a correlation was made by the Spearman method. The activities of the enzymes and the data of the correlation analysis suggested antioxidant defense system imbalance and metabolic disturbances in patients with LS. Close functional correlations between GR and GP, GR and G6PDH persisted in patients with both types of the disease. Functional relationships between GR and GDAR remained only in patients with PL LS (r = 0.946; p < 0.001). That between GR and GGT was impaired in patients with LS. A correlation between the activity of antioxidant enzymes and the proliferative activity of blood cells was found in patients with LB LS, which may be used as an additional biochemical test in the differential diagnosis of LS. PMID- 19642582 TI - [Impact of HBV infection and alcohol surrogates on the lipid composition of lymphocytic membranes]. AB - Our study was undertaken to reveal the specific features of changes in the content of different fractions of total and lymphocytic membrane phospholipids under the influence of HBV infection and alcohol substitutes. The lipid spectrum of lymphocytic membranes was determined in 50 healthy individuals, 50 patients with acute viral hepatitis, and 62 patients with toxic hepatitis. Once HBV infection occurs, there is a reduction in the content of total phospholipids, free cholesterol, phosphatidylcholine, and phosphatidylethanolamine and an increase in the level of triglycerides, free fatty acids, cholesterol esters, and lysophospholipids. There was also a decrease in the absolute content of total phospholipids and free cholesterol. The effect of alcohol substitutes was manifested by the higher concentrations of lysophospholipids, phosphatidylcholine, and phosphatidylethanolamine in the lymphocytic membranes. PMID- 19642583 TI - [The National Standard of the Russian Federation. Synovial fluid cytological study (a draft)]. PMID- 19642584 TI - [Effect of ladasten on the psychophysiological parameters of healthy volunteers]. AB - The ability of the antiasthenic drug ladasten (single dose, 100 mg) to influence psychophysiological functions was evaluated in laboratory experiments with participation of healthy volunteers. It was established that ladasten does not exhibit behavioral toxicity and improves psychophysiological parameters in the state of mental fatigue. The drug effects were more pronounced in stress-labile individuals. PMID- 19642585 TI - [Different effect of eleuterococcus on various psychophysiological parameters of healthy humans depending on their chronotype and the day time]. AB - The administration of a liquid extract of eleuterococcus as a psychotonic drug by young healthy humans leads to changes in some psychophysiological parameters, including an increase in the aural memory volume, decrease in reactive anxiety, and shortening of individual minute. These effects were dependent on the daytime (morning versus evening) and the individual chronotype (circadian features) of each volunteer. PMID- 19642586 TI - [Hypotensive effect of oxatriazolo-5-olate derivative in chronic experiments on SHR rats]. AB - Long-term peroral administration of the oxatriazolo-5-olate derivative azasydnon 6 leads to a decrease in the systolic arterial blood pressure in SHR rats. The hypotensive effect of azasydnon-6 is mediated by stimulation of the sGC-cGMP pathway, which triggers vasodilatation of SMC in vessels. The drug effect is inhibited by 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one, a selective sGC inhibitor. During long-term treatment, no tolerance to azasydnon-6 is developed in isolated arterial vessels. PMID- 19642587 TI - [Experimental pharmacokinetics of the new neurotensine-derived antipsychotic drug dilept]. AB - The metabolism and pharmacokinetics of a new neurotensine-derived dipeptide drug dilept (N-caproyl-L-prolyltyrosine methyl ester) and its tentative metabolites after intravenous and peroral administration of the parent drug and its tabletized form in rats have been studied by HPLC-ESI(-)-MS/MS method. It is established that unchanged dilept (detected in the blood plasma for no less than 30 min) as well as N-caproyl-L-proline and N-caproyl-L-prolyl-L-tyrosine (both detected in the blood over more than 4 h) are the major metabolites in the bloodstream upon peroral administration of the drug. The proposed structures of metabolites were confirmed by countersynthesis. Dilept and N-caproyl-L-prolyl-L tyrosine penetrate through the blood - brain barrier. The drug is rapidly absorbed, distributed, and metabolized in the rat organism. Peroral administration of dilept in rats in the form of tablets (at a dose of 200 mg/kg) resulted in a significant increase in intestinal absorption, as evidenced by a 22% improvement in the bioavailability, whereas dilept alone showed an absolute bioavailability of less than 1%. PMID- 19642588 TI - [HPLC-MS determination of 2-ethyl-6-methyl-3-oxypyridine]. AB - An HPLC-ESI-MS method has been developed for determining 2-ethyl-6-methyl-3 oxypyridine (EMO) in human urine upon peroral administration of this substance in form ofmexidol. Various sample preparation (extraction) procedures were tested and compared for evaluating the recovery and matrix effect. Solid-phase extraction procedure followed by derivation with dansyl chloride is proposed as a method of choice. The recovery of analyte was 48.1 +/- 3.4%, and the matrix effect was 99.4 +/- 4.1%. The MS and MS/MS spectra of EMO and its dansyl derivatives are presented and interpreted. The analyses were performed using a mass spectrometer of the ion trap type with electrospray ionization at atmospheric pressure, operating in the regime of positive ion detection. PMID- 19642589 TI - [Experimental study of the pharmacokinetics of acetylsalicylic acid upon transdermal administration]. AB - A comparative analysis of the concentrations of acetylsalicylic acid (ASA) and its metabolite, salicylic acid (SA), in the blood was performed and the other pharmacokinetic parameters were studied after conventional intragastric and transdermal administration in rabbits. It is established that the ASA concentration in the blood upon transdermal administration in a dose of 100 mg/kg is above the minimum therapeutic level during 24 h. Prolonged action of a transdermal therapeutic system (TTS) in comparison to intragastric administration was proved. After the transdermal administration via TTS, the ASA half elimination time and the mean retention time increased in comparison to the values upon intragastric administration. The ASA bioavailability upon the transdermal administration increased by a factor of 4.5 in comparison to the case of peroral administration. PMID- 19642590 TI - [Free amino acid pool in rat blood plasma under different conditions of alcoholization and correction with L-NAME and L-arginine]. AB - The features of disturbances of the free amino acid pool under conditions of alcoholization in different regimes and its correction with L-NAME and L-arginine have been studied in rats. The most pronounced dysbalance of free amino acid was observed in animals upon interrupted alcoholization. The treatment with L-NAME and L-arginine on the background of chronic and interrupted alcoholization was found to normalize most indices of the of free amino acid pool. However, only the treatment with L-arginine led to a decrease in the level of ammonium in the blood plasma. PMID- 19642591 TI - [Effect of bischofit mineral ointment on the allergic contact dermatitis caused by 2,4-dinitrochlorobenzene]. AB - Bischofit-based ointment is shown to have a beneficial effect on the course of model contact dermatitis caused by 2,4-dinitrochlorobenzene. PMID- 19642592 TI - [Experimental study of the mechanisms of the tissue repair activity of complex and individual agents isolated from Delphinium elatum]. AB - It is demonstrated in experiment that the entire complex and individual agents isolated from the above-ground part of bee larkspur Delphinium elatum stimulate the reparative regeneration of skin in white mongrel mice. The maximum activity was exhibited by the alkaloid fraction of Delphinium elatum. PMID- 19642593 TI - [Structural and functional organization of the cerebral dopaminergic system]. AB - The structural and functional organization of the cerebral dopaminergic system is considered. The synthesis of dopamine, distribution of dopaminergic structures, structure and classification of dopamin receptors in the brain, and functions of dopamine are discussed. Dopamin among the main catecholamine neurotransmitters participating in the control of locomotor activity, cognition, emotion, positive reinforcement, food intake, and endocrine regulation. Moreover, several neurological diseases such as Parkinson's disease, schizophrenia, and hyperprolactinemia are associated with dysregulation of dopaminergic neurotransmission. Therefore, the search for and development of new dopaminergic drugs is of great interest. PMID- 19642594 TI - [Effect of medicinal plants on the excretory renal function (a review)]. AB - The review summarizes verified data on the medicinal plants of world flora that influence the kidney excretory function. The biologically active substances of herbal preparations, the mechanisms of the renal effects, and the accompanying pharmacological properties of nephrotropic plants are considered. PMID- 19642595 TI - [Antioxidants]. PMID- 19642596 TI - Lack of varied endometrial expression of proprotein convertase 6 in infertile women with minimal grade endometriosis and idiopathic infertility. AB - OBJECTIVE: Proprotein convertase 6 (PC6) is known to be the key enzyme involved in the transformation of many hormones, cytokines and their receptors into their active forms. Experimental in vitro studies have also proven that lack of PC6 in the endometrium prevents decidualisation. Therefore in our study we have aimed at determining whether infertility in some patients might be attributable to decreased expression of PC6. MATERIAL AND METHODS: With the use of RealTime PCR we have studied the expression level of PC6 in receptive phase endometria from 36 idiopathic infertile patients, 26 infertile patients with minimal grade endometriosis and compared those results with fertile, age-matched controls. The endometria were collected 7-9 days after ovulation. RESULTS: There were no statistically significant differences regarding the expression of PC6 in endometria from patients with idiopathic infertility, infertile patients with endometriosis and controls. CONCLUSIONS: Since there is no detectable difference in PC6 expression, the decreased expression of PC6 is unlikely to cause infertility. PMID- 19642597 TI - [Concetration of anticardiolipin antybodies in peritonel fluid and in fluid from lymphocytes culture in women with endometriosis]. AB - AIM: The aim of our work was to study both the concentration of anticardiolipin antibodies (aCL) in peritoneal fluid in women with endometriosis and to examine peritoneal lymphocyte ability to produce anticardiolipin antibodies. MATERIAL AND METHODS: Study group included 30 women with endometriosis. The clinical stages of the disease were assessed by the revised American Fertility Society (rAFS) classification. Reference group included fifteen healthy women, with excluded endometriosis and other pathological disorders within the pelvis. The concentration of aCL in the peritoneal fluid and in fluid from lymphocyte culture was measured by enzyme-linked immunosorbent ELISA assay. RESULTS: Statistical analysis showed significantly increased mean concentration of aCL in peritoneal fluid in women with endometriosis compared to women from the reference group (p<0.0001). The concentration of aCL in fluid from lymphocyte culture was also significantly higher in samples from women with endometriosis than from the reference group (p<0.0001). The highest mean levels of aCL in peritoneal fluid and in fluid from lymphocyte culture were observed in samples from women with stage I of the disease. CONCLUSIONS: An increased level of anticardiolipin antibodies in peritoneal fluid in women with endometriosis and increased antibodies production by lymphocytes may suggest an impairment of humoral immunity and its intensification in the early stages of the disease. PMID- 19642598 TI - [Efficacy of densitometry and fracture risk assessment tool FRAX in making therapeutic decisions in osteoporosis--a study on female patients of university of medical sciences endocrinology outpatient clinic]. AB - INTRODUCTION: Contemporary understanding of osteoporosis is based on the assessment of fracture risk. Evaluation of clinical risk factors of fracture with or without densitometry (DEXA) allows to identify patients requiring pharmacological treatment. AIM: The aim of the study was to estimate the usefulness of DEXA in assessment of fracture risk in women >50 years old. MATERIALS AND METHODS: In 296 previously untreated for osteoporosis women of Endocrinology Outpatient Clinic aged 50 to 85 years (mean 68.8+/-7.8) 10-year fracture risk using FRAX tool was computed from clinical risk factors alone (FRAX, FRAX hip) and after measurement of BMD (FRAX BMD). Then FRAX parameters were compared in 4 age categories. Fracture risk was confronted with therapeutic thresholds proposed in Poland. RESULTS: 10-year fracture risk by FRAX increased with age. The most frequent risk factors were: previous fracture and family history of fractures. FRAX and FRAX BMD were significantly different in the 50-59 year-olds and 60-69 year-olds. Statistically significant difference was found for FRAX hip and FRAX hip BMD in 50-59 year old women. FRAX and FRAXhip were better predictors of fractures than FRAX BMD in patients >80 years old. In 50-79 year old women qualification for treatment was more effective when risk was assessed according to FRAX BMD. DEXA performance did not change the number of women over 80 who were eligible for treatment according to FRAX. CONCLUSIONS: BMD is crucial for the 10-year risk assessment in 50-69 year-olds without previous fracture, as an increasing number of patients need therapy. In >80 year old women clinical risk factors alone are sufficient to make therapeutic decisions. DEXA in these women has no influence on the risk of future fractures, including hip fracture. In 60-69 women with previous fracture DEXA is a good predictor for future fractures but has no value as far as therapeutic decisions are concerned. PMID- 19642599 TI - [Serum resistin concentrations in cases of gestational diabetes mellitus with good glycemic control and in cord blood]. AB - AIM: Resistin is believed to play a certain role in the pathogenesis of gestational diabetes mellitus (GDM). The aim of the study was to assess resistin concentrations in women with diet-treated GDM and good glycemic control, in healthy pregnant women and in cord blood, depending on the advancement of the pregnancy, maternal body mass index (BMI) and index of insulin resistance (HOMA IR), as well as on somatic features of the newborns. MATERIALS AND METHODS: The study group consisted of 20 women with GDM whereas 20 healthy women constituting the control group. They were examined twice: at 23-32 weeks and at 35-37 weeks of gestation. Serum resistin concentration was assessed using RIA method. RESULTS: In the control group, maternal resistin concentration was higher (p<0.03) after the second examination than the first one. In the GDM group, maternal resistin concentration was similar to that in the control group in both examinations. No correlations were found either between maternal resistin and insulin concentrations or between maternal resistin concentration and BMI or HOMA-IR. No correlations were found between maternal resistin concentration or cord blood resistin concentration and somatic features of newborns, either. In both groups, resistin concentration in cord blood was higher than in maternal blood during both examinations. CONCLUSIONS: Our results indicate that maternal resistin concentration increases as pregnancy advances. In women with diet-treated GDM and good glycemic control resistin concentration is similar to that observed in healthy pregnant women. No relationship was found between resistin concentration in cord blood and somatic features of the newborns. PMID- 19642600 TI - [Activin A as a possible marker for hypoxia and intraventricular haemorrhage in newborns]. AB - The article presents general information about activin A, a glycoprotein that belongs to the transforming growth factor beta superfamily. Structure, mechanism and role of activin as a possible marker of hypoxia and intraventricular haemorrhage were described. PMID- 19642601 TI - [Female sexual response cycle]. AB - The key to understand female sexual response cycle is a multidimensional approach to sexual reactions, where emotional satisfaction (emotional intimacy with the partner) might be more important than physical satisfaction (orgasm). Such holistic approach might in fact make the diagnosis and treatment of female sexual dysfunctions, which are becoming increasingly common in clinical and gynecological practice, easier and more effective. The aim of the study is to present contemporary model of female sexual response cycle and to encourage specialists to view female sexuality in more broad and holistic perspective. PMID- 19642602 TI - Antenatal diagnosis of sacrococcygeal teratoma--two different case reports. AB - Sacrococcygeal teratoma (SCT) is the most common fetal tumour. It may be readily diagnosed by two-dimensional ultrasonography in the early second trimester. Three dimensional ultrasonography is recommended as a supplemental examination to obtain further detailed information for multidisciplinary management of SCT. In the following article we present two cases of sacrococcygeal teratomas which exhibited two different courses. In the first case, sacrococcygeal teratoma was diagnosed in the early second trimester. The condition of the fetus worsened during the follow-up and the parents opted for the termination of the pregnancy. The other one presented at a later gestational age. The baby was born alive, immediately operated upon and did well until the age of 1, when we checked her condition for the last time. PMID- 19642603 TI - Embolization of renal angiomyolipoma in pregnancy: case report. AB - BACKGROUND: Renal angiomyolipoma is a rare benign tumour composed of adipose tissue, blood vessels and smooth muscles. However it can locally grow to a great size and its numerous blood vessels may cause major bleeding requiring immediate intervention. CASE: At 20th week of pregnancy a previously healthy 26-year old pregnant woman with an episode of sudden and severe pain in the left flank followed by fainting was diagnosed with a bleeding tumour of the left kidney. The diagnosis was based on ultrasonography and magnetic resonance imaging (MRI). Diagnostic angiography was followed by selective embolization of the tumour blood vessels. At 38th week of pregnancy elective caesarean section was performed and after the puerperium the tumour was resected. CONCLUSION: Embolization of renal angiomyolipoma bleeding vessels during pregnancy can be an effective therapeutic approach protecting against further bleeding and haemorrhagic shock thereby obviating the need to perform urgent surgery and allowing the woman to carry her pregnancy to term safely in outpatient setting. PMID- 19642604 TI - [Tumour in the ureter stump 13 years after nephrectomy--a rare case of endometriosis]. AB - Endometriosis is found in the urinary tract in 1-2% of women suffering from this disease. The most common site is urinary bladder (81%). In the ureter it is found in only 15% of cases and it mainly involves the pelvic part. The authors present a case of 49-year old woman who was diagnosed with an endometriotic tumour in the stump of the ureter, 13 years after left nephrectomy performed for hydronephrosis and lack of the kidney's function confirmed in renal scintigraphy. After laser ablation and hormonal therapy the tumour burden was diminished and symptoms resolved. PMID- 19642605 TI - [The statement of Polish Gynecological Society Experts on the barrier agents for adhesion prevention after gynaecological surgery]. PMID- 19642606 TI - [Recommendations of The Polish Society of Obsterics and Gynaecology regarding prevention and treatment of pelvic organ prolapse and urinary incotinence in patients qualified to hysterectomy]. AB - To develop guidelines regarding prevention and treatment of pelvic organ prolapse and stress urinary incontinence in patients qualified to hysterectomy. The Polish Gynecological Society formed a work group to develop guidelines. The work group formulated the following guidelines: 1. Since the hysterectomy per se is a risk factor for pelvic organ prolapse, more conservative procedures to hysterectomy should be considered and applied, whenever it is possible. 2. Pelvic organ prolapse is not the indication for hysterectomy. 3. Not all lesions of the uterine cervix without concomitant pathological changes of the uterine corpus are indications for hysterectomy. 4. During both abdominal and laparoscopic hysterectomy the fixation of vaginal vault to sacro-uterine and round ligaments, McCall procedure, Burch procedure and paravaginal defect repair should be done as a prevention or treatment of pelvic organ prolapse. 5. During vaginal hysterectomy, sacrospinal colpopexy or McCall procedure is recommended. 6. In cases of hysterectomy performed due to oncological indications, prophylactic fixation of the vaginal vault to sacro-uterine and round ligaments is recommended. In these cases, the repair of the defects of DeLancey second and third level are not recommended because of postradiotherapy vaginal vault shortening and stenosis. In most of oncological indications for hysterectomies, the surgical treatment of stress urinary incontinence should be postponed until the radiotherapy has been completed. PMID- 19642607 TI - [Proposal of screening fetal heart examination form granted by Polish Ministry of Health Program Kardio-Prenatal 2008]. PMID- 19642608 TI - Digital master. PMID- 19642609 TI - Presenting DEViSE: data exchange for visualizing security events. PMID- 19642610 TI - Making augmented reality practical on mobile phones, part 1. PMID- 19642611 TI - Visual-analytics evaluation. PMID- 19642613 TI - To score or not to score? Tripling insights for participatory design. PMID- 19642612 TI - Generating synthetic syndromic-surveillance data for evaluating visual-analytics techniques. PMID- 19642614 TI - Integrating statistics and visualization for exploratory power: from long-term case studies to design guidelines. PMID- 19642615 TI - Recovering reasoning processes from user interactions. PMID- 19642616 TI - Full-body avatar control with environment awareness. PMID- 19642617 TI - Visual realism enhances realistic response in an immersive virtual environment. PMID- 19642618 TI - Linking multidimensional feature space cluster visualization to multifield surface extraction. PMID- 19642619 TI - Sketching tangible interfaces: creating an electronic palette for the design community. PMID- 19642620 TI - Quaternary tin(IV) antimony(III) sulfide decorated with lanthanum(III) ethylenediamine complexes: [La(en)4SbSnS5]2 x 0.5 H2O. AB - A quaternary tin(IV) antimony(III) sulfide decorated by lanthanum(III) ethylenediamine complexes, namely, [La(en)(4)SbSnS(5)](2) x 0.5 H(2)O (1; en = ethylenediamine), has been solvothermally synthesized and structurally, thermally, and optically characterized. Its structure features an isolated hexanuclear molecule of [La(en)(4)SbSnS(5)](2). The intermolecule hydrogen-bond interactions result in a three-dimensional supramolecular network, which remains intact upon dehydration. PMID- 19642621 TI - In vivo imaging of S-layer nanoarrays on Corynebacterium glutamicum. AB - Crystalline bacterial cell surface layers (S-layers) are monomolecular arrays of (glyco)proteins that have recently produced a wealth of new opportunities in nanotechnology. Whereas the in vitro imaging of isolated S-layers is well established, their direct imaging on live cells remains very challenging. Here we use atomic force microscopy (AFM) to visualize S-layer nanoarrays on living Corynebacterium glutamicum bacteria. We demonstrate the presence of two highly ordered surface layers. The most external layer represents the hexagonal S-layer, and the inner layer displays regular patterns of nanogrooves that could act as a biomolecular template promoting the 2-D assembly of S-layer monomers. These nanoscale analyses open new avenues for understanding the structure of protein monomolecular arrays, which is a crucial challenge in current nanoscience and life science research. PMID- 19642622 TI - A high-spin organometallic Fe-S compound: structural and Mossbauer spectroscopic studies of [phenyltris((tert-butylthio)methyl)borate]Fe(Me). AB - The synthesis and structure of the pseudotetrahedral, sulfur-rich, high-spin organoiron(II) [phenyltris((tert-butylthio)methyl)borate]Fe(Me), [PhTt(tBu)]Fe(Me), 1, are reported. Low-temperature Mossbauer spectroscopic studies reveal an isomer shift of delta = 0.60(3) mm/s and DeltaE(Q) = 0.00(1) mm/s and an S = 2 ground multiplet with a negative zero-field splitting, D = 33(3) cm(-1), E/D approximately = 0.01. The small separation of the ground doublet, Delta approximately = 0.01 cm(-1), allows for observation of X-band EPR signals at g(eff) approximately = 10 (g(z) = 2.6, g(x,y) = 2.00). The relatively large negative zero-field splitting and a highly anisotropic magnetic hyperfine tensor, containing a large orbital z component, {-10(4), -10(4), +33.8(2) MHz}, are concordant with the presence of unquenched orbital angular momentum. Density functional theory (DFT) calculations predict that the lowest-lying orbitals have predominantly d(xy)- and d(x(2)-y(2))-like character, separated by an energy gap small enough to allow mixing through spin-orbit coupling, to generate a negative zero-field splitting, consistent with the experimental observations. The experimental and DFT-calculated isomer shifts are in good agreement (delta(calcd) = 0.5 mm/s). The unusual (for a high-spin ferrous site) null electric field gradients can be qualitatively explained in the frame of the spin-orbit coupling mixing. The very small Fermi contact component of the magnetic hyperfine tensor (A(FC)(exp) = -9 MHz) is not well described by the DFT approach (A(FC)(calcd) = +2 MHz). To our knowledge, this is the first study of a sulfur-coordinated high spin organoiron(II) complex. PMID- 19642624 TI - Manipulation of the spontaneous emission in mesoporous synthetic opals impregnated with fluorescent guests. AB - The spontaneous emission of light from light-emitting materials adsorbed within the ordered pores of monodispersed mesoporous silica spheres (MMSS) has been investigated. By taking advantage of the ordered starburst pores of MMSS, we can provide a simple strategy for fabricating synthetic opals consisting of homogeneous individual building blocks in which fluorescent guests are uniformly and stably impregnated. In this study, tris(8-hydroxyquinolinato)aluminum(III) (Alq(3)) and Rhodamine B (Rh B) are selected as the fluorescent guests. The former has a wider emission band than the reflection spectrum of MMSS synthetic opals, whereas the emission band of the latter is considerably narrower than the reflection spectrum of the opals. The spontaneous emissions of these functionalized synthetic opals are clearly influenced by the stop band governed by the Bragg equation. In the case of the Alq(3)-MMSS conjugate, the shape of the Alq(3) emission spectrum varies in accordance with the shift in the stop band. The emission of the Rh B-MMSS conjugate is noticeably narrowed, and its intensity is enhanced when the excitation intensity is increased. These results are well explained by an inhibition of spontaneous emission caused by a reduction in the density of optical states within the stop band. The results of this study indicate that MMSS synthetic opals are promising for use in novel optical applications in which the spontaneous emission can be manipulated. PMID- 19642625 TI - Oligothiophene functionalized dimethyldihydropyrenes I: syntheses and photochromicity. AB - The syntheses of 2,7-di-tert-butyldimethyldihydrobenzo[e]pyrenes with thienyl (6), terthienyl (7), and pentathienyl (14) side chains at the 4,5- positions, ter and pentathienyl side chains at the 4-position with ter- (39) and pentathienylcarbonyl (40) side chains at the 10- and 11-positions, 2-naphthoyl-7 tert-butyldimethyldihydropyrenes with ter- (53), penta- (54), and septithienyl (55) side chains at the 4,9-positions are described. These compounds are all photochromic and open to the corresponding cyclophanedienes with long wavelength (>490 nm) light, and as such, the conjugative path could change considerably, making them suitable to investigate as potentially switchable conducting molecules. In this paper, the syntheses and the photochemical and thermal isomerizations are studied; in the accompanying paper, the electrochemical and conductive properties are studied. Here, a comparison of the relative opening rates to that of the benzo[e]pyrene 4 (with no thienyl substituents) is made, and all of the above photochromes show considerably enhanced photo-opening of the DHPs to the CPDs. As examples, 14, 40, and 54 were cycled between the open and closed forms, and no decomposition was observed; however, when 54 was irradiated for 40 h with 254 nm light, some radicals did form, which enhanced the thermal closing rate, and so extensive irradiation with short wave UV is better avoided. The thermal closing reactions were also studied, and all of the above compounds close faster than benzo-CPD 4', though for the highly photochromic ter- and pentathienyl benzo-CPDs 39' and 40', the rate was not too enhanced from that of 4' and so are probably the best compromise between fast photochromicity and slow thermal reversion. PMID- 19642627 TI - Iron-catalyzed cascade arene-aldehyde addition/cyclizations for the highly efficient synthesis of xanthenes and its analogous: observation of a C-C bond cleavage in indole-based triarylmethanes. AB - An efficient, general, and one-pot procedure for the synthesis of multisubstituted xanthene derivatives through Fe(III)-catalyzed reactions of 2 aryloxybenzaldehydes with electron-rich arenes has been developed. This method offers several advantages such as high selectivities, mild reaction conditions, and easily accessible starting materials. A mechanistic study revealed that a C-C bond cleavage of a triarylmethane intermediate might be involved in the domino process. PMID- 19642626 TI - Synthesis and optical properties of aqueous soluble indolylfulgimides. AB - Three novel aqueous soluble fulgimides, trifluoromethyl carboxylic acid indolylfulgimide 4, dicarboxylic acid indolylfulgimide 5, and carboxylic acid indolylfulgimide 6, were synthesized. Both 4 and 5 can switch back and forth between open and closed forms upon illumination with specific wavelengths of light, whereas 6 can only switch from the closed form to the open form. In sodium phosphate buffer (pH 7.4) at 37 degrees C, an unusual hydrolysis of the trifluoromethyl group of the closed form of 4 resulted in 5, which has an additional carboxylic acid group. The closed form of 5 was further decarboxylated to generate 6, which was not photochromic. In buffer, the open form of 4 degraded 20% after 10 days, while the closed form of 4 was converted to 5 rapidly. In buffer, both forms of 5 degraded less than 20% after 21 days at 37 degrees C, and 5 underwent 670 photochemical cycles before degrading by 20%. It is the most robust fulgimide yet reported in aqueous solution. PMID- 19642628 TI - Enolization regioselectivity involving stereoisomeric 4a-methyl-5 methoxyperhydrobenzo[7]annulen-2-ones. AB - Efficient synthetic routes to the four isomers 17b-20b of the title ketone are described. Entry begins from the Wieland-Miescher homologue 3 whose pair of carbonyl groups are amenable to regiochemical manipulation. The compositions of the reaction mixtures generated under kinetic or thermodynamic control were defined by (1)H NMR analysis subsequent to chromatographic purification. The regiochemical trends are correlated with B3LYP/6-31G* calculations, the results of which conform to the preferred introduction of a 1,2- or 2,3-double bond. PMID- 19642629 TI - Reactivity of neutral Mo(S2C6H4)3 in aqueous media: an alternative functional model of sulfite oxidase. AB - The kinetics of the reaction of neutral [Mo(S2C6H4)3] with hydrogen sulfite to produce the anionic Mo(V) complex, [Mo(S2C6H4)3]-, and sulfate have been investigated. It has been shown that [Mo(S2C6H4)3] acts as the electron-proton sink in the oxygenation reaction of HSO3(-) by water. Reaction rates, monitored by UV/vis stopped-flow spectrometry, were studied in THF/water media as a function of the concentration of HSO3(-) and molybdenum complex, pH, ionic strength, and temperature. The reaction exhibits pH-dependent HSO3(-) saturation kinetics, and it is first-order in complex concentration. The kinetic data and MS ESI spectra are consistent with the formation of [Mo O(S2C6H4)2(S2C6H5)]- (1) adduct as a crucial intermediate that transfers the oxygen atom to HSO3(-) yielding the Mo(V) species quantitatively. PMID- 19642630 TI - Kinetic study of the electrochemical oxidation of salicylic acid and salicylaldehyde using UV/vis spectroscopy and multivariate calibration. AB - The electrochemical oxidation of salicylic acid (SA), salicylaldehyde (SH), and their mixtures at Ti/IrO2-SnO2-Sb2O5 electrodes was studied using in situ UV/vis spectroscopy. Plackett-Burman's experimental design was employed to simultaneously investigate the effect of current density, temperature, mass transfer, composition of the electrode materials, initial concentration, and supporting electrolyte on the electrochemical oxidation of SA, revealing that temperature and the applied current density are the two major factors. The kinetics of the electrochemical oxidation of SA and SH was thus investigated at different temperatures and current densities, showing that the electrochemical oxidation of SA and SH is governed by the hydroxyl radical reaction and follows first-order kinetics with the apparent activation energy of 24.8 and 17.2 kJ/mol, respectively. The competitive effects of SA and SH during the electrochemical oxidation of their mixtures were further studied using UV/vis spectroscopy and multivariate calibration. PMID- 19642631 TI - Vector correlation analysis for inelastic and reactive collisions between partners possessing spin and orbital angular momentum. AB - A general reactive collision of the type A + B --> C + D is considered where both the collision partners (A and B) or the products (C and D) may possess internal, i.e., spin, orbital or rotational, angular momenta. Compact expressions are derived using a rigorous quantum mechanical analysis for the angular momentum anisotropy of either of the products (C or D) arising from an initially polarized distribution of the reactant angular momentum. The angular momentum distribution of the product is expressed in terms of canonical spherical tensors multiplied by anisotropy-transforming coefficients c(K(i)q(k))(K)(K(r),L). These coefficients act as transformation coefficients between the angular momentum anisotropy of the reactants and that of the product. They are independent of scattering angle but depend on the details of the scattering dynamics. The relationship between the coefficients c(K(i)q(k))(K)(K(r),L) and the body-fixed scattering S matrix is given and the methodology for the quantum mechanical calculation of the anisotropy-transforming coefficients is clearly laid out. The anisotropy transforming coefficients are amenable to direct experimental measurement in a similar manner to vector correlation and alignment parameters in photodissociation processes. A key aspect of the theory is the use of projections of both reactant and product angular momenta onto the product recoil vector direction. An important new conservation rule is revealed through the analysis, namely that if the state multipole for reactant angular momentum distribution has a projection q(k) onto the product recoil vector the state multipoles for the product angular momentum distribution all have this same projection. Expressions are also presented for the distribution of the product angular momentum when its components are evaluated relative to the space-fixed Z-axis. Notes with detailed derivations of all the formulas are available as Supporting Information. PMID- 19642632 TI - Reactivity of C2H5+ with benzene: formation of ethylbenzenium ions and implications for Titan's ionospheric chemistry. AB - The reaction of ethyl cation with benzene has been investigated in a combined experimental and theoretical approach. Under single collision conditions, proton transfer affording protonated benzene concomitant with neutral ethene represents the major reaction channel. From pressure-dependent measurements, an absolute cross section of 7 +/- 2 A(2) at hyperthermal energies (about 1.0 eV in the center of mass frame) is derived for this channel, from which a phenomenological rate constant of about 2.9 x 10(-10) cm(3) s(-1) is estimated at low energies. The energy behavior of the cross section as well as several side reactions leading to C-C coupling imply that the reaction of C(2)H(5)(+) with C(6)H(6) proceeds via a long-lived association product, presumably the covalently bound protonated ethylbenzene (ethylbenzenium ion). With regard to chemical processes in the atmosphere of Titan, present results imply that termolecular association of C(2)H(5)(+) with benzene to produce protonated ethylbenzene is very likely to occur. The condensation of alkyl cations with arenes thus provides an alternative route for the growth of larger hydrocarbon molecules. PMID- 19642633 TI - Combined crossed molecular beam and theoretical studies of the N(2D) + CH4 reaction and implications for atmospheric models of Titan. AB - The dynamics of the H-displacement channel in the reaction N((2)D) + CH(4) has been investigated by the crossed molecular beam (CMB) technique with mass spectrometric detection and time-of-flight (TOF) analysis at five different collision energies (from 22.2 up to 65.1 kJ/mol). The CMB results have identified two distinct isomers as primary reaction products, methanimine and methylnitrene, the yield of which significantly varies with the total available energy. From the derived center-of-mass product angular and translational energy distributions the reaction micromechanisms, the product energy partitioning and the relative branching ratios of the competing reaction channels leading to the two isomers have been obtained. The interpretation of the scattering results is assisted by new ab initio electronic structure calculations of stationary points and product energetics for the CH(4)N ground state doublet potential energy surface. Differently from previous theoretical studies, both insertion and H-abstraction pathways have been found to be barrierless at all levels of theory employed in this work. A comparison between experimental results on the two isomer branching ratio and RRKM estimates, based on the new electronic structure calculations, confirms the highly nonstatistical nature of the N((2)D) + CH(4) reaction, with the production of the CH(3)N isomer dominated by dynamical effects. The implications for the chemical models of the atmosphere of Titan are discussed. PMID- 19642634 TI - Theoretical temperature dependence of the charge-carrier mobility in semiconducting polymers. AB - We present a theory of the temperature and electric field dependence on the mobility of polarons in conjugated polymers in terms of a tight-binding and stochastic approach. The polaron mobility is shown to have a strong dependence on the electric field, with two distinct regimes of temperature dependence. Lattice thermal oscillations enhance polaron mean velocity for electric fields of 1.0 mV/A or higher. In contrast, its mobility is damped by thermal oscillations under weaker electric fields. This semiconductor/metallic analogous behavior comes from the difference between the inertial content acquired by polarons under stronger/weaker electric fields. These new results and their analysis shed new light on several experimental controversies. PMID- 19642635 TI - Molecular design of 1,2,4,5-tetrazine-based high-energy density materials. AB - The heats of formation (HOFs) for a series of 1,2,4,5-tetrazine derivatives were calculated by using density functional theory (DFT), Hartree Fork (HF), and Moller-Plesset (MP2) as well as semiempirical methods. The effects of different basis bets on HOFs were also considered. Our results show that the -CN or -N3 group plays a very important role in increasing the HOF values of the 1,2,4,5 tetrazine derivatives. An analysis of the bond dissociation energies for the weakest bonds indicates that substitutions of the -N3, -NH2, -CN, -OH, or -Cl group are favorable for enhancing the thermal stability of 1,2,4,5-tetrazine, but the -NHNH2, -NHNO2, -NO2, -NF2, or -COOH group produces opposite effects. The calculated detonation velocities and pressures indicate that the -NF2 or -NO2 group is very helpful for enhancing the detonation performance for the derivatives, but the case is quite the contrary for the -CN, -NH2, or -OH group. Considered the detonation performance and thermal stability, three derivatives may be regarded as potential candidates of high-energy density materials (HEDMs). PMID- 19642636 TI - An unprecedentedly huge square-grid copper(II)-organic framework material built from a bulky pyrene-derived elongated cross-shaped scaffold. AB - A new bulky pyrene-derived elongated cross-shaped organic scaffold was successfully incorporated into a highly porous, noninterpenetrated square-grid copper(II)-organic framework material with the unprecedentedly huge dimensions of 25.5 x 25.5 A(2), while the layer-to-layer NH...N interaction leads to a unique hydrogen-bonded 6(4).8(2)-nbo net. PMID- 19642638 TI - Carbenes introduction. PMID- 19642637 TI - A new surface for immobilizing and maintaining the function of enzymes in a freeze-dried state. AB - We describe a new surface produced by plasma treatment for immobilizing proteins in the dry state. The need for surfaces suitable for immobilizing proteins is increasing because of demand for microarray diagnostic services, biosensors, and chemical processing. Storage of surface attached proteins in the dry state offers benefits of long shelf life, protection from proteases, easier transportation and convenient storage. In this work, we produced plasma-modified polyethylene surfaces and tested them using two important enzymes for which convenient functional assays are available, namely, horseradish peroxidase and catalase. Over 80% of the function of horseradish peroxidase is retained after freeze drying, and this function is unaltered after 4 months of storage at 4 degrees C on the treated polyethylene surface. The factors important for maintenance of surface attached enzyme stability were (1) plasma immersion ion implantation (PIII) treatment of the surface, (2) freeze-drying with sucrose in the buffer solution, (3) dry storage with desiccant, and (4) maintaining the freeze-dried protein at a reduced temperature. Other than sucrose, no other additives are needed. PMID- 19642639 TI - Conformational heterogeneity and spin-labeled -SH groups: pulsed EPR of Na,K ATPase. AB - Membranous Na,K-ATPase from shark salt gland and from pig kidney was spin-labeled on class I -SH groups in the presence of glycerol, or on class II -SH groups in the absence of glycerol. The class I-labeled preparations retain full enzymatic activity, whereas the class II-labeled preparations are at least partially inactivated. This provides an excellent testbed on which to demonstrate how advanced electron paramagnetic resonance (EPR) can provide novel information on specific residues in unique environments in a complex, membrane-bound transport system. The polarity of the environment, and the librational dynamics and conformational exchange, of the spin-labeled groups were studied with pulsed EPR by using electron spin echo envelope modulation (ESEEM) spectroscopy and spin echo detected (ED) EPR spectroscopy, respectively. 2H-ESEEM spectra of membranes dispersed in D2O reveal that class I groups of the shark enzyme are more exposed to water than are those of the pig enzyme or class II groups of either species, consistent with the more superficial membrane location in the former case. Spin echo decay curves indicate conformational heterogeneity at low temperatures (<150 K), but a more homogeneous conformational state at higher temperatures that is characterized by a single phase-memory T2M relaxation time. Conventional EPR lineshapes also demonstrate conformational microheterogeneity at low temperatures: the inhomogeneously broadened lines narrow progressively with increasing temperature reaching an almost pure Lorentzian line shape at temperatures of ca. 220 K and above. The inhomogeneous broadening at low temperature is well described by a Gaussian distribution of Lorentzian lines. ED spectra as a function of echo-delay time demonstrate the onset of rapid librational motions of appreciable amplitude, and slower conformational exchange, at temperatures above 220 K. These motions could drive transitions between the different conformational substates, which are frozen in at lower temperatures but contribute to the pathways between the principal enzymatic intermediates at higher temperatures. PMID- 19642642 TI - Crystallographic snapshots of nonaged and aged conjugates of soman with acetylcholinesterase, and of a ternary complex of the aged conjugate with pralidoxime. AB - Organophosphate compounds (OP) are potent inhibitors of acetylcholinesterases (AChEs) and can cause lethal poisoning in humans. Inhibition of AChEs by the OP soman involves phosphonylation of the catalytic serine, and subsequent dealkylation produces a form known as the "aged" enzyme. The nonaged form can be reactivated to a certain extent by nucleophiles, such as pralidoxime (2-PAM), whereas aged forms of OP-inhibited AChEs are totally resistant to reactivation. Here, we solved the X-ray crystal structures of AChE from Torpedo californica (TcAChE) conjugated with soman before and after aging. The absolute configuration of the soman stereoisomer adduct in the nonaged conjugate is P(S)C(R). A structural reorientation of the catalytic His440 side chain was observed during the aging process. Furthermore, the crystal structure of the ternary complex of the aged conjugate with 2-PAM revealed that the orientation of the oxime function does not permit nucleophilic attack on the phosphorus atom, thus providing a plausible explanation for its failure to reactivate the aged soman/AChE conjugate. Together, these three crystal structures provide an experimental basis for the design of new reactivators. PMID- 19642643 TI - Mass spectrometric identification of Au68(SR)34 molecular gold nanoclusters with 34-electron shell closing. AB - The molecular formula Au(68)(SCH(2)CH(2)Ph)(34) has been assigned to the 14 kDa nanocluster using MALDI-TOF mass spectrometry. The 34-electron shell closing in a macroscopically obtained thiolated gold nanocluster is demonstrated. The Au(68) nanocluster is predicted to have a 49 atom Marks decahedral core with 19 inner core atoms and 30 outer atoms chelating with the staple motifs. The nanoclusters' predicted formulation is [Au](19+30) [Au(SR)(2)](11) [Au(2)(SR)(3)](4). PMID- 19642644 TI - Quantum mechanical design and structure of the Li@B10H14 basket with a remarkably enhanced electro-optical response. AB - An innovative type of lithium decahydroborate (Li@B(10)H(14)) complex with a basketlike complexant of decaborane (B(10)H(14)) has been designed using quantum mechanical methods. As Li atom binds in a handle fashion to terminal electrophilic boron atoms of the decaborane basket, its NBO charge q (Li) is found to be 0.876, close to +1. This shows that the Li atom has been ionized to form a cation and an anion at the open end of B(10)H(14). The most fascinating feature of this Li doping is its loosely bound valence electron, which has been pulled into the cavity of the B(10)H(14) basket and become diffuse by the electron-deficient morphological features of the open end of the B(10)H(14) basket. Strikingly, the first hyperpolarizability (beta(0)) of Li@B(10)H(14) is about 340 times larger than that of B(10)H(14), computed to be 23,075 au (199 x 10(-30) esu) and 68 au, respectively. Besides this, the intercalation of the Li atom to the B(10)H(14) basket brings some distinctive changes in its Raman, (11)B NMR, and UV-vis spectra along with its other electronic properties that might be used by the experimentalists to identify this novel kind of Li@B(10)H(14) complex with a large electro-optical response. This study may evoke the possibility to explore a new thriving area, i.e., alkali metal-boranes for NLO application. PMID- 19642645 TI - Fischer carbene complexes in organic synthesis: metal-assisted and metal templated reactions. PMID- 19642646 TI - Electrochemical, linear optical, and nonlinear optical properties and interpretation by density functional theory calculations of (4-N,N dimethylaminostyryl)-pyridinium pendant group associated with polypyridinic ligands and respective multifunctional metal complexes (Ru(II) or Zn(II)). AB - The synthesis, linear optical and nonlinear optical properties, as well as the electrochemical behavior of a series of pro-ligands containing the 4-(4-N,N dimethylaminostyryl)-1-methyl pyridinium (DASP(+)) group as a push-pull moiety covalently linked to terpyridine or bipyridine as chelating ligands are reported in this full paper. The corresponding multifunctional Ru(II) and Zn(II) complexes were prepared and investigated. The structural, electronic, and optical properties of the pro-ligands and the ruthenium complexes were investigated using density functional theory (DFT) and time-dependent (TD) DFT calculations. A fairly good agreement was observed between the experimental and the calculated electronic spectra of the pro-ligands and their corresponding ruthenium complexes. A quenching of luminescence was evidenced in all ruthenium complexes compared with the free pro-ligands but even the terpyridine-functionalized metal complexes exhibited detectable luminescence at room temperature. Second order nonlinear optical (NLO) measurements were performed by Harmonic Light Scattering and the contribution of the DASP(+) moieties (and their relative ordering) and the metal-polypyridyl core need to be considered to explain the nonlinear optical properties of the metal complexes. PMID- 19642647 TI - Photoinduced Intramolecular addition of 3-acyl-2-haloindoles to alkenes. AB - 1,2-Fused indoles and pyrroles were prepared via an efficient intramolecular photoaddition reaction of 1-(omega-alkenyl)-2-haloindole-3-carbaldehydes and 1 (omega-alkenyl)-2-chloropyrrole-3-carbaldehydes. The presence of an acyl group was necessary for the photocyclization reactions. The halogen-atom-retained exo- and endo-cyclization products were generally produced with results similar to those of an atom-transfer cyclization reaction. In contrast, unsaturated cyclization products were obtained in the photoreaction of substrates having methyl groups on the vinyl group. PMID- 19642648 TI - Methanol as a reaction medium and reagent in substrate reactions of rhodium porphyrins. AB - Methanol solutions of rhodium(III) tetra(p-sulfonatophenyl) porphyrin [(TSPP)Rh(III)] have a hydrogen ion dependent equilibrium between bis-methanol, monomethoxy monomethanol, and bis-methoxy complexes. Reactions of dihydrogen (D(2)) with solutions of [(TSPP)Rh(III)] complexes in methanol produce equilibrium distributions of a rhodium hydride [(TSPP)Rh(III)-D(CD(3)OD)](-4) and rhodium(I) complex [(TSPP)Rh(I)(CD(3)OD)](-5). The rhodium hydride complex in methanol functions as a weak acid with an acid dissociation constant of 1.1(0.1) x 10(-9) at 298 K. Patterns of rhodium hydride substrate reactions in methanol are illustrated by addition with ethene, acetaldehyde, and carbon monoxide to form rhodium alkyl, alpha-hydroxyethyl, and formyl complexes, respectively. The free energy change for the addition reaction of [(TSPP)Rh(III)-D(CD(3)OD)](-4) with CO in methanol to produce a formyl complex (DeltaG(o)(298K) = -4.7(0.1) kcal mol(-1)) is remarkably close to DeltaG(o)(298K) values for analogous reactions in water and benzene. Addition reactions of the rhodium hydride ([(TSPP)Rh(III) D(CD(3)OD)](-4)) with vinyl olefins invariably yield the anti-Markovnikov product which places the rhodium porphyrin on the less hindered terminal primary carbon center. Addition of the rhodium-methoxide unit in [(TSPP)Rh(III) OCD(3)(CD(3)OD)](-4) with olefins to form beta-methoxyalkyl complexes places rhodium on the terminal carbon for alkene hydrocarbons and vinyl acetate, but vinyl olefins that have pi-electron withdrawing substituents have a thermodynamic preference for placing rhodium on the interior carbon where negative charge is better accommodated. Equilibrium thermodynamic values for addition of the Rh OCD(3) unit to olefins in methanol are evaluated and compared with values for Rh OH addition to olefins in water. PMID- 19642650 TI - Complement component C2, inhibiting a latent serine protease in the classical pathway of complement activation. AB - The innate immune response to infection or injury involves an antigen-antibody triggered classical pathway (CP) of complement activation, in which soluble and cell surface plasma proteins cooperatively effect elimination of foreign organisms and damaged host cells. However, protracted or dysfunctional complement activation can lead to inflammatory diseases. Complement component 2 bound to C4b is cleaved by classical (C1s) or lectin (MASP2) proteases to produce C4bC2a, a very short-lived C3 convertase (t(1/2) 2 min) that in turn cleaves C3 to C3a and C3b, leading ultimately to formation of Membrane Attack Complex (MAC) and lysis of bacteria and damaged cells. C2 has the same serine protease domain as C4bC2a but in an inactive zymogen-like conformation, requiring cofactor-induced conformational change for activity. Here, we show that C2 has catalytic protease activity in its own right above pH 7, in the absence of cofactor, processing C3 and C3-derived chromogenic peptide fragments. In contrast to the instability of C3 convertase (t(1/2) 2 min, pH 7), the C2 enzyme is indefinitely stable under alkaline conditions, facilitating studies of its catalytic properties and development of small molecule inhibitors. We characterize the catalytic activity of C2 against C3 and short paranitroanilide peptide substrates, and identify potent small molecule inhibitors of C2 that also inhibit classical pathway C3 convertase, MAC formation, and hemolysis of sensitized sheep erythrocytes. These results provide a new avenue and valuable new insights to inhibiting CP complement activation relevant to inflammatory diseases. PMID- 19642649 TI - Synthesis of alpha-ketoester- and alpha-hydroxyester-substituted isoindazoles via the thermodynamic coarctate cyclization of ester-terminated azo-ene-yne systems. AB - The synthesis of isoindazoles bearing alpha-ketoester and alpha-hydroxyester groups via the coarctate cyclization of ester-terminated azo-ene-yne precursors is described. Whereas previous studies on isoindazole formation have shown the reaction to proceed through a kinetic coarctate pathway, functionalization of the terminal acetylene with a methyl ester sufficiently stabilizes the carbene intermediate to make the coarctate cyclization the thermodynamic pathway. Density functional theory (DFT) computations reveal ca. 8-9 kcal mol(-1) lower energy transition states for the coarctate pathway compared to the parent system. PMID- 19642651 TI - Interaction of human DNA polymerase alpha and DNA polymerase I from Bacillus stearothermophilus with hypoxanthine and 8-oxoguanine nucleotides. AB - To better understand how DNA polymerases interact with mutagenic bases, we examined how human DNA polymerase alpha (pol alpha), a B family enzyme, and DNA polymerase from Bacillus stearothermophilus (BF), an A family enzyme, generate adenine:hypoxanthine and adenine:8-oxo-7,8-dihydroguanine (8-oxoG) base pairs. Pol alpha strongly discriminated against polymerizing dATP opposite 8-oxoG, and removing N1, N(6), or N7 further inhibited incorporation, whereas removing N3 from dATP dramatically increased incorporation (32-fold). Eliminating N(6) from 3 deaza-dATP now greatly reduced incorporation, suggesting that incorporation of dATP (analogues) opposite 8-oxoguanine proceeds via a Hoogsteen base pair and that pol alpha uses N3 of a purine dNTP to block this incorporation. Pol alpha also polymerized 8-oxo-dGTP across from a templating A, and removing N(6) from the template adenine inhibited incorporation of 8-oxoG. The effects of N1, N(6), and N7 demonstrated a strong interdependence during formation of adenine:hypoxanthine base pairs by pol alpha, and N3 of dATP again helps prevent polymerization opposite a templating hypoxanthine. BF very efficiently polymerized 8-oxo-dGTP opposite adenine, and N1 and N7 of adenine appear to play important roles. BF incorporates dATP opposite 8-oxoG less efficiently, and modifying N1, N(6), or N7 greatly inhibits incorporation. N(6) and, to a lesser extent, N1 help drive hypoxanthine:adenine base-pair formation by BF. The mechanistic implications of these results showing that different polymerases interact very differently with base lesions are discussed. PMID- 19642652 TI - Importance of Coriolis Coupling in Isotopic Branching in (He, HD+) collisions. AB - A three-dimensional time-dependent quantum mechanical wave packet approach is used to calculate the reaction probability (P(R)) and integral reaction cross section values for both channels of the reaction He + HD(+)(v = 1; j = 0) --> HeH (D)(+) + D (H) over a range of translational energy (E(trans)) on the McLaughlin Thompson-Joseph-Sathyamurthy potential energy surface including the Coriolis coupling (CC) term in the Hamiltonian. The reaction probability plots as a function of translational energy for different J values exhibit several oscillations, which are characteristic of the system. The sigma(R) values obtained by including CC and not including it are nearly the same over the range of E(trans) investigated for the HeD(+) channel. For the HeH(+) channel, on the other hand, sigma(R) values obtained from CC calculations are significantly smaller than those obtained from coupled state calculations. These results are compared with the available experimental results. The computed branching ratios (Gamma(sigma) = sigma(R) (HeH(+))/sigma(R) (HeD(+))) are also compared with the available experimental results. PMID- 19642653 TI - Dual fluorescent photochromic colorants bearing pyrano[3,2-c]chromen-5-one moiety. AB - In this study, the photochromic processes of 8-N,N-dimethylamino-2,2-dimethyl-2H pyrano[3,2-c]chromen-5-one (1) and its derivatives (2, 3) are investigated with steady-state, temperature-dependent and time-resolved absorption and emission spectroscopy. The differences among compounds 1-3 lie in their various substituents anchored at the pyran moiety that is subject to the photoinduced ring-opening reaction. Compounds 1 and 2 exhibit salient photochromism with a very unique phenomenon, in which fluorescence is observed in 1 for both the ring closed form (1-CF, lambda(max) approximately 445 nm) and the ring-open form (1 OF, lambda(max) approximately 650 nm in CH2Cl2). The yields of forward and reverse photochromism processes were determined to be 0.40 and 1.0% for 1. Along with fluorescence quantum yields of 9.5 x 10(-2) and 5.8 x 10(-3) for 1-CF and 1 OF, respectively, 1 enables fluorescence detection while it exhibits photochromism in both directions, that is, a photoinduced on/off fluorescence switch. An increase in on/off ratiometric fluorescence between 1-OF and 1-CF can reach a factor of 4.0 upon excitation at the absorption isosbestic point. The activation energies for the ground-state OFtrans --> CF thermal bleaching processes were determined to be 58.2 and 54.8 kJ/mol, with frequency factors of 1.7 x 10(5) and 3.6 x 10(5) s(-1) for 1 and 2, respectively. Conversely, bromo substituted 3 did not undergo photochromic reaction, as evidenced by the lack of changes in the absorption spectrum after a prolonged (2 h) 354 nm (0.2 W/cm2) photolysis, manifesting the fact that other relaxation processes, such as enhanced intersystem crossing, may govern the deactivation of 3 (3-CF) upon excitation. PMID- 19642655 TI - Study on the gel to crystal transition of a novel sugar-appended gelator. AB - 4-(4'-Ethoxyphenyl)phenyl-beta-O-d-glucoside (1) was synthesized. A perfect crystal of 1 was obtained from an acetonitrile solution. In a mixture of water/1,4-dioxane (8/2, v/v), a gel formed at first and then collapsed into a needlelike crystal. The crystal and the gel were characterized by X-ray diffraction, UV-vis absorption, circular dichroism, Fourier transform infrared spectroscopy, and electron microscopy. It was found that the crystal formed from the gel had the same diffraction pattern as that of the single crystal from the acetonitrile solution, suggesting identical molecular packing. In a monoclinic cell containing two molecules, molecules took a "T" arrangement with an antiparallel direction. In contrast, the diffraction pattern of xerogel from water/1,4-dioxane (8/2, v/v) displayed a d-spacing ratio of 1:1/2:1/3 (2.39, 1.18, and 0.78 nm), indicating an interdigitated bilayer structure. A molecular packing model from gel to crystal where molecular sheets would insert into each other with a glide movement was suggested. On the basis of the understanding of the deformation mechanism, an additive was introduced to obtain a stable gel. PMID- 19642654 TI - Responsive polymer nanoparticles formed by poly(ether amine) containing coumarin units and a poly(ethylene oxide) short chain. AB - We reported a novel poly(ether amine) (PEAC) containing poly(ethylene oxide) (PEO) short blocks and coumarin units, which was synthesized by nucleophilic addition/ring-opening polymerization of diepoxy and diamine monomers. PEAC can be directly dispersed in aqueous solution as uniformly sized nanoparticles 50-60 nm in diameter. The whole process for aggregation of PEAC was revealed by transmission electron microscopy (TEM) and ultraviolet-visible (UV-vis) spectra. The results show that these polymeric nanoparticles possess a very sharp response to temperature and light, and can form complex micromicelles with nanoparticles inside. PMID- 19642656 TI - Nonprotein based enrichment method to analyze peptide cross-linking in protein complexes. AB - Cross-linking analysis of protein complexes and structures by tandem mass spectrometry (MS/MS) has advantages in speed, sensitivity, specificity, and the capability of handling complicated protein assemblies. However, detection and accurate assignment of the cross-linked peptides are often challenging due to their low abundance and complicated fragmentation behavior in collision-induced dissociation (CID). To simplify the MS analysis and improve the signal-to-noise ratio of the cross-linked peptides, we developed a novel peptide enrichment strategy that utilizes a cross-linker with a cryptic thiol group and using beads modified with a photocleavable cross-linker. The functional cross-linkers were designed to react with the primary amino groups in proteins. Human serum albumin was used as a model protein to detect intra- and intermolecular cross-linkages. Use of this protein-free selective retrieval method eliminates the contamination that can result from avidin-biotin based retrieval systems and simplifies data analysis. These features may make the method suitable to investigate protein protein interactions in biological samples. PMID- 19642658 TI - Crystal growth, structural properties, and photophysical characterization of Ln4Na2K2M2O13 (M = Nb, Ta; Ln = Nd, Sm, Eu, Gd). AB - Single crystals of Ln(4)Na(2)K(2)M(2)O(13) (Ln = Nd, Sm, Eu, Gd; M = Nb, Ta) were grown out of a reactive high temperature hydroxide melt. The structures were determined by single crystal X-ray diffraction. Ln(4)Na(2)K(2)M(2)O(13) crystallizes in the monoclinic space group C2/c in which niobium and tantalum are located in a rare 5-coordinate, square pyramidal coordination environment. Optical band gaps were estimated from diffuse reflectance UV/vis spectra. The magnetic susceptibility data were measured, and the intense room temperature photoluminescence of the europium containing compounds was studied. PMID- 19642657 TI - Downscaling limits and confinement effects in the miniaturization of porous polymer monoliths in narrow bore capillaries. AB - Monolithic poly(butyl methacrylate-co-ethylene dimethacrylate) columns have been prepared in capillaries ranging in inner diameter from 5 to 75 microm using thermally initiated free-radical polymerization of a mixture of butyl methacrylate, ethylene dimethacrylate, and porogens at different temperatures. Scanning electron microscopy and the measurement of hydrodynamic properties reveal that the downward scalability of the monolithic columns is greatly affected by the confinement effect of the capillary wall resulting from the decreased volume-to-surface ratio as the capillary diameter is decreased. The downscaling process is affected most by the polymerization temperature, the diffusion of the propagating radicals, and the density of coverage of polymerizable groups on the inner walls of the capillary. Optimization of all these factors enables the preparation of monolithic structures in capillaries with inner diameters as low as 5 microm while retaining the desirable properties of monoliths prepared in much larger capillaries. Under these conditions, formation of undesired dense polymer layers attached to the capillary wall was minimized. The chromatographic performance of 10, 25, and 50 microm capillaries evaluated in the reversed phase gradient separation of three proteins showed no change in elution times at identical flow velocities and gradient times, while peak elution width was the smallest with the narrowest capillary. PMID- 19642659 TI - Solution-processed germanium nanocrystal thin films as materials for low-cost optical and electronic devices. AB - Solution-processed nanocrystal films have attracted significant interest as potential semiconductor materials with size-tunable optical and electronic properties that can be deposited with low-cost printing and coating techniques. Significant progress has been reported with groups II-VI and IV-VI nanocrystal films because the electrically insulating ligands that solubilize the nanocrystals can be easily exchanged or removed after film deposition. Although progress to date has been slow for group IV silicon and germanium nanocrystal films, this paper reports solution-processed germanium nanocrystal films with promising electrical conductivities. Stable germanium nanocrystal colloids are produced via nonthermal plasma synthesis and subsequent alkene surface functionalization. Electrical characterization of drop-cast germanium nanocrystal films reveals that the films are insulating as deposited but have conductivities as large as 10(-6) and 5x10(-4) S/cm after annealing at 250 and 500 degrees C, respectively. Mass spectrometry, thermogravimetric analysis, and infrared spectroscopy indicate that the increase in conductivity coincides with the decomposition and departure of the alkyl ligands from the films. PMID- 19642660 TI - An efficient and diastereoselective synthesis of PSI-6130: a clinically efficacious inhibitor of HCV NS5B polymerase. AB - R7128 is the prodrug of 2'-deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130), a potent and selective inhibitor of HCV NS5B polymerase. Currently, R7128 is in clinical trials for the treatment of HCV infection. To support clinical development efforts, we needed an efficient and scalable synthesis of PSI-6130. We describe an improved, diastereoselective synthetic route starting with protected d-glyceraldehyde. No chiral reagents or catalysts were used to produce the three new contiguous stereocenters. Introduction of fluorine at the C-2 tertiary carbon was accomplished in a highly regio- and stereoselective manner through nucleophilic substitution on a cyclic sulfate. Scale-limiting chromatographic purifications were eliminated through the use of crystalline intermediates. PMID- 19642661 TI - Band structure, density of states, and optical susceptibilities of a novel lithium indium orthoborate Li3InB2O6. AB - By use of the structural parameters of the single crystal lithium indium orthoborate obtained by Penin et al. (Solid State Sci. 2001, 3, 461-468), from X- ray diffraction data, we present a first-principle study of the electronic structure and the linear optical properties for the novel lithium indium orthoborate Li3InB2O6. A full-potential linear augmented plane wave method within density functional theory with the Engel-Vosko exchange correlation was used. This compound has a wide direct energy band gap of about 3.8 eV with both the valence band maximum and conduction band minimum located at the center of the Brillouin zone. Our calculations of the partial density of states shows that the upper valence band originates predominantly from the O-p, B- p, and In-p states, and the lower conduction band is dominated by the O-s/p, In-p, and B-p states. Thus the O-p states in the upper valence band and lower conduction band has a significant effect on the energy band gap dispersion. The uniaxial anisotropy [deltaepsilon=(epsilon0zz-epsilon0xx)/epsilon0tot] is about -0.041. PMID- 19642662 TI - What is important to prevent oxidative stress? A theoretical study on electron transfer reactions between carotenoids and free radicals. AB - Oxidative stress is related to the development of a large number of health disorders. Therefore, the study of molecular systems capable of preventing its onset by fighting free radicals is a crucial area of research. Carotenoids are one of the most efficient families of compounds fulfilling this purpose. In the present work, the free-radical-scavenger efficiency, expressed as the one electron-donating capability, of different carotenoids has been studied using density functional theory. A large number of free radicals were considered, as well as environments of different polarity. A new donor-acceptor map is proposed that allows a rapid evaluation of full electron-transfer processes. Its efficiency for predicting the feasibility of electron transfer (ET) between carotenoids and free radicals was tested and validated through comparison with the corresponding Gibbs free energies of reaction. Our results demonstrate that ET reactions between carotenoids and free radicals are strongly influenced by the nature of the latter. Moreover, it is proposed that the electron affinity (EA) of the reacting free radical has an important effect on the viability of these reactions. The reactions were found to become exergonic when the EA of the free radical involved reaches a value of approximately 5 eV. PMID- 19642663 TI - Self-assembled cylindrical and vesicular molecular templates for polyaniline nanofibers and nanotapes. AB - We report a soft template approach based on a custom-designed novel surfactant cum-dopant for size and shape tuning of polyaniline nanomaterials such as nanofibers and nanotapes via emulsion and dispersion polymerization routes. A new amphiphilic 4-(3-dodecyl-8-enylphenyloxy) butane sulfonic acid was synthesized by ring-opening of butanesultone with renewable resource cardanol. The new amphiphilic dopant forms spherical micelles in water and its critical micelle concentration was determined by dye encapsulation and surface tension methods. In the emulsion route, the amphiphilic dopant complexed with aniline to produce cylindrical micellar aggregates that template exclusively for polyaniline nanofibers. The dispersion of aniline+dopant in water/toluene solvent mixture produces vesicles that selectively template for polyaniline nanotapes. The mechanism of the polyaniline nanomaterials formation was investigated by dynamic light scattering (DLS) and high-resolution transmission electron microscopy (HR TEM). DLS of the polymerization templates in water proved the presence of micrometer range aggregates, and TEM images confirmed the shape of the cylindrical and vesicular templates. The polyaniline nanomaterials were found soluble in water and polar organic solvents for structural characterization and composition analysis by 1H NMR spectroscopy. Absorbance spectra of the nanomaterials showed free carrier tail above 900 nm in the near IR region for the delocalization of electrons in the polaron band corresponding to expanded conformation of polyaniline chains. Wide angle X-ray diffraction showed two new peaks at low angle region with d-spacing of 26.5 and 13.6 A corresponding to lamellar ordering of polyaniline chains followed by interdigitations of the amphiphilic dopant in the nanomaterials. PMID- 19642664 TI - Metal-binding affinity and selectivity of nonstandard natural amino acid residues from DFT/CDM calculations. AB - Unnatural amino acid residues are increasingly being used in metalloprotein design and engineering to expand the repertoire of protein structures/folds and functions. However, natural but nonstandard amino acid residues (not in the basic set of 20) possessing metal-ligating groups such as selenocysteine (Sec), pyrrolysine (Pyl), and gamma-carboxyglutamic acid (Gla) have attracted little attention, and their potential as metal-binding entities in metalloprotein engineering has not been assessed. In particular, the metal-binding affinity/selectivity of these three rare residues remains unclear. Herein, the metal-binding affinity/selectivity of the Gla, Pyl, and Sec side chains have been systematically studied using a combined density functional theory and continuum dielectric method. The calculations reveal an advantage of using these noncanonical protein building blocks instead of the standard 20 amino acid residues. Gla2-, Pyl0, and Sec- have greater potential in trapping the metal cation than their standard amino acid counterparts. They prefer binding to Zn2+ rather than to Mg2+ or Ca2+ in a protein cavity due to the better electron accepting ability and lower coordination number preference of Zn2+, as compared to Mg2+ and Ca2+. Between Ca2+ and Mg2+, Gla2- prefers Ca2+, whereas Pyl0 and Sec poorly discriminate between the two metal cations. The results herein suggest that Gla2-, Pyl0, and Sec- could be employed as very efficient metal-binding entities in engineering metalloproteins with preprogrammed properties. PMID- 19642665 TI - Gas phase absorption studies of photoactive yellow protein chromophore derivatives. AB - Photoabsorption spectra of deprotonated trans p-coumaric acid and two of its methyl substituted derivatives have been studied in gas phase both experimentally and theoretically. We have focused on the spectroscopic effect of the location of the two possible deprotonation sites on the trans p-coumaric acid which originate to either a phenoxide or a carboxylate. Surprisingly, the three chromophores were found to have the same absorption maximum at 430 nm, in spite of having different deprotonation positions. However, the absorption of the chromophore in polar solution is substantially different for the distinct deprotonation locations. We also report on the time scales and pathways of relaxation after photoexcitation for the three photoactive yellow protein chromophore derivatives. As a result of these experiments, we could detect the phenoxide isomer within the deprotonated trans p-coumaric acid in gas phase; however, the occurrence of the carboxylate is uncertain. Several computational methods were used simultaneously to provide insights and assistance in the interpretation of our experimental results. The calculated excitation energies S(0)-S(1) are in good agreement with experiment for those systems having a negative charge on a phenoxide moiety. Although our augmented multiconfigurational quasidegenerate perturbation theory calculations agree with experiment in the description of the absorption spectrum of anions with a carboxylate functional group, there are some puzzling disagreements between experiment and some calculational methods in the description of these systems. PMID- 19642666 TI - Toward detecting the formation of a single helical turn by 2D IR cross peaks between the amide-I and -II modes. AB - We have combined two-dimensional infrared (2D IR) spectroscopy and isotope substitutions to reveal the vibrational couplings between a pair of amide-I and II modes that are several residues away but directly connected through a hydrogen bond in a helical peptide. This strategy is demonstrated on a 3(10)-helical hexapeptide, Z-Aib-L-Leu-(Aib)2-Gly-Aib-OtBu, and its 13C=18O-Leu monolabeled and 13C=18O-Leu/15N-Gly bis-labeled isotopomers in CDCl3. The isotope-dependent amide I/II cross peaks clearly show that the second and fourth peptide linkages are vibrationally coupled as they are in proximity, forming a 3(10)-helical turn. The experimental spectra are compared to simulations based on a vibrational exciton Hamiltonian model that fully takes into account the amide-I and -II modes. The amide-II local mode frequency is evaluated by a new model based on the effects of hydrogen-bond geometry and sites. Ab initio nearest-neighbor coupling maps of the amide-I/I, -I/II, -II/I and -II/II modes are generated by isotopically isolating the local modes of N-acetyl-glycine N'-methylamide (AcGlyNHMe). Longer range couplings are modeled by transition charge interactions. The effects of the capping groups are incorporated and isotope effects are analyzed based on ab initio calculations of six model compounds. The main features of the 2D IR spectra are reproduced by this modeling. The conformational sensitivity of the isotope-dependent amide-I/II cross peaks is discussed in comparison with the calculated spectra for a semiextended structure. Our experimental and theoretical study demonstrates that the combination of 2D IR and 13C=18O/15N labeling is a useful structural method for detecting helical turn formation with residue-level specificity. PMID- 19642667 TI - Silicon-containing soybean-oil-based copolymers. Synthesis and properties. AB - New silicon-containing soybean-oil-based copolymers were prepared from soybean oil, styrene, divinylbenzene, and p-trimethylsilylstyrene by cationic polymerization using boron trifluoride etherate as initiator. Soxhlet extraction and NMR spectroscopy indicate that the copolymers consist of a cross-linked network plasticized with varying amounts of oligomers and unreacted oil. This soluble fraction increases when the SiST content in the feed increases, according to a lower reactivity of this monomer. The thermal, dynamomechanical, and flame retardant properties of these materials were examined. Thermosets with glass transition temperatures ranging from 50 to 62 degrees C, which are thermally stable below 350 degrees C, and with LOI values from 22.6 to 29.7 were obtained. Their properties suggest that these materials may prove to be useful alternatives for current non-renewable-based thermosets and that the flame-retardant properties of vegetable-oil-based thermosets can be improved by adding covalently bonded silicon to the polymer. PMID- 19642668 TI - Effect of L-leucine graft content on aqueous solution behavior and membrane-lytic activity of a pH-responsive pseudopeptide. AB - A series of pH-responsive polymers have been synthesized by grafting L-leucine onto the pendant carboxylic acid groups of the linear pseudopeptide, poly(L lysine iso-phthalamide). The effect of the degree of grafting on aqueous solution properties, cell membrane-disruptive activity, and in vitro cytotoxicity was examined by UV-visible and fluorescence spectroscopy, hemolysis, alamar blue staining, and propidium iodide fluorescence assays. Modification of poly(L-lysine iso-phthalamide) with < or =23.6 mol % L-leucine caused a marginal effect on the pH-mediated hydrophobic association and hemolytic activity. Increasing the degree of grafting from 31.9 to 61.2 mol % resulted in polymers with progressively enhanced hydrophobic association and cell membrane disruption, thus confirming that the pH responsiveness and the extent of hydrophobic association and membrane disruption of the polymers can be modulated by varying the degree of grafting with hydrophobic amino acids. The pH responses were demonstrated to be concentration-dependent. At certain degrees of leucine grafting, the polymers were nonmembrane-lytic at physiological pH but mediated considerable membrane lysis at endosomal pH values (5.0-6.8), a feature critical for potential drug delivery applications. PMID- 19642669 TI - Effect of peptide sequence on surface properties and self-assembly of an amphiphilic pH-responsive peptide. AB - Peptides that undergo a morphological change when exposed to a stimulus have been investigated for their surface and self-assembly properties. Two 15-residue sequences were designed and synthesized for the purpose of determining the role of sequence on surface properties and peptide self-assembly. The KhK (KKKFLIVIGSIIKKK) and Alternating Kh (KFLKKIVKIGKKSII) sequences were synthesized via microwave peptide synthesis according to the automated base-labile Fmoc strategy. Despite having the same amino acid content, KhK solutions exhibited an increase in contact angle with increasing pH, whereas Alternating Kh solutions demonstrated a decrease in contact angle with increasing pH. Further analysis by transmission electron microscopy (TEM) and scanning electron microscopy (SEM) showed marked differences in the peptide solution and peptide particle morphology. Circular dichroism (CD) spectroscopy indicated that KhK consisted of primarily beta-sheet conformations at acidic and neutral pH. In Alternating Kh CD spectra, random coil conformations were predominant at acidic and neutral pH. PMID- 19642670 TI - Characterization of the rheological, mucoadhesive, and drug release properties of highly structured gel platforms for intravaginal drug delivery. AB - This investigation describes the formulation and characterization of rheologically structured vehicles (RSVs) designed for improved drug delivery to the vagina. Interactive, multicomponent, polymeric platforms were manufactured containing hydroxyethylcellulose (HEC, 5% w/w) polyvinylpyrrolidone (PVP, 4% w/w), Pluronic (PL, 0 or 10% w/w), and either polycarbophil (PC, 3% w/w) or poly(methylvinylether-co-maleic anhydride) (Gantrez S97, 3% w/w) as a mucoadhesive agent. The rheological (torsional and dynamic), mechanical (compressional), and mucoadhesive properties were characterized and shown to be dependent upon the mucoadhesive agent used and the inclusion/exclusion of PL. The dynamic rheological properties of the gel platforms were also assessed following dilution with simulated vaginal fluid (to mimic in vivo dilution). RSVs containing PC were more rheologically structured than comparator formulations containing GAN. This trend was also reflected in formulation hardness, compressibility, consistency, and syringeability. Moreover, formulations containing PL (10% w/w) were more rheologically structured than formulations devoid of PL. Dilution with simulated vaginal fluids significantly decreased rheological structure, although RSVs still retained a highly elastic structure (G' > G'' and tan delta < 1). Furthermore, RSVs exhibited sustained drug release properties that were shown to be dependent upon their rheological structure. It is considered that these semisolid drug delivery systems may be useful as site retentive platforms for the sustained delivery of therapeutic agents to the vagina. PMID- 19642671 TI - Dissolution and gelation of cellulose in TBAF/DMSO solutions: the roles of fluoride ions and water. AB - Solutions of cellulose in a mixture of tetrabutylammonium fluoride and dimethyl sulfoxide (TBAF/DMSO) containing small and varying amounts of water were studied by nuclear magnetic resonance (NMR). By measuring the composition dependences of (19)F NMR and (1)H NMR chemical shifts and line widths, details on the dissolution and gelation mechanisms for cellulose in TBAF/DMSO were elucidated. Our results suggest that the strongly electronegative fluoride ions act as hydrogen bond acceptors to cellulose hydroxyl groups, thus dissolving the polymer by breaking the cellulose-cellulose hydrogen bonds and by rendering the chains an effective negative charge. It was found that the fluoride ions also interact strongly with water. Small amounts of water remove the fluoride ions from the cellulose chains and allow reformation of the cellulose-cellulose hydrogen bonds, which leads to formation of highly viscous solutions or gels even at low cellulose concentrations. PMID- 19642672 TI - Inhibition of suicidal erythrocyte death by xanthohumol. AB - Xanthohumol is a proapoptotic hop-derived beer component with anticancer and antimicrobial activities. Similar to nucleated cells, erythrocytes may undergo suicidal cell death or eryptosis, which is triggered by oxidative stress (tert butylhydroperoxide, TBOOH) or energy depletion (removal of glucose). The triggers increase cytosolic Ca(2+) concentration, leading to activation of Ca(2+) sensitive K(+) channels with subsequent cell shrinkage and to cell membrane scrambling with subsequent phosphatidylserine exposure at the erythrocyte surface. Eryptotic cells are cleared from the circulating blood, leading to anemia, and may adhere to the vascular wall, thus impeding microcirculation. The present experiments explored whether xanthohumol influences eryptosis using flow cytometry. Exposure of human erythrocytes to 0.3 mM TBOOH or incubation in glucose-free solution significantly increased Fluo3 fluorescence (Ca(2+) concentration) as well as annexin V-binding (cell membrane scrambling) and decreased forward scatter (cell volume), effects significantly blunted by xanthohumol. In conclusion, xanthohumol is a potent inhibitor of suicidal erythrocyte death in vitro. PMID- 19642673 TI - Kafirin microparticle encapsulation of catechin and sorghum condensed tannins. AB - To exploit the porous nature of previously developed kafirin microparticles, encapsulation of the bioactive polyphenols, catechin and sorghum condensed tannins, was investigated. The antioxidant release profiles of the encapsulated substances were studied under simulated gastric conditions. Kafirin microparticles encapsulating catechin or sorghum condensed tannins were similar in size to control kafirin microparticles (5-6 mum). TEM showed that kafirin microparticles encapsulating catechin had a rough porous surface. Microparticles encapsulating sorghum condensed tannins were irregular in shape, some apparently joined together, with a mixture of rough and smooth surfaces. Over a period of 4 h, catechin and sorghum condensed tannin encapsulated kafirin microparticles showed virtually no protein digestion but released approximately 70 and 50%, respectively, of total antioxidant activity. Thus, the use of kafirin microparticles to encapsulate catechin and sorghum condensed tannins has potential as an effective method of controlled release of dietary antioxidants. PMID- 19642674 TI - Drug design, in vitro pharmacology, and structure-activity relationships of 3 acylamino-2-aminopropionic acid derivatives, a novel class of partial agonists at the glycine site on the N-methyl-D-aspartate (NMDA) receptor complex. AB - Retaining agonistic activity at the glycine coagonist site of the NMDA receptor in molecules derived from glycine or d-serine has proven to be difficult because in the vicinity of the alpha-amino acid group little substitution is tolerated. We have solved this problem by replacing the hydroxy group of d-serine with an amido group, thus keeping the hydrogen donor function and allowing for further substitution and exploration of the adjacent space. Heterocyclic substitutions resulted in a series of 3-acylamino-2-aminopropionic acid derivatives, with high affinities in a binding assay for the glycine site. In a functional assay assessing the activation of the glycine site, these compounds displayed a wide range of intrinsic efficacies, from antagonism to a high degree of partial agonism. Structure-activity relationships reveal that lipophilic substituents, presumably filling an additional hydrophobic pocket, are accepted by the glycine site, provided that they are separated from the alpha-amino acid group by a short linker. PMID- 19642675 TI - Influence of the side chain next to C-terminal benzimidazole in opioid pseudopeptides containing the Dmt-Tic pharmacophore. AB - To improve the structure-activity studies of the lead delta opioid agonist H-Dmt Tic-Asp*-Bid, we synthesized and pharmacologically characterized a series of analogues in which the side chain next to 1H-benzimidazole-2-yl (Bid) was substituted by those endowed with different chemical properties. Interesting results were obtained: (1) only Gly, Ala, and Asp resulted in delta agonism, (2) Phe yielded delta antagonism, (3) and all other residues except Glu (devoid of any activity) gave mu agonism. PMID- 19642676 TI - Enhanced optical activity by achiral rod-like molecules nanosegregated in the B4 structure of achiral bent-core molecules. AB - Chirality in a mixture system consisting of bent-core 1,3-phenylene bis[4-(4-8 alkoxyphenyliminomethyl)benzoates] (P8-O-PIMB) and rod-like n-pentyl cyanobiphenyl (5CB) molecules has been studied. Precise circular dichroism (CD) spectra using thin sample cells indicate mainly two characteristics: (1) the origin of CD signals is due to chiral-segregated bent-core molecules in the B(4) phase, where 5CB is in the isotropic phase; (2) the enhanced CD signal is detected in the B(X) phase, where 5CB is in the nematic phase. These results suggest that 5CB molecules are embedded in the network of helical nanofilaments formed by P8-O-PIMB and form helical superstructure with the same handedness as the helical nanofilaments in the B(X) phase, resulting in the giant CD signals. PMID- 19642678 TI - Shape-selective enantioselective hydrogenation on Pt nanoparticles. AB - The structure sensitivity of enantioselective hydrogenations on chirally modified metals was investigated using Pt nanoparticles of different shapes. All three samples had an average particle size of 10 nm, but the fraction of dominantly cubic, cubooctahedral, and octahedral particles varied with decreasing {100} and increasing {111} faces in the same order. In the absence of chiral modifier the hydrogenation of ethyl pyruvate was independent of the shape of the Pt nanoparticles; variation of the specific reaction rates did not exceed the experimental error on all self-prepared catalysts and on a commercial Pt/Al(2)O(3) used as reference. Addition of cinchonidine or quinine induced a significant rate enhancement by a factor of 4-15, and the rate was always higher with quinine. Also, 72-92% ees were achieved, and the reaction was shape selective: both the rate and the ee increased with increasing Pt{111}/Pt{100} ratio. A similar correlation in the hydrogenation of ketopantolactone confirmed that decarbonylation or aldol-type side reactions of ethyl pyruvate were not the reason for structure sensitivity. A combined catalytic and theoretical study revealed that the probable origin of the particle shape dependency of enantioselective hydrogenation is the adsorption behavior of the cinchona alkaloid. DFT studies of cinchonidine interacting with Pt(100) and Pt(111) terraces indicated a remarkably stronger interaction on the former crystallographic face by ca. 155 kJ/mol. The higher adsorption strength on Pt(100) was corroborated experimentally by the faster hydrogenation of the homoaromatic ring of the alkaloid, which fragment interacts the strongest with Pt during its adsorption. Thus, an ideal catalyst for the hydrogenation of activated ketones contains dominantly Pt{111} terraces, which crystallographic face is more active and affords higher enantioselectivity, combined with the higher stability of the modifier. PMID- 19642680 TI - Internal return of carbon dioxide in decarboxylation: catalysis of separation and 12C/13C kinetic isotope effects. AB - It has been proposed that the decarboxylation of mandelylthiamin, the adduct of benzoylformate and thiamin, is uniquely catalyzed by protonated pyridines through a preassociation mechanism in which proton transfer competes with the internal return of carbon dioxide. Application of this mechanism suggests that the observed primary (12)C/(13)C kinetic isotope effect in the absence of catalyst is reduced in magnitude because diffusion of carbon dioxide is partially rate determining. Where proton transfer blocks the internal return of carbon dioxide, the separation of carbon dioxide is facilitated, and the observed isotope effect increases toward the intrinsic value for carbon-carbon bond breaking. Headspace analysis of carbon dioxide formed over the course of the reaction shows that protonated pyridine increases the magnitude of the observed (12)C/(13)C KIE, consistent with the proposed mechanism. PMID- 19642679 TI - Multiplex single-nucleotide polymorphism typing by nanoparticle-coupled DNA templated reactions. AB - A novel chip-based detection approach for single-nucleotide polymorphism (SNP) typing based on nanoparticle-coupled DNA-templated ligation reactions is reported. In contrast to conventional methods or recently developed techniques, this approach does not need costly instrumentation and complex stringency washing processes and offers both rapid multiplex SNP detection capability and ultrahigh sensitivity. The ability of the approach to quickly identify the precise location of the single-base mismatch may provide a time-efficient method for high throughput multiplex SNP genotyping. PMID- 19642681 TI - Matching active site and substrate structures for an RNA editing reaction. AB - The RNA-editing adenosine deaminases (ADARs) catalyze deamination of adenosine to inosine in a double-stranded structure found in various RNA substrates, including mRNAs. Here we present recent efforts to define structure/activity relationships for the ADAR reaction. We describe the synthesis of new phosphoramidites for the incorporation of 7-substituted-8-aza-7-deazaadenosine derivatives into RNA. These reagents were used to introduce the analogues into mimics of the R/G-editing site found in the pre-mRNA for the human glutamate receptor B subunit (GluR B). Analysis of the kinetics of the ADAR2 reaction with analogue-containing RNAs indicated 8-aza-7-deazaadenosine is an excellent substrate for this enzyme with a deamination rate eight times greater than that for adenosine. However, replacing the C7 hydrogen in this analogue with bromine, iodine, or propargyl alcohol failed to increase the deamination rate further but rather decreased the rate. Modeling of nucleotide binding in the enzyme active site suggested amino acid residues that may be involved in nucleotide recognition. We carried out a functional screen of a library of ADAR2 mutants expressed in S. cerevisiae that varied the identity of these residues to identify active deaminases with altered active sites. One of these mutants (ADAR2 R455A) was able to substantially overcome the inhibitory effect of the bulky C7 substituents (-Br, -I, propargyl alcohol). These results advance our understanding of the importance of functional groups found in the edited nucleotide and the role of specific active site residues of ADAR2. PMID- 19642682 TI - Confined-plume chemical deposition: rapid synthesis of crystalline coatings of known hard or superhard materials on inorganic or organic supports by resonant IR decomposition of molecular precursors. AB - A one-step process for preparing microcrystalline coatings of known superhard, very hard, or ultraincompressible ceramic compositions on either inorganic or organic supports is reported. Midinfrared pulsed-laser irradiation of preceramic chemical precursors layered between IR-transmissive hard/soft supports under temporal and spatial confinement at a laser wavelength resonant with a precursor vibrational band gives one-step deposition of crystalline ceramic coatings without incurring noticeable collateral thermal damage to the support material. Reaction plume formation at the precursor/laser beam interface initiates confined plume, chemical deposition (CPCD) of crystalline ceramic product. Continuous ceramic coatings are produced by rastering the laser beam over a sample specimen. CPCD processing of the Re-B single-source precursor, (B(3)H(8))Re(CO)(4), the dual-source mixtures, Ru(3)(CO)(12)/B(10)H(14) or W(CO)(6)/B(10)H(14), and the boron/carbon single-source precursor, o-B(10)C(2)H(12), confined between Si wafer or NaCl plates gives microcrystalline deposits of ReB(2), RuB(2), WB(4), or B(4)C, respectively. CPCD processing of Kevlar fabric wetted by (B(3)H(8))Re(CO)(4) produces an oriented, microcrystalline coating of ReB(2) on the Kevlar fabric without incurring noticeable thermal damage of the polymer support. Similarly, microcrystalline coatings of ReB(2) can be formed on IR transmissive IR2, Teflon, or Ultralene polymer films. PMID- 19642683 TI - Catalytic reactions of carbene precursors on bulk gold metal. AB - Bulk gold metal powder, consisting of particles (5-50 microm) much larger than nanoparticles, catalyzes the coupling of carbenes generated from diazoalkanes (R(2)C=N(2)) and 3,3-diphenylcyclopropene (DPCP) to form olefins. It also catalyzes cyclopropanation reactions of these carbene precursors with styrenes. The catalytic activity of the gold powder depends on the nature of the gold particles, as determined by TEM and SEM studies. The reactions can be understood in terms of mechanisms that involve the generation of carbene R(2)C: intermediates adsorbed on the gold surface. PMID- 19642686 TI - Nonuniform compressive strain in horizontally aligned single-walled carbon nanotubes grown on single crystal quartz. AB - Interactions with the substrate that allow near perfect horizontal alignment in combination with large difference in the coefficient of thermal expansion are shown to lead to uniaxial compressive strain in as-grown single-walled carbon nanotubes on single crystal quartz. Temperature dependence of Raman G-band spectra along the length of individual nanotubes reveals that the compressive strain is nonuniform and can be larger than 1% locally at room temperature. A response of 27 cm(-1) upshift per % compressive strain is estimated for the G band longitudinal optical phonon mode of semiconducting nanotubes. Comparison of Raman and atomic force microscope images suggests that the nonuniformity of the compression arises from the surface roughness induced by polishing. Effects of device fabrication steps on the nonuniform strain are also examined and implications on electrical performance are discussed. PMID- 19642684 TI - The use of differential receptors to pattern peptide phosphorylation. AB - An array sensing scheme for the differentiation of small peptides and their phosphorylated analogues is introduced. The technique involves a series of receptors created by appending random peptides to a C(3v) symmetric scaffold that binds phosphomonoesters. Five specific peptide sequences were selected through a screening technique. In addition to cross reactivity being created by the peptides in the receptors, three metal ions and three pH indicators are used to create a suite of 45 indicator displacement assays. The colorimetric data from the 45 sensing ensembles is collected in a 96-well plate reader, and linear discriminant analysis gives patterns resulting in 100% classification of the peptides. The approach demonstrates a generalizable principle to create pattern based recognition protocols for complex analytes. PMID- 19642687 TI - Synthesis of 3-deoxypentacyclic triterpene derivatives as inhibitors of glycogen phosphorylase. AB - The 3-deoxy-2-keto derivatives 5 and 7 of oleanolic acid (1) and ursolic acid (2), respectively, served as precursors to the synthesis of 35 3-deoxy derivatives of pentacyclic triterpenes. The synthesized compounds were biologically assayed for their inhibitory activity against rabbit muscle glycogen phosphorylase a (GPa). Among this series of compounds, 2alpha-hydroxyurs-12-en-28 oic acid (18) (IC(50) = 1.2 microM) exhibited the most potent activity. Preliminary structure-activity relationship analysis for the 3-deoxy triterpene derivatives as GP inhibitors is also discussed. PMID- 19642688 TI - Notopterygium forbesii Boiss extract and its active constituent phenethyl ferulate attenuate pro-inflammatory responses to lipopolysaccharide in RAW 264.7 macrophages. A "protective" role for oxidative stress? AB - Oxidative stress and oxidative modification of biomolecules are involved in several physiological and pathophysiological processes. We have previously reported that Notopterygium forbesii Boiss (NF), a traditional Chinese medicine, and its active constituents, including phenethyl ferulate (PF), bergaptol, and isoimperatorin, induced oxidative stress with increased levels of reactive species and heme oxygenase-1 in human fetal hepatocytes. The current study determined the effects of NF and PF on the inflammatory effects of lipopolysaccharide (LPS). Exposure of RAW 264.7 macrophages to LPS increased the expression of inducible nitric oxide synthase and cyclooxygenase 2 and stimulated the formation of reactive nitrogen species. In a coculture system, the LPS activated macrophages also induced expression of cell adhesion molecules (including E-selectin, intercellular cell adhesion molecule 1, and vascular cell adhesion molecule 1) in human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC). Preincubation of macrophages with NF or PF attenuated the effects of LPS on macrophages as well as their effects on HUVEC and VSMC. These inhibitory effects of NF and PF were decreased in the presence of N-acetyl-l-cysteine (NAC). At the same time, NAC also reduced NF- or PF-induced increases in reactive oxygen species (ROS) and Hsp32 protein levels and the formation of protein carbonyls in the macrophages. These results suggest that NF- or PF-induced ROS generation and oxidative modifications of intracellular proteins may be responsible for the inhibitory actions of NF and PF on LPS induced inflammatory responses. These data add to the growing literature that ROS may sometimes be anti-inflammatory. PMID- 19642690 TI - In vivo bioluminescence imaging of furin activity in breast cancer cells using bioluminogenic substrates. AB - Furin, a proprotein convertases family endoprotease, processes numerous physiological substrates and is overexpressed in cancer and inflammatory conditions. Noninvasive imaging of furin activity will offer a valuable tool to probe furin function over the course of tumor growth and migration in the same animals in real time and directly assess the inhibition efficacy of drugs in vivo. Here, we report successful bioluminescence imaging of furin activity in xenografted MBA-MB-468 breast cancer tumors in mice with bioluminogenic probes. The probes are conjugates of furin substrate, a consensus amino acid motif R-X K/R-R (X, any amino acid), with the firefly luciferase substrate D aminoluciferin. In the presence of the luciferase reporter, the probes are unable to produce bioluminescent emission without furin activation. Blocking experiments with a furin inhibitor and control experiments with a scrambled probe showed that the bioluminescence emission in the presence of firefly luciferase is furin dependent and specific. After furin activation, a 30-fold increase in the bioluminescent emission was observed in vitro, and on average, a 7-8-fold contrast between the probe and control was seen in the same tumor xenografts in mice. Direct imaging of furin activity may facilitate the study of furin function in tumorigenicity and the discovery of new drugs for furin-targeted cancer therapy. PMID- 19642691 TI - Ammonium-directed oxidation of cyclic allylic and homoallylic amines. AB - The ammonium-directed olefinic oxidation of a range of cyclic allylic and homoallylic amines has been investigated. Functionalization of a range of allylic 3-(N,N-dibenzylamino)cycloalk-1-enes with m-CPBA in the presence of Cl(3)CCO(2)H gives exclusively the corresponding syn-epoxide for the 5-membered ring (>99:1 dr), the anti-epoxide for the 8-membered ring (>99:1 dr), and predominantly the anti-epoxide for the 7-membered ring (94:6 dr). Oxidation of the homoallylic amines 3-(N-benzylamino)methylcyclohex-1-ene and 3-(N,N dibenzylamino)methylcyclohex-1-ene gave, in both cases, the corresponding N protected 1,2-anti-2,3-syn-3-aminomethylcyclohexane-1,2-diol with high levels of diastereoselectivity (>or=90:10 dr). The versatile synthetic intermediates resulting from these oxidation reactions are readily transformed into a range of amino diols. PMID- 19642692 TI - Photoinduced electron and energy transfer in aryldihydropyridines. AB - Dimethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylates (Hantzsch DHPs) fluoresce weakly in fluid solution. However, these compounds exhibit an efficient fluorescence both in a viscous medium (glycerin) at room temperature and in a glassy matrix at 77 K (but no phosphorescence, since ISC is negligible). DHPs bearing an aryl group in position 4 have been synthesized. These contain two different pi systems separated by an sp(3) carbon (DHP-Ar dyads). The occurrence of energy and electron transfer processes between the chromophores is investigated through luminescence measurements. In particular, when (3)Ar emits at a slow rate (e.g., Ar = phenanthryl) or not at all (Ar = nitrophenyl) the intradyad forward/backward electron transfer sequence offers a path for arriving at the DHP-localized triplet and the corresponding phosphorescence is observed. When (3)Ar emits at a faster rate (Ar = acylphenyl), the phosphorescence from either of the two localized triplets, (3)Ar or (3)DHP, can be observed depending on lambda(exc). When the aryl group has a triplet energy lower than that of (3)DHP, this functions as emitting (4-cyano-1-naphthyl) or nonemitting (MeO(2)CCH horizontal lineCHC(6)H(4)) energy sink. The results document the possibility of building tailor-made Hantzsch aryldihydropyridines as versatile photoactivated dyads. PMID- 19642689 TI - Cys-diabody quantum dot conjugates (immunoQdots) for cancer marker detection. AB - The present work demonstrates the use of small bivalent engineered antibody fragments, cys-diabodies, for biological modification of nanoscale particles such as quantum dots (Qdots) for detection of target antigens. Novel bioconjugated quantum dots known as immunoQdots (iQdots) were developed by thiol-specific oriented coupling of tumor specific cys-diabodies, at a position away from the antigen binding site to amino PEG CdSe/ZnS Qdots. Initially, amino PEG Qdot 655 were coupled with reduced anti-HER2 cys-diabody by amine-sulfhydryl-reactive linker [N-epsilon-maleimidocaproyloxy] succinimide ester (EMCS) to produce anti HER2 iQdot 655. Spectral characterization of the conjugate revealed that the spectrum was symmetrical and essentially identical to unconjugated Qdot. Specific receptor binding activity of anti-HER2 iQdot 655 was confirmed by flow cytometry on HER2 positive and negative cells. Immunofluorescence results showed homogeneous surface labeling of the cell membrane with Qdot 655 conjugate. In addition, cys-diabodies specific for HER2, as well as prostate stem cell antigen (PSCA), were conjugated successfully with amino PEG Qdot 800. All of these iQdots retain the photoluminescence properties of the unconjugated Qdot 800 as well as the antigen binding specificity of the cys-diabody as demonstrated by flow cytometry. Simultaneous detection of two tumor antigens on LNCaP/PSCA prostate cancer cells (which express PSCA and HER2) in culture was possible using two iQdots, anti-HER2 iQdot 655 and anti-PSCA iQdot 800. Thus, these iQdots are potentially useful as optical probes for sensitive, multiplexed detection of surface markers on tumor cells. The present thiol-specific conjugation method demonstrates a general approach for site-specific oriented coupling of cys diabodies to a wide variety of nanoparticles without disturbing the antigen binding site and maintaining small size compared to intact antibody. PMID- 19642693 TI - Mechanistic insights on the magnesium(II) ion-activated reduction of methyl benzoylformate with chelated NADH peptide beta-lactam models. AB - Mechanistic details of the Mg(2+) ion-activated enantioselective reduction of methyl benzoylformate have been investigated at a B3LYP/6-31G* theory level, using peptide NADH models 1 rigidified with a beta-lactam ring. Computation of the reaction pathway revealed important structural differences between the intermediate NADH/Mg(2+)/ArCOCO(2)R ternary complexes 3 and the corresponding transition states leading to enantiomeric methyl mandelates. Thus, ternary complexes showed the dihydronicotinamide moiety placed quasiequatorial to a seven membered chelation pseudoplane including the two amide carbonyls and the Mg(2+) cation, whereas productive transition states were strongly deformed with the dihydronicotinamide group oriented quasiaxial to the chelation pseudoplane. This chelation model was further applied to acyclic nonrigidified NADH models and, based on the fluxional mobility of the peptide chain bonds, experimental enantioselectivities were correctly predicted. Parallel experiments were also conducted in deuterated acetonitrile, using NMR techniques, to study the structure of the binary complexes 2 (NADH/Mg(2+)) and ternary complexes 3 (NADH/Mg(2+)/PhCOCO(2)Me). Finally, owing to the incorporation of two diastereotopic trimethylsilyl NMR-tags in the beta-lactam-NADH peptidomimetics, a nonproductive ternary complex predicted by calculations could be observed and its structure characterized on the basis of ROESY experiments and molecular modeling. PMID- 19642694 TI - Effect of the previous composting on volatiles production during biomass pyrolysis. AB - Composting is a biological process of decomposition of organic materials in an aerobic environment, which modifies the chemical composition and the thermal behavior of biomass. During composting, fungi and bacteria promote the decomposition of hemicellulosic and cellulosic fractions, increasing the lignin proportion. Its product, compost, is usually used as an amendment to soil; however, its physicochemical characteristics turn it into an interesting feedstock in pyrolysis or gasification facilities. The changes that composting produces on biomass pyrolysis can be explained using an autocatalytic kinetic model (Prout-Tompkins). Thus, by means of a similar set of kinetic parameters for both the biomass and compost, it is possible to simulate the thermogravimetric analysis data (TG and DTG curves) of the materials as a sum of thermal degradations of its main pseudocomponents, hemicellulose, cellulose, lignin, and extractives. TG analysis coupled to mass spectrometry (MS) allows monitoring of the gas production during pyrolysis. Water and carbon oxide MS profiles can be simulated by an optimized linear combination of previously calculated DTG curves of pseudocomponents; however, in order to simulate the hydrogen MS signal, it is necessary to consider the char obtained in the course of the volatilization process. During pyrolysis, hydrogen production has two origins, volatilization of biomass pseudocomponents and charring. The last mechanism explains approximately 75% of the hydrogen obtained from compost. The pseudocomponent that produces more hydrogen by weight unit is lignin, showing a specific hydrogen production much higher than carbohydrates (3:1:8 for hemicellulose/cellulose/lignin). This fact, together with the greater lignin content in compost, explains the positive effect of composting on hydrogen production. PMID- 19642695 TI - Development and validation of an LC-MS method for quantitation of ergot alkaloids in lateral saphenous vein tissue. AB - A liquid chromatography-mass spectrometry (LC-MS) method for simultaneous quantitation of seven ergot alkaloids (lysergic acid, ergonovine, ergovaline, ergocornine, ergotamine, ergocryptine, and ergocristine) in vascular tissue was developed and validated. Reverse-phase chromatography, coupled to an electrospray ionization source, was used to separate and ionize alkaloids. Singly protonated molecular ions for each alkaloid and methysergide (internal standard), were detected by single-ion monitoring (SIM). Calibration curves were obtained over a linear range of 0.1 to 40 pmol on column with correlation coefficients better than 0.994. Method recoveries were 68.4% to 111.0%. Intra-assay precision was 3.4% to 16.1%. Matrix effects were observed and overcome by introducing matrix components into calibrant solutions to create matrix-diluted standards. Limits of detection and quantitation were 0.05 pmol and 0.1 pmol, respectively. Method ruggedness tests resulted in recoveries of 86.1 to 122% with an interassay precision of 7.9% to 22.8%. These results indicate that this method is suitable for quantitation of alkaloids extracted from in vitro-exposed vascular tissue. PMID- 19642696 TI - On the mechanism of Lewis base catalyzed aldol addition reactions: kinetic and spectroscopic investigations using rapid-injection NMR. AB - The mechanistic foundations of the Lewis base catalyzed aldol addition reactions have been investigated. From a combination of low-temperature spectroscopic studies ((29)Si and (31)P NMR) and kinetic analyses using a rapid-injection NMR apparatus (RINMR), a correlation of the ground states and transition structures for the aldolization reactions has been formulated. The aldol addition of the tert-butylsilyl ketene acetal of tert-butyl propanoate with 1-naphthaldehyde is efficiently catalyzed by a combination of silicon tetrachloride and chiral phosphoramide Lewis bases. The rates and selectivities of the aldol additions are highly dependent on the structure of the Lewis bases: bisphosphoramides give the highest rate and selectivity, whereas a related monophosphoramide reacts slowly and with low selectivity. The monophosphoramide shows no nonlinear behavior. All of the additions show a first-order kinetic dependence on silyl ketene acetal and 1-naphthaldehyde and a zeroth-order dependence on silicon tetrachloride. The kinetic order in catalyst is structure dependent and is either half-, two-thirds , or first-order. All of the phosphoramides are saturated with silicon tetrachloride in some form, and the resting-state species are mixtures of monomeric and dimeric, pentacoordinate cationic, or hexacoordinate neutral complexes. These data allow the formulation of a unified mechanistic scheme based on the postulate of a common reactive intermediate for all catalysts. PMID- 19642697 TI - High-affinity peptide-based collagen targeting using synthetic phage mimics: from phage display to dendrimer display. AB - Peptides derived from phage display typically show significantly weaker binding than their respective high affinity phage, which can bind to protein surfaces in a multivalent fashion. Here we show that mimicking key aspects of the multivalent architecture of the phage on an AB(5) dendritic wedge can enhance the affinity of a phage-display derived collagen binding peptide 100-fold (K(d) = 550 nM), allowing direct visualization of collagen architectures in native tissues with a higher specificity than that of the native collagen binding protein CNA35. The dendrimer display approach introduced here represents a well-defined, highly versatile platform for the affinity enhancement of phage display-derived peptides that is likely to be broadly applicable. PMID- 19642698 TI - Catalytic enantioselective synthesis of alpha,beta-diamino acid derivatives. AB - Highly enantio- and diastereoselective organocatalytic Mannich additions of alpha isothiocyanato imides to sulfonyl imines are reported. Enantiomerically enriched syn-alpha,beta-diamino acid derivatives can be obtained in excellent yields using catalyst loadings as low as 0.25 mol %. PMID- 19642699 TI - A {Co32} nanosphere supported by p-tert-butylthiacalix[4]arene. AB - Calixarene-capped Co(32) clusters are constructed by a sodalite Co(II)(24) cage and an encapsulated Co(III)(8) cube. The spherical units are arranged into three isomeric structures, two of which are stacked by the bcc lattices and the third of which is assembled by the cubic closest packing of the spherical units. PMID- 19642700 TI - Fluorescence enhancement of coumarin thiourea derivatives by Hg2+, Ag+, and silver nanoparticles. AB - Fluorescence enhancement by factors of 5-12 times 8-alkyl thiourido-7-ethoxy-4 methyl coumarin derivatives was observed upon complexation with Hg(2+), Ag(+), and Ag nanoparticles. The study reveals a chelation-enhanced fluorescence (CHEF) mechanism with the formation of 1:2 complexes in Hg(2+)/coumarin derivatives and 1:1 complexes in Ag(+)/coumarin derivatives. The activation parameters of the complexation processes were evaluated with energy of activation values in the case of Ag(+) being nearly twice those in the case of Hg(2+) complexation. Isokinetic studies indicate an enthalpy-controlled mechanism in the Hg(2+)/coumarin derivatives complex formation. No fluorescence enhancement was observed with Fe(3+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), La(3+), and Ce(3+), making the present coumarin thiourea derivatives selective chemosensors of both Hg(2+) and Ag(+) ions with different complexation time scales between these two ions. Fluorescence enhancement of the studied coumarin thiourea derivatives using silver nanomaterials occurs almost instantaneously and can be induced by silver nanoparticles in the picomolar (pM) concentration ranges. PMID- 19642702 TI - Fe-g-C3N4-catalyzed oxidation of benzene to phenol using hydrogen peroxide and visible light. AB - A bioinspired iron-based catalyst with semiconductor photocatalytic functions in combination with a high surface area holds promise for synthetic chemistry via combining photocatalysis with organosynthesis. Here exemplified for phenol synthesis, Fe-g-C(3)N(4)/SBA-15 is able to oxidize benzene to phenol with H(2)O(2) even without the aid of strong acids or alkaline promoters. By taking advantage of both catalysis and photocatalysis functions of g-C(3)N(4) nanoparticles, the yield of the phenol can be markedly promoted. PMID- 19642701 TI - Fundamental reaction mechanism and free energy profile for (-)-cocaine hydrolysis catalyzed by cocaine esterase. AB - The fundamental reaction mechanism of cocaine esterase (CocE)-catalyzed hydrolysis of (-)-cocaine and the corresponding free energy profile have been studied by performing pseudobond first-principles quantum mechanical/molecular mechanical free energy (QM/MM-FE) calculations. On the basis of the QM/MM-FE results, the entire hydrolysis reaction consists of four reaction steps, including the nucleophilic attack on the carbonyl carbon of (-)-cocaine benzoyl ester by the hydroxyl group of Ser117, dissociation of (-)-cocaine benzoyl ester, nucleophilic attack on the carbonyl carbon of (-)-cocaine benzoyl ester by water, and finally dissociation between the (-)-cocaine benzoyl group and Ser117 of CocE. The third reaction step involving the nucleophilic attack of a water molecule was found to be rate-determining, which is remarkably different from (-) cocaine hydrolysis catalyzed by wild-type butyrylcholinesterase (BChE; where the formation of the prereactive BChE-(-)-cocaine complex is rate-determining) or its mutants containing Tyr332Gly or Tyr332Ala mutation (where the first chemical reaction step is rate-determining). Besides, the role of Asp259 in the catalytic triad of CocE does not follow the general concept of the "charge-relay system" for all serine esterases. The free energy barrier calculated for the rate determining step of CocE-catalyzed hydrolysis of (-)-cocaine is 17.9 kcal/mol, which is in good agreement with the experimentally derived activation free energy of 16.2 kcal/mol. In the present study, where many sodium ions are present, the effects of counterions are found to be significant in determining the free energy barrier. The finding of the significant effects of counterions on the free energy barrier may also be valuable in guiding future mechanistic studies on other charged enzymes. PMID- 19642703 TI - Highly versatile rare earth tantalate pyrochlore nanophosphors. AB - Rare earth tantalate materials are of considerable interest in energy and environmentally related applications including photocatalytic H(2) generation or contaminant decomposition, ion conductivity for batteries and fuel cells, and phosphors for light-emitting diodes (LEDs). These Eu-doped rare earth tantalate pyrochlore nanoparticles, K(1-2x)LnTa(2)O(7-x):Eu(3+) (Ln = Lu, Y, Gd; x = (1)/(3) for Gd, x = 0 for Lu and Y), have quantum yields up to 78% when excited with blue light (464 nm), which is remarkable for nanoparticle forms that can suffer efficiency loss by surface effects or poor crystallinity, and are furthermore quite suitable for LED applications. The Gd analogue with its framework distortions has particularly high quantum yields. The blue excitation peak matches the emission of the GaN LED. The combination of the high quantum yield under blue excitation, low thermal quenching, and chemical stability renders these new materials promising red phosphors for blue-excitation white LEDs for solid-state lighting. In addition, the pyrochlore lattice is very accommodating to dopants and vacancies and will incorporate virtually any metal and coordination environment ranging from four-coordinate to eight-coordinate. Thus, there are virtually unlimited possibilities for tailoring and optimizing photoluminescent properties, as demonstrated by these scoping studies. PMID- 19642704 TI - Structural polymorphism and multifunctionality of myelin basic protein. AB - Central nervous system myelin is a dynamic entity arising from membrane processes extended from oligodendrocytes, which form a tightly wrapped multilamellar structure around neurons enabling rapid and efficient signal propagation. The gene of oligodendrocyte lineage (golli) gives rise to a variety of developmentally regulated splice isoforms of myelin basic protein (MBP), denoted golli for early forms and classic for later ones. In mature myelin, the predominant splice isoform of classic MBP is 18.5 kDa; its central role is to maintain the structural integrity of the myelin sheath, by holding together the apposing cytoplasmic leaflets of the oligodendrocyte membrane in a tight, spiral, multilamellar arrangement. This protein's extreme physicochemical properties, net charge of +19 at neutral pH, low proportion of hydrophobic residues, alternating regions of predicted intrinsic disorder and order, induced folding upon association with membranes and other proteins, and diversification via combinatorial post-translational modifications, define not only its role as a molecular Velcro in compact myelin, but as a multifunctional hub that may also bind to a number of other proteins and small molecule ligands in myelinating oligodendrocytes. In particular, MBP may link the underlying cytoskeleton and proteins containing SH3 domains to the membrane, allowing it to transduce transmembrane signals to the cytosol. These associations are facilitated by MBP being an intrinsically disordered protein, creating a large effective protein surface, and by the formation of transient and/or induced ordered secondary structure elements for molecular recognition. These processes can be modulated by a molecular barcode of numerous post-translational modifications and interactions with proteins such as calmodulin. In the human demyelinating disease multiple sclerosis, an aberrant pattern of modifications may contribute to demyelination and confound inherent attempts at repair. The conformational dynamics of the various isoforms and modified variants of MBP and their interactions with other proteins potentially allow them to participate in events coupling extracellular signals to cytoskeletal organization during myelination or remyelination. Various biophysical and cell biological approaches are beginning to elucidate these properties of MBP and are leading to a new understanding of the role of this protein as a linker and/or hub in structural and signaling networks in oligodendrocytes and myelin. PMID- 19642706 TI - The proteomic analysis of primary cortical astrocyte cell culture after morphine administration. AB - Astrocytes are supportive cells, necessary for ensure optimal environment for neural cells functioning. They are involved in extracellular K+ level regulation and neurotransmitters removal. They are also dependent for myelination and synapses formation. They may make a contribution in signal propagation in the central nervous system, for example, through Ca2+ signaling. With the use of neonatal pure astrocyte cell culture, we investigated changes in astrocyte's proteomes under the influence of morphine. We found 10 major proteins, which show different expression between physiological cell culture and morphine treatment. With 2D gel electrophoresis and nanoLC-ESI-MS/MS, we identified proteins and characterized their potential role in morphine dependence. Observed differences were also confirmed by Western blotting. Our data suggests a role for astrocytes in the formation of the morphine dependence at the molecular level. This finding may support interpretation of causes of morphine dependence formation based only on behavioral data. PMID- 19642705 TI - Dynamic cycling with Hsp90 stabilizes neuronal nitric oxide synthase through calmodulin-dependent inhibition of ubiquitination. AB - NO production by neuronal nitric oxide synthase (nNOS) requires calmodulin and is enhanced by the chaperone Hsp90, which cycles dynamically with the enzyme. The proteasomal degradation of nNOS is enhanced by suicide inactivation and by treatment with Hsp90 inhibitors, the latter suggesting that dynamic cycling with Hsp90 stabilizes nNOS. Here, we use a purified ubiquitinating system containing CHIP (carboxyl terminus of Hsp70-interacting protein) as the E3 ligase to show that Hsp90 inhibits CHIP-dependent nNOS ubiquitination. Like the established Hsp90 enhancement of NO synthesis, Hsp90 inhibition of nNOS ubiquitination is Ca2+/calmodulin-dependent, suggesting that the same interaction of Hsp90 with the enzyme is responsible for both enhancement of nNOS activity and inhibition of ubiquitination. It is established that CHIP binds to Hsp90 as well as to Hsp70, but we show here the two chaperones have opposing actions on nNOS ubiquitination, with Hsp70 stimulating and Hsp90 inhibiting. We have used two mechanism-based inactivators, guanabenz and NG-amino-L-arginine, to alter the heme/substrate binding cleft and promote nNOS ubiquitination that can be inhibited by Hsp90. We envision that, as nNOS undergoes toxic damage, the heme/substrate binding cleft opens exposing hydrophobic residues as the initial step in unfolding. As long as Hsp90 can form even transient complexes with the opening cleft, ubiquitination by Hsp70-dependent ubiquitin E3 ligases, like CHIP, is inhibited. When unfolding of the cleft progresses to a state that cannot cycle with Hsp90, Hsp70-dependent ubiquitination is unopposed. In this way, the Hsp70/Hsp90 machinery makes the quality control decision for stabilization versus degradation of nNOS. PMID- 19642707 TI - Impact of additional disabilities on adaptive behavior and support profiles for people with intellectual disabilities. AB - Numerous researchers have reported a high incidence of additional disabilities coexisting with intellectual disabilities. Although an intuitive link can be made between the existence of multiple disabilities and greater need for support, little has been reported about this relationship. Using measures of adaptive functioning and support needs, we examined the extent to which adaptive and challenging behaviors and consequent support needs (including medical) were impacted by the presence and severity of additional disabilities for individuals with intellectual disabilities. Results show that adaptive behaviors and support needs were meaningfully related to the number and severity of additional disabilities present, whereas this was not so for challenging behaviors. Findings are discussed in terms of contemporary models of disability and functioning. PMID- 19642708 TI - The Down syndrome advantage: fact or fiction? AB - The "Down syndrome advantage" is the popular conception that children with Down syndrome are easier to rear than children with other developmental disabilities. We assessed whether mothers of children with developmental disabilities would demonstrate a consistent Down syndrome advantage as their children aged from 12 to 18 years. Results did not reveal significant differences between mothers of children with Down syndrome and mothers of children with other developmental disabilities on most maternal functioning variables. Although the prior group reported a consistent advantage in terms of personal reward and subjective well being, these diagnostic group differences disappeared when maternal age and child adaptive behavior were controlled. We concluded that these variables may help to explain the Down syndrome advantage. PMID- 19642709 TI - Monoamine oxidase a promoter gene associated with problem behavior in adults with intellectual/developmental disabilities. AB - A functional polymorphism in the promoter of the gene encoding monoamine oxidase A has been associated with problem behavior in various populations. We examined the association of MAOA alleles in adult males with intellectual/developmental disabilities with and without established histories of problem behavior. These data were compared with a gender, ethnicity, and age-matched contrast sample. About 43% (15/35) of adults with intellectual/developmental disabilities and problem behavior possessed the low-efficiency version of the MAOA gene. In comparison, 20% (7/35) of adults with intellectual/developmental disabilities and no problem behavior and 20% (7/35) of the contrast group had the short-allele MAOA polymorphism. Therefore, a common variant in the MAOA gene may be associated with problem behavior in adults with intellectual/developmental disabilities. PMID- 19642710 TI - Functional skills of individuals with fragile x syndrome: a lifespan cross sectional analysis. AB - Parents of 1,105 male and 283 female children with fragile X syndrome described functional skill attainment in eating, dressing, toileting, bathing/hygiene, communication, articulation, and reading. The majority of adult children had mastered many skills independently. Most adults were verbal, used the toilet, dressed, ate independently, bathed, and used a towel independently. However, some skills were not as well-developed, such as using complex sentences, reading, or speaking at a typical rate. As expected, significant differences were found between males and females. The findings highlight major skill attainments, identify skills that should be the target of specific intervention programs, suggest variable trajectories to be tested more precisely through direct assessments and longitudinally, and provide baseline data for treatment studies. PMID- 19642712 TI - Risk of fall for individuals with intellectual disability. AB - Our aim was to identify risk factors for falling and establish a method to assess risk for falls in adults with intellectual disabilities. In a cross-sectional survey of 144 Japanese adults, we found that age, presence of epilepsy, and presence of paretic conditions were independent risk factors. The Tinetti balance and gait instrument was successfully administered to this population and resulted in high diagnostic accuracy (sensitivity 88.9%, specificity 91.9%) for identifying individuals at risk when the cutoff score was set at 25. Participants whose balance and gait deteriorated showed a decrease in the Tinetti score of at least 2 points per year. Thus, the Tinetti instrument may be an effective tool to detect an increased risk of fall in this population. PMID- 19642713 TI - Mother-child play: children with Down syndrome and typical development. AB - Child solitary and collaborative mother-child play with 21 children with Down syndrome and 33 mental-age-matched typically developing children were compared. In solitary play, children with Down syndrome showed less exploratory but similar symbolic play compared to typically developing children. From solitary to collaborative play, children with Down syndrome increased their exploratory play, attaining the same level as typically developing children. Pretense significantly increased from solitary to collaborative play only in typically developing children. Differences between mothers' play in the two groups mirrored those between their children. Both groups showed similar attunement and synchrony. Mothers contribute to the play development of children with Down syndrome through their own adaptation to their children's limitations and potentialities. PMID- 19642717 TI - Effect of time on clinical efficacy of topical anesthesia. AB - The objective of this study was to determine the effect of time on the clinical efficacy of topical anesthetic in reducing pain from needle insertion alone as well as injection of anesthetic. This was a randomized, double-blind, placebo controlled, split-mouth, clinical trial which enrolled 90 subjects, equally divided into 3 groups based upon time (2, 5, or 10 minutes) of topical anesthetic (5% lidocaine) application. Each group was further subdivided into 2: needle insertion only in the palate or needle insertion with deposition of anesthetic (0.5 mL 3% mepivacaine plain). Each subject received drug on one side and placebo on the other. Subjects recorded pain on a 100-mm visual analog scale (VAS). The results showed that for needle insertion only, 5% lidocaine reduced pain as determined by a significant difference in mean VAS after 2 minutes (20.1 mm, P < .002), 5 minutes (15.7 mm, P < .022), and 10 minutes (13.7 mm, P < .04), as analyzed by paired t tests. For needle insertion plus injection of local anesthetic, a significant difference in mean VAS was noted only after 10 minutes (14.9 mm, P < .031), yet pain scores for both topical anesthetic and placebo were elevated at this time point resulting in no reduction in actual pain. Time of application did not result in a significant difference in effect for either needle insertion only or needle insertion plus injection of local anesthetic, as analyzed by 1-way analysis of variance (ANOVA). In conclusion, topical anesthetic reduces pain of needle insertion if left on palatal mucosa for 2, 5, or 10 minutes, but has no clinical pain relief for anesthetic injection. PMID- 19642719 TI - Negative pressure pulmonary edema after oral and maxillofacial surgery. AB - Negative pressure pulmonary edema (NPPE) following upper airway obstruction (UAO) has been reported in several clinical situations. The main cause of NPPE is reported to be increased negative intrathoracic pressure. We present a case of NPPE that occurred after general anesthesia for plate removal after jaw deformity surgery. After completion of the surgery, administration of inhaled anesthetics was stopped and the patient opened his eyes on verbal command. Immediately after extubation, the patient stopped breathing and became cyanotic. Acute UAO following laryngospasm was suspected. Soon after reintubation, pink, frothy fluid came out of the endotracheal tube, and a tentative diagnosis of NPPE was made. Continuous positive airway pressure was applied. In addition, furosemide and dexamethasone were administered. By the next day, the symptoms had almost disappeared. PMID- 19642718 TI - Review and management of the dental patient with Long QT syndrome (LQTS). AB - Long QT syndrome (LQTS) is a unique cardiovascular condition, with both congenital and acquired forms that afflict patients. These patients show a lengthening of the repolarization phase of the cardiac cycle, which can be best visualized on an electrocardiogram (ECG). The ECG changes can include QT interval (the time between the start of the Q wave and the end of the T wave, as seen on an ECG) and T wave abnormalities, as well as progression to torsades de pointes and ventricular fibrillation. The ECG changes are most commonly elicited by physical activity, emotional stress, and certain medications. This condition represents a challenge for the oral and maxillofacial surgeon. Patients with LQTS must receive proper medical management and a controlled and anxiety-free surgical environment. The purpose of this article was to present a review of LQTS and provide recommendations for effective surgical management. Additionally, a case report of a patient with LQTS, treated by one of the authors, has been included. PMID- 19642720 TI - Cardiovascular monitoring: physiological and technical considerations. AB - The American Dental Association and several dental specialty organizations have published guidelines that detail requirements for monitoring patients during various levels of sedation and, in some cases, general anesthesia. In general, all of these are consistent with those guidelines suggested by the American Society of Anesthesiologists Task Force for Sedation and Analgesia by Non Anesthesiologists. It is well-accepted that the principal negative impact of sedation and anesthesia pertains to the compromise of respiratory function, but attentive monitoring of cardiovascular function is also important. While monitoring per se is a technical issue, an appreciation of its purpose and the interpretation of the information provided require an understanding of basic cardiovascular anatomy and physiology. The focus of this continuing education article is to address essential physiological aspects of cardiovascular function and to understand the appropriate use of monitors, including the interpretation of the information they provide. PMID- 19642727 TI - Update in surgical pathology. PMID- 19642728 TI - Nonneoplastic kidney diseases in adult tumor nephrectomy and nephroureterectomy specimens: common, harmful, yet underappreciated. AB - CONTEXT: Nonneoplastic kidney diseases, such as arterionephrosclerosis and/or diabetic nephropathy, are commonly encountered in tumor nephrectomy and nephroureterectomy specimens. Although any nonneoplastic kidney disease may be encountered in these resection specimens by chance, additional diseases that may be related to the underlying neoplasm or its treatment regimen include thrombotic microangiopathy, Amyloid A amyloidosis, membranous nephropathy, immunoglobulin A nephropathy, membranoproliferative glomerulonephritis, pauci-immune crescentic glomerulonephritis, focal segmental glomerulosclerosis, minimal-change disease, acute interstitial nephritis, and xanthogranulomatous pyelonephritis. Given the morbidity of chronic kidney disease and the relatively favorable 5-year survival rates for urothelial and renal cell carcinomas, accurate evaluation of the nonneoplastic kidney parenchyma is important. OBJECTIVES: We will discuss our approach for evaluating the nonneoplastic kidney parenchyma in tumor nephrectomy and nephroureterectomy specimens. The pathologic features of the aforementioned kidney diseases as well as pertinent references will be reviewed. The identification of glomerular abnormalities, including mesangial sclerosis or hypercellularity, segmental sclerosis, crescent formation, glomerulitis, or glomerular basement membrane alterations, should lead to additional immunofluorescence and electron microscopic studies. Safeguards to ensure that the nonneoplastic parenchyma is not overlooked include adding this important parameter to synoptic reports and obtaining periodic acid-Schiff and/or Jones methenamine silver stains prior to microscopic evaluation of the neoplasm. DATA SOURCES: Relevant literature and University of Chicago Medical Center pathology archives. CONCLUSIONS: The practicing surgical pathologist should be aware of the importance of both correctly classifying the resected renal or urothelial neoplasm and the concomitant nonneoplastic kidney disease that may be present in these specimens. PMID- 19642729 TI - Recent developments in the pathology of renal tumors: morphology and molecular characteristics of select entities. AB - CONTEXT: Renal cell carcinoma is a heterogeneous group of tumors with distinct histopathologic features, molecular characteristics, and clinical outcome. These tumors can be sporadic as well as familial or associated with syndromes. The genetic abnormalities underlying these syndromes have been identified and were subsequently found in corresponding sporadic renal tumors. OBJECTIVE: To review the recent molecular and genetic advancements relating to sporadic and familial renal carcinomas as well as those related to Xp11.2 translocation-associated renal cell carcinoma and renal medullary carcinoma. DATA SOURCES: Literature review, personal experience, and material from the University of Chicago. CONCLUSIONS: Molecular genetic diagnostic techniques will continue to introduce new biomarkers that will aid in the differential diagnosis of difficult cases. The identification of specific signaling pathways that are defective in certain renal tumors also makes possible the development of new therapies that selectively target the aberrant activity of the defective proteins. PMID- 19642730 TI - Molecular biology underlying the clinical heterogeneity of prostate cancer: an update. AB - CONTEXT: Recent studies have uncovered a number of possible mechanisms by which prostate cancers can become resistant to systemic androgen deprivation, most involving androgen-independent reactivation of the androgen receptor. Genome-wide expression analysis with microarrays has identified a wide array of genes that are differentially expressed in metastatic prostate cancers compared to primary nonrecurrent tumors. Recently, recurrent gene fusions between TMPRSS2 and ETS family genes have been identified and extensively studied for their role in prostatic carcinoma. OBJECTIVE: To review the recent developments in the molecular biology of prostate cancer, including those pertaining to the androgen receptor and the newly identified TMPRSS2-related translocations. DATA SOURCES: Literature review and personal experience. CONCLUSIONS: Prostatic adenocarcinoma is a heterogeneous group of neoplasms with a broad spectrum of pathologic and molecular characteristics and clinical behaviors. Numerous mechanisms contribute to the development of resistance to androgen ablation therapy, resulting in ligand-independent reactivation of the androgen receptor, including amplification, mutation, phosphorylation, and activation of coreceptors. Multiple translocations of members of the ETS oncogene family are present in approximately half of clinically localized prostate cancers. TMPRSS2:ERG gene rearrangement appears to be an early event in prostate cancer and is not observed in benign or hyperplastic prostatic epithelium. Duplication of TMPRSS2:ERG appears to predict a worse prognosis. The relationship between TMPRSS2:ERG gene rearrangement and other morphologic and prognostic parameters of prostate cancer is still unclear. PMID- 19642732 TI - Update on immunohistochemical methods relevant to dermatopathology. AB - CONTEXT: Dermatopathology covers a large variety of entities, some having very similar histologic appearances. Immunohistochemistry is an incredibly helpful tool that is useful in diagnosis as well as prognosis of selected skin tumors. OBJECTIVE: To provide a comprehensive review of recent trends and immunohistochemical stains used by dermatopathologists. Emphasis is placed on new stains as well as novel uses of existing stains. DATA SOURCES: All data were gathered from published journal articles available through the National Center for Biotechnology Information PubMed database. CONCLUSIONS: New immunohistochemical targets are continually being found, contributing to more accurate diagnosis and classification of skin tumors. The presence of specific markers can be used to determine the aggressiveness of malignancies and design treatment strategies. In addition, application of existing stains can help determine intravascular spread of malignancy in primary cutaneous lesions. And use of rapid immunohistochemical staining techniques on frozen sections can assist in more complete excision of tumor margins. Immunohistochemistry is a highly versatile and growing tool of dermatopathologists. PMID- 19642731 TI - Insights into selected genetic diseases affecting the female reproductive tract and their implication for pathologic evaluation of gynecologic specimens. AB - CONTEXT: Recent advances in the understanding of genetic conditions involving the female genital tract and mechanisms of carcinogenesis in this setting affect patient management and thus necessitate appropriate pathologic evaluation of specimens. In the past, specimens from prophylactic surgery were a rarity; however, they are now more frequently encountered and often require a significant variation from routine processing methods. Pathologists also receive more specimens requiring prospective workup for possible underlying genetic conditions such as microsatellite instability. OBJECTIVE: To summarize the current knowledge of important genetic and hereditary conditions affecting the female reproductive organs while highlighting the resulting practical significance for specimen handling, "grossing," and microscopic evaluation in gynecologic pathology. DATA SOURCES: This update is based on a review of recent peer-reviewed literature and the experience with cases at the parent institutions. CONCLUSIONS: Gynecologic specimens received from patients with certain genetic conditions require specific clinicopathologic knowledge for appropriate pathologic examination. The evaluation of prophylactic resection specimens focuses on the detection of cancer precursors and possible occult disease, which may require a more thorough and detailed examination than an obvious carcinoma. Standardized protocols for handling prophylactic gynecologic resection specimens are available for some, but not all, types of specimens. The prospective evaluation of a gynecologic pathology specimen for potential genetic conditions such as microsatellite instability is a very recent subject. Currently, well-established protocols are not available; however, as clinical and prognostic significance has become more clearly elucidated, familiarity with this evolving field is increasingly important to properly assess these pathologic specimens. PMID- 19642733 TI - Update on diagnostic practice: tumors of the nervous system. AB - CONTEXT: Changes in the practice of diagnosing brain tumors are formally reflected in the evolution of the World Health Organization classification. Beyond this classification, the practice of diagnostic pathology is also changing with the availability of new tests and the introduction of new treatment options. OBJECTIVE: Glioblastomas, oligodendrogliomas, glioneuronal tumors, and primitive pediatric tumors are discussed in an exemplary way to illustrate these changes. DATA SOURCES: Review of relevant publications through Medline database searches. CONCLUSIONS: The example of glioblastomas shows how new predictive markers may help identify subgroups of tumors that respond to certain therapy regimens. The development of new treatment strategies also leads to different questions in the assessment of brain tumors, as seen in the example of pseudoprogression or the changes in tumor growth pattern in patients taking bevacizumab. Oligodendrogliomas illustrate how the identification of 1p/19q loss as a cytogenetic aberration aids our understanding of these tumors and changes diagnostic practice but also introduces new challenges in classification. Glioneuronal tumors are an evolving group of lesions. Besides a growing list of usually low-grade entities with well-defined morphologic features, these also include more poorly defined cases in which a component of infiltrating glioma is often associated with focal neuronal elements. The latter is biologically interesting but of uncertain clinical significance. Oligodendrogliomas and glioneuronal tumors both illustrate the importance of effective communication between the pathologist and the treating oncologist in the discussion of these patients. Finally, the discussion of primitive pediatric tumors stresses the clinical importance of the distinction between different entities, like atypical teratoid rhabdoid tumor, "central" (supratentorial) primitive neuroectodermal tumor, "peripheral" primitive neuroectodermal tumor, and medulloblastoma. In medulloblastomas, the recognition of different variants is emerging as a prognostic factor that may in the future also predict therapy responsiveness. PMID- 19642734 TI - Recent developments in liver pathology. AB - CONTEXT: Hepatocellular carcinoma is the sixth most common malignancy and the third leading cause of cancer deaths worldwide, making pathologic identification of precursor lesions essential. Recent molecular genetic, pathologic, and clinical data have led to the stratification of hepatic adenomas into subgroups with unique molecular profiles and varying potential for malignant transformation, as well as to the reclassification of telangiectatic focal nodular hyperplasia as telangiectatic adenoma. Clinical, morphologic, and molecular genetic studies have also established juvenile hemochromatosis and pediatric nonalcoholic steatohepatitis as entities distinct from their adult counterparts. OBJECTIVE: To review the recent molecular genetic characterization of telangiectatic hepatic adenomas and juvenile hemochromatosis, as well as the recent clinicopathologic characterization of pediatric nonalcoholic steatohepatitis. DATA SOURCES: Literature review, personal experience, and material from the University of Chicago. CONCLUSIONS: Basic science and translational research have led to the classification of many pathologic entities of the liver according to molecular genetic and protein expression profiles that correspond to traditional morphologic categories. Insights into signal transduction pathways that are activated in, and protein expression patterns unique to, an individual disease may lead to the development of new therapeutic agents and novel diagnostic biomarkers. PMID- 19642735 TI - Update on esophagitis: controversial and underdiagnosed causes. AB - CONTEXT: Esophagitis is a common cause of symptoms for which patients seek the advice of a physician. Esophagitis of differing etiologies often demonstrate overlapping histopathologic features, making their distinction difficult. This is especially true in esophageal disorders associated with increased numbers of intraepithelial eosinophils, some of which have just recently been recognized. OBJECTIVE: This review discusses the important clinical and pathologic features of the 2 most common disorders associated with esophageal eosinophilic infiltrates--reflux esophagitis and eosinophilic esophagitis--with special emphasis on features that allow the surgical pathologist to distinguish between these disorders. The various forms of drug-induced esophagitis are also discussed because these are frequently underrecognized by pathologists. DATA SOURCES: Data were extracted from articles identified through PubMed-based research. Histologic figures have been taken from the personal case collection of the author. CONCLUSIONS: Reflux and eosinophilic esophagitis demonstrate overlapping histologic features, which may make their distinction difficult. Drug-induced esophagitis is probably a common phenomenon but is underrecognized by pathologists. PMID- 19642736 TI - Update in nonneoplastic lung diseases. AB - CONTEXT: Nonneoplastic lung diseases include a wide range of pathologic disorders from asthma to interstitial lung disease to pulmonary hypertension. Recent advances in our understanding of the pathophysiology of many of these disorders may ultimately impact diagnosis, therapy, and prognosis. It is important for the practicing pathologist to be aware of this new information and to understand how it impacts the diagnosis, treatment, and outcome of these diseases. OBJECTIVE: To update current progress toward elucidating the pathophysiology of pulmonary alveolar proteinosis, idiopathic pulmonary hemosiderosis, and pulmonary arterial hypertension, as well as to present classification systems for pulmonary hypertension, asthma, and interstitial lung disease and describe how these advances relate to the current practice of pulmonary pathology. DATA SOURCES: Published literature from PubMed (National Library of Medicine) and primary material from the authors' institution. CONCLUSIONS: Improved understanding of the pathophysiology of pulmonary alveolar proteinosis, pulmonary hypertension, and idiopathic hemosiderosis may impact the role of the surgical pathologist. New markers of disease may need to be assessed by immunohistochemistry or molecular techniques. The classification systems for interstitial lung disease, asthma, and pulmonary hypertension are evolving, and surgical pathologists should consider the clinicopathologic context of their diagnoses of these entities. PMID- 19642737 TI - Update in neoplastic lung diseases and mesothelioma. AB - CONTEXT: Lung cancer is a common disease frequently seen by the surgical pathologist. Although secondary to improvements in screening and radiologic techniques and aggressive resection of small pulmonary nodules, the diagnosis of preneoplastic lesions is increasing in frequency and importance. Consequently, a greater understanding of their role in the development of lung carcinoma is needed for optimal patient care. Two lesions often encountered as small pulmonary nodules are bronchioloalveolar carcinoma and adenocarcinoma, which can be challenging to distinguish. Recently, updates to the TNM classification of non small cell lung carcinoma have been reported that directly impact prognosis and treatment algorithms. Identification of new molecular targets in pleural mesothelioma and in preneoplastic lesions may lead to improved therapeutic strategies. OBJECTIVE: To present recent advances in our understanding of neoplastic lung diseases and mesothelioma and to describe how these advances relate to the current practice of pulmonary pathology. DATA SOURCES: Published literature from PubMed (National Library of Medicine) and primary material from the authors' institution. CONCLUSIONS: It is important for the surgical pathologist to understand current diagnostic classifications of non-small cell lung cancer and to be aware of the range of preneoplastic lesions, as well as the features useful for distinguishing bronchioloalveolar carcinoma from adenocarcinoma in small pulmonary nodules. Although pleural mesothelioma has distinct features, it can also overlap histologically with adenocarcinoma, and immunohistochemistry can greatly aid in accurate diagnosis. New therapies targeting molecular markers in both non-small cell lung cancer and mesothelioma rely on accurate histopathologic diagnosis of these entities. PMID- 19642738 TI - Lobular neoplasia of the breast: an update. AB - CONTEXT: Lobular neoplasias (LNs) of the breast include atypical lobular neoplasia and lobular carcinoma in situ. Recent evidence suggests that LN is not only a risk factor for invasive lobular carcinoma, but is also a nonobligate precursor. Pleomorphic lobular carcinoma in situ (PLCIS) is a subtype of LN that has high-grade nuclei and other features that may mimic high-grade ductal carcinoma in situ. The management and follow-up of patients diagnosed with LN on core biopsy is a current issue of debate. However, recent genomic and molecular studies have identified candidate genes that may be important in understanding the pathogenesis of atypical lobular neoplasia and lobular carcinoma in situ, and thus may lead to other therapeutic interventions. OBJECTIVE: To review the literature on LN of the breast and discuss current issues in the diagnosis and management of this entity, with particular attention to the relatively newly recognized lesion PLCIS. Because the management of PLCIS varies from the other LN lesions, the recognition of PLCIS by the pathologist is necessary. Current issues in the molecular pathogenesis of LN are also presented. DATA SOURCES: Extensive review of the literature. Hematoxylin-eosin-stained and immunohistochemical stained tissue from the author's personal collection. CONCLUSIONS: Although morphology and immunohistochemical stains, such as E-cadherin, are important in the diagnosis and understanding of LN, genomic and molecular studies may guide the way these lesions are handled in the future. Recognizing PLCIS is important both for patient management and for our future understanding of LN pathogenesis. PMID- 19642739 TI - Diffuse large B-cell lymphoma--more than a diffuse collection of large B cells: an entity in search of a meaningful classification. AB - CONTEXT: Diffuse large B-cell lymphoma is a heterogeneous group of lymphomas. In this review, we present a brief description of the large number of entities recognized in the recently published (2008) World Health Organization classification of tumors of hematopoietic and lymphoid tissues. OBJECTIVE: We highlight the unique clinicopathologic and molecular genetic features of these new and previously recognized entities, to illustrate the rational for the development of this classification. To help simplify the understanding of this now large and complex group of diseases, we have attempted to create broader subgroups of related entities. We discuss large B-cell lymphoma that are not otherwise specified, those that are based on anatomic site, those that have unique histology or phenotype or genotype, those that are associated with Epstein Barr virus or Kaposi sarcoma-associated herpesvirus and herpesvirus 8, and those that are unclassifiable. DATA SOURCES: World Health Organization classification of tumors of hematopoietic and lymphoid tissues (2008), published literature from PubMed (National Library of Medicine), and primary material from the authors' institution were reviewed. CONCLUSIONS: Recognition of the different subtypes of diffuse large B-cell lymphoma as described in the World Health Organization classification scheme will lead to improved understanding of the unique clinicopathologic and genetic features associated with these subtypes of lymphoma. PMID- 19642740 TI - Frozen section and the surgical pathologist: a point of view. AB - Frozen section is a prominent point of intersection between surgeons and pathologists. It is regarded as the most definitive--but not the sole--form of intraoperative consultation. Its role in tissue triage, diagnosis, and intraoperative management should not be misconstrued as a shortcut to a definitive diagnosis. Although the pathologist remains in control of the tissue disposition, frozen sections are ideally requested and executed as a collaborative effort. Frivolous requests with no direct consequences for the conduct of a given procedure should not be honored. Frozen section plays a material role in resident education and may be the last vestige of general surgical pathology in an era of organ system specialization. Frozen section will retain its relevance only in the context of broad clinical knowledge by the pathologist and judicious utilization by the surgeon, both in the ultimate service of the patient. PMID- 19642741 TI - Resident preparation for practice: a white paper from the College of American Pathologists and Association of Pathology Chairs. PMID- 19642744 TI - Felt needs of parents who have a 0- to 3-month-old child with a cleft lip and palate. AB - OBJECTIVE: To describe the felt needs of parents who have children from birth to 3 months of age with a cleft lip and palate. DESIGN: Parents were interviewed using structured and semistructured questions at 1 week and 1, 2, and 3 months after birth. PARTICIPANTS: Fifteen parents, including 12 mothers and three fathers, of patients with cleft lip and palate aged 0 to 3 months were interviewed. RESULTS: During the first week after birth, the majority of parents needed to know about feeding and surgery. At 1, 2, and 3 months after birth, more information was required, especially on different surgeries during those periods and speech problems. In addition, a number of parents requested funding for every period, and very few had expectations of moral support from health care professionals. CONCLUSIONS: The felt needs expressed in this study changed according to periods of time and mainly concerned feeding, speech problems, and surgery, as well as financial support. The needs of parents, particularly during the transitional period, should be considered as a provision of holistic care for patients with cleft lip and palate and their families. PMID- 19642745 TI - Simultaneous harvesting of cancellous iliac bone for alveolar cleft closure and dermis for augmentation of median tubercle. AB - Children with repaired cleft lip/palate require secondary closure of the alveolar cleft and, often, nasolabial revision. We describe a technique performed in 61 patients for harvesting bone for the alveolar defect and dermis for augmentation of the median tubercle, taking both from the posterior iliac region. The advantages of the posterior approach are as follows: (1) the same donor site is used for cancellous bone and dermal graft and (2) the child's appearance is improved along with alveolar cleft grafting. PMID- 19642746 TI - Correlation between facial morphology and esthetics in patients with repaired complete unilateral cleft lip and palate. AB - OBJECTIVE: The purpose of this study was to determine if there were correlations between anthropometric nasolabial measurements and subjective assessments of nasal esthetics in individuals with repaired complete unilateral cleft lip and palate (CUCLP). PARTICIPANTS: The sample consisted of 28 individuals with repaired CUCLP and 20 age- and gender-matched individuals without clefts. OUTCOME MEASURES: Nasolabial morphology was assessed using 2D and 3D measurements made on frontal photographs, lateral cephalometric radiographs, and plaster nose casts. A panel of orthodontists rated nasal esthetics from frontal, lateral, three quarter, and basal view photographs and plaster nose casts using visual analog scales, and they also order ranked the nose casts. Based on the nasal esthetics ratings and rankings, two groups that had the best and the worst esthetics representing the extremes of nasolabial esthetics were statistically identified. Measurements were compared between the cleft and noncleft and the best and worst groups using t tests and analysis of variance. RESULTS: Differences in anthropometric measurements between the groups were identified. The columellar width and nose base and nasolabial angles significantly differed between the best and worst groups (p < .05). Differences in panel ratings of nasolabial esthetics between the best and worst groups were statistically detected using lateral and three-quarter view photographs (p < .05). CONCLUSIONS: Although morphologic differences between the cleft and noncleft and between the best and worst groups were identified, the slight morphologic differences noted were not sufficient to explain the subjective esthetic evaluation by the panel. PMID- 19642747 TI - Congenital nasal pyriform aperture stenosis: diagnosis and management. AB - OBJECTIVES: To review diagnosis and treatment modalities in congenital nasal pyriform aperture stenosis in a newborn population. STUDY DESIGN: A 6-year retrospective case series review. Mean follow-up of 21.8 months. SETTING: University hospital, tertiary care center. PATIENTS: Twenty-one consecutive patients treated for congenital nasal pyriform aperture stenosis. Diagnosis was suspected on physical examination and confirmed by computed tomography scan. Associated abnormalities were present in 15 patients. SURGICAL TREATMENT: Nineteen patients underwent surgical treatment focused on external bony margins of pyriform aperture and the osseous anterior edge of the inferior turbinate, drilling by a sublabial approach and associated with a partial turbinectomy in seven cases. A stent was placed for 7 to 10 days. A conservative treatment based on topical nasal decongestants and gastroesophageal reflux treatment was proposed for two patients. RESULTS: Postoperative follow-up revealed septal ulceration in five cases with septal perforation in one case and development of synechiae in two cases. Follow-up revealed normal nasal breathing and pyriform aperture growth after surgery. CONCLUSION: Our experience confirmed the link described between congenital nasal pyriform aperture stenosis and holoprosencephaly, but associated extracraniofacial malformations suggest that congenital nasal pyriform aperture stenosis should be integrated in a systemic malformative syndrome or genetic disorder and lead us to propose an exhaustive dysmorphology assessment. Some infants may be treated by conservative management, and severely affected patients may undergo surgery by a sublabial approach. PMID- 19642748 TI - Modified Von Langenbeck cleft palate repair using an anterior triangular flap: decreased incidence of anterior oronasal fistulas. AB - OBJECTIVE: A complication following cleft palate surgery is the development of oronasal fistulas. Despite recent advances aimed at addressing this concern, rates of postoperative fistulas have remained unchanged and are reported at between 3% and 60%. Oronasal fistulas commonly occur between the hard and soft palate and at the anterior portion of the cleft. These fistulas lead to functional problems with nasal emission, hypernasal speech, and food regurgitation through the nose. For clefts of the secondary palate, we developed a modification of the Von Langenbeck technique in which an anterior triangular flap is used to decrease the incidence of postoperative fistulas. METHOD: A triangular flap composed of oromucosa was designed for isolated clefts of the secondary palate only. It is based at the anterior margin of the cleft and is used as a turnover flap to allow closure of the often very tight anterior nasal side. A retrospective chart analysis was performed from 2000 to 2007. All patients who had isolated clefts of the secondary palate and had undergone a modified Von Langenbeck procedure were included in the study. Patients were evaluated 4 to 8 weeks postoperatively for the presence of oronasal fistulas. RESULTS: With the introduction of the anterior triangular flap, we show that 0 of 182 patients developed a postoperative oronasal fistula. CONCLUSIONS: This modification of the standard Von Langenbeck uses an anterior triangular flap and confers the advantage of assisting in nasal side closure of the anterior margin of the cleft; in doing so, it reduces the rate of fistula formation. PMID- 19642749 TI - Rapid maxillary expansion after secondary alveolar bone grafting in patients with alveolar cleft. AB - OBJECTIVE: To test the hypothesis that it is possible to perform rapid maxillary expansion (RME) after alveolar bone grafting in patients with clefts of the lip and palate (CLP) without compromising the final result of the bone graft. DESIGN: Occlusal and periapical radiographs of the grafted area of 17 unilateral and 11 bilateral patients with CLP (n = 28) were obtained before and after RME. SETTING AND SAMPLE POPULATION: Hospital for Rehabilitation of Craniofacial Anomalies (HRAC), University of Sao Paulo. Twenty-eighty patients with CLP who had undergone RME. INTERVENTIONS: RME was performed in patients with CLP who had already undergone RME before secondary bone grafting but with relapse of the maxillary dental arch constriction, as well as in patients with CLP who had never undergone expansion before bone grafting. OUTCOME MEASURE: Qualitative evaluation in occlusal and periapical radiographs after alveolar bone grafting. RESULTS: Findings showed opening of the midpalatal suture in 42.8% of patients in this study. Regardless of the success rate of RME, the alveolar bone grafting was not affected when the procedures were inverted. CONCLUSION: The hypothesis was accepted. RME can be performed after secondary alveolar bone grafting without affecting it. PMID- 19642750 TI - Dentoalveolar relationships of Malay children with unilateral cleft lip and palate. AB - OBJECTIVE: To determine the treatment outcome based on dentoalveolar relationships among Malay children born with nonsyndromic complete unilateral cleft lip and palate (UCLP). DESIGN: Retrospective cohort study. SETTING AND SAMPLE POPULATION: The Department of Orthodontics at the School of Dental Science and the Reconstructive Sciences Unit, School of Medical Science, Universiti Sains Malaysia. Dental study models of 82 UCLP Malay children aged 8 to 10 years were evaluated. All subjects had their cleft lip and palate repaired, but no alveolar bone graft or any orthodontic treatment was performed. OUTCOME MEASURE: The outcome of dental arch relationships was assessed using the Goslon Yardstick Index: a dental measure with outcomes ranked on a scale ranging from 1 to 5. Agreement of rating was assessed with weighted kappa statistics; both intraexaminer and interexaminer agreements were high, indicating good reproducibility. RESULTS: A total of 2.4% of the sample was in grade 1, 24.4% in grade 2, 35.4% in grade 3, 31.7% in grade 4, and 6.1% in grade 5. The mean Goslon index score was 3.15. CONCLUSION: Dentoalveolar relationship outcomes of UCLP Malay children are intermediate according to the Goslon Yardstick. Interpretation of results should consider the ethnic differences in the craniofacial complex. PMID- 19642751 TI - Craniofacial and pharyngeal cephalometric morphology in seven-year-old boys with unoperated submucous cleft palate and without a cleft. AB - OBJECTIVE: To evaluate cephalometrically the craniofacial and pharyngeal morphology in 7-year-old boys with unoperated submucous cleft palate and to compare the findings with the morphology of 7-year-old boys without clefts. SETTING AND PATIENTS: Thirty-two boys with unoperated submucous cleft palate and 49 boys without a cleft were compared retrospectively from lateral cephalograms taken at the mean age of 7 years (range, 5.5 to 8.6 years). DESIGN: A retrospective case-control study. OUTCOME MEASURE: Linear and angular measurements were obtained from lateral cephalograms. A Student's t test was used in the statistical analysis. RESULTS: The maxilla of the boys with submucous cleft palate was shorter and slightly more retrusive in relation to the cranial base than that of boys without clefts. Also, the mandible of the boys with submucous cleft palate was smaller, with a steeper mandibular plane. The relationship between the jaws was similar in both groups; although, those without clefts showed higher values for soft tissue maxillary prominence. In the pharyngeal area, the boys with submucous cleft palate had larger nasopharyngeal depths, smaller hypopharyngeal depths, and shorter soft palates than the boys without a cleft. CONCLUSIONS: This small study suggests that the boys with unoperated submucous cleft palate have minor distinctive morphological features in the maxillary, mandibular, and pharyngeal areas. PMID- 19642752 TI - Increased frequency of left-handedness in patients with unilateral coronal synostosis. AB - OBJECTIVE: Left-handedness reportedly has been more common in persons with neurological afflictions (e.g., stroke) and malformations (e.g., cleft lip with or without cleft palate) that demonstrate marked unilateral involvement. Coronal synostosis is also more frequently unilateral, affecting the right side more commonly than the left. We sought to compare left-handedness in patients with unilateral coronal synostosis versus healthy controls. SUBJECTS: All patients aged 3 years or older with nonsyndromic unilateral coronal synostosis and healthy controls recruited by pediatricians blinded to the study. MAIN OUTCOME MEASURES: Prospective data obtained for all participants included age, gender, and handedness. In patients with unilateral coronal synostosis, the side of synostosis and age at surgery were documented. Left-handedness in the study and control groups was compared using chi-square analysis. Left-handedness also was analyzed in the study group according to side of fusion. RESULTS: Eighty-six patients with nonsyndromic unilateral coronal synostosis comprised the study group; there were 96 controls. The mean ages of the study (8.8 years) and control groups (9.8 years) were not statistically different (p > .05). There were more girls in the study group (67%) than in the control group (56%), but this difference was not statistically significant (p > .05). Left-handedness was documented in 30.2% of the study group and 11.4% of the control group (p < .005). Left-handedness was twice as common in patients with left versus right unilateral coronal synostosis (44.4% versus 20.4%; p < .05). CONCLUSIONS: Left-handedness is nearly three times more common in patients with unilateral coronal synostosis than in controls and four times more likely in patients with left-sided fusion. PMID- 19642753 TI - Lateral approach to the levator veli palatini: a preliminary report. AB - The abnormal anatomy in the cleft palate has been of interest to surgeons for a long time. Different authors have independently evolved the techniques of radical reconstruction of the palatal musculature and have suggested the medial approach to dissect the levator. We hereby report the technique in which the levator is identified through the lateral incision of the soft palate. This lateral approach helps in the complete release of the levator from all abnormal attachments and ensures reconstruction of an effective sling. This technique is of particular benefit in a palate re-repair. PMID- 19642754 TI - Dysphagia and nutrition problems in infants with apert syndrome. AB - OBJECTIVE: The purpose of this study was to identify and describe the nature of dysphagia and nutrition difficulties in infants with Apert syndrome. DESIGN: The study comprised a review of the medical, nutrition, and feeding records of 13 consecutive infants still feeding by the bottle who had been referred to the Craniofacial Unit and analyses of swallow function from videofluoroscopic swallow investigations. MAIN OUTCOME MEASURES: Outcome measures included qualitative analyses of bottle-feeding and nutritional status and quantitative functional severity ratings of dysphagia based on videofluoroscopic swallow investigations using the O'Neil et al. (1999) Dysphagia Outcome Severity Scale. RESULTS: The main qualitative descriptors of oral feeding in this cohort included uncoordinated suck-swallow-breathe patterns, inability to maintain sucking bursts, and changes in respiratory patterns as the feed progressed. Videofluoroscopic evaluations (N = 7) showed silent laryngeal penetration or aspiration in more than half of the cohort. Failure to thrive was a frequent occurrence seen in seven infants, and 9 of the 10 required dietetic intervention and enteral supplements. (Nutritional records were not located for three infants.) CONCLUSIONS: In view of the small sample size and retrospective nature of the study, the results need to be interpreted with caution. However, the study adds to current limited knowledge on feeding and nutrition in Apert syndrome. Further prospective multidisciplinary and objective research is clearly warranted. PMID- 19642755 TI - Biomechanical properties of the human soft palate. AB - OBJECTIVE: To measure biomechanical properties of the human soft palate and the variation across anatomic regions. DESIGN: Ex vivo analysis of human tissue. PATIENTS/PARTICIPANTS: Ten palates harvested from 10 normal adult human cadavers (age range, 37 to 90 years). INTERVENTIONS: Computer-controlled uniaxial stress relaxation mechanical properties tested in physiological saline at 37 degrees C. MAIN OUTCOME MEASURES: Measurement of Young modulus, Poisson ratio, and determination of viscoelastic constants c, tau(1), and tau(2) by curve-fitting of the reduced relaxation function to the data. RESULTS: One hundred sections were tested from the 10 palates, representative of 10 anatomic zones. The mean Young modulus range was 585 Pa at the posterior free edge to 1409 Pa at regions of attachment. The mean Poisson ratio in the inferior-superior direction was 0.45 (SD 0.26) and in the lateral direction, was 0.30 (SD 0.21). The mean viscoelastic constants for 1-mm extensions were C = -0.1056 (+/-0.1303), tau(1) = 11.0369 (+/ 9.1865) seconds, and tau(2) = 0.2128 (+/-0.0792) seconds, and for 2-mm extensions were C = -0.1111 (+/-0.1466), tau(1) = 14.3725 (+/-5.2701) seconds, and tau(2) = 0.2094 (+/-0.0544) seconds. CONCLUSIONS: The results show agreement with values of the Young modulus estimated by authors (Ettema and Kuehn, 1994; Berry et al., 1999) undertaking finite element modeling of the palate. However, other modulus measurements based on closing pressure are considerably different. The spatial distribution of viscoelastic parameters across the palate shows good consistency. PMID- 19642756 TI - Nasopharyngeal intubation in Robin sequence: technique and management. AB - OBJECTIVE: To provide a detailed description of the nasopharyngeal intubation (NPI) technique and photographs, which should be helpful for those who may need to perform it for treating the airway obstruction in Robin sequence. DESIGN: To describe and illustrate the NPI technique and the necessary considerations for its application. SETTING: Hospital de Reabilitacao de Anomalias Craniofacial of University of Sao Paulo, Brazil. RESULT: The NPI procedure involves the use of a whitish, Portex, number 3.0 or 3.5, silicone tube, introduced 8 cm deep into the infant's nostril and fixed with Micropore tape. The tube is to be removed at least twice a day for proper hygiene (with running water, detergent, and swabs) and should be changed every 7 days. This procedure is taught to the children's parents or caretakers by the nurse during hospitalization. CONCLUSION: The technique is so simple that it can be performed by the parents themselves, allowing continuation of the treatment at home. PMID- 19642757 TI - New diagram for cleft lip and palate description: the clock diagram. AB - OBJECTIVES: The current classification diagrams for cleft lip and palate are descriptions of the components involved in the cleft, but they do not consider in detail the severity of distortion. We sought to establish a new diagram (the Clock Diagram) for cleft lip and palate, which describes the pathology according to the severity of distortion of the nose, lip, and primary and secondary palate, and to apply this classification scheme toward treatment selection. METHODS: The method is based on surgical results obtained from 1043 cleft lip and palate patients operated by the author between 1996 and 2007, under the protocol based on our classification. To further illustrate the classification and diagram method, two types of clefts are described, using the proposed diagram and compared with Kernahan's diagram. RESULTS: This new diagram describes the cleft's severity using terminology from our clinic's classification of cleft severity. In comparison with Kernahan's diagram, the Clock Diagram more effectively demonstrates a cleft's severity. I have observed a higher incidence of lip and palate revision in severe clefts. CONCLUSIONS: The Outreach Program Lima Clock Diagram classifies the severity of the cleft and affords an individualized description of cleft morphology. I have observed a direct relation between cleft severity and the number of poor outcomes in our patients. PMID- 19642758 TI - Coping strategies and social support in the family impact of cleft lip and palate and parents' adjustment and psychological distress. AB - OBJECTIVE: To examine the role of parents' coping strategies and social support in the family impact of cleft lip and palate (CLP) and levels of adjustment and psychological distress and to investigate whether a child's age, type of cleft, or other reported medical problems influenced such outcomes. DESIGN: A cross sectional study. PARTICIPANTS: One hundred three parents of children or young adults with CLP recruited from families attending a multidisciplinary cleft lip and palate clinic. OUTCOME MEASURES: Family impact, psychological distress, and positive adjustment were assessed using validated psychological questionnaires. RESULTS: Findings indicated that while there were many impacts of a child's CLP, negative outcomes (family impact, psychological distress) were not high. In contrast, parents reported high levels of positive adjustment or stress-related growth as a result of their child's condition. Participants also reported high levels of social support and relied more on the use of approach rather than avoidance-oriented coping strategies. Having more support from friends and family was associated with less negative family impact, lower psychological distress, and better adjustment. Greater use of approach coping was associated with more positive adjustment; whereas, avoidant coping was associated with a greater family impact and more psychological distress. Having a younger child and/or a child with medical problems in addition to CLP was associated with a greater impact on the family. CONCLUSIONS: How parents cope with their child's condition and the levels of support received may have implications for caregivers, the family unit, and the delivery of more family-oriented CLP services. PMID- 19642759 TI - Throat swabs taken on the operating table prior to cleft palate repair and their relevance to outcome: a prospective study. AB - OBJECTIVE: The main objective of this study was to determine whether bacteria cultured from oral swabs taken at the time of surgery predicted postoperative fistula formation. DESIGN: The study was a prospective longitudinal audit. SETTING: The setting was a designated U.K. N.H.S. cleft center. PATIENTS: Subjects consisted of the patients of a single cleft surgeon who were undergoing surgery for cleft palate repair or cleft fistula repair. INTERVENTIONS: Oral microbiological swabs were taken from patients while they were on the operating table just before surgery. MAIN OUTCOME MEASURES: The results from microbiological culture of the swabs were recorded, as was the presence or absence of a fistula at 6 months postoperatively. Additional collected information was related to the severity of the cleft, whether the operating microscope was used during surgery, and whether the patient had developed a postoperative upper respiratory tract infection. RESULTS: Positive swab cultures were not significantly associated with fistula formation. Use of the operating microscope was not associated with an increase or decrease in the number of fistulas. A fistula developed in all patients who experienced a postoperative upper respiratory tract infection. CONCLUSIONS: The practice of performing routine preoperative mouth swabs should be abandoned because the presence of bacteria in the mouth does not increase the risk of fistula formation. PMID- 19642761 TI - Qualitative approaches in craniofacial research. AB - This article proposes the customary use of qualitative methods as complementary research tools to enhance the evidence base in the craniofacial field. The recognition given to qualitative approaches in other healthcare areas and their value in enhancing understanding of lay and professional beliefs and behaviors is contrasted with the paucity of qualitative studies to date in the craniofacial field. Research tools from the qualitative repertoire are briefly introduced and their underpinning principles are explained. The contribution made to research with children and families in wider healthcare areas and in the craniofacial field to date is outlined. Future potential applications of these methods to craniofacial research are discussed. It is suggested that qualitative methods be integrated into craniofacial research as part of the standard toolbox of inquiry, and that interdisciplinary collaborations with colleagues from the social sciences appropriately skilled in the methods should be developed. PMID- 19642760 TI - The frequency of palatal anomalies in Saethre-Chotzen syndrome. AB - OBJECTIVE: Saethre-Chotzen Syndrome (SCS) is an autosomal dominant disorder with widespread phenotypic variability. Cardinal features include coronal synostosis, blepharoptosis, and limb abnormalities. Cleft palate can also occur, but there are few reports on its frequency. This study was undertaken to determine the prevalence of palatal anomalies in this population. DESIGN: We retrospectively reviewed the records of 51 patients with SCS seen at Children's Hospital Boston over the past 30 years. Palatal findings in our patients were compared with those in the literature. To illustrate the phenotypic variability in SCS, we describe an unusual infant who presented for evaluation of cleft palate and blepharoptosis. Her father had only blepharoptosis; this was the clue to the diagnosis, which was confirmed by finding a deletion in the TWIST gene. RESULTS: In our patients, high-arched palate was noted in 43%, bifid uvula in 10%, and cleft palate in 6%. These figures differed slightly from the combined percentages in published reports: 24% with high-arched palate, 2% with bifid uvula, and 5% with cleft palate. CONCLUSIONS: Palatal anomalies are relatively common in SCS. This entity should be considered in the differential diagnosis of a child with cleft palate, particularly in the presence of blepharoptosis, nasal deviation, and limb abnormalities in the patient or in family members. PMID- 19642763 TI - Dentoskeletal effects of maxillary protraction in cleft patients with repetitive weekly protocol of alternate rapid maxillary expansions and constrictions. AB - OBJECTIVE: To evaluate the amount of maxillary protraction with face mask in complete unilateral cleft lip and palate patients submitted to two distinct rapid maxillary expansion (RME) protocols. MATERIAL AND METHODS: The sample consisted of 20 individuals (nine boys and 11 girls; mean age of 10.4 +/- 2.62 years) with unilateral complete cleft lip and palate who had a constricted maxilla in the vertical and transverse dimensions. Ten patients underwent 1 week of RME with screw activation of one complete turn per day, followed by 23 weeks of maxillary protraction (group 1). The other 10 patients underwent 7 weeks of alternate rapid maxillary expansion and constriction, with one complete turn per day, followed by 17 weeks of maxillary protraction (group 2); both groups underwent a total of 6 months of treatment. Cephalometric measurements were taken at different times: pretreatment (T1), soon after RME (T2), and after 6 months of treatment (T3). Each measurement was analyzed with mixed models for repeated measures, and the covariance structure chosen was compound symmetry. RESULTS: The maxilla displaced slightly forward and downward with a counterclockwise rotation; the mandible rotated downward and backward, resulting in an increase in anterior facial height; the sagittal maxillomandibular relationship was improved; the maxillary molars and incisors were protruded and extruded; and the mandibular incisors were retroclined. CONCLUSION: There was no significant difference between the groups in evaluation time. PMID- 19642764 TI - A survey of cleft team patient experience in obtaining dental care. AB - OBJECTIVE: To assess patient experiences in obtaining dental care in a team setting without an affiliated dental school. DESIGN AND PARTICIPANTS: Three hundred seventy-four patients in the cleft team database met inclusion criteria of diagnosis of cleft lip and/or palate, and current age of 7 to 12 years. Demographic information and experiences in obtaining dental care were ascertained using a standardized series of questions. A callback protocol was employed to maximize response rate. Results were analyzed with t-tests using contingency tables. OUTCOME MEASURES AND RESULTS: One hundred seventy-one parents/caregivers were interviewed of a possible 374 (response rate 45.7%). Mean age was 9.87 years. The insurance distribution was as follows: 113 private insurance (66.1%), 35 Medicaid (20.5%), and 23 had no insurance (13.5%). The dental checkup distribution was as follows: 145 regular dental checkups (84.8%) and 26 no regular checkups (15.2%). Patients with private insurance were more likely to obtain dental care than were patients with Medicaid (p = .002) or patients without insurance (p = .0027). Patients with Medicaid were more likely to report provider refusal of care than were patients with private insurance (p = .0001) or patients without insurance (p = .0001). Patients with private insurance were more likely to report satisfaction with their dental care than were patients with Medicaid (p = .0003). CONCLUSIONS: We report an 84.8% regular checkup rate among our study population and a significantly different reported experience in obtaining care depending on insurance type. The reasons underlying the differences between privately insured patients and Medicaid patients appear multifactorial. PMID- 19642765 TI - Esthetic analysis of gingival components of smile and degree of satisfaction in individuals with cleft lip and palate. AB - OBJECTIVE: To evaluate soft tissue characteristics in individuals with cleft lip and palate and the degree of satisfaction of these individuals after rehabilitation. SETTING: Hospital for Rehabilitation of Craniofacial Anomalies, Brazil. PATIENTS: Forty-five individuals with repaired complete unilateral cleft lip and palate, aged 15 to 30 years. INTERVENTIONS: One hundred thirty-five frontal facial photographs were obtained at rest and in natural and forced smile. Specialists in periodontics evaluated the soft tissue characteristics. Both patients and specialists evaluated the smiles and scored them as esthetically unpleasant, acceptable, or pleasant. MAIN OUTCOME MEASURES: Comparison of the cleft area with the contralateral region was performed for evaluation of soft tissue. The results of the degree of satisfaction with smile were expressed as percentages and means. The findings between patients and periodontists experienced or inexperienced with cleft care were compared. RESULTS: Statistically significant differences were observed for alveolar process deficiency and absence of papilla in the esthetic area between groups (p < .05). Results show 84.4% of individuals considered their smile as esthetically pleasant. Specialists in periodontics of both groups scored the natural smile and forced smile as esthetically acceptable. There was a statistically significant difference in the mean of patients compared with both groups of specialists in periodontics (p < .05). CONCLUSIONS: Evaluation and knowledge of the soft tissue characteristics is extremely important for successful rehabilitation. The esthetic values and degree of patient satisfaction are essential for treatment success, since smile reconstruction should be esthetically pleasant to the patient. PMID- 19642766 TI - Causal attributions in parents of babies with a cleft lip and/or palate and their association with psychological well-being. AB - OBJECTIVE: This study aimed to assess causal attributions of parents of babies with a cleft lip and/or palate. Evidence from causal attribution theory and attribution studies in other medical conditions led to the hypothesis that parents who make internal attributions (self-blame) will have poorer psychological well-being. DESIGN: A cross-sectional survey. SETTING: Postal questionnaires were sent to parents of children under the care of the South Thames Cleft Service at Guy's Hospital. PARTICIPANTS: PARTICIPANTS were recruited if they had a baby between 12 and 24 months old with a cleft lip and/or palate. Of 204 parents, 42 responded. MAIN OUTCOME MEASURES: A semistructured questionnaire about causal beliefs was completed alongside validated questionnaires measuring anxiety, depression (Hospital Anxiety and Depression Scale), and perceived stress (Perceived Stress Scale). RESULTS: Causal attributions were grouped according to type (environmental, chance, self-blame, and no belief) and loci (external or internal). The most common attribution made was to external factors (54.4%), followed by no causal attribution (38.1%). Parents making an internal (self-blaming) attribution (16.7%) had significantly (p < .05) higher scores on the Hospital Anxiety and Depression Scale anxiety measure (r = .32) and Perceived Stress Scale (r = .33), but not on the Hospital Anxiety and Depression Scale depression measure (p = .283). CONCLUSIONS: The high number of parents making an external attribution can be explained by causal attribution theory. However, the percentage of parents making no causal attribution was higher than seen in previous research. Surprisingly, no parents blamed others. The main hypothesis was tentatively accepted because there were significantly higher anxiety and stress scores in parents who self-blamed; although, depression scores were not significantly higher. PMID- 19642767 TI - Maxillofacial aspects in malignant osteopetrosis. AB - OBJECTIVE: Malignant osteopetrosis (MO) is a rare hereditary disease that affects young children. Its physiopathology is explained by a basic defect in osteoclast precursor cells, with a radiographic image of diffuse sclerosis and increased bone density. The bone contains an increased number of structurally abnormal osteoclasts. Infections commonly occur because the neutrophils exhibit reduced chemotactic response and decreased ability of bacterial phagocytosis. PATIENT: A white female patient aged 9 months, of mixed descent, was diagnosed at birth as having MO after bone marrow biopsy. Dental examination revealed the presence of four teeth, all of which had enamel hypoplasia and no carious lesions. After bone marrow transplantation (BMT), an erythematous lesion appeared on the alveolar ridge on day 2, with signs of tooth exfoliation. On day 7, there was gingival bleeding, edema, and erythema at the region of the maxillary incisors with grade 3 mobility, without changes in food intake. RESULTS: Concerning the oral cavity, the patient maintained grade 1 tooth mobility without tooth exfoliation or other oral alterations. CONCLUSION: Accurate diagnosis and careful therapeutic planning are important to avoid the secondary complications of the disease. PMID- 19642768 TI - Intraoral photographs for rating dental arch relationships in unilateral cleft lip and palate. AB - BACKGROUND AND PURPOSE: The Goslon Yardstick is one of the most commonly used methods to assess dental arch relationships of patients with unilateral cleft lip and palate. This system was originally applied to dental casts. For reasons of economy and convenience, we aimed to determine whether intraoral photographs could substitute for dental casts for rating dental arch relationships. METHODS: Records of 58 patients with nonsyndromic complete unilateral cleft lip and palate from the Chang Gung Craniofacial Center, Taipei, Taiwan, were used in this study. A set of dental casts and digital intraoral photographs taken at around 9 years of age were available for all patients. An experienced examiner rated the dental casts using the Goslon Yardstick to provide the reference scores. The other three examiners rated the intraoral photographs and repeated the rating 1 week later to calculate inter- and intraexaminer reliability. The photographic scores for each examiner were then compared with the reference scores to determine the validity of the photographs. RESULTS: The results showed no significant difference between the rating of dental casts and photographs using the Goslon Yardstick. Reliability was also high for rating on photographs. CONCLUSIONS: Intraoral photographs appear to be a viable alternative to the application of the Goslon Yardstick on dental casts. PMID- 19642769 TI - Transport distraction osteogenesis for closing full-thickness calvarial defects in sheep. AB - OBJECTIVE: To prove the hypothesis that transport distraction osteogenesis can be applied to the skull to close critical-size calvarial defects. DESIGN: A sheep model was developed to investigate this hypothesis. In four sheep, bilateral parietal bone windows were created and adjacent osteotomies performed. On the tested side, an adjacent bone segment was transported into the defect. The contralateral side was left untreated as a control. MAIN OUTCOME MEASURES: After completion of the distraction and consolidation period, a computed tomography study was performed, and the animals were sacrificed. The newly formed bone was examined macroscopically and histologically. RESULTS: A successful closure of the defect with transport distraction was achieved in all of the animals. The control side healed spontaneously in one (younger) sheep but did not heal in the other three animals. The closure of the bony defect with transport distraction was evident macroscopically as well as on the computerized tomography. Microscopic examination showed new healthy bone formation on the treated side. CONCLUSION: We conclude that transport distraction is an effective tool in closing full thickness calvarial defects in adult sheep. Further investigation is needed before applying this promising technique in humans. PMID- 19642770 TI - Treatment outcome after one-stage repair in children with complete unilateral cleft lip and palate assessed with the Goslon Yardstick. AB - OBJECTIVE: To compare results of Golson Yardstick measurement of dental arch relationships in a sample of 10-year-old Polish children with results of the Golson measurement in published reports. MATERIALS AND METHODS: Plaster models of 28 consecutively treated subjects with unilateral cleft lip and palate (UCLP) that was repaired with a one-stage simultaneous closure performed in the first year of life. All individuals were born between 1994 and 1995. The Goslon score (categories 1 to 5) was allocated. Intra- and interrater agreement was assessed with kappa statistics and Pearson correlation coefficient. Independent t tests were employed to detect difference between the score in the present and other published samples. RESULTS: Mean Goslon score equaled 2.44; 57% of the patients were allocated Goslon category 1 or 2, 32% were rated Goslon 3, and 11% of the patients were assigned category 4 or 5. Intrarater agreement was between 0.75 and 0.77. Interrater agreement was 0.79. CONCLUSIONS: Dental arch relationship following one-stage repair was comparable with the results of the centers with the best outcome. PMID- 19642771 TI - Flexible laryngeal mask airway for cleft palate surgery in children: a randomized clinical trial on efficacy and safety. AB - OBJECTIVE: To evaluate the efficacy of a flexible laryngeal mask airway in children undergoing palatoplasty. DESIGN: Prospective, randomized, single-center study. SETTING: Jawaharlal Institute of Postgraduate Medical Education and Research. PATIENTS: Sixty-six children (American Society of Anesthesiologists physical status 1 and 2) scheduled to undergo palatoplasty were assigned randomly to an endotracheal intubation group (RAE group, n = 33) and a flexible laryngeal mask airway group (FLMA group, n = 33). MAIN OUTCOME MEASURES: Peak airway pressure, inspired and expired tidal volume, end-tidal carbon dioxide, lung compliance, and airway resistance were continuously measured after placement of the assigned airway. The percentage leak around the airway was quantified as the leak fraction. Parametric data between groups were analyzed using an unpaired Student's t test and within groups using a one-way analysis of variance. Nonparametric variables were analyzed using the Fisher exact test. RESULTS: In two children, the flexible laryngeal mask airway was displaced from its original position; whereas, one endotrachial tube advanced endobronchially. The leak fraction was significantly higher in the RAE group when compared with that in FLMA group (13.34% +/- 13.74% versus 5.96% +/- 3.78%, p < .05) until the throat pack was applied. Peak airway pressure and resistance were significantly higher in the RAE group compared with the FLMA group at all time intervals, p < .05. During emergence, frequency of coughing, desaturation, and laryngospasm were increased in the RAE group. CONCLUSION: A flexible laryngeal airway mask is suitable for maintaining the airway and helps in smooth emergence in children undergoing palatoplasty. PMID- 19642772 TI - Methodology for speech assessment in the Scandcleft project--an international randomized clinical trial on palatal surgery: experiences from a pilot study. AB - OBJECTIVE: To present the methodology for speech assessment in the Scandcleft project and discuss issues from a pilot study. DESIGN: Description of methodology and blinded test for speech assessment. Speech samples and instructions for data collection and analysis for comparisons of speech outcomes across five included languages were developed and tested. PARTICIPANTS AND MATERIALS: Randomly selected video recordings of 10 5-year-old children from each language (n = 50) were included in the project. Speech material consisted of test consonants in single words, connected speech, and syllable chains with nasal consonants. Five experienced speech and language pathologists participated as observers. MAIN OUTCOME MEASURES: Narrow phonetic transcription of test consonants translated into cleft speech characteristics, ordinal scale rating of resonance, and perceived velopharyngeal closure (VPC). A velopharyngeal composite score (VPC sum) was extrapolated from raw data. Intra-agreement comparisons were performed. RESULTS: Range for intra-agreement for consonant analysis was 53% to 89%, for hypernasality on high vowels in single words the range was 20% to 80%, and the agreement between the VPC-sum and the overall rating of VPC was 78%. CONCLUSIONS: Pooling data of speakers of different languages in the same trial and comparing speech outcome across trials seems possible if the assessment of speech concerns consonants and is confined to speech units that are phonetically similar across languages. Agreed conventions and rules are important. A composite variable for perceptual assessment of velopharyngeal function during speech seems usable; whereas, the method for hypernasality evaluation requires further testing. PMID- 19642773 TI - Enamel defects in maxillary central incisors of infants with unilateral cleft lip. AB - OBJECTIVE: To evaluate the presence of enamel alterations in deciduous maxillary central incisors of infants with unilateral cleft lip and alveolar ridge, with or without cleft palate, and to compare the occurrence and location of these alterations between the central incisor adjacent to the cleft and the contralateral incisor. DESIGN: Intraoral clinical examination was performed after tooth cleaning and drying by a single examiner with the aid of a dental mirror, dental probe, and artificial light, with the child positioned on a dental chair. The defects were recorded in a standardized manner according to the criteria of the Modified Developmental Defects of Enamel Index. SETTING: Hospital for Rehabilitation of Craniofacial Anomalies (HRAC) at Bauru, Sao Paulo, Brazil. PATIENTS: One hundred one infants were evaluated. All were white, of both genders, aged 12 to 36 months and had at least two thirds of the crowns of maxillary incisors erupted. RESULTS: Demarcated opacity was the most common defect at both cleft and noncleft sides, followed by diffuse opacity. The occurrence of hypoplasia at the cleft side was 11.8%. Most defects affected less than one third of the crown. CONCLUSION: The occurrence of enamel defects in deciduous maxillary central incisors of patients with unilateral cleft lip was 42.6%, mainly affecting the cleft side as to both number and severity. PMID- 19642774 TI - Coping with a cleft: psychosocial adjustment of adolescents with a cleft lip and palate and their parents. AB - OBJECTIVE: To explore the nature of psychosocial adjustment in young people with a cleft as well as in their parents, within the framework of Lazarus and Folkman's (1984) transactional model of stress and coping. DESIGN, PARTICIPANTS, SETTING: A cross-sectional postal questionnaire design study was used, involving young people aged between 11 and 16 years and their parents. There were 145 families from two cleft services participating in the study. OUTCOME MEASURES: Participants completed measures of psychological adjustment, coping, social experiences, satisfaction with appearance, cleft-related factors, and demographic information. RESULTS: Young people with a cleft and their mothers did not report psychosocial adjustment difficulties above that of the normal population. An insufficient number of fathers were recruited for substantive analysis to be conducted using their data. CONCLUSIONS: The findings show little evidence of significant psychosocial adjustment difficulties for adolescents with a cleft or for their mothers. The concepts of adjustment, coping, satisfaction with appearance, and maternal mental health in this population are discussed. The results highlight the importance of timely interventions and seeking multiple perspectives in clinical management of a cleft. Questions are raised about the completion of self-report measures for future research in this population. PMID- 19642775 TI - Dental development in children with growth hormone insensitivity syndrome: Demirjian analysis of serial panoramic radiographs. AB - OBJECTIVE: This study evaluates the effects of 8 years of insulinlike growth factor-I therapy on tooth development in patients with growth hormone insensitivity syndrome. METHODS: Forty-nine panoramic radiographs were evaluated from eight patients (six boys, two girls). Seven teeth in the mandibular left region were graded according to the Demirjian system. Radiographs were taken at the start of insulinlike growth factor-I therapy and were continued at approximately yearly intervals for 8 years. RESULTS: Three of six boys and one of two girls who began treatment with insulinlike growth factor-I at earlier ages experienced an increase in the rate of tooth development. One of six boys who began treatment with insulinlike growth factor-I at a later age had a slower rate of dental development. The patients had more rapid tooth maturation during the beginning of treatment. By the end of treatment, all patients had normal dental maturity for their age. CONCLUSIONS: Treatment of growth hormone insensitivity syndrome with insulinlike growth factor-I appears to lead to an increase in dental maturation, particularly in younger patients. After 8 years all patients had achieved normal dental development. PMID- 19642776 TI - Gastroesophageal reflux in severe cases of Robin sequence treated with nasopharyngeal intubation. AB - OBJECTIVE: To study the prevalence of abnormal gastroesophageal reflux in infants with Robin sequence who had severe respiratory obstruction treated with nasopharyngeal intubation and to evaluate the efficacy of nonsurgical treatment. DESIGN: Longitudinal prospective study. SETTING: Hospital de Reabilitacao de Anomalias Craniofaciais, University of Sao Paulo, Brazil. PATIENTS: Twenty infants with severe isolated Robin sequence treated with nasopharyngeal intubation. INTERVENTIONS: We performed 24-hour esophageal pH monitoring on each child at 2, 4, and 6 months of age. Respiratory and feeding status were evaluated. We considered abnormal gastroesophageal reflux as reflux index values above the 95th percentile of the Vandenplas reference for normal children. RESULTS: The prevalence of reflux index above the 95th percentile at the first exam was 6/20, a value significantly higher than the reference (5/103, p < .01). At the second and third exams, reflux index values were decreased. Ninety percent of the infants showed improvement of respiratory difficulty and developed oral feeding capacity. CONCLUSIONS: The prevalence of abnormal gastroesophageal reflux is higher in infants with severe cases of Robin sequence than in normal infants. Nonsurgical procedures improved respiratory and feeding difficulties of most of these infants. PMID- 19642779 TI - Five-year Irish trial of CLI patients with TASC II type C/D lesions undergoing subintimal angioplasty or bypass surgery based on plaque echolucency. AB - PURPOSE: To report a 5-year observational parallel group study comparing the effectiveness of subintimal angioplasty (SIA) to bypass grafting (BG) for treatment of TASC II type C/D lesions in the lower limb arteries of patients with critical limb ischemia (CLI). METHODS: Of 1076 patients referred with PVD from 2002 to 2007, 206 SIAs in 190 patients (104 women; mean age 73+/-13 years) and 128 bypass grafts in 119 patients (77 men; mean age 70+/-14 years) were enrolled in the study. All patients had Rutherford classification 4-6 ischemia manifested as rest pain and/or tissue loss. Primary endpoints were (1) survival free from amputation and (2) sustained clinical improvement [+2 Rutherford category and/or ABI increase >0.15 without target lesion revascularization (TLR)]. Secondary endpoints were major adverse events (MAE), the binary restenosis rate, freedom from TLR, and a special quality-adjusted life year (QALY) endpoint (Q-TWiST) that incorporated both length and quality of life to evaluate treatments. A cost analysis was also performed. RESULTS: At 5 years, clinical improvement was sustained in 82.8% of the SIA group versus 68.2% of the BG patients (p = 0.106). Five-year all-cause survival was similar for SIA (78.6%) and BG (80.1%; p = 0.734), as was amputation-free survival (SIA 72.9% versus BG 71.2%; p = 0.976). Hyperfibrinogenemia (p = 0.009) and C-reactive protein (p = 0.019) had negative effects on survival without amputation. Five-year freedom from binary restenosis rates were 72.8% for SIA versus 65.3% for BG (p = 0.700). While the 5-year freedom from TLR rates (SIA 85.9% versus BS 72.1%, p = 0.262) were not statistically significant, the risk of MAE (p<0.002) and length of hospital stay (p<0.0001) were significantly reduced in the SIA group. Q-TWiST significantly improved (p<0.001) and cost-per-QALY (SIA euro5663 versus BG euro9172, p<0.002) was reduced with SIA. The 5-year risk of re-intervention (p>0.05) and mean number of procedures (p = 0.078) were similar. CONCLUSION: Five-year freedom from MAE was enhanced by 20% in the SIA group, with substantial cost reduction and better Q-TWiST. SIA is a minimally invasive technique that expands amputation-free and symptom-free survival. SIA is poised to bring about a paradigm shift in the management of CLI. PMID- 19642780 TI - In-vivo imaging of changes in abdominal aortic aneurysm thrombus volume during the cardiac cycle. AB - PURPOSE: To evaluate in-vivo thrombus compressibility in abdominal aortic aneurysms (AAAs) to hopefully shed light on the biomechanical importance of intraluminal thrombus. METHODS: Dynamic electrocardiographically-gated computed tomographic angiography was performed in 17 AAA patients (15 men; mean age 73 years, range 69-76): 11 scheduled for surgical repair and 6 under routine surveillance. The volumes of intraluminal thrombus, the lumen, and the total aneurysm were quantified for each phase of the cardiac cycle. Thrombus compressibility was defined as the percent change in thrombus volume between diastole and peak systole. Continuous data are presented as medians and interquartile ranges (IQR). RESULTS: A substantial interpatient variability was observed in thrombus compressibility, ranging from 0.4% to 43.6% (0.2 to 13.5 mL, respectively). Both thrombus and lumen volumes varied substantially during the cardiac cycle. As lumen volume increased (5.2%, IQR 2.8%-8.8%), thrombus volume decreased (3.0%, IQR 1.0%-4.6%). Total aneurysm volume remained relatively constant (1.3%, IQR 0.4-1.9%). Changes in lumen volume were inversely correlated with changes in thrombus volume (r = -0.73; p = 0.001). CONCLUSION: In-vivo thrombus compressibility varied from patient to patient, and this variation was irrespective of aneurysm size, pulse pressure, and thrombus volume. This suggests that thrombus might act as a biomechanical buffer in some, while it has virtually no effect in others. Whether differences in thrombus compressibility alter the risk of rupture will be the focus of future research. PMID- 19642781 TI - Commentary: AAA rupture prediction: the potential benefit of dynamic (ECG-Gated) 64-slice CTA to assess aortic pathology. PMID- 19642782 TI - The arch and beyond: bare stents in the ascending aorta. AB - PURPOSE: To describe the management of complications from an unsuccessful hybrid repair of an aortic arch aneurysm. CASE REPORT: A 63-year-old man with acute type B dissection and retrograde dissection into the aortic arch underwent emergent hybrid repair, with partial debranching (ascending aorta to left carotid artery bypass) and proximal stent-graft deployment. At 3 months, computed tomography (CT) showed stent-graft migration, causing a large type I endoleak; flow through the patent left subclavian artery (LSA) caused a large type II endoleak. At a second operation, a bilateral subclavian-to-carotid transposition was performed; the LSA was ligated and a Zenith TX2 thoracic endograft was deployed to seal the leak. Recurrent type I endoleak a year later prompted the final endovascular solution: total supra-aortic vessel debranching, proximal stent-graft deployment, and the unprecedented use of bare Z stents in the ascending aorta. CT at 18 months confirmed stable stent-graft position and no endoleak. CONCLUSION: Based on this initial experience, bare Z stents can be used to enhance proximal aortic stent-graft fixation and accommodation within the aortic arch. PMID- 19642783 TI - Multidetector CTA in the quantification of internal carotid artery stenosis: value of different reformation techniques and axial source images compared with selective carotid arteriography. AB - PURPOSE: To evaluate the role of 4 different reformation techniques and axial images from multidetector computed tomographic angiography (MDCTA) versus selective carotid arteriography (SCA) in patients with internal carotid artery (ICA) stenosis. METHODS: Imaging studies from 50 patients (43 men; mean age 70.3+/-8.0 years, range 51-85) with known cerebrovascular disease who underwent MDCTA and SCA in a single university hospital were retrospectively analyzed. Axial images, multiplanar reformation (MPR), curved planar reformation (CPR), volume rendering threshold (VRT), and virtual angioscopy (VA) images were reviewed by 2 independent observers who were blinded to the results of SCA, which served as the gold standard. The degree of stenosis was categorized as 0%-49%, 50%-69%, or 70%-99%; a stenosis >70% was considered as hemodynamically significant. RESULTS: Thirty-four hemodynamically significant stenoses were identified on SCA. The agreement with SCA images was good for both observers using axial CT images (kappa = 0.89 for observer 1 and 0.88 for observer 2); corresponding results for MPR and CPR were kappa = 0.91 and 0.92 for observer 1 and 0.88 and 0.91 for observer 2, respectively. VRT (kappa = 0.72 for observer 1 and 0.66 for observer 2) and VA (kappa = 0.74 for observer 1 and 0.70 for observer 2) showed a slightly inferior correlation with SCA images. Sensitivities for reformations and axial CT images were 100% each; corresponding specificities ranged from 85% to 95%. CONCLUSION: Axial images as well as all 4 reformation techniques agreed well with SCA in the grading of ICA stenosis. PMID- 19642784 TI - Imaging of cerebral arterial occlusive disease: do we really look for the right things? PMID- 19642785 TI - Comparison of aortomonoiliac endovascular aneurysm repair versus a bifurcated stent-graft: analysis of perioperative morbidity and mortality. AB - PURPOSE: To compare the perioperative morbidity and mortality following endovascular aneurysm repair (EVAR) with a bifurcated stent-graft versus an aortomonoiliac stent-graft combined with a femorofemoral crossover graft. METHODS: A prospectively maintained database of patients undergoing EVAR over a 7 year period (January 2001 to June 2008) was interrogated retrospectively to identify all patients receiving either a bifurcated or an aortomonoiliac stent graft. Patients undergoing emergency treatment or renal/mesenteric fenestrated or iliac branched EVAR were excluded. Data retrieval found 210 patients (194 men; mean age 75 years) who had been treated with 41 aortomonoiliac stent-grafts and 169 bifurcated devices. The impact of preoperative and intraoperative variables on postoperative morbidity was assessed by means of univariate and multivariate logistic regression analysis. RESULTS: Significant postoperative complications occurred in 41% (17/41) of aortomonoiliac stent-graft patients compared to 14% (23/169) of bifurcated stent-graft patients (p = 0.0001). Univariate logistic regression analyses identified patient age, operating time, and implantation of an aortomonoiliac stent-graft as significant predictors of postoperative complications. In a multivariate logistic regression model, only implantation of an aortomonoiliac stent-graft was independently associated with postoperative complications (p = 0.003). CONCLUSION: Compared to EVAR with a bifurcated device, the implantation of an aortomonoiliac stent-graft and crossover bypass is associated with higher patient morbidity similar to rates reported after open repair. These patients comprise a high-risk endovascular group and require careful postoperative management in order to minimize complications. PMID- 19642786 TI - Influence of obesity on in-hospital and midterm outcomes after endovascular repair of abdominal aortic aneurysm. AB - PURPOSE: To evaluate the influence of obesity on outcomes after endovascular aneurysm repair (EVAR). METHODS: A retrospective analysis was conducted of 80 patients (77 men; mean age 75.0+/-7.6 years) undergoing elective EVAR for abdominal aortic aneurysm (AAA) between 2001 and 2008. Patients were stratified on presence of obesity [body mass index (BMI) >or=30 kg/m(2)). Outcomes in hospital and during follow-up were compared between obese and non-obese patients. RESULTS: In this cohort, 26 (33%) patients had a BMI >or=30 kg/m(2). Mean BMI in the non-obese group was 25.6 kg/m(2) versus 34.1 kg/m(2) in the obese group (p<0.001). In obese patients, EVAR operating time was longer compared to non obese patients: 217 versus 177 minutes (p = 0.006). One obese patient died after EVAR (p = 0.325); the combined operative mortality and major complication rate was 8% (n = 2) in the obese group versus 7% (n = 4) in the non-obese group (p = NS). Endoleak occurred in 25% (n = 6) of the obese group versus 14% (n = 7) of the non-obese group (p = 0.261). Postoperative intensive care for >24 hours (65% versus 70%, p = 0.796) and overall length of stay (3.9 versus 3.8 days, p = 0.845) did not differ significantly; neither did all-cause mortality during 2 years of follow-up (p = 0.688). CONCLUSION: Obesity is associated with extended operation times during EVAR, but increasing BMI appears to have little influence on outcomes after EVAR. A preferential approach to offering EVAR for obese patients may be reasonable. PMID- 19642787 TI - Effect of curvature on displacement forces acting on aortic endografts: a 3 dimensional computational analysis. AB - PURPOSE: To determine the effect of curvature on the magnitude and direction of displacement forces acting on aortic endografts in 3-dimensional (3D) computational models. METHOD: A 3D computer model was constructed based on magnetic resonance angiography data from a patient with an infrarenal aortic aneurysm. Computational fluid dynamics tools were used to simulate realistic flow and pressure conditions of the patient. An aortic endograft was deployed in the model, and the displacement forces acting on the endograft were calculated and expressed in Newtons (N). Additional models were created to determine the effects of reducing endograft curvature, neck angulation, and iliac angulation on displacement forces. RESULTS: The aortic endograft had a curved configuration as a result of the patient's anatomy, with curvature in the anterolateral direction. Total displacement force acting on the endograft was 5.0 N, with 28% of the force in a downward (caudal) direction and 72% of the force in a sideways (anterolateral) direction. Elimination of endograft curvature (planar graft configuration) reduced total displacement force to 0.8 N, with the largest component of force (70%) acting in the sideways direction. Straightening the aortic neck in the curved endograft configuration reduced the total force acting on the endograft to 4.2 N, with a reduction of the sideways component to 55% of the total force. Straightening the iliac limbs of the endograft reduced the total force acting on the endograft to 2.1 N but increased the sideways component to 91% of the total force. CONCLUSION: The largest component of the force acting on the aortic endograft is in the sideways direction, with respect to the blood flow, rather than in the downward (caudal) direction as is commonly assumed. Increased curvature of the aortic endograft increases the magnitude of the sideways displacement force. The degree of angulation of the proximal and distal ends of the endograft influence the magnitude and direction of displacement force. These factors may have a significant influence on the propensity of endografts to migrate in vivo. PMID- 19642788 TI - Nitinol stent implantation in long superficial femoral artery lesions: 12-month results of the DURABILITY I study. AB - PURPOSE: To evaluate the long-term efficacy and integrity of the PROTEGE EverFlex stent in superficial femoral artery (SFA) lesions in symptomatic patients with peripheral artery disease (PAD). METHODS: A prospective, multicenter, nonrandomized study enrolled 151 subjects (111 men; mean age 67.8 years, range 42 93) undergoing percutaneous treatment of de novo, restenotic, or reoccluded SFA lesions between August 11, 2006, and June 26, 2007. Subjects were scheduled to receive a single stent and be evaluated through 12 months following the implant procedure. Occlusions were present in 40% of the patients. Mean lesion length was 96.4 mm (range 10-150). RESULTS: A total of 161 stents (158 EverFlex) were implanted in the 151 patients: single stents in 93.4% (141/151) and a second stent in 6.6% (10/151). One-year follow-up information was available for 88.7% (134/151) of the study participants; of the remaining 17 subjects, 6 subjects withdrew from the study, 2 were lost to follow-up, and 9 died. Freedom from restenosis data were available for 99.3% (133/134) of the subjects who completed a 12-month follow-up visit. The mean Rutherford classification fell from 2.8+/ 0.8 (range 1-5) at baseline to 0.6+/-1.1 (range 0-5) at 12 months. The mean ankle brachial index rose from 0.6+/-0.2 (range 0-1.4) at baseline to 0.9+/-0.2 (range 0-1.2) at 12 months. The rates for freedom from >50% restenosis at 6 and 12 months were 91.3% (95% CI 84.9% to 95.2%) and 72.2% (95% CI 63.8% to 79.6%), respectively. The freedom from target lesion revascularization rate at 12 months was 79.1% (95% CI 71.2% to 85.6%). The 1-year stent fracture rate was 8.1% (95% CI 4.0% to 14.4%). CONCLUSION: The high freedom from >50% restenosis and low fracture rate at 12 months suggests that the PROTEGE EverFlex stent offers a safe and acceptably efficacious means of treating SFA lesions in symptomatic subjects with PAD. PMID- 19642789 TI - Infragenicular stent implantation for below-the-knee atherosclerotic disease: clinical evidence from an international collaborative meta-analysis on 640 patients. AB - PURPOSE: To report a systematic review of the literature published on the outcomes of stenting for below-the-knee disease in patients with critical limb ischemia (CLI). METHODS: Potentially relevant studies of stent implantation in the infragenicular arteries in >or=5 patients with >or=1-month follow-up were systematically sought in BioMedCentral, ClinicalTrials.gov, The Cochrane Collaboration Register of Controlled Trials (CENTRAL), Google Scholar, and PubMed. Data were abstracted and pooled with a random-effect model to generate risk estimates with 95% confidence intervals (CI). Interaction tests were performed to compare different stent types. A risk of bias assessment was conducted separately, as were appraisals for small study bias, statistical heterogeneity, and inconsistency. RESULTS: Eighteen nonrandomized studies were retrieved comprising 640 patients. After a median follow-up of 12 months, binary in-stent restenosis occurred in 25.7% (95% CI 11.6% to 40.0%), primary patency in 78.9% (95% CI 71.8% to 86.0%), improvement in Rutherford class in 91.3% (95% CI 85.5% to 97.1%), target vessel revascularization in 10.1% (95% CI 6.2% to 13.9%), and limb salvage in 96.4% (95% CI 94.7% to 98.1%). Head-to-head comparisons showed that sirolimus-eluting stents were superior to balloon-expandable bare metal stents in preventing restenosis and increasing primary patency (both p<0.001); sirolimus-eluting stents were also better than paclitaxel-eluting stents in terms of primary patency (p<0.001) and repeat revascularizations (p = 0.014). CONCLUSION: Percutaneous infragenicular stent implantation after failed or unsuccessful balloon angioplasty is associated with favorable clinical results in patients with CLI. Notwithstanding limitations of primary studies, sirolimus eluting stents appear superior to bare metal and paclitaxel-eluting stents in terms of angiographic and/or clinical outcomes. PMID- 19642791 TI - Recurrent laryngeal nerve injury following uncomplicated carotid angioplasty and stenting. AB - PURPOSE: To describe a unique instance of cranial nerve injury related to uncomplicated carotid artery stenting (CAS). CASE REPORT: A 74-year-old woman with a history of expressive aphasia and right upper/lower extremity weakness underwent staged CAS procedures under local anesthesia and conscious sedation. After routine predilation with a 4-mm balloon, a tapered 7 x 10 x 30-mm Acculink stent was placed and dilated with a 5-mm balloon. At 1 month after the second procedure, the carotid stents were patent bilaterally, but the patient reported voice fatigue and hoarseness along with dysphagia to liquids that started 2 days after her second procedure. Brain scans ruled out stroke. Direct laryngoscopy showed left vocal cord paralysis and a mobile right vocal cord; computed tomography revealed adduction of the left vocal cord consistent with a left recurrent laryngeal nerve injury. Radiography did not show any evidence of stent fracture. Electromyography was suggestive of right recurrent laryngeal nerve paralysis and only mild abnormalities on the left. A repeat laryngoscopy performed 4 months after the initial evaluation revealed persistent left vocal fold paralysis and no abnormalities on the right. The patient was referred for voice therapy; at 18 months, the stents were patent, and her vocal symptoms had significantly improved. CONCLUSION: While minimally invasive endovascular techniques evolve for management of vascular disease, the anatomical structures at risk during open procedures may be injured with endovascular approaches as well. PMID- 19642790 TI - An experimental and numerical comparison of the rupture locations of an abdominal aortic aneurysm. AB - PURPOSE: To identify the rupture locations of idealized physical models of abdominal aortic aneurysm (AAA) using an in-vitro setup and to compare the findings to those predicted numerically. METHODS: Five idealized AAAs were manufactured using Sylgard 184 silicone rubber, which had been mechanically characterized from tensile tests, tear tests, and finite element analysis. The models were then inflated to the point of rupture and recorded using a high-speed camera. Numerical modeling attempted to confirm these rupture locations. Regional variations in wall thickness of the silicone models was also quantified and applied to numerical models. RESULTS: Four of the 5 models tested ruptured at inflection points in the proximal and distal regions of the aneurysm sac and not at regions of maximum diameter. These findings agree with high stress regions computed numerically. Wall stress appears to be independent of wall thickness, with high stress occurring at regions of inflection regardless of wall thickness variations. CONCLUSION: According to these experimental and numerical findings, AAAs experience higher stresses at regions of inflection compared to regions of maximum diameter. Ruptures of the idealized silicone models occurred predominantly at the inflection points, as numerically predicted. Regions of inflection can be easily identified from basic 3-dimensional reconstruction; as ruptures appear to occur at inflection points, these findings may provide a useful insight into the clinical significance of inflection regions. This approach will be applied to patient-specific models in a future study. PMID- 19642792 TI - Commentary: Recurrent laryngeal nerve injury following CAS: fortunately, NOT a recurrent problem! PMID- 19642793 TI - Preoperative thrombus volume predicts sac regression after endovascular aneurysm repair. AB - PURPOSE: To examine whether preoperative aneurysm thrombus volume correlated with abdominal aortic aneurysm (AAA) sac regression following endovascular aneurysm repair (EVAR). METHODS: Clinical records and computed tomographic angiograms (CTAs) from patients undergoing EVAR from 2003 to 2008 were reviewed. Inclusion criteria for this study were available preoperative CTA images, >or=12-month follow-up with surveillance imaging, lack of re-intervention at 12 months, and treatment with commercially available devices. Patients with ruptured AAAs, those requiring an aortomonoiliac stent-graft, and clinical trial cases were excluded. Based on these criteria, satisfactory images and clinical follow-up were available in 100 patients (90 men; mean age 76.8 years, range 55-95). Preoperative CTAs were categorized as demonstrating "minimal," "moderate," or "severe" aneurysm thrombus load by 2 independent examiners blinded to clinical outcome. Percentage of the aortic cross-sectional area occluded by clot (% clot area) was calculated as [(total area) - (luminal area)]/(total area). Multivariate logistic regression analysis was performed to determine predictors of sac shrinkage at long-term follow-up. RESULTS: AAA thrombus was classified as minimal in 24%, moderate in 23%, and severe in 53%. Thrombus area averaged 11%+/ 13%, 41%+/-14%, and 72+/-12% in each group, respectively. By multivariate analysis, minimal thrombus (OR = 1.47) and greater AAA diameter (OR = 1.3) were independent predictors of sac regression at 1, 6, and 12 months (all p<0.05). Presence of neck plaque and endoleak were also independent predictors of sac expansion (p<0.05). Patients with severe preoperative thrombus were less likely to demonstrate sac regression even in the absence of endoleak. Thrombus judgment (subjective) and percent clot area (objective) were strongly correlated (R = 0.82, p<0.05). Interobserver agreement on thrombus judgment was 86%. CONCLUSION: Thrombus burden on preoperative CTA is a strong independent predictor of sac regression following EVAR. If validated by prospective studies, relative thrombus burden should be incorporated into postoperative surveillance algorithms to define procedural success and optimize the timing and cost-effectiveness of cross sectional imaging. PMID- 19642794 TI - Lipoprotein(a) and other serum lipid subfractions influencing primary patency after infrainguinal percutaneous transluminal angioplasty. AB - PURPOSE: To evaluate the influence of serum lipid subfraction concentrations on arterial patency after percutaneous transluminal angioplasty (PTA) in patients with infrainguinal peripheral artery occlusive disease (PAOD). METHODS: From January 2007 to June 2008, a prospective study was conducted involving 39 patients (29 men; mean age 68.6+/-10.0 years) with infrainguinal PAOD in 41 limbs who had preprocedural lipid assessment and underwent successful PTA (<30% residual stenosis). Patient demographics, Fontaine clinical stage classification, Texas University Classification of ulcers, coexisting medical conditions, endovascular procedures, and lipid profiles were collected in a database. Follow up included clinical and duplex ultrasound evaluation at discharge and at 1, 3, 6, and 12 months. To analyze any correlation between various lipid subfractions and the loss of primary patency (Cox proportional hazards modeling), the patients were dichotomized into high and low groups according to these thresholds: LDL-C >100 mg/dL, HDL-C <40 mg/dL, Lp(a) >30 mg/dL, and an Apo(B)/Apo(A) ratio >0.8 mg/dL. RESULTS: Mean follow-up was 7.5 months (range 3-12). After 1, 3, and 6 months, the primary patency rates by Kaplan-Meier analysis were 94.9%, 73.7%, and 64.1%, respectively. Restenosis at 6 months was significantly related to female gender (HR 95.9, 95% CI 6.8 to 1352.5, p = 0.001), HDL-C <40 mg/dL (HR 86.9, 95% CI 6.4 to 1183.1, p = 0.001), LDL-C >100 mg/dL (HR 9.6, 95% CI 1.6 to 57.4, p = 0.013), and Lp(a) >30 mg/dL (HR 6.1, 95% CI 1.4 to 26.3, p = 0.016). CONCLUSION: Our results suggest that Lp(a), LDL-C, and HDL-C are independent risk factors for restenosis after infrainguinal PTA. PMID- 19642795 TI - A standardized multi-branched thoracoabdominal stent-graft for endovascular aneurysm repair. AB - PURPOSE: To assess the feasibility of endovascular thoracoabdominal aortic aneurysm (TAAA) repair using a standard off-the-shelf multi-branched stent-graft. METHODS: The aortic anatomy of 66 patients (45 men; mean age 74 years, range 57 87) referred for endovascular repair of TAAA was measured using 3-dimensional reconstructed images from computed tomographic angiograms. In particular, the orientation and longitudinal position of the orifice of each celiac artery, right renal artery, and left renal artery were measured relative to the location of the superior mesenteric artery (SMA) orifice. Based on prior experience, branch insertion with a standard endograft was considered feasible under the following conditions: (1) no more than 4 indispensable (target) arteries to the abdominal viscera, (2) the celiac artery and SMA were 6 to 10 mm in diameter, (3) the renal arteries were 4 to 8 mm in diameter, (4) all target arteries were accessible from a transbrachial approach, (5) the distance between each cuff and the corresponding arterial orifice was 4 indispensable visceral or renal branches, and 3 patients had inaccessible upward directed renal artery branches. Three of the remaining 59 patients had renal arteries outside the boundaries defined by conditions 5 and 6 when the hypothetical stent-graft was positioned with its SMA cuff 25 mm proximal to the corresponding SMA orifice. However, if the stent-graft were deployed in a more caudal location, only 1 of these 3 renal arteries would have been out of range. Therefore, 58 (88%) of 66 patients met all the eligibility criteria for repair using the off-the-shelf stent-graft. CONCLUSION: A standardized, off-the-shelf, multi-branched stent graft is applicable in 88% of cases of TAAA that would otherwise have been treated using customized stent-grafts. The use of a pre-made stent-graft has the potential to eliminate long manufacturing delays and expand the scope of endovascular repair of TAAA. PMID- 19642796 TI - Comparison of open and endovascular repair of ruptured abdominal aortic aneurysms from the ACS-NSQIP 2005-07. AB - PURPOSE: To compare endovascular (EVAR) and open surgical repair (OSR) for ruptured abdominal aortic aneurysms (RAAA) in terms of preoperative hemodynamic status and comorbidities. METHODS: The 2005 to 2007 American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database was interrogated to find all patients undergoing repair for RAAA. Of the 567 RAAA repairs identified, 121 (21%) were endovascular and 446 (79%) were open. Demographics, comorbidities, and preoperative hemodynamic status were compared by repair method. RESULTS: Age, sex, and race were similar between repair cohorts. EVAR patients had greater incidences of recent myocardial infarction (7% versus 2%, p<0.05), revascularization or amputation for peripheral vascular disease (8% versus 3%, p<0.05), and cerebrovascular disease (22% versus 11%, p<0.01). Preoperative hemodynamic status was similar based on need for >4 units of blood (3% versus 6%, p = 0.31), intubation (12% versus 17%, p = 0.18), impaired sensorium (7% versus 11%, p = 0.25), coma (4% versus 5%, p = 0.65), acute renal failure (2% versus 2%, p = 0.60), and ASA class 5 (29% versus 34%, p = 0.29). Open repair was associated with greater operative time (3.3 versus 2.6 hours, p<0.01) and intraoperative blood transfusions (8 versus 2 units, p<0.001). Overall mortality was 33.5% (EVAR 24% versus OSR 36%; OR 1.8, 95% CI 1.1 to 2.8, p<0.05). After adjusting for preoperative comorbidities and all preoperative hemodynamic variables, mortality after open repair was greater than after EVAR (OR 1.9, 95% CI 1.1 to 3.2, p<0.05). Overall postoperative complications were greater after open repair (62% versus 47%, p<0.01). Graft failure requiring reintervention was higher after EVAR (4% versus 1%, p<0.05), while rates of return to the operating room for a major operation were similar (21% versus 24%, p = 0.43). CONCLUSION: For RAAA within NSQIP hospitals in recent years, preoperative hemodynamic status was similar between EVAR and OSR, but EVAR patients had greater comorbidities. Despite this and after accounting for minor differences in hemodynamic status, EVAR mortality was lower than OSR mortality. Institutions with adequate experience and resources should attempt endovascular repair for RAAA when anatomy allows. PMID- 19642797 TI - Optimal technique for imaging iliac segments during endovascular repair of abdominal aortic aneurysms. AB - PURPOSE: To determine if oblique angulation of the image intensifier is adequate to image the entire length of the common iliac artery during endovascular aneurysm repair or if additional caudal tilt is necessary. METHODS: Using a 3D workstation, the apparent level of the iliac bifurcation (distal limit of the stent-graft) was determined on computed tomographic angiography by profiling the common iliac segment in oblique angulation only and repeated with a combination of oblique angulation and caudal tilt. Two independent observers measured twice the apparent length of the iliac segment in both profiles for 50 patients according to a set protocol. Intra- and interobserver variability was calculated using the Bland and Altman method; the differences between the two different profiles were tested using paired t tests. RESULTS: Of the 50 CTA datasets reviewed, 2 datasets were excluded owing to extensive calcification of the iliac system that prevented accurate interpretation of the image. Of the 96 segments studied, the iliac segments appeared longer (better profiled) with a combination of caudal tilt and oblique angulation in 80%, with an average discrepancy of 9 mm for observer 1 (range -1 to +28) and 7 mm for observer 2 (0 to +26). The effect of caudal tilt was statistically significant for individual observers (p = 0.001 and 0.024, respectively). Forty-six percent of iliac segments measured by observer 1 and 35% by observer 2 showed that the addition of caudal tilt resulted in improved profiling by at least 10 mm. Although inter- and intraobserver variation was significant, the gain in apparent iliac length with the addition of caudal tilt was preserved. CONCLUSION: When profiled with oblique angulation alone, the location of the iliac bifurcation may appear higher than its true location, resulting in underutilization of the iliac segment by >10 mm in over a third of the patients. The problem is corrected by employing additional caudal tilt. PMID- 19642798 TI - Magnitude and direction of pulsatile displacement forces acting on thoracic aortic endografts. AB - PURPOSE: To assess 3-dimensional (3D) pulsatile displacement forces (DF) acting on thoracic endografts using 3D computational techniques. METHODS: A novel computational method to quantitate the pulsatile 3D flow and pressure fields and aortic wall dynamics in patient-specific anatomical models based on cardiac-gated computed tomography (CT) scans was used to construct simulations of the proximal and mid-descending thoracic aorta. Endografts of varying lengths and diameters were implanted in these patient-specific models. The magnitude and direction of the DF vector were calculated and expressed in Newtons (N). This DF included the effects of both the pressure and shearing stresses of blood. RESULTS: The magnitude of DF increased with endografts of increasing diameter and length. A 36 mm endograft in the mid-descending aorta had a mean DF of 21.7 N with a peak systolic DF of 27.8 N and an end-diastolic DF of 16.7 N. Conversely, a 30-mm endograft in the proximal descending aorta had a mean DF of 14.9 N, with peak systolic and end-diastolic DFs of 18.9 and 11.5, respectively. The orientation of the DF acting on the endograft varied depending on aortic angulation and tortuosity; in general, the vector was perpendicular to the greater curvature of the endograft rather than along the downstream longitudinal centerline axis of the aorta as is commonly believed. The DF vector pointed primarily in the cranial direction for the proximal descending endograft and in the sideways direction for the mid-descending endograft simulation. Furthermore, it was shown that elevated pressure plays an important role in the magnitude and direction of DF; an increase in mean blood pressure resulted in an approximately linearly proportional increase in DF. CONCLUSION: The orientation of the DF varies depending on curvature and location of the endograft, but in all instances, it is in the cranial rather than caudal direction on axial imaging. This is counter to the intuitive notion that displacement forces act in the downward direction of blood flow. Therefore, we postulate that migration of thoracic endografts may be different from abdominal endografts since it may involve upward rather than downward movement of the graft. Computational methods can enhance the understanding of the magnitude and orientation of the loads experienced in vivo by thoracic aortic endografts and therefore improve their design and performance. PMID- 19642799 TI - A new trematode (Digenea: Mesotretidae) from the horseshoe bat Rhinolophus ferrumequinum (Chiroptera: Rhinolophidae) in China. AB - A new species of Mesotretes (Trematoda: Mesotretidae) parasitizing the small intestine of Rhinolophus ferrumequinum was obtained by the examination of 48 bats collected from 4 localities in Henan Province, China, from August 2003 to January 2005. This species, Mesotretes jiyuanensis n. sp., is similar to Mesotretes orientalis and Mesotretes hangzhouensis, but mainly differs from them in the ratio of the oral sucker and the ventral sucker, and the distance of the intestinal bifurcation from anterior edge of acetabulum, as well as from the former in the extension of the vitellarium. Mesotretes jiyuanensis n. sp. differs from Mesotretes peregrinus chiefly in the shape of the testes and the distribution of cuticular spines. The ratio of the oral sucker and the ventral sucker in this species also differs from that of M. peregrinus. PMID- 19642800 TI - Epizootiology of Babesia bovis and Babesia bigemina in free-ranging white-tailed deer in northeastern Mexico. AB - Species of Rhipicephalus (Boophilus) ticks are the vectors of babesiosis (cattle fever tick), which are distributed worldwide. White-tailed deer (Odocoileus virginianus) are important secondary hosts for the cattle fever ticks, Rhipicephalus (B.) annulatus and Rhipicephalus (B.) microplus. White-tailed deer are capable of sustaining Boophilus spp. tick populations in the presence or absence of cattle. The objectives of this study were to determine the frequency of Babesia bovis and Babesia bigemina and the prevalence of antibodies to them and identify possible risk factors for bovine babesiosis in white-tailed deer in 3 northeastern states of Mexico. Whole blood and serum samples (n = 457) were collected from white-tailed deer in the states of Coahuila, Nuevo Leon, and Tamaulipas during the spring of 2004. Samples were tested for B. bovis and B. bigemina by nested polymerase chain reaction (n-PCR) (the primers for B. bovis identified the gene Rap-1 and B. bigemina were specific primers) and by an indirect immunofluorescence antibody test (IFAT). A questionnaire was given to each ranch to obtain information about management practices. Logistic regression methods were used to test the association between management factors and the dependent variable of positive n-PCR or IFAT. Nineteen (4.2%) samples were positive to B. bigemina and 6 (1.7%) were positive to B. bovis by n-PCR. Serological testing showed 59.9% (n = 274) of deer sampled were positive to B. bovis and 5.4% (n = 25) were positive to B. bigemina antibodies. The logistic model varied with different dependent variables. With positive n-PCR and B. bigemina as the dependent variable, 3 factors were associated: habitat (presence of brush and exotic grasses; odds ratio (OR), 3.3; 95% confidence interval (CI), 1.3-8.5), grazing system (continuous grazing OR 4.0; CI, 1.3-12.2), and tick treatment frequency (3-4 mo; OR 7.0, CI 1.4-34.3; 5-6 mo; OR, 11.0; CI, 1.9-62.7; > 6 mo; OR, 4.6; CI, 0.9-23.3). These findings suggest that white-tailed deer may act as a reservoir for the 2 bovine Babesia spp. and that white-tailed deer may be important in the epidemiology of babesiosis. However, evidence is not available to support whether white-tailed deer are, or are not, likely to be a host that could complete the transmission cycle of Babesia spp. These results suggest that additional research is needed to demonstrate the importance of white tailed deer as a Babesia spp. infection source for ticks. PMID- 19642801 TI - A new gyrodactylid (Monogenea) genus on gray bichir, Polypterus senegalus (Polypteridae) from Senegal (West Africa). AB - Diplogyrodactylus martini n. g. et sp., a viviparous monogenean, is described from the gills of gray bichir Polypterus senegalus Cuvier, 1829, in Senegal. This new genus can be readily distinguished from the other described viviparous genera based on the morphology of the attachment apparatus. The haptor is equipped with a pair of centrally positioned hamuli, a simple ventral bar without membrane and 8 pairs of marginal hooks of 2 types, 5 pairs of hooks with well-defined large falculate sickles, and 3 pairs of smaller hooks with well-articulated sickles. The new genus is unique in having a teardrop-shaped muscular tubular male copulatory organ which lacks spines. A partial sequence of the internal transcribed spacer (ITS rDNA) was obtained from 4 specimens of D. martini. The relationship among D. martini and other genera of the Gyrodactylidae is discussed based on the similarities of the attachment apparatus. PMID- 19642802 TI - Clinical and epidemiological features of visceral leishmaniasis and HIV co infection in fifteen patients from Brazil. AB - Cases of visceral leishmaniasis (VL) in the course of human immunodeficiency virus (HIV) infection have regularly been recorded, mainly in southern Europe. HIV infection can increase the risk of VL development by 10-100 times in endemic areas. We describe the occurrence of this co-infection in 15 patients from Brazil. The mean age of the patients was 38 +/- 8.8 yr, with 86.6% males. The mean time between HIV diagnosis and the onset of visceral leishmaniasis was 44 +/ 39 mo. The main signs and symptoms presented at admission were splenomegaly (73%), weight loss (73%), cough (67%), fever (67%), asthenia (60%), and diarrhea (60%). The mean T CD4+ lymphocyte count was 173.7 +/- 225.6 cells/mm3, and viral load was 51,030 +/- 133,737/mm3. Treatment consisted of pentavalent antimonials (67% of cases). Most (87%) patients recovered from VL infection; death occurred in 1 patient due to septic shock. VL is an important opportunistic infection in HIV patients, which is potentially fatal, even when correct treatment is completed. Treatment should be done with pentavalent antimonials or amphotericin B in the case of relapse. Although there is no consensus, secondary prophylaxis should be considered in severe cases. PMID- 19642803 TI - A new anoplocephalid cestode from the southern bog lemming Synaptomys cooperi. AB - A new cestode species, Anoplocephaloides bulmeri n. sp. (Cestoda: Anoplocephalidae), is described from the southern bog lemming Synaptomys cooperi (Baird) from Virginia. The general morphology of A. bulmeri strongly suggests that it belongs to the monophyletic Anoplocephaloides Baer 1923 s. str. It differs unequivocally from the other species of Anoplocephaloides s. str. by the distribution of testes in the poral part of the proglottid and also by the number of testes and the maximum length of the cirrus sac and seminal receptacle. Anoplocephaloides bulmeri most closely resembles Anoplocephaloides kontrimavichusi Rausch, 1976, a host-specific parasite of the northern bog lemming, Synaptomys borealis (Richardson). PMID- 19642804 TI - Optimization of an experimental model for the recovery of adult Haplorchis pumilio (Heterophyidae: Digenea). AB - Recent studies in Vietnam and other Asian countries have shown that fish-borne zoonotic intestinal trematodes (FZT) occur very frequently in humans. The dominant intestinal FZT in Vietnamese fish are species of Haplorchis, in particular H. pumilio. However, basic studies on the biology and pathology of adult H. pumilio are difficult because of the lack of a standardized experimental animal model. The objective of this study was to establish and optimize such an animal-infection model for H. pumilio. Using metacercariae isolated from naturally infected fish, experiments were conducted to identify a suitable experimental animal host species, as well as the optimum metacercariae infection dose, and to determine the post-infection interval for patency. In a series of experiments, mice (Mus musculus) and chickens (Gallus gallus dom.) were infected with different numbers of metacercariae, and worm recoveries were made at varying intervals post-infection (PI). Based on the mean number of adult flukes recovered/number of metacercariae inoculated and the percent of hosts infected, mice were significantly more susceptible to infection than were chickens. The proportion of metacercariae developing to the adult stage increased with dose size. The peak worm recovery (geometric mean) was found to be day 7, although not all recovered flukes were gravid until day 9 PI. These results describe a mouse infection model with good predictability for intestinal flukes, such as H. pumilio, results which could facilitate investigations on important biological and pathological aspects of intestinal fluke infections. PMID- 19642805 TI - Redescription of Rhadinorhynchus ornatus (Acanthocephala: Rhadinorhynchidae) from skipjack tuna, Katsuwonus pelamis, collected in the Pacific Ocean off South America, with special reference to new morphological features. AB - Adults of Rhadinorhynchus ornatus Van Cleave, 1918 were collected from the small intestine of skipjack tuna, Katsuwonus pelamis (Linnaeus), in the high seas of the Pacific Ocean off the west coast of South America (new parasite locality record) and described using optical microscopy and a scanning electron microscope (SEM). Our specimens were somewhat comparable to those described from North America and Japan, but had more trunk spines. Definitive differences between the length and thickness of each of the dorsal and ventral proboscis hooks are noted for the first time, with most ventral middle hooks being relatively shorter and more robust than dorsal middle hooks. The SEM documented, for the first time, the different surface topography of the tegument in the proboscis, the neck, and in 3 trunk regions; the presence of microtrichs in the mid- and posterior trunk regions; the elevated base of trunk spines; the circular arrangement of basal proboscis hooks; the different morphology of all dorsal and ventral proboscis hooks and the striations of their surface; the ribbed surface topography of eggs; the elevated slit-like female gonopore; and the rimmed edge of the bursa. The presence of microtrichs on the tegumental surface is further supported by transmission electron microscopy studies. This is the first report of microtrichs in any species of Acanthocephala and the second report of striations in proboscis hooks. The geographical distribution of R. ornatus appears to correspond, at least in part, to that of its epipelagic primary host, K. pelamis, throughout the world in waters ranging in temperature from 14.7 to 30 C. PMID- 19642806 TI - A new heligmonellid species (Nematoda) from Oligoryzomys nigripes (Rodentia: Sigmodontinae) in the Atlantic Forest, Brazil. AB - Stilestrongylus lanfrediae n. sp. is described from the small intestine of Oligoryzomys nigripes (Cricetidae: Sigmodontinae) collected in the Atlantic Forest (Rio de Janeiro State, Teresopolis, Brazil). The new species shows some similarities to Stilestrongylus stilesi, Stilestrongylus freitasi, Stilestrongylus inexpectatus, Stilestrongylus moreli, and Stilestrongylus andalgala, but it can be distinguished from these species by the following combination of characters: 26 ridges in males and 25 in females at the mid-body, asymmetrical caudal bursa with a pattern of type 2-2-1, rays 6 markedly shorter than other lateral rays, rays 8 inserted asymmetrically on dorsal trunk and shorter than other species, and a proportion of spicule length in relation to body length (SpL/BL) of 25-29%. The new species is also distinguished from other species of Stilestrongylus by the asymmetry of the branches of the dorsal ray and by having the longest spicules. PMID- 19642807 TI - Placental malaria and lack of prenatal care in an area of unstable malaria transmission in eastern Sudan. AB - A cross-sectional study was conducted in Gadarif Hospital in eastern Sudan to determine the prevalence, and evaluate the risk factors, of placental malaria. Two hundred and thirty-six delivering women were enrolled in the study. Socio demographic characteristics were gathered through questionnaires. Maternal hemoglobin was measured, ABO blood groups were determined, and placental histological examinations for malaria were performed. The birth weight of the newborn was also recorded. The mean (SD) maternal age was 25.5 (6.0) yr and the mean (SD) hemoglobin was 9.8 (0.9) g/dl. Placental histology showed acute malaria infections in 13 (5.5%) and chronic infections in 5 (2.1%) women; 28 (11.9%) of the placentas revealed past infection and 190 (80.5%) indicated no infection. Lack of prenatal care was significantly associated with placental infections (OR = 12.0, 95% CI = 2.3-16.2; P = 0.003). There was no significant association between placental malaria infections and maternal age, parity, and blood group. Thirty-two (13.5%) of these pregnancy outcomes resulted in low birthweight babies. There was, however, no significant association between placental malaria and low birth weight (OR = 2.0, 95% CI = 0.4-4.1; P = 0.1). Thus, placental malaria infections affect pregnant women in this area of eastern Sudan regardless of their age or parity. Prenatal care should be encouraged to reduce malaria in the area. Much more research regarding malaria and pregnancy is needed. PMID- 19642808 TI - Redescription of the frog bladder fluke Gorgoderina attenuata from the northern leopard frog, Rana pipiens. AB - Morphological characters used to differentiate North American bladder flukes, Gorgoderina spp., are problematic and different authors use different morphological characteristics for distinguishing species. More importantly, no type specimens exist for 4 of the 12 North American species infecting anuran and caudatan hosts. A redescription of Gorgoderina attenuata (Stafford, 1902) Stafford, 1905 is based on new collections from 6 species of anurans from Arkansas, Nebraska, New York, and Wisconsin. Morphological comparisons between gravid G. attenuata recovered from bullfrogs and northern leopard frogs indicated statistically significant differences in 11 of 28 morphological characters examined. However, there was overlap among all of these characters, and it is unclear whether these morphological types represent host-induced morphological changes in worm morphology or cryptic species. Based on our findings, we suggest that morphological and molecular data from G. attenuata-like worms recovered from the other 23 definitive hosts reported for G. attenuata need to be collected to resolve this issue. PMID- 19642809 TI - Estrogen-related fecundity reduction of Lymnaea ollula following Fasciola gigantica infection. AB - Infection by trematode parasites generally affects life history traits of their intermediate hosts. Reduction in life expectancy and reproductive capacity have previously been documented in Fasciola gigantica-infected Lymnaea ollula, but the influence of the endocrine system on this specific host-parasite interaction has not been previously examined. In the present study, we observed survival, growth pattern, and reproductive output of L. ollula following exposure to F. gigantica. Both the survival and the growth pattern of infected snails were similar to those of the non-infected control group. However, a significant difference was apparent in fecundity, as infected snails consistently showed lower levels of egg and embryo production throughout a 7-wk observation period. Semi-quantitative RT-PCR also revealed down-regulation of estrogen receptor expression in infected snails during the first 4 wk of infection. Nonetheless, the inhibition of estrogen signaling was transient, as they regained expression in the later phase of infection. It is, therefore, suggested that other hormones of the complex endocrine system may be involved in the reduced fecundity of L. ollula following F. gigantica infection. PMID- 19642810 TI - Community structure and seasonal dynamics of Dactylogyrus Spp. (Monogenea) on the fathead minnow (Pimephales promelas ) from the Salt Valley Watershed, Lancaster County, Nebraska. AB - The gill monogene communities of Pimephales promelas (fathead minnow) in 3 distinct sites on converging streams were investigated from 2004 to 2006 in 3 different seasons. Thirty collections of P. promelas were made in southeastern Nebraska along 3 converging tributaries: Elk Creek (40.88534 degrees N, 96.83366 degrees W), West Oak Creek (40.9082 degrees N, 96.81432 degrees W), and Oak Creek (40.91402 degrees N, 96.770583 degrees W), Lancaster County, Nebraska. In all, 103 P. promelas were collected from Elk Creek, 115 from West Oak Creek, and 78 from Oak Creek and examined for gill monogenes. Among the P. promelas collected, 93.5% were infected with up to 3 species of Dactylogyrus, including Dactylogyrus simplex Mizelle, 1937, Dactylogyrus bychowskyi Mizelle, 1937, and Dactylogyrus pectenatus Mayes, 1977. Mean intensities at Elk Creek, West Oak Creek, and Oak Creek were 17.6, 22.8, and 25.1, and prevalences 88, 95, and 97%, respectively. At these 3 sites: (1) P. promelas does not share Dactylogyrus species with Semotilus atromaculatus (Creek chub) or Notropis stramineus (Sand shiner); (2) fish size and sex are not predictive of Dactylogyrus infection; (3) Dactylogyrus spp. vary (not always predictably) in their seasonal occurrence; (4) populations of Dactylogyrus spp. respond to environmental differences among sites; and (5) the community structure of Dactylogyrus spp. (order of abundance) is independent of environment. PMID- 19642811 TI - Parasites gained: alien parasites switching to native hosts. AB - Three parasitic copepods new to the well-studied Mediterranean fauna are reported. Two of them, Mitrapus oblongus (Pillai, 1964) and Clavellisa ilishae Pillai, 1962, are of Indo-Pacific origin and are considered here to have co invaded the Mediterranean through the Suez Canal on Erythrean (Red Sea) immigrant hosts. Both are reported here from native Mediterranean clupeid fish hosts; this is the first evidence of host switching of any metazoan parasites from Erythrean immigrants to native fish hosts. The third parasite, Nothobomolochus fradei Marques, 1965, was previously known from the Gulf of Guinea and the Arabian Gulf. Possible explanations of its presence on clupeid hosts in Egyptian waters off Alexandria are discussed. The parasite utilizes an Erythrean immigrant clupeid and a native Mediterranean species as hosts. This account provides evidence of parasite and host faunal mixing on an unexpected scale. PMID- 19642812 TI - Fetal inflammatory response is often present at early stages of intra-amniotic infection, and its distribution along cord is variable. AB - This study investigates the hypotheses that (1) the fetal inflammatory response to intra-amniotic infection can occur in early stages of maternal inflammatory response and (2) a difference in early cord inflammation exists at different sites in the cord. Placentas accessioned in our department over a 4-year period with a differential in umbilical vessel inflammation between proximal and distal sections were evaluated for cord inflammation using a 0 to 4 graded scale. Cases were also evaluated for acute chorionic vasculitis and extent of maternal inflammatory response. Of 5566 placentas, 1004 (18%) had some degree of cord inflammation; 120 (12%) had a differential in inflammation between the 2 cord sites. Greater cord inflammation was divided almost equally between proximal (59) and distal (61) sections. Twenty-two cases had 1 or both arteries involved in 1 cord section only. The proximal section had the greater degree of inflammation in 21 (95%) of these cases. Early or no maternal inflammatory response was seen in 63 of 120 cases (52%). Acute chorionic vasculitis was identified in 57 of 106 cases (54%) with at least 2 chorionic vessels present. Fetal inflammatory response can be seen in early amniotic infection, occasionally without finding maternal inflammatory response. The absence of differences in cord vein inflammation depending on cord site and the finding that arteritis occurs close to the placental cord insertion site suggest that cord vessel blood flow dynamics play a role in neutrophil margination. At least 2 cord sections representing proximal and distal sites are recommended to exclude fetal inflammatory response. PMID- 19642813 TI - Placenta accreta in a separate uterine horn. AB - We report the case of a 30-year-old woman who presented with intrauterine fetal demise of a 17-2/7-week male fetus. The patient failed misoprostol induction and was taken for surgical evaluation. At the time of surgery an ectopic pregnancy in a noncommunicating rudimentary uterine horn was found. Histologic examination of the excised remnant uterine horn showed there was a placenta accreta. PMID- 19642815 TI - Learned discourses: timely scientific opinions. PMID- 19642814 TI - The number of CD68(+) (Hofbauer) cells is decreased in placentas with chorioamnionitis and with advancing gestational age. AB - Hofbauer cells are placental macrophages found in chorionic villous stroma; they express classic monocyte/macrophage markers, such as CD68. Little is known about their participation in placental disease and immunologic interactions at the placental interface. The aim of this study was to quantify the amount of Hofbauer cells in placentas complicated, or not, by chorioamnionitis and in placentas from different gestational ages. Fifty-eight 2nd- and 3rd-trimester placentas with the histologic diagnosis of acute chorioamnionitis were compared with 42 control placentas matched according to gestational age. Immunohistochemistry evaluation was performed with a monoclonal anti-CD68 antibody. Five areas of each placenta were photographed and 5 investigators, with the help of a computerized image analysis program, independently evaluated the number of CD68(+) cells. Our results showed that there are significantly fewer CD68(+) cells per villous area in placentas diagnosed with chorioamnionitis than in those of controls (P < 0.001). Moreover, there was a significant overall decrease in the number of these cells in 3rd as compared with 2nd trimester placentas (P = 0.02), as well as in placentas from term as compared to preterm pregnancies (P = 0.004). Our data indicate that CD68(+) Hofbauer cells may be involved in placental infection and possibly associated with the developmental maturation of the fetoplacental unit. PMID- 19642816 TI - Understanding ourselves and the role of "innovation" in science. PMID- 19642817 TI - Using proxies to elucidate environmental threats to endangered species. PMID- 19642818 TI - Risk assessment and orphaned/abandoned mines in Canada--what role do aboriginal communities play in risk assessment? PMID- 19642819 TI - The biospheric life support system: a unifying concept for ecotoxicologists and ecologists. PMID- 19642820 TI - Tropospheric ozone and plant perchlorate concentrations: is there a connection? PMID- 19642821 TI - Often overlooked: biological QA/QC. PMID- 19642823 TI - A conceptual selenium management model. AB - We describe herein a conceptual selenium (Se) management model, directed toward coal mining in western Canada, but which can be applied to other coal mines and, with appropriate modification, to other industrial sources of Se to aquatic and terrestrial environments. This conceptual model provides a transparent means to integrate and synthesize existing information that can be used to provide an adaptive approach for managing ecological exposures and associated risk. It is particularly useful for visualizing and subsequently developing management interventions for Se control and risk reduction. The model provides a structured process by which critical information needs can be identified and addressed. It effectively provides the foundation for making management decisions related to Se discharges to aquatic and terrestrial environments by showing interrelationships of the various media and receptors as well as primary sources, release mechanisms, secondary sources, and exposure pathways. PMID- 19642824 TI - Selenium: when a good nutrient goes bad. PMID- 19642827 TI - Erratum. PMID- 19642826 TI - Testing and applying a fish vitellogenesis model to evaluate laboratory and field biomarkers of endocrine disruption in Atlantic croaker (Micropogonias undulatus) exposed to hypoxia. AB - Recently, hypoxia has been shown to act as an endocrine disruptor. We used a model of vitellogenesis in a female sciaenid fish to simulate the effects of hypoxia and to determine if reproductive impairment observed in field-caught fish could be attributed to dissolved oxygen conditions at the sampling sites. The model is a set of coupled, ordinary differential equations that simulate major biochemical reactions from the secretion of gonadotropin to production of vitellogenin. Various intermediate variables in the model correspond to commonly measured biomarkers, and we assume a direct relationship between cumulative vitellogenin (VTG) and the gonadosomatic index (GSI). Model predictions were compared to results of laboratory studies that examined the effects of hypoxia on Atlantic croaker (Micropogonias undulatus) reproduction. When hypoxia was assumed to cause reduced gonadotropin and impaired aromatase activity, model predictions of VTG production were similar to laboratory-measured reductions in GSI. The model was then applied to reproductive biomarkers measured in fish from normoxic and hypoxic locations in Pensacola Bay (FL, U.S.A.). We simulated the relationship between reduced estradiol-17beta and VTG production under hypoxia, and we compared these results with field data. Good agreement between field and simulation results suggested that croaker collected from hypoxic sites in October were exposed to hypoxic conditions for an extended period during gonadal recrudescence and that hypoxia was a dominant cause for the reduced GSIs. Monte Carlo uncertainty analyses suggested that the maximum rate of free testosterone production is the most sensitive parameter. Our simulations demonstrated that the model can be used identifying the mechanism underlying endocrine disruption and for interpreting field-measured biomarkers in situations of multiple stressors. PMID- 19642828 TI - Use of caged Nucella lapillus and Crassostrea gigas to monitor tributyltin induced bioeffects in Irish coastal waters. AB - Caging studies have been previously reported to be useful for providing valuable information on biological effects of mollusks over short periods of time where resident species are absent. The degree of imposex in caged dog whelk (Nucella lapillus), was measured using the vas deferens sequence index (VSDI) and the Relative Penis Size Index (RPSI) and the extent of shell thickening in caged Pacific oyster (Crassostrea gigas) was investigated at t = 0 and t = 18 weeks. Nucella lapillus, when provided with mussels as a food source at the control site at Omey Island on the west Irish coast, did not demonstrate imposex features, whereas those transplanted to port areas did. Dunmore East exhibited the highest level of imposex (3.25 VDSI and 2.37 RPSI). Shell thickening was evident in C. gigas transplanted to Dunmore East, with low effects evident at the control location, Omey Island, and Dublin Bay at t = 18 weeks. Dry weight whole-body concentrations of organotins were most elevated in all species held at Dunmore East compared with other locations. Greatest delta15N and delta13C enrichment was observed within the tissues of the predatory N. lapillus in all three test sites. Increased assimilation in the Dublin Bay oysters might have been influenced by the presence of more nutrients at this location. Surficial sediment organotin levels were most elevated in the Dunmore East <2-mm fraction (22,707 microg tributyltin/kg dry weight), whereas low organotin levels were determined from Dublin and Omey Island sediments. The valuable application of cost-effective caging techniques to deliver integrated biological effects and chemical measurements in the absence of resident gastropod populations in potential organotin/tributyltin hotspot locations is discussed. PMID- 19642829 TI - Aging effects on cobalt availability in soils. AB - Aging processes in soils can significantly affect the potential biological availability of introduced metals via incorporation into crystal lattices, diffusion into micropores, or formation of metal precipitates on the surfaces of soil minerals. Over time, metals in contact with the soil solid phase are less freely exchangeable with the soil solution and, hence, less available to soil biota. In the present study, the effects of aging on the fate and behavior of added divalent cobalt (Co2+) in a range of soils with varying physicochemical characteristics was assessed using isotope-exchange techniques, chemical extraction, and plant growth. Following addition to soil, the Co2+ salt rapidly partitioned to the soil solid phase. Particularly in soils with neutral to alkaline pH, a large percentage of the surface-bound Co was fixed in forms no longer in equilibrium with soil solution cobalt through aging reactions. Using techniques commonly applied to estimate metal bioavailability in soil, the lability (E values), plant availability (L values), and extractability of added Co2+ salts with the mild chemical extractants calcium chloride (CaCl2) and ammonium nitrate (NH4NO3) were observed to markedly decrease with time, particularly in soils with high pH or those containing appreciable quantities of iron/ manganese oxyhydroxide minerals. Results indicated rapid partitioning of added Co2+ into isotopically nonexchangeable pools, with more than 60% of the aging occurring within 15 d in most soils. Soil pH was the primary factor controlling the rate of cobalt aging and extent of exchangeability in the soils examined. Understanding the influence of long-term aging on cobalt availability in soils is necessary to accurately assess the potential risk associated with cobalt contamination of soil environments. PMID- 19642830 TI - Effect of 17beta-estradiol on the immunocompetence of Japanese sea bass (Lateolabrax japonicus). AB - Environmental contaminants can interfere with hormonal regulation in both vertebrates and invertebrates, and these contaminants may disrupt the endocrine system of human and other organisms. Evidence is growing that contaminants may be partly responsible for the observed increase of disease in marine organisms by adversely affecting their immunity. Fish are commonly used as sentinel organisms in vertebrate immunotoxicology; however, to date, studies have been undertaken only on a single size group of fish (juvenile/adult) and for acute exposure. In the present study, Lateolabrax japonicus fingerlings and juveniles were exposed to two sublethal concentrations (200 and 2,000 ng/L) of 17beta-estradiol (E2) for 30 d under laboratory conditions, and alterations in immune parameters comprising differential leukocyte count, respiratory burst, myeloperoxidase, immunoglobulin levels, serum lysozyme, and bactericidal activity were investigated to establish whether estrogen produced immunomodulation and to understand the effects of long term exposure on these immune parameters in fish fingerlings and juveniles. The results revealed a significant elevation of respiratory burst activity, myeloperoxidase, immunoglobulin levels, and differential leukocyte counts of the fish exposed to estrogen compared to the control. The remaining parameters were significantly reduced in the experimental groups when compared to the control. The results indicated that sublethal E(2) exposure induced immunomodulation in both fingerling and juvenile L. japonicus, and the changes caused by estrogen might affect the function of immune system in fish. PMID- 19642831 TI - Modeling zinc regulation in small mammals. AB - Due to large zinc discharges into the global environment, both terrestrial and aquatic environments have been polluted with zinc. The embanked floodplains of the lower Rhine River in the Netherlands contain large amounts of heavy metals, including zinc. These large amounts of heavy metals may pose risks to flora and fauna by accumulation in food webs, and risk assessment may be required. However, toxicokinetic models for zinc metabolism in mammalian wildlife species are currently lacking. The present study describes the development of a zinc kinetics model that predicts internal zinc concentrations in small mammals by modeling zinc absorption and excretion dependent on the dietary zinc intake using adapted Michaelis-Menten equations. The equations were parameterized based on experimental data reported in the scientific literature. Within the dietary zinc range of 3 to 104 mg/kg dry weight, the model predicts internal zinc concentrations and shows that the internal zinc is regulated within this range. Outside this range, the model could not be calibrated due to a lack of data. Validation of the model with four small mammal species living in an embanked floodplain along a distributary of the Rhine River illustrated that the model predicts internal zinc concentrations differing up to a factor of 1.6 (Common shrew) to 1.7 (Common vole) from field measurements. PMID- 19642832 TI - Comparative aquatic toxicity of propranolol and its photodegraded mixtures: algae and rotifer screening. AB - Transformation products of pharmaceuticals formed by human metabolism within sewage treatment plant or receiving waters are predicted, in most cases, to be less toxic than the parent compound to common aquatic species. However, there is little available data to demonstrate whether this is generally the case. In the present study, a framework was developed to guide testing of transformation products using phototransformation of the beta-blocker propranolol to test the hypothesis for this particular transformation route. Phototransformation is an important depletion mechanism of some pharmaceuticals in surface waters with fast reaction rate constants at environmentally relevant conditions. Samples of propranolol in deionized water (DIW) and river water (RW) were exposed to a solar simulator (lambda: 295-800 nm) and comparative toxicity of propranolol and its degraded mixtures measured using algal (Pseudokirchneriella subcapitata) and rotifer (Brachionus calyciflorus) screening tests. Results suggested a reduction of toxicity in photodegraded mixtures compared to the parent active pharmaceutical ingredient in all samples tested. Chemical analysis of effect test solutions supported the hypothesis that propranolol was transformed into compounds that appear to be less toxic to the organisms tested under the study conditions. Although the reactions were much faster in RW than in DIW, profiles of transformation products were similar in both matrices at two starting concentrations (1 and 10 mg/L). Results for propranolol implied that the reduction of toxicity using algal and rotifer screening tests was probably due to the production of more hydrophilic and more polar transformation products. Such results will provide useful insights into the environmental risk assessment of pharmaceuticals by taking into account their transformation products. PMID- 19642833 TI - Bayesian multilevel discrete interval hazard analysis to predict dichlorodiphenyldichloroethylene mortality in Hyalella azteca based on body residues. AB - We exposed Hyalella azteca to p,p'-dichlorodiphenyldichloroethylene for intervals of 1 to 4 d and followed mortality out to 10 d. Mortality was determined as the cessation of heartbeat; dead organism body residue was determined daily. To model mortality probability, body residues of the living organisms were estimated using published kinetic data with concentration-dependent rate constants. The estimated residues compared favorably with measured residues in the dead organisms (predicted body residue = 1.302 +/- 0.142 measured body residue + 10.351 +/- 15.766, r2 = 0.64, n = 50). The response data were collected at discrete intervals; thus, it was not possible to determine the exact time of death for organisms. Consequently, we analyzed the mortality data using discrete interval analysis, in a Bayesian hierarchical framework, with body residue as the dose metric. The predicted body residues to produce mortality were similar across the duration of exposure when postexposure mortality was considered. The concentration for 50% mortality was 0.47 MUmol/g (148.6 tg/g, range 0.32-0.66 MUmol/g), and predictions of response indicted 95% (range 73-99.9%) mortality at 0.79 MUmol/g (250 MUg/g) and 4% (range 1.2-9.6%) mortality at 0.16 MUmol/g (50 MUg/g). The lethal residue for 50% mortality based on interval analysis for short term exposures with postexposure mortality resulted in values similar to long term continuous exposures for exposure durations of more than 600 h. PMID- 19642835 TI - Melatonin and oxidative stress. PMID- 19642834 TI - Clinicopathologic features of histiocytic lesions following ALL, with a review of the literature. AB - We describe the clinicopathologic features of 15 patients who had histiocytic lesions that followed acute lymphoblastic leukemia (ALL). Twenty-one separate histiocytic lesions were evaluated that covered a wide spectrum, some conforming to the usual categories of juvenile xanthogranulomas (5), Langerhans' cell histiocytosis (1), Langerhans' cell sarcoma (4), Rosai-Dorfman disease (1), and histiocytic sarcoma (4). Most were atypical for the category by histology, phenotype, or abnormally high turnover rate. Seven low-grade lesions defied easy categorization and were characterized only as "atypical histiocytic lesion" following ALL. For those evaluated, the molecular signature of the prior leukemia was present in the histiocytic lesion. In 3 of 15 patients, the leukemia and histiocytic lesion shared immunoglobulin H or monoclonal TCR gene rearrangements and, in 4 of 15 patients, clonal identity was documented by fluorescence in situ hybridization. Four patients died of progressive disease, 3 of whom had histiocytic sarcoma and 1 who had an atypical lesion. One patient died of recurrent ALL. The other 10 patients are alive, 7 after recurrences and treatment with surgery and/or chemotherapy. The post-ALL lesions are more aggressive than their native counterparts, but despite the demonstration of the presence of the leukemia signature in 7 of 15 patients, the prognosis is generally favorable, except for patients with histiocytic sarcoma. It remains unclear whether the histiocytic lesions arise as a line from the original ALL or whether transdifferentiation is involved. PMID- 19642836 TI - Effect of melatonin on myocardial oxidative stress induced by experimental obstructive jaundice. AB - OBJECTIVE: melatonin has been demonstrated to have active antioxidant properties in different tissues during experimental cholestasis. The aim of this research was to study myocardial oxidative stress on obstructive jaundice, and to analyze the effect of melatonin on myocardial oxidative lesions. MATERIAL AND METHODS: we achieved cholestasis by ligature and sectioning of the main bile duct. Melatonin was administered intraperitoneally (500 microg/kg/day). We measured malondialdehyde (MDA), reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) and glutathione peroxydase (GPx) antioxidant enzyme levels in the heart tissue. RESULTS: obstructive cholestasis increased MDA and decreased GSH as well as all antioxidant enzymes. Melatonin administration significantly decreased MDA values, and increased GSH and antioxidant enzymes on the icteric animal myocardium. CONCLUSIONS: melatonin treatment prevents oxidative stress in the cardiac tissue as induced by experimental cholestasis. PMID- 19642837 TI - Prevalence of sexual and physical abuse in patients with obstructed defecation: impact on biofeedback treatment. AB - BACKGROUND: obstructed defecation is one of the most common subtypes of constipation, and it is frequently responsive to biofeedback treatment. AIMS: since a history of sexual and physical abuse may be present in patients with obstructed defecation, we assessed the incidence of abuse history in patients with obstructed defecation referred to a general gastroenterology practice, and whether such a history may lead to a different outcome of biofeedback training in these patients. PATIENTS AND METHODS: one hundred and twenty-one patients (17 men, 104 women, age 53 +/- 15 years) with obstructed defecation were studied by retrospective chart review. Their history of sexual, physical and psychological abuse was obtained by a standard interview, and biofeedback training was carried out by means of a three-balloon technique. RESULTS: a history of sexual/physical or psychological abuse was present in 12.4% patients. Biofeedback training yielded a successful improvement of obstructed defecation in 93% patients without abuse and in 100% of patients with abuse; this difference was not statistically different (p = 0.53). CONCLUSIONS: the prevalence of sexual/physical or psychological abuse in a population of patients with obstructed defecation referred to a general gastroenterology practice is relatively low; such a history seems not to affect the outcome of biofeedback training in these patients. PMID- 19642838 TI - Efficacy of pediatric colonoscopy used as push enteroscopy in the management of capsule endoscopy findings. AB - BACKGROUND: recent advances in endoscopy have enabled us to explore the small intestine more efficiently, both with capsule endoscopy and double-balloon enteroscopy. However, these methods are not available in all hospitals. Therefore, when capsule endoscopy reveals proximal jejunal lesions, a possible alternative for treatment could involve push enteroscopy combined with colonoscopy. Lesions can thus be marked for subsequent monitoring. OBJECTIVES: to describe the efficacy of pediatric colonoscopy for diagnosis, the marking of the area explored, and therapeutic options. MATERIAL AND METHODS: between October 2007 and September 2008 a total of 21 enteroscopies were performed using a pediatric colonoscope. Nine of these were used to take jejunal biopsy samples due to suspected disease of the mucosa. In 10 of the remaining 12, capsule endoscopy revealed lesions (vascular malformations or jejunal bleeding), and in 2 intestinal transit time was analyzed due to suspected jejunal stenosis. We used a PENTAX EC-3470-LK pediatric colonoscope, whose 11.6-mm sectional diameter and 3.8 mm working channel make it possible to administer all the usual endoscopic treatments. RESULTS: therapeutic endoscopy was performed on 7 men and 5 women (mean age 63.3 years). Jejunal lesions were observed in 10 cases (5 cases of angiodysplasia, 2 cases of jejunal stenosis, 1 case of nonmalignant thickened jejunal folds, 1 eroded submucosal tumor, and 1 case of duodenal and jejunal varices). The most distal area was marked with India ink (2), hemoclips (4), or both to help locate the lesions using simple abdominal radiography or capsule endoscopy. CONCLUSIONS: jejunal enteroscopy enabled a firm diagnosis to be made in most of the patients studied. We were able to treat 58% of patients and mark the areas explored for subsequent follow-up. With hemoclips we were able to locate the most distal point explored using simple abdominal radiography. PMID- 19642839 TI - Onset and disappearance rates of gastroesophageal reflux symptoms in the Spanish population, and their impact on quality of life. AB - BACKGROUND: few studies have reported the onset and disappearance rates of gastroesophageal reflux symptoms (GERS) in the population. AIM: to assess the occurrence and disappearance rates of GERS in Spain, and their impact on health related quality of life (HRQL). PARTICIPANTS AND METHODS: participants were selected at random from the general population of Madrid in age and sex strata. They were interviewed at home twice, 6 months apart. Heartburn, acid regurgitation and consultation were assessed with the gastroesophageal reflux questionnaire, and HRQL with the SF-36. RESULTS: 709 individuals were included, and 451 (63.6%) were re-interviewed 6 months later. Among the 325 individuals without GERS, 9 developed weekly symptoms (2.2% [95% CI: 0.8, 3.4%]); 2 (22%) consulted because of GERS. Among the 34 subjects reporting weekly GERS initially, 26 did not report them at 6-months. Onset of GERS was associated with worsening scores in the physical summary of SF-36 (delta = -6.6 [95% CI: -11.8, -1.42]), while disappearance with an improved score (delta = -3.0 [95% CI: 0.0, 5.9]). CONCLUSION: despite the lower prevalence of GERS in Spain, the occurrence rate is 2.2% in 6 months; however symptoms disappeared in more than half of subjects six months later. Developing GERS was associated with reduced HRQL, and their disappearance with improvement. PMID- 19642840 TI - More on sedation in digestive endoscopy. PMID- 19642841 TI - Cholangioscopy through a large balloon papillary dilation with two frontal endoscopes: therapeutic and infantile. PMID- 19642842 TI - Polycystic liver disease. PMID- 19642843 TI - Pancreatic fusocellular sarcoma. The importance of endoscopic ultrasound-guided fine needle aspiration in the differential diagnosis of solid pancreatic tumors. AB - In the presence of a pancreatic tumor, the main diagnostic problem is to determine the benign o malignant nature of the lesion, and then to evaluate its resectability. A preoperative biopsy was usually rejected based on the fact that negative results do not exclude malignancy, that such biopsy may hamper the possibility of curative surgery because of potential seeding along the biopsy s trajectory, that surgical morbidity and mortality are low, and also because of the high diagnostic sensitivity of the various imaging techniques. Biopsy for solid pancreatic tumors was limited to irresectable tumors, and isolated cases with suspicion of tuberculosis, lymphoma or neuroendocrine tumors. Nowadays the performance of a pancreatic biopsy is becoming essential for the correct management of solid lesions, and is useful not only to establish malignancy, but also for a better knowledge of all kind of pathologies and, thus, for better therapeutic management. In this context, endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) has proven a safe technique with a low rate of complications and a diagnostic accuracy superior to other procedures, this being considered the method of choice for the study of solid pancreatic lesions. An illustrative example is the case we report in this article -a patient diagnosed of a solid, locally advanced-stage pancreatic tumor with imaging techniques (abdominal ultrasounds and EUS) under EUS-guided FNA; the procedure could establish a final diagnosis of pancreatic fusocellular sarcoma. PMID- 19642844 TI - [Mesenteric fibromatosis: a rare entity]. PMID- 19642845 TI - [Appendagitis: unusual cause of abdominal pain]. PMID- 19642846 TI - [Gastric volvulus like infrequent cause of abdominal pain]. PMID- 19642847 TI - Incidental pseudomyxoma peritonei of the appendix diagnosed by computed tomography with sagittal reconstruction in a woman suffering from postmenopausal metrorrhagia. PMID- 19642848 TI - [Granular cell tumor of the appendix]. PMID- 19642849 TI - [Procalcitonin: an allied in the management of the patient submitted to abdominal surgery]. PMID- 19642850 TI - [Stump appendicitis: report of two cases an review of literature]. PMID- 19642851 TI - [Primary unknown hepatocarcinoma like a cause of spontaneous hemoperitoneum]. PMID- 19642852 TI - [Acute abdomen after a postraumatic diaphragmatic hernia]. PMID- 19642853 TI - Osteogenesis and trophic factor secretion are influenced by the composition of hydroxyapatite/poly(lactide-co-glycolide) composite scaffolds. AB - The use of composite biomaterials for bone repair capitalizes on the beneficial aspects of individual materials while tailoring the mechanical properties of the composite. We hypothesized that substrate composition would modulate the osteogenic response and secretion of potent trophic factors by human mesenchymal stem cells (hMSCs). Composite scaffolds were prepared by combining nanosized hydroxyapatite (HA) and microspheres formed of poly(lactic-co-glycolic acid) (PLG) at varying ratios between 0:1 and 5:1. Scaffolds were seeded with hMSCs for culture in osteogenic conditions or subcutaneous implantation into nude rats. Compressive moduli increased with HA content in a near-linear fashion. The osteogenic differentiation of hMSCs increased in a dose-dependent manner as determined by alkaline phosphatase activity and osteopontin secretion after 4 weeks of culture. Further, endogenous secretion of vascular endothelial growth factor was sustained at significantly higher levels over 28 days for hMSCs seeded in 2.5:1 and 5:1 HA:PLG scaffolds. Eight weeks after implantation, scaffolds with higher HA:PLG ratios exhibited greater vascularization and more mineralized tissue. These data demonstrate that the mechanical properties, osteogenic differentiation, as well as the timing and duration of trophic factor secretion by hMSCs can be tailored through controlling the composition of the polymer bioceramic composite. PMID- 19642854 TI - Hypoxic preconditioning of human mesenchymal stem cells overcomes hypoxia-induced inhibition of osteogenic differentiation. AB - Osteogenic differentiation of human mesenchymal stem cells (hMSCs) into osteoblasts is a prerequisite for subsequent bone formation. Numerous studies have explored osteogenic differentiation under standard tissue culture conditions, which usually employ 21% of oxygen. However, bone precursor cells such as hMSCs reside in stem cell niches of low-oxygen atmospheres. Furthermore, they are subjected to low oxygen concentrations when cultured on three dimensional scaffolds in vitro, and even more so after transplantation when vascularization has yet to be established. Similarly, hMSCs are exposed to low oxygen in the fracture microenvironment following bony injury. Recent studies revealed that hypoxic preconditioning improves cellular engraftment and survival in low-oxygen atmospheres. In our study we investigated the osteogenic differentiation potential of hMSCs under 2% O(2) (hypoxia) in comparison to a standard tissue culture oxygen atmosphere of 21% (normoxia). We assessed the osteogenic differentiation of hMSCs following hypoxic preconditioning to address whether this pretreatment is beneficial for subsequent differentiation processes as well. To validate our findings we carefully characterized the extent of hypoxia exerted and its effect on cell survival and proliferation. We found that hMSCs proliferate better if cultured under 2% of oxygen. We confirmed that osteogenic differentiation of hMSCs is indeed inhibited if osteogenic induction is carried out under constant hypoxia. Finally, we showed for the first time that hypoxic preconditioning of hMSCs prior to osteogenic induction restores osteogenic differentiation of hMSCs under hypoxic conditions. Collectively, our results indicate that maintaining constant levels of oxygen improves the osteogenic potential of hMSCs and suggest that low oxygen concentrations may preserve the stemness of hMSCs. In addition, our data support the hypothesis that if low-oxygen atmospheres are expected at the site of implantation, hypoxic pretreatment may be beneficial for the cells' subsequent in vivo performance. PMID- 19642855 TI - Adult human bone marrow- and adipose tissue-derived stromal cells support the formation of prevascular-like structures from endothelial cells in vitro. AB - Inadequate vascularization of in vitro-engineered tissue constructs after implantation is a major problem in most tissue-engineering applications. In this study we evaluated whether adipose tissue-derived stromal cells (ASCs), similar to bone marrow-derived stromal cells (BMSCs), can support the organization of endothelial cells into prevascular-like structures using an in vitro model. In addition, we investigated the mechanisms leading to the support of endothelial organization by these cells. We cultured human umbilical vein endothelial cells (HUVECs), ASCs, and BMSCs either alone or in combination in fibrin-embedded spheroids for 14 days. We found that BMSCs and ASCs formed cellular networks that expressed alpha smooth muscle actin and, in the case of ASCs, also CD34. Further, BMSCs and ASCs secreted hepatocyte growth factor and tissue inhibitor of metalloproteinase 1 and 2. In addition, ASC-conditioned medium induced HUVEC outgrowth, whereas BMSC-conditioned medium and hepatocyte growth factor supplemented medium did not. Finally, both BMSCs and ASCs supported HUVEC organization into prevascular-like structures when cocultured. Our results suggest that both BMSCs and ASCs can support the formation of prevascular-like structures in vitro. Further, our findings indicate that cell-cell contacts and reciprocal signaling play an important role in the formation of these prevascular structures. PMID- 19642856 TI - Transplantation of a tissue-engineered human vascularized cardiac muscle. AB - Myocardial regeneration strategies have been hampered by the lack of sources for human cardiomyocytes (CMs) and by the significant donor cell loss following transplantation. We assessed the ability of a three-dimensional tissue-engineered human vascularized cardiac muscle to engraft in the in vivo rat heart and to promote functional vascularization. Human embryonic stem cell-derived CMs alone or with human endothelial cells (human umbilical vein endothelial cells) and embryonic fibroblasts (triculture constructs) were seeded onto biodegradable porous scaffolds. The resulting tissue constructs were transplanted to the in vivo rat heart and formed cardiac tissue grafts. Immunostaining studies for human specific CD31 and alpha-smooth muscle actin demonstrated the formation of both donor (human) and host (rat)-derived vasculature within the engrafted triculture tissue constructs. Intraventricular injection of fluorescent microspheres or lectin resulted in their incorporation by human-derived vessels, confirming their functional integration with host coronary vasculature. Finally, the number of blood vessels was significantly greater in the triculture tissue constructs (60.3 +/- 8/mm(3), p < 0.05) when compared with scaffolds containing only CMs (39.0 +/- 14.4/mm(3)). In conclusion, a tissue-engineered human vascularized cardiac muscle can be established ex vivo and transplanted in vivo to form stable grafts. By utilizing a multicellular preparation we were able to increase biograft vascularization and to show that the preexisting human vessels can become functional and contribute to tissue perfusion. PMID- 19642858 TI - Hemolysis index: quality indicator or criterion for sample rejection? PMID- 19642859 TI - Neutrophil CD64: a diagnostic marker for infection and sepsis. AB - Neutrophilic granulocytes express Fcgamma receptor (FcgammaR) [cluster of differentiation 64 (CD64) antigen] only when they are activated. Neutrophil CD64, demonstrated using flow cytometry, can be used as a diagnostic marker of infection and sepsis. Neutrophil CD64 is superior to C-reactive protein and hematological determinations for detecting systemic infection or sepsis, since it combines high sensitivity (90% or more) with high specificity (90%-100%) in both adults and children. In addition, the test performs well in distinguishing infection from flares in autoimmune inflammatory diseases and has somewhat more limited utility for differentiating bacterial from viral infection. This review summarizes the available literature regarding CD64 as a marker of infection, and outlines future clinical studies for confirming the diagnostic performance of this promising marker. PMID- 19642860 TI - Differential expression of microRNAs in the placentae of Chinese patients with severe pre-eclampsia. AB - BACKGROUND: The pathogenesis of pre-eclampsia (PE) is incompletely understood. The placenta is considered to play a key role in this disease. Recent research showed that many microRNAs (miRNAs) are expressed in human placenta. Our aim in this study was to determine differential expression of miRNAs in placenta with severe PE, and normal placenta. METHODS: Differential expression of miRNAs in placenta (four severe PE and a control group of four normal pregnant women) was first screened using microarray analysis. Following this, some differential miRNAs were selected and validated using real-time quantitative reverse transcription-polymerase chain reaction in placenta from women with severe PE (n=24), and a healthy control group (n=26). RESULTS: We found the following miRNAs were significantly increased in placenta from women with severe PE: miR 16, miR-29b, miR-195, miR-26b, miR-181a, miR-335 and miR-222. Gene ontology analysis of the target genes revealed enrichment for specific biological process categories, i.e., regulation of cellular physiological process including miR-16, miR-29b, miR-195, miR-26b and miR-335, and signal transduction including miR-181a and miR-222. CONCLUSIONS: These different miRNAs may play an important role in pathogenesis of PE and may become diagnostic markers for PE. PMID- 19642862 TI - Clinical efficacy of two cardiac troponin I assays. PMID- 19642861 TI - Anti-citrullinated protein antibody and rheumatoid factor in patients with end stage renal disease. AB - BACKGROUND: Patients with end-stage renal disease (ESRD) and on hemodialysis (HD) are at increased risk for developing rheumatoid arthritis (RA), as a result of defective immunity. Our aim was to examine if ESRD and the length of HD treatment impact the clinical utility of antibodies to cyclic citrullinated peptides (anti CCP) and rheumatoid factor (RF) as diagnostic tools for RA. METHODS: We included 94 subjects in our study: 37 healthy volunteers and 57 patients with ESRD who had been undergoing HD for 1-12 years, and without confirmed RA. In order to test our hypothesis, we measured and correlated anti-CCP and RF as laboratory markers of RA. RESULTS: Our study showed that there is no significant difference between values for anti-CCP (p=0.11) and RF (p=0.98) in control subjects as well as in patients undergoing HD, regardless of the length of time that patients had been undergoing HD treatment. CONCLUSIONS: Our study indicates that HD does not impair the specificity of anti-CCP and RF for RA in patients where the disease has not yet developed. Future prospective studies may show whether there is any use in determinating RF, and especially anti-CCP, as early predictors of RA in patients with ESRD who are at greater risk of developing this condition. PMID- 19642863 TI - Impeded centrifugation in plasmocytoma serum. PMID- 19642864 TI - Ex vivo serotype-specific transduction of equine joint tissue by self complementary adeno-associated viral vectors. AB - Cell transplantation for the treatment of joint disease is an important clinical tool. Genetic modification of cells before transplantation has shown enhanced healing. Ex vivo genetic modification of joint tissue cells with various adeno associated virus (AAV) serotypes has not been investigated. The transduction efficiencies of self-complementary AAV serotypes (1-6 and 8) were determined in joint tissue containing chondrocytes and synoviocytes isolated from equine models. When comparing scAAV serotypes for efficient transduction ex vivo, in chondrocytes versus synoviocytes, serotypes 6 and 2, and serotypes 3 and 2, respectively, appeared superior for gene expression. Unlike adenoviral vectors, no upregulation of inflammatory markers, such as matrix metalloproteinases and aggrecanase, was seen on treatment of joint tissue with AAV vectors ex vivo. Our findings also corroborate that ex vivo transduction of joint tissue can result in high transgene protein levels over time, and transplantation modalities might be feasible using AAV vectors in the treatment of joint-related diseases. PMID- 19642866 TI - Mechanical stress-related calvaria bone augmentation by onlayed octacalcium phosphate-collagen implant. AB - Previous studies have suggested that the biodegradability of octacalcium phosphate-collagen (OCP/Col) composite by osteoclasts is accelerated in association with mechanical stress suffered by the host tissue around the implant. The present study was designed to investigate whether alleviation of mechanical stress restores the bone regenerative properties of OCP/Col, as previously shown in nonload-bearing sites. OCP/Col discs supported with a polytetrafluoroethylene (PTFE) ring, which has a higher modulus than OCP/Col, were implanted in a rat subperiosteal pocket for up to 12 weeks. The structural features of the implant and biological responses were analyzed by X-ray diffraction, Fourier transform infrared spectroscopy, histomorphometry, histochemistry, and tissue mRNA expression around the implants. The effect of compression was analyzed using mouse stromal ST-2 cells by deforming the cell seeded OCP/Col discs in vitro with or without a PTFE ring. The results clearly indicated the restoration of bone formation by the alleviation of mechanical stress and the upregulation of osteoblast-related genes, such as osterix on the other hand, the implantation of OCP/Col on calvaria or in an in vitro test without PTFE support resulted in the upregulation of osteoclast-related genes, such as tartrate-resistant acid phosphatase (TRAP) and cathepsin K, in the tissues or receptor activator of the nuclear factor-kappaB ligand (RANKL) in ST-2 cells. The results confirmed that calvaria augmentation is enhanced by implanting OCP/Col if suitable conditions regarding mechanical stress are provided. PMID- 19642865 TI - Rapamycin promotes the osteoblastic differentiation of human embryonic stem cells by blocking the mTOR pathway and stimulating the BMP/Smad pathway. AB - Studies revealed that PI3K/AKT/mTOR signaling is important in the regulation of human embryonic stem cell (hESC) self-renewal and differentiation. However, its action on osteogenic differentiation of hESCs is poorly understood. We tested the effects of pharmacological PI3K/AKT/mTOR inhibitors on their potential to induce osteogenic differentiation of hESCs. Under feeder-free culture conditions, rapamycin (an mTOR inhibitor) potently inhibited the activities of mTOR and p70S6K in undifferentiated hESCs; however, LY294002 (a PI3K inhibitor) and an AKT inhibitor had no effects. Treatment with any of these inhibitors down-regulated the hESC markers Oct4 and Nanog, but only rapamycin induced the up-regulation of the early osteogenic markers BMP2 and Runx2. We also observed that hESCs differentiated when treated with FK506, a structural analog of rapamycin, but did not exhibit an osteogenic phenotype. Increases in Smad1/5/8 phosphorylation and Id1-4 mRNA expression indicated that rapamycin significantly stimulated BMP/Smad signaling. After inducing both hESCs and human embryoid bodies (hEBs) for 2-3 weeks with rapamycin, osteoblastic differentiation was further characterized by the expression of osteoblastic marker mRNAs and/or proteins (osterix, osteocalcin, osteoprotegerin, osteonectin, and bone sialoprotein), alkaline phosphatase activity, and alizarin red S staining for mineralized bone nodule formation. No significant differences in the osteogenic phenotypes of rapamycin differentiated hESCs and hEBs were detected. Our results suggest that, among these 3 inhibitors, only rapamycin functions as a potent stimulator of osteoblastic differentiation of hESCs, and it does so by modulating rapamycin sensitive mTOR and BMP/Smad signaling. PMID- 19642867 TI - Specific induction of migration and invasion of pancreatic carcinoma cells by RhoC, which differs from RhoA in its localisation and activity. AB - RhoA and RhoC are highly related Rho GTPases, but differentially control cellular behaviour. We combined molecular, cellular, and biochemical experiments to characterise differences between these highly similar GTPases. Our findings demonstrate that enhanced expression of RhoC results in a striking increase in the migration and invasion of pancreatic carcinoma cells, whereas forced expression of RhoA decreases these actions. These isoform-specific functions correlate with differences in the cellular activity of RhoA and RhoC in human cells, with RhoC being more active than RhoA in activity assays and serum response factor-dependent gene transcription. Subcellular localisation studies revealed that RhoC is predominantly localised in the membrane-containing fraction, whereas RhoA is mainly localised in the cytoplasmic fraction. These differences are not mediated by a different interaction with RhoGDIs. In vitro GTP/GDP binding analyses demonstrate different affinity of RhoC for GTP[S] and faster intrinsic and guanine nucleotide exchange factor (GEF)-stimulated GDP/GTP exchange rates compared to RhoA. Moreover, the catalytic domains of SopE and Dbs are efficacious GEFs for RhoC. mRNA expression of RhoC is markedly enhanced in advanced pancreatic cancer stages, and thus the differences discovered between RhoA and RhoC might provide explanations for their different influences on cell migration and tumour invasion. PMID- 19642869 TI - Autoregulatory control of the p53 response by Siah-1L-mediated HIPK2 degradation. AB - The different activities of the tumor suppressor p53 are tightly regulated by various negative and positive feedback loops, which allow accurate control of its function. Here we show that the p53-inducible ubiquitin E3 ligase Siah-1L can bind to the p53 phosphorylating kinase HIPK2 and thus allows its ubiquitination and proteasomal elimination. Siah-1L also eliminates the HIPK family member HIPK3, indicating that its activity is not restricted to one member of the HIPK family. The stimulating effect of HIPK2 on p53-triggered transcription is counteracted by Siah-1L, thus showing the occurrence of another negative feedback loop controlling the p53 response. PMID- 19642870 TI - Structural analysis of the choline-binding protein ChoX in a semi-closed and ligand-free conformation. AB - The periplasmic ligand-binding protein ChoX is part of the ABC transport system ChoVWX that imports choline as a nutrient into the soil bacterium Sinorhizobium meliloti. We have recently reported the crystal structures of ChoX in complex with its ligands choline and acetylcholine and the structure of a fully closed but substrate-free state of ChoX. This latter structure revealed an architecture of the ligand-binding site that is superimposable to the closed, ligand-bound form of ChoX. We report here the crystal structure of ChoX in an unusual, ligand free conformation that represents a semi-closed form of ChoX. The analysis revealed a subdomain movement in the N-lobe of ChoX. Comparison with the two well characterized substrate binding proteins, MBP and HisJ, suggests the presence of a similar subdomain in these proteins. PMID- 19642868 TI - Mechanisms of liver disease: cross-talk between the NF-kappaB and JNK pathways. AB - The liver plays a central role in the transformation and degradation of endogenous and exogenous chemicals, and in the removal of unwanted cells such as damaged, genetically mutated and virus-infected cells. Because of this function, the liver is susceptible to toxicity caused by the products generated during these natural occurrences. Hepatocyte death is the major feature of liver injury. In response to liver injury, specific intracellular processes are initiated to maintain liver integrity. Inflammatory cytokines including tumor necrosis factor (TNF)alpha and interleukin-6 (IL-6) are key mediators of these processes and activate different cellular response such as proliferation, survival and death. TNFalpha induces specific signaling pathways in hepatocytes that lead to activation of either pro-survival mediators or effectors of cell death. Whereas activation of transcription factor NF-kappaB promotes survival, c-Jun N-terminal kinases (JNKs) and caspases are strategic effectors of cell death in the TNFalpha mediated signaling pathway. This review summarizes recent advances in the mechanisms of TNFalpha-induced hepatotoxicity and suggests that NF-kappaB plays a protective role against JNK-induced hepatocyte death. Identification of the mechanisms regulating interplay between the NF-kappaB and JNK pathways is required in the search for novel targets for the treatment of liver disease, including hepatitis and hepatocellular carcinoma. PMID- 19642871 TI - Immunologic hurdles of therapeutic stem cell transplantation. AB - Detailed knowledge of the immunologic properties of embryonic stem (ES) cells is a prerequisite for safe applications of ES cell-based regenerative medicine. Recently, the long-standing assumption that ES cells are ignored by immunocompetent hosts was disproved. Instead, it is becoming increasingly clear that ES cells actively protect themselves via several immunomodulatory and immunoevasive mechanisms against cytotoxic T-lymphocytes and natural killer cells. Here we review current knowledge about the immunologic properties of ES cells and discuss the implications for ES cell-based regenerative medicine, for the immunobiology of the embryo as a semi-allogeneic graft, and for the regenerative capacity of adult stem cells. PMID- 19642872 TI - Ancestral vascular tube formation and its adoption by tumors. AB - Similar to growing and metabolically active tissues, tumors require a dense vasculature to gain access to oxygen and nutrients. However, blood vessels in tumors differ from vessels in normal tissues in many respects. In particular, the tumor vasculature is in an active state of angiogenesis or vasculogenesis, and it is immature and leaky. Blood vessels are multicellular tubes formed by polarized endothelial cells, which face the patent vascular lumen with their apical cell surface, whereas their basal cell surface faces extracellular matrix on the outside of the vessels. The same cell polarity can be found in other tubular structures, such as in the bronchial tubes of the lung or the kidney tubules. In contrast, blood vessels in invertebrates often have a vascular lumen lined by basal cell surfaces. These vessels are often formed by a process named 'ancestral vascular tube formation'. Here, we discuss the hypothesis that the supply of tumors with blood can be achieved by both endothelial cell-lined tubes as well as tubes formed by the tumor cells themselves using the ancestral vascular tube formation mechanism. We discuss this hypothesis with a particular focus on gastrointestinal tumors. PMID- 19642873 TI - Dissection of gene regulatory networks in embryonic stem cells by means of high throughput sequencing. AB - Transcription factor regulation of gene expression and chromatin-controlled epigenetic memory systems are closely cooperating in establishing the pluripotent state of embryonic stem (ES) cells and maintaining cell fate decisions throughout development of an organism. A thorough understanding of the regulatory transcriptional circuitry that rules the underlying plastic yet heritable gene expression programs in ES cells is of great importance. With the advent of next generation sequencing technologies facilitating the quantitative assessment of functional genomics assays it is now feasible to interrogate transcription networks at a genome-wide scale. Here, we discuss the application of next generation sequencing in elucidating the molecular mechanisms underlying ES cell function. PMID- 19642874 TI - Cellular plasticity of the pancreas. AB - Cell replacement therapy holds promises for treatment of patients suffering from diabetes mellitus. When determining the appropriate strategies to amplify the amount of transplantable beta-cells, sufficient knowledge of the developmental programs regulating beta-cell differentiation is crucial. Here, we describe the plasticity of the different pancreatic cell types in vivo and in vitro and their potential to serve as beta-cell progenitor. PMID- 19642875 TI - Interplay between host cell and hepatitis C virus in regulating viral replication. AB - Viral life cycle as that of the hepatitis C virus (HCV) completely relies on host cell infrastructure, presupposing that the virus has evolved mechanisms to utilize and control all cellular molecules or pathways required for viral life cycle. Hence, HCV must have acquired the ability to gain access to key pathways controlling processes, such as cell growth, apoptosis and protein synthesis, which are all considered to also be crucial for liver regeneration. This occurs in a balanced way permitting persistent replication of viral genomes and production of infectious particles without endangering host cell viability and survival. In particular during the last decade, accumulating evidence indicates that HCV utilizes signaling pathways of the host with major impact on cellular growth, viability, cell cycle or cellular metabolism, such as epidermal growth factor-receptor mediated signals, the PI3K/Akt cascade or the family of Src kinases. Furthermore, HCV specifically interacts with parts of the cellular machinery involved in protein translation, processing, maturation and transport, such as components of the translation complex, the heat shock protein family, the immunophilins or the vesicle-associated membrane protein-associated proteins A and B. The present review focuses on the interplay between viral proteins and these factors of the host cell enabling the virus to utilize host cell infrastructure. PMID- 19642876 TI - The chemokine scavenging receptor D6 limits acute toxic liver injury in vivo. AB - The chemokine decoy receptor D6 is a promiscuous chemokine receptor lacking classical signaling functions. It negatively regulates inflammation by targeting CC chemokines to cellular internalization and degradation. Here we analyze the function of D6 in acute CCl(4)-induced liver damage in constitutive D6(-/-) and wild-type mice. The degree of liver injury was assessed by liver histology, serum transaminases, IL-6, and TNFalpha mRNA expression. Protein levels of D6 ligands (CCL2, CCL3, CCL5) and the non-D6-ligand CXCL9 within the livers were determined by ELISAs. The intrahepatic infiltration of immune cells was characterized by FACS. Genetic deletion of D6 led to prolonged liver damage after acute CCl(4) administration. The augmented liver damage in D6(-/-) mice was associated with increased protein levels of intrahepatic inflammatory chemokines CCL2, CCL3, and CCL5 after 48 h, whereas CXCL9 was not different between knockout and wild-type mice. Functionally, increased intra-hepatic CC chemokine concentrations led to increased infiltration of CD45(+) leukocytes, which were mainly identified as T and NK cells. In conclusion, the chemokine scavenger receptor D6 has a non redundant role in acute toxic liver injury in vivo. These results support the importance of post-translational chemokine regulation and describe a new mechanism of immune modulation within the liver. PMID- 19642877 TI - Hepatic differentiation of pluripotent stem cells. AB - In regenerative medicine pluripotent stem cells are considered to be a valuable self-renewing source for therapeutic cell transplantations, given that a functional organ-specific phenotype can be acquired by in vitro differentiation protocols. Furthermore, derivatives of pluripotent stem cells that mimic fetal progenitor stages could serve as an important tool to analyze organ development with in vitro approaches. Because of ethical issues regarding the generation of human embryonic stem (ES) cells, other sources for pluripotent stem cells are intensively studied. Like in less developed vertebrates, pluripotent stem cells can be generated from the female germline even in mammals, via parthenogenetic activation of oocytes. Recently, testis-derived pluripotent stem cells were derived from the male germline. Therefore, we compared two different hepatic differentiation approaches and analyzed the generation of definitive endoderm progenitor cells and their further maturation into a hepatic phenotype using murine parthenogenetic ES cells, germline-derived pluripotent stem cells, and ES cells. Applying quantitative RT-PCR, both germline-derived pluripotent cell lines show similar differentiation capabilities as normal murine ES cells and can be considered an alternative source for pluripotent stem cells in regenerative medicine. PMID- 19642878 TI - Hepatic and pancreatic stellate cells in focus. AB - Stellate cells are vitamin A-storing cells of liver and pancreas and have been described in all vertebrates ranging from lampreys (primitive fish) to humans, demonstrating their major importance. This cell type is thought to contribute to fibrosis, a condition characterized by an excess deposition of extracellular matrix proteins. Recently, the expression of stem/progenitor cell markers, such as CD133 (prominin-1) and Oct4, was discovered in hepatic stellate cells (HSCs) of rats. Moreover, HSCs possess signaling pathways important for maintenance of stemness and cell differentiation, such as hedgehog, beta-catenin-dependent Wnt, and Notch signaling, and are resistant to CD95-mediated apoptosis. In analogy to a stem cell niche, some characteristics of quiescent HSC are maintained by aid of a special microenvironment located in the space of Disse. Finally, stellate cells display a differentiation potential as investigated in vitro and in vivo. Collectively all these properties are congruently found in stem/progenitor cells and support the concept that stellate cells are undifferentiated cells, which might play an important role in liver regeneration. The present review highlights findings related to this novel aspect of stellate cell biology. PMID- 19642879 TI - Approaching the bad and avoiding the good: lateral prefrontal cortical asymmetry distinguishes between action and valence. AB - Goal pursuit in humans sometimes involves approaching unpleasant and avoiding pleasant stimuli, such as when a dieter chooses to eat vegetables (although he does not like them) instead of doughnuts (which he greatly prefers). Previous neuroscience investigations have established a left-right prefrontal asymmetry between approaching pleasant and avoiding unpleasant stimuli, but these investigations typically do not untangle the roles of action motivation (approach vs. avoidance) and stimulus valence (pleasant vs. unpleasant) in this asymmetry. Additionally, studies on asymmetry have been conducted almost exclusively using electroencephalography and have been difficult to replicate using functional magnetic resonance imaging (fMRI). The present fMRI study uses a novel goal pursuit task that separates action motivation from stimulus valence and a region of-interest analysis approach to address these limitations. Results suggest that prefrontal asymmetry is associated with action motivation and not with stimulus valence. Specifically, there was increased left (vs. right) activation in dorsolateral prefrontal cortex during approach (vs. avoidance) actions regardless of the stimulus valence, but no such effect was observed for pleasant compared to unpleasant stimuli. This asymmetry effect during approach-avoidance action motivations occurred in the dorsolateral but not orbito-frontal aspects of prefrontal cortex. Also, individual differences in approach-avoidance motivation moderated the effect such that increasing trait approach motivation was associated with greater left-sided asymmetry during approach actions (regardless of the stimulus valence). Together, these results support the notion that prefrontal asymmetry is associated with action motivation regardless of stimulus valence and, as such, might be linked with goal pursuit processes more broadly. PMID- 19642881 TI - Effects of a body-oriented response measure on the neural substrate of imagined perspective rotations. AB - Previous behavioral studies suggest that response measures related to the body, such as pointing, serve to anchor participants to their physical body during mental rotation tasks in which their perspective must be shifted elsewhere. This study investigated whether such measures engage spatial and low-level cortical motor areas of the brain more readily than non-body-related measures. We directly compared activation found in two imagined perspective rotation tasks, using responses that varied in the degree to which they emphasized the human body. In the body minimize condition, participants imagined rotating themselves around an object and judged whether a prescribed part of the object would be visible from the imagined viewpoint. In the body maximize condition, participants imagined rotating around the object and then located the prescribed object part with respect to their bodies. A direct comparison of neural activation in both conditions revealed distinct yet overlapping neural regions. The body maximize condition yielded activation in low-level cortical motor areas such as premotor cortex and primary motor cortex, as well as bilateral spatial processing areas. The body minimize condition yielded activation in nonmotoric egocentric processing regions. However, both conditions showed activation in the parietal occipital region that is thought to be involved in egocentric transformations. These findings are discussed in the context of recent hypotheses regarding the role of the body percept in imagined egocentric transformations. PMID- 19642882 TI - Influence of COMT gene polymorphism on fMRI-assessed sustained and transient activity during a working memory task. AB - The catechol O-methyltransferase (COMT) gene--encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)- contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic-phasic hypothesis, individuals carrying the low-enzyme activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic-phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic-phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val(158)met polymorphism on different components of working memory. PMID- 19642880 TI - Orbito-frontal cortex is necessary for temporal context memory. AB - Lesion and neuroimaging studies suggest that orbito-frontal cortex (OFC) supports temporal aspects of episodic memory. However, it is unclear whether OFC contributes to the encoding and/or retrieval of temporal context and whether it is selective for temporal relative to nontemporal (spatial) context memory. We addressed this issue with two complimentary studies: functional magnetic resonance imaging to measure OFC activity associated with successful temporal and spatial context memory during encoding and retrieval in healthy young participants, and a neuropsychological investigation to measure changes in spatial and temporal context memory in OFC lesion patients. Imaging results revealed that OFC contributed to encoding and retrieval of associations between objects and their temporal but not their spatial contexts. Consistent with this, OFC patients exhibited impairments in temporal but not spatial source memory accuracy. These results suggest that OFC plays a critical role in the formation and subsequent retrieval of temporal context. PMID- 19642883 TI - Dopamine, paranormal belief, and the detection of meaningful stimuli. AB - Dopamine (DA) is suggested to improve perceptual and cognitive decisions by increasing the signal-to-noise ratio. Somewhat paradoxically, a hyperdopaminergia (arguably more accentuated in the right hemisphere) has also been implied in the genesis of unusual experiences such as hallucinations and paranormal thought. To test these opposing assumptions, we used two lateralized decision tasks, one with lexical (tapping left-hemisphere functions), the other with facial stimuli (tapping right-hemisphere functions). Participants were 40 healthy right-handed men, of whom 20 reported unusual, "paranormal" experiences and beliefs ("believers"), whereas the remaining participants were unexperienced and critical ("skeptics"). In a between-subject design, levodopa (200 mg) or placebo administration was balanced between belief groups (double-blind procedure). For each task and visual field, we calculated sensitivity (d') and response tendency (criterion) derived from signal detection theory. Results showed the typical right visual field advantage for the lexical decision task and a higher d' for verbal than facial stimuli. For the skeptics, d' was lower in the levodopa than in the placebo group. Criterion analyses revealed that believers favored false alarms over misses, whereas skeptics displayed the opposite preference. Unexpectedly, under levodopa, these decision preferences were lower in both groups. We thus infer that levodopa (1) decreases sensitivity in perceptual cognitive decisions, but only in skeptics, and (2) makes skeptics less and believers slightly more conservative. These results stand at odd to the common view that DA generally improves signal-to-noise ratios. Paranormal ideation seems an important personality dimension and should be assessed in investigations on the detection of signals in noise. PMID- 19642884 TI - Dissociable neural patterns of facial identity across changes in viewpoint. AB - We examined the neural response patterns for facial identity independent of viewpoint and for viewpoint independent of identity. Neural activation patterns for identity and viewpoint were collected in an fMRI experiment. Faces appeared in identity-constant blocks, with variable viewpoint, and in viewpoint-constant blocks, with variable identity. Pattern-based classifiers were used to discriminate neural response patterns for all possible pairs of identities and viewpoints. To increase the likelihood of detecting distinct neural activation patterns for identity, we tested maximally dissimilar "face"-"antiface" pairs and normal face pairs. Neural response patterns for four of six identity pairs, including the "face"-"antiface" pairs, were discriminated at levels above chance. A behavioral experiment showed accord between perceptual and neural discrimination, indicating that the classifier tapped a high-level visual identity code. Neural activity patterns across a broad span of ventral temporal (VT) cortex, including fusiform gyrus and lateral occipital areas (LOC), were required for identity discrimination. For viewpoint, five of six viewpoint pairs were discriminated neurally. Viewpoint discrimination was most accurate with a broad span of VT cortex, but the neural and perceptual discrimination patterns differed. Less accurate discrimination of viewpoint, more consistent with human perception, was found in right posterior superior temporal sulcus, suggesting redundant viewpoint codes optimized for different functions. This study provides the first evidence that it is possible to dissociate neural activation patterns for identity and viewpoint independently. PMID- 19642885 TI - The role of temporo-parietal cortex in subcortical visual extinction. AB - Visual extinction is an intriguing defect of awareness in stroke patients, referring to the unsuccessful perception of contralesional events under conditions of competition. Previous studies have investigated the cortical and subcortical brain structures that, when damaged or inactivated, provoke visual extinction. The present experiment asked how lesions of subcortical structures may contribute to the appearance of visual extinction. We investigated whether lesions centering on right basal ganglia may induce dysfunction in distant, structurally intact cortical structures. Normalized perfusion-weighted MRI was used to identify structurally intact but abnormally perfused brain tissue, that is, zones that are receiving enough blood supply to remain structurally intact but not enough to function normally. We compared patients with right basal ganglia lesions showing versus not showing visual extinction. In the extinction patients, the contrast revealed cortical malperfusion that clustered around the right TPJ. It seems as if malfunction of this area is a critical aspect in visual extinction not only after cortical lesion but also in the case of subcortical basal ganglia damage. Our results support the idea that a normally functioning TPJ area plays a decisive role for the attentional network involved in detecting of visual stimuli under conditions of competition. PMID- 19642887 TI - The neural basis of personal goal processing when envisioning future events. AB - Episodic future thinking allows humans to mentally simulate virtually infinite future possibilities, yet this device is fundamentally goal-directed and should not be equated with fantasizing or wishful thinking. The purpose of this fMRI study was to investigate the neural basis of such goal-directed processing during future-event simulation. Participants were scanned while they imagined future events that were related to their personal goals (personal future events) and future events that were plausible but unrelated to their personal goals (nonpersonal future events). Results showed that imaging personal future events elicited stronger activation in ventral medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC) compared to imaging nonpersonal future events. Moreover, these brain activations overlapped with activations elicited by a second task that assessed semantic self-knowledge (i.e., making judgments on one's own personality traits), suggesting that ventral MPFC and PCC mediate self referential processing across different functional domains. It is suggested that these brain regions may support a collection of processes that evaluate, code, and contextualize the relevance of mental representations with regard to personal goals. The implications of these findings for the understanding of the function instantiated by the default network of the brain are also discussed. PMID- 19642886 TI - Functional overlap between regions involved in speech perception and in monitoring one's own voice during speech production. AB - The fluency and the reliability of speech production suggest a mechanism that links motor commands and sensory feedback. Here, we examined the neural organization supporting such links by using fMRI to identify regions in which activity during speech production is modulated according to whether auditory feedback matches the predicted outcome or not and by examining the overlap with the network recruited during passive listening to speech sounds. We used real time signal processing to compare brain activity when participants whispered a consonant-vowel-consonant word ("Ted") and either heard this clearly or heard voice-gated masking noise. We compared this to when they listened to yoked stimuli (identical recordings of "Ted" or noise) without speaking. Activity along the STS and superior temporal gyrus bilaterally was significantly greater if the auditory stimulus was (a) processed as the auditory concomitant of speaking and (b) did not match the predicted outcome (noise). The network exhibiting this Feedback Type x Production/Perception interaction includes a superior temporal gyrus/middle temporal gyrus region that is activated more when listening to speech than to noise. This is consistent with speech production and speech perception being linked in a control system that predicts the sensory outcome of speech acts and that processes an error signal in speech-sensitive regions when this and the sensory data do not match. PMID- 19642888 TI - Connecting the dots: how local structure affects global integration in infants. AB - Glass patterns are moires created from a sparse random-dot field paired with its spatially shifted copy. Because discrimination of these patterns is not based on local features, they have been used extensively to study global integration processes. Here, we investigated whether 4- to 5.5-month-old infants are sensitive to the global structure of Glass patterns by measuring visual-evoked potentials. Although we found strong responses to the appearance of the constituent dots, we found sensitivity to the global structure of the Glass patterns in the infants only over a very limited range of spatial separation. In contrast, we observed robust responses in the infants when we connected the dot pairs of the Glass pattern with lines. Moreover, both infants and adults showed differential responses to exchanges between line patterns portraying different global structures. A control study varying luminance contrast in adults suggests that infant sensitivity to global structure is not primarily limited by reduced element visibility. Together our results suggest that the insensitivity to structure in conventional Glass patterns is due to inefficiencies in extracting the local orientation cues generated by the dot pairs. Once the local orientations are made unambiguous or when the interpolation span is small, infants can integrate these signals over the image. PMID- 19642889 TI - The neural basis for spatial relations. AB - Studies in semantics traditionally focus on knowledge of objects. By contrast, less is known about how objects relate to each other. In an fMRI study, we tested the hypothesis that the neural processing of categorical spatial relations between objects is distinct from the processing of the identity of objects. Attending to the categorical spatial relations compared with attending to the identity of objects resulted in greater activity in superior and inferior parietal cortices (especially on the left) and posterior middle frontal cortices bilaterally. In an accompanying lesion study, we tested the hypothesis that comparable areas would be necessary to represent categorical spatial relations and that the hemispheres differ in their biases to process categorical or coordinate spatial relations. Voxel-based lesion symptom mapping results were consistent with the fMRI observations. Damage to a network comprising left inferior frontal, supramarginal, and angular gyri resulted in behavioral impairment on categorical spatial judgments. Homologous right brain damage also produced such deficits, albeit less severely. The reverse pattern was observed for coordinate spatial processing. Right brain damage to the middle temporal gyrus produced more severe deficits than left hemisphere damage. Additional analyses suggested that some areas process both kinds of spatial relations conjointly and others distinctly. The left angular and inferior frontal gyrus processes coordinate spatial information over and above the categorical processing. The anterior superior temporal gyrus appears to process categorical spatial information uniquely. No areas within the right hemisphere processed categorical spatial information uniquely. Taken together, these findings suggest that the functional neuroanatomy of categorical and coordinate processing is more nuanced than implied by a simple hemispheric dichotomy. PMID- 19642890 TI - Word retrieval failures in old age: the relationship between structure and function. AB - A common complaint of normal aging is the increase in word-finding failures such as tip-of-the-tongue states (TOTs). Behavioral research identifies TOTs as phonological retrieval failures, and recent findings [Shafto, M. A., Burke, D. M., Stamatakis, E. A., Tam, P., & Tyler, L. K. On the tip-of-the-tongue: Neural correlates of increased word-finding failures in normal aging. Journal of Cognitive Neuroscience, 19, 2060-2070, 2007] link age-related increases in TOTs to atrophy in left insula, a region implicated in phonological production. Here, younger and older adults performed a picture naming task in the fMRI scanner. During successful naming, left insula activity was not affected by age or gray matter integrity. Age differences only emerged during TOTs, with younger but not older adults generating a "boost" of activity during TOTs compared to successful naming. Older adults also had less activity than younger adults during TOTs compared to "don't know" responses, and across all participants, less TOT activity was affiliated with lower gray matter density. For older adults, lower levels of activity during TOTs accompanied higher TOT rates, supporting the role of an age-related neural mechanism impacting older more than younger adults. Results support a neural account of word retrieval in old age wherein, despite widespread age-related atrophy, word production processes are not universally impacted by age. However, atrophy undermines older adults' ability to modulate neural responses needed to overcome retrieval failures. PMID- 19642891 TI - Characterizing the spatio-temporal dynamics of the neural events occurring prior to and up to overt recognition of famous faces. AB - Although it is generally acknowledged that familiar face recognition is fast, mandatory, and proceeds outside conscious control, it is still unclear whether processes leading to familiar face recognition occur in a linear (i.e., gradual) or a nonlinear (i.e., all-or-none) manner. To test these two alternative accounts, we recorded scalp ERPs while participants indicated whether they recognize as familiar the faces of famous and unfamiliar persons gradually revealed in a descending sequence of frames, from the noisier to the least noisy. This presentation procedure allowed us to characterize the changes in scalp ERP responses occurring prior to and up to overt recognition. Our main finding is that gradual and all-or-none processes are possibly involved during overt recognition of familiar faces. Although the N170 and the N250 face-sensitive responses displayed an abrupt activity change at the moment of overt recognition of famous faces, later ERPs encompassing the N400 and late positive component exhibited an incremental increase in amplitude as the point of recognition approached. In addition, famous faces that were not overtly recognized at one trial before recognition elicited larger ERP potentials than unfamiliar faces, probably reflecting a covert recognition process. Overall, these findings present evidence that recognition of familiar faces implicates spatio-temporally complex neural processes exhibiting differential pattern activity changes as a function of recognition state. PMID- 19642892 TI - Quantification of the neutralization of cytokine biological activity by antibody: the ten-fold reduction bioassay of interleukin-6 as growth factor. AB - The measurement of neutralizing antibodies (NAbs) to biological therapeutic agents is important clinically as well as for the preclinical evaluation of product immunogenicity. To determine whether the theoretical concepts and experimental data from studies of the nature of antibody neutralization of interferons (IFNs) can apply to unrelated protein effector molecules, neutralization experiments were undertaken with interleukin-6 (IL-6), a proinflammatory, highly pleiotropic cytokine. By following IL-6 induction of hybridoma cell growth, we demonstrated that anti-IL-6 monoclonal and polyclonal NAbs can be measured with a bioassay design structured to reduce 10 Laboratory Units (LU)/mL to 1 LU/mL. Results are reported in Ten-fold Reduction Units (TRU)/mL, as recommended for the standardization of IFN NAb unitage. The bioassay was shown to be sensitive, reproducible, and robust in measuring IL-6 potency and NAb titer, as well as for evaluating dose-response curve slope differences. This bioassay design should be applicable to any cytokine, growth factor, protein hormone, or similar effector molecules for which an adequately sensitive cellular response can be quantified. PMID- 19642894 TI - Interleukin-6 trans-signaling regulates glycogen consumption after D galactosamine-induced liver damage. AB - The cytokine interleukin-6 (IL-6) is important for liver regeneration. IL-6 can stimulate target cells either by binding to the membrane-bound IL-6 receptor (IL 6R) leading to dimerization and activation of gp130 or by binding to a soluble IL 6R that results in an activation of gp130 independently of membrane-bound IL-6R, a process called trans-signaling. We have established a transgenic mouse line, in which only trans-signaling is abrogated whereas signaling via the membrane-bound IL-6R is intact. In the present study we employed this mouse model to ask whether the activity of IL-6 during repair of mild liver damage acts via classic or trans signaling. We analyzed liver regeneration and showed that intracellular signaling, proliferation, and glycogenolysis are reduced in the transgenic mice and thus are regulated by IL-6 trans-signaling. Taken together our results show that upon liver damage, activation of the gp130 pathway depends on the sIL-6R. PMID- 19642895 TI - Heterogeneous interleukin-15 inducibilities in murine B16 melanoma and RM-1 prostate carcinoma by interferon-alpha treatment. AB - Long-term treatment of mouse cancer cells with interferon-alpha (IFN-alpha) converts parental B16 melanoma cells to B16alpha vaccine cells. Inoculation of syngeneic mice with UV-irradiated B16alpha vaccine cells triggers immunity to the parental B16 tumor that is mediated by host macrophages, T cells, and NK cells. Lymph node cells from mice inoculated with irradiated B16alpha vaccine cells, but not with irradiated parental cells, proliferate when cultured in vitro, suggesting long-term in vivo activation of lymphoid cells. Both IL-15 mRNA and IL 15 protein are highly induced in B16alpha vaccine cells. The bulk of the induced IL-15 is shown to be cell-associated, either cytoplasmic or membranous. The current study investigated the feasibility of applying the B16alpha vaccination protocol to generate a cancer vaccine against murine RM-1 prostate carcinoma. In comparison to B16alpha vaccine cells, long-term IFN-alpha-treated RM-1 cells (RM 1alpha vaccine cells) showed significant IL-15 mRNA induction but relatively low IL-15 protein up-regulation. When UV-irradiated, a 3-fold increase in intracellular IL-15 was observed in RM-1alpha vaccine cells, suggesting UV damage may have negated a possible control mechanism for IL-15 synthesis. Efficacy of in vivo vaccination of syngeneic mice with UV-irradiated RM-1alpha and B16alpha vaccine cells showed correlation between high IL-15 level and high vaccine efficacy in B16alpha cells compared to low IL-15 level and low vaccine efficacy in RM-1alpha cells. This supports the concept that the induction of IL-15 in tumor cells can be useful for creating whole-cell cancer vaccines. PMID- 19642896 TI - GAGE, an antiapoptotic protein binds and modulates the expression of nucleophosmin/B23 and interferon regulatory factor 1. AB - The GAGE family of highly related tumor antigens is expressed in a variety of tumors. This albeit silent gene expression resulted in resistance of cells to various apoptotic agents such as Fas, interferon-gamma, Taxol, or gamma radiation. We now report that GAGE overexpression in either HeLa (expressing endogenous GAGE) or HEK293 (devoid of GAGE expression) rendered those cells unsusceptible to cell death induced by IFN-gamma. We investigated the underlying mechanism of GAGE-induced cell survival upon treatment with IFN-gamma in this report. We showed that GAGE overexpression resulted in down-regulation of a key player of IFN-gamma-signaling pathway, interferon regulatory factor 1 (IRF1), and its target genes caspase-1 and caspase-7. An interaction between GAGE and IRF1 is detected in cells. Furthermore, GAGE interacted with a multifunctional protein nucleophosmin (NPM)/B23 and increased its abundance by stabilizing the protein. Increased level of NPM/B23 in conjunction with decreased level of IRF1 could aid GAGE-induced resistance to IFN-gamma. Our results suggest that GAGE could rescue cell death induced by IFN-gamma by altering the level of key players in cell death pathways. As GAGE is silent in most healthy tissues, targeting GAGE could result in therapeutic interventions in cancer therapy. PMID- 19642897 TI - The effect of high mobility group box-1 protein on splenic dendritic cell maturation in rats. AB - High mobility group box-1 protein (HMGB1), a recently described late-acting cytokine that mediates lethality of sepsis and systemic inflammation, also plays a role in mediating dendritic cell (DC) maturation and activation. The present study was performed to clarify the effects of HMGB1 on splenic DCs and its potential regulating mechanism underlying T-cell-mediated immunity. DCs isolated from the spleens of normal rats were treated with HMGB1 of different dosage (0.1, 1, or 10 microg/mL) for different duration (24, 48, or 72 h). Expressions of co stimulatory molecules, including CD80, CD86, and MHC-II on DCs surface, and cytokines, including interleukin (IL)-12, tumor necrosis factor (TNF)-alpha, were analyzed to identify DCs maturation and activation. The activated DCs were assessed for their capacity to stimulate the proliferation and differentiation of T cells. Expression of the receptor for advanced glycation end products (RAGE) on DCs and nuclear factor (NF)-kappaB activation in T lymphocytes were also determined. Stimulation with HMGB1 markedly up-regulated the co-stimulatory molecules and cytokines expressions, and they peaked at 48 h when DCs was treated with 1 microg/mL HMGB1. Treatment with anti-RAGE antibody prevented the maturation of DCs. DCs treated with HMGB1 (1 microg/mL for 48 h) promoted T-cell proliferation as well as differentiation, and markedly up-regulated IL-2, IL-2R expression and intranuclear NF-kappaB activation. The results suggested that HMGB1 appear to be a potential immunostimulatory signal that induced DC maturation and T-cell-mediated immunity, and RAGE was a potential receptor associated with maturation and differentiation of DCs. Moreover, HMGB1 might have a dual regulatory effect on immune functions of DCs varying with different concentration and stimulation time. PMID- 19642898 TI - Methicillin-resistant Staphylococcus aureus colonization of house officers. AB - We performed a prospective prevalence survey of methicillin-resistant Staphylococcus aureus (MRSA) carriage in the nares of 50 medical and 50 surgical house officers. None of the 50 internal medicine house officers and 5 of the 50 general surgery house officers had MRSA nares colonization (P = .03). None of the MRSA isolates recovered from the surgical house officers were identical. PMID- 19642899 TI - Patients' beliefs and perceptions of their participation to increase healthcare worker compliance with hand hygiene. AB - BACKGROUND: Research suggests that patients could improve healthcare workers' compliance with hand hygiene recommendations by reminding them to cleanse their hands. OBJECTIVE: To assess patients' perceptions of a patient-participation program to improve healthcare workers' compliance with hand hygiene. DESIGN: Cross-sectional survey of patient knowledge and perceptions of healthcare associated infections, hand hygiene, and patient participation, defined as the active involvement of patients in various aspects of their health care. SETTING: Large Swiss teaching hospital. RESULTS: Of 194 patients who participated, most responded that they would not feel comfortable asking a nurse (148 respondents [76%]) or a physician (150 [77%]) to perform hand hygiene, and 57 (29%) believed that this would help prevent healthcare-associated infections. In contrast, an explicit invitation from a healthcare worker to ask about hand hygiene doubled the intention to ask a nurse (from 34% to 83% of respondents; P < .001) and to ask a physician (from 30% to 78%; P < .001). In multivariate analysis, being nonreligious, having an expansive personality, being concerned about healthcare associated infections, and believing that patient participation would prevent healthcare-associated infections were associated with the intention to ask a nurse or a physician to perform hand hygiene (P < .05). Being of Jewish, Eastern Orthodox, or Buddhist faith was associated also with increased intention to ask a nurse (P < .05), compared with being of Christian faith. CONCLUSIONS: This study identifies several sociodemographic characteristics associated with the intention to ask nurses and physicians about hand hygiene and underscores the importance of a direct invitation from healthcare workers to increase patient participation and foster patient empowerment. These findings could guide the development of future hand hygiene-promotion strategies. PMID- 19642900 TI - Hepatitis C virus transmission in hemodialysis units: importance of infection control practices and aseptic technique. AB - We investigated 4 hepatitis C virus (HCV) infection outbreaks at hemodialysis units to identify practices associated with transmission. Apparent failures to follow recommended infection control precautions resulted in patient-to-patient HCV transmission, through cross-contamination of the environment or intravenous medication vials. Fastidious attention to aseptic technique and infection control precautions are essential to prevent HCV transmission. PMID- 19642901 TI - Rotavirus infection in neonates at a university hospital in Korea. AB - To develop measures to prevent neonatal rotavirus infection, we carried out rotavirus surveillance testing on all the newborns who were admitted to a newborn nursery in Korea during 1 year. We investigated the characteristics of neonatal rotavirus infection and found that it occurred throughout the year with the G4P[6] strain exclusively. Most newborns were infected nosocomially and showed no symptoms. We concluded that rotavirus might be transmitted from asymptomatic infected newborns who were born outside the hospital. We recommend isolation and rotavirus surveillance testing for all transfer patients. PMID- 19642902 TI - Risk factors for spinal surgical site infection, Houston, Texas. AB - OBJECTIVE: Because of an increase in the rate of surgical site infections (SSIs) following spinal procedures at the study hospital, we conducted a study to determine risk factors associated with the development of a SSI. DESIGN: Case control study. SETTING: A community hospital in Houston, Texas, with more than 500 beds. PATIENTS: Fifty-five case patients who developed SSI after spinal surgery and 179 control patients who did not develop SSI after spinal surgery. METHODS: We examined patient- and hospital-associated risk factors for SSI by using existing data on patients who underwent spinal operations at the study hospital between December 2003 and August 2005. Multivariable analysis was conducted using logistic regression to determine significant risk factors associated with SSI. RESULTS: The presence of comorbidities (odds ratio [OR], 3.15 [95% confidence interval (CI), 1.20-8.26]) and surgical duration greater than the population median of 100 minutes (OR, 2.48 [95% CI, 1.12-5.49]) were identified as independent risk factors for SSI. The use of only povidone-iodine for preoperative skin antisepsis was found to be protective (OR, 0.16 [95% CI, 0.06-0.45]). Specific operating room, hospital staff involved in the procedures, workers' compensation status, method of hair removal, smoking status, or incontinence were not statistically significant. CONCLUSIONS: The presence of comorbidities and increased surgical duration are risks for postoperative infection. The use of only povidone-iodine was found to decrease the risk of infection. PMID- 19642903 TI - Fas expression in conjunctival epithelial cells of patients with cystic fibrosis. AB - Cystic fibrosis (CF) is a genetic disease caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene resulting in absent or deficient expression and function of CFTR protein. It has recently been reported that CFTR may also be involved in the apoptotic process of epithelial cells. In this study we examined the expression of Fas on conjunctival epithelial cells and the serum and tear fluid concentrations of soluble Fas (sFas) in patients with cystic fibrosis. This article studied 25 patients with CF and 25 normal subjects. Conjunctival epithelial cells were obtained by impression cytology, and processed and analyzed for flow cytometry. The amount of sFas in serum and tear fluid was measured by enzyme-linked immunosorbent assay (ELISA). The analysis of Fas expression showed significant increases in the CF patients compared with the control group (P = 0.000012). There was no difference in the concentration of serum and tear fluid sFas between CF patients and controls (P = 0.0515 and P < 0.05, respectively). Fas expression in cystic fibrosis conjunctival epithelium could play an important role in controlling local inflammatory cell apoptosis and may confirm the role of Fas in maintaining ocular immune privilege. PMID- 19642904 TI - Antioxidant supplementation alters cytokine production from monocytes. AB - We studied in 10 healthy subjects the effect of chronic enteral supplementation of antioxidants (vitamins E, C, A, allopurinol, and N-acetylcysteine) on cytokine production by monocytes at rest, end exercise (60-min cycling at 60% of maximum oxygen consumption), and 60 min post-exercise (recovery). The percentage and the mean fluorescent intensity (MFI) of both unstimulated and lipopolysaccharide (LPS)-stimulated tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6-producing monocytes were detected using flow cytometry. Antioxidants decreased the percentage of unstimulated IL-6-producing monocytes following exercise, while their MFI increased at rest. The percentage of LPS-stimulated monocytes increased after exercise and they produced more IL-6 both at rest and following exercise. The percentage of unstimulated and LPS-stimulated IL-1beta producing monocytes was not affected by antioxidants. The MFI of IL-1beta produced unstimulated monocytes was increased after antioxidants both at rest and following exercise. After antioxidants, LPS-stimulated monocytes produced more IL 1beta following exercise. Antioxidants decreased the percentage of TNF-alpha spontaneously-produced monocytes following exercise, which produced more TNF alpha at recovery. Antioxidants did not affect the percentage of LPS-stimulated monocytes producing TNF-alpha, while LPS-stimulated production of TNF-alpha increased both at rest and following exercise. Antioxidants differentially affect TNF-alpha, IL-1beta, and IL-6 production by monocytes, with a general tendency of augmenting cytokine production. PMID- 19642905 TI - A pilot study of interferon-gamma-induced specific oral tolerance induction (ISOTI) for immunoglobulin E-mediated anaphylactic food allergy. AB - Food-induced anaphylaxis is a life-threatening, IgE-mediated disease. No specific therapeutic recommendations, aside from the avoidance of offending foods, exist at this time. However, specific oral tolerance induction for food allergy has been investigated by several groups. In this study, specific oral tolerance induction was attempted using interferon-gamma (IFN-gamma) as an adjuvant for IgE mediated anaphylactic food allergies. A total of 25 patients with IgE-mediated anaphylactic food allergy to milk, eggs, or wheat were selected. IFN-gamma induced specific oral tolerance induction (ISOTI) was conducted on 10 patients, while five patients were only treated with food, five patients received only IFN gamma therapy, and five patients did not receive any treatment. Tolerance for IgE mediated anaphylactic food allergy was successfully induced in all patients (10/10) with ISOTI, while no patients acquired tolerance for allergenic foods in the control groups. Food-specific IgE levels were increased, and skin prick test reactions significantly decreased after the completion of ISOTI. IFN-gamma induced specific oral tolerance induction (ISOTI) is a promisingly effective treatment for IgE-mediated anaphylactic food allergy. IFN-gamma may be an important cytokine in tolerance induction. Simultaneous allergen stimulation with nonspecific immunomodulation of IFN-gamma was essential for specific tolerance induction in IgE-mediated anaphylactic food allergy. PMID- 19642906 TI - Down-regulation of GRIM-19 expression is associated with hyperactivation of STAT3 induced gene expression and tumor growth in human cervical cancers. AB - Cervical cancer is the most common malignant disease responsible for the deaths of a large number of women in the developing world. Although certain strains of human papillomavirus (HPV) have been identified as the cause of this disease, events that lead to formation of malignant tumors are not fully clear. STAT3 is a major oncogenic transcription factor involved in the development and progression of a number of human tumors. However, the mechanisms that result in loss of control over STAT3 activity are not understood. Gene associated with Retinoid Interferon-induced Mortality-19 (GRIM-19) is a tumor-suppressive protein identified using a genetic technique in the interferon/retinoid-induced cell death pathway. Here, we show that reduction in GRIM-19 protein levels occur in a number of primary human cervical cancers. Consequently, these tumors tend to express a high basal level of STAT3 and its downstream target genes. More importantly, using a surrogate model, we show that restoration of GRIM-19 levels reestablishes the control over STAT3-dependent gene expression and tumor growth in vivo. GRIM-19 suppressed the expression of tumor invasion- and angiogenesis associated factors to limit tumor growth. This study identifies another major novel molecular pathway inactivated during the development of human cervical cancer. PMID- 19642907 TI - Chemokine CXCL1/KC and its receptor CXCR2 are responsible for neutrophil chemotaxis in adenoviral keratitis. AB - Epidemic keratoconjunctivitis (EKC), caused by human adenovirus (HAdV), is one of the most common ocular infections and results in corneal inflammation and subepithelial infiltrates. Adenoviral keratitis causes significant morbidity to the patients, and is characterized by infiltration of leukocytes in the corneal stroma, and expression of chemokines. The exact role of these chemokines in adenoviral infection has not been studied due to lack of animal models. Here, we have characterized the role of chemokine CXCL1/KC and receptor CXCR2 in adenoviral keratitis using a novel mouse model. Analysis of chemokine expression, leukocyte infiltration, and development of keratitis was performed by ELISA, flow cytometry, and histopathology, respectively. Deficiency of CXCL1 and CXCR2 resulted in delayed infiltration of neutrophils, but not inflammatory monocytes in HAdV-37 corneal infection. CXCL1(-/-) mice showed decreased expression of CXCL2/MIP-2, but not CCL2/MCP-1. CXCR2(-/-) mice showed increased expression of CXCL1 and CXCL2, but not CCL2. Both CXCL1(-/-) and CXCR2(-/-) mice demonstrated keratitis similar to wild-type mice. In conclusion, both CXCL1 and CXCR2 play an important role in chemokine expression and neutrophil infiltration following adenoviral corneal infection, but have a redundant role in the development of keratitis. PMID- 19642908 TI - Predictive markers of blood cytokine and chemokine in recurrent brain infarction. AB - The mechanism of the inflammatory response in the vascular wall in atherothrombosis and during the progression of atherosclerosis has attracted attention. We focused on the potential usefulness of inflammatory markers in chronic recurrent brain infarction, and analyzed the role of inflammatory markers in atherosclerosis of the intracranial artery. The subjects were 2 groups of patients treated between 2004 and 2006: a group of outpatients with recurrent infarction (group RI), who developed atherothrombotic brain infarction twice; another group of outpatients with brain infarction without recurrence (group BI), who developed brain infarction once and remained free of recurrence for >1 year; and a group of control subjects with normal brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) (group C). Plasma samples were collected from each group of patients for the simultaneous measurement of 17 kinds of candidate inflammatory markers, using a fluorescent microbead array system, and the results were compared with head MRA findings. The levels of high sensitivity C-reactive protein (hsCRP) and monocyte chemoattractant protein-1 (MCP-1) were significantly higher in group RI patients than in groups C and BI. Subjects with a hsCRP level > or =0.3 and a MCP-1 level > or =200 in the serum have, respectively, a 1.92 and 2.98 relative risk to have a potential recurrent infarction. Regarding the relation of inflammatory marker levels with MRA findings, group RI showed significantly higher levels of hsCRP at M1 lesions and MCP-1 at A1 and M1 lesions than group BI (P < 0.05). In conclusion, the MCP-1 level as well as hsCRP in the blood can be a potential predictive marker of recurrent thrombotic brain infarction, and may reflect inflammation that promotes intracranial large-artery atherosclerosis. PMID- 19642910 TI - Purification of triamcinolone acetonide suspension for intravitreal use: the centrifugation method. PMID- 19642909 TI - Cardiac function and the proinflammatory cytokine response after recovery from cardiac arrest in swine. AB - Increased levels of cytokines have been reported after resuscitation from cardiac arrest. We hypothesized that proinflammatory cytokines, released in response to ischemia/reperfusion, increase following resuscitation and play a role in post cardiac arrest myocardial dysfunction. Ventricular fibrillation (VF) was induced by coronary occlusion in 20 swine. After 7 min of VF, resuscitation was performed as per guidelines. Plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and IL-6 were measured 15 min after the start of resuscitation in all animals and at intervals of 6 h in resuscitated animals. Intravascular pressures and cardiac output (CO) were also recorded. TNF-alpha abruptly increased after resuscitation, peaking at 15 min following return of spontaneous circulation, and declined to baseline levels after 3 h. IL-1beta increased more slowly, reaching a maximum 2 h after reperfusion. IL-6 concentrations were not significantly different from control values at any time point. Males demonstrated greater elevations of TNF-alpha and IL-1beta than females. Stroke work was significantly depressed at all time points with a nadir at 15-30 min after reperfusion, corresponding to the peak TNF-alpha values. The anti-TNF-alpha antibody infliximab attenuated the decrease in myocardial function observed 30 min after reperfusion. TNF-alpha increases during recovery from cardiac arrest are associated with depression of left ventricle (LV) function. The effect of TNF-alpha can be attenuated by anti-TNF-alpha antibodies. PMID- 19642911 TI - Body mass and atherogenic dyslipidemia as major determinants of blood levels of B type natriuretic peptides in Arab subjects with acute coronary syndromes. AB - INTRODUCTION: The plasma B-type natriuretic peptide (BNP) level is elevated in cardiac ischemia and may be useful in assessing prognosis in acute coronary syndromes (ACS). This study aimed to: (1) establish BNP levels and its determinants in a healthy Gulf Arab population and in a group of patients with acute myocardial infarction and (2) investigate associations between BNP levels and markers of myocardial damage (ejection fractions, cardiac troponin I [cTnI] levels) and inflammation (serum C-reactive protein [CRP]). SUBJECTS AND METHODS: We studied 2 groups of Arab subjects: (1) Healthy control (HC), 142 healthy control subjects; (2) Coronary heart disease (CHD), 257 patients with proven acute myocardial infarction within 1 day of admission. Each subject was assessed clinically, and ejection fractions (left ventricular ejection fraction [LVEF]) were determined by echocardiography in those with CHD. Fasting blood samples were processed for full blood counts and serum glucose, urea, creatinine, uric acid, and lipids (total cholesterol [TC], triglycerides [TG], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein [LDL], and apolipoprotein B [apoB]), cTnI, BNP, and high-sensitivity (hs) CRP levels. The results were compared between groups, and the associations of BNP with other parameters were explored. RESULTS: In comparison to HC, the CHD group had a greater waist-hip ratio (WHR) (P < 0.01), worse atherogenic profile, worse renal function, and higher values for CRP and BNP (all P < 0.001). There were no significant differences in values for BNP related to age, diabetes, hypertension, WHR, and hematocrit, although there was a consistent trend in both HC and CHD groups toward a negative relationship of BNP with body mass, TG, and apoB levels, and a positive relationship with HDL, independent only for HDL and apoB on multiple logistic regression. No correlations could be established with cTnI, CRP, and LVEF. The patterns of cross-correlations did not differ significantly with diabetic status. CONCLUSION: In an Arab population with CHD, blood levels of BNP are higher than in a healthy control population and appear correlated to body mass and atherogenic lipids but not CRP, troponin, or ejection fraction. BNP levels did not appear to be influenced by the classical CHD risk factors of diabetes, hypertension, cigarette smoking, hematocrit, or WHR. The independent link with atherogenic dyslipidemia suggests that BNP is important in atherogenesis and may not be just an index of cardiac contractile dysfunction. PMID- 19642912 TI - Lipid profiles and associated gene polymorphisms in young Asian Indian patients with acute myocardial infarction and the metabolic syndrome. AB - BACKGROUND: The objective of this study was to examine the association between serum lipid levels and the metabolic syndrome, together with polymorphisms in lipid-associated genes, in young Asian Indians with acute myocardial infarction (AMI). METHODS: The study population comprised 492 patients who were 45 years old or younger. We assessed lipid levels and the frequencies of the cholesteryl ester transfer protein (CETP) Taq-1 B, lipoprotein lipase (LPL)S447X, -93 T/G, apolipoprotein B (APO B) 96bp ins/del, lipoprotein(a) (LP[a]) pentanucleotide repeat, and apolipoprotein E (APO) E epsilon 2/3/4 polymorphisms in relation to the metabolic syndrome using both National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) and International Diabetes Federation (IDF) definitions. RESULTS: The metabolic syndrome as defined by the NCEP ATP III criteria was found in 301 (61%) patients and in 295 (60%) patients according to the IDF criteria. Hypercholesterolemia (64.5%), hypertriglyceridaemia (78.7%), low high-density lipoprotein cholesterol (HDL-C) (70.1%), and raised non-HDL-C (68.0%) occurred significantly more frequently in patients with the metabolic syndrome defined by the NCEP ATP III criteria. Similar results were observed for the IDF definition. A significant relationship with the LPL -93 T/G polymorphism was found, with the minor G allele occurring more frequently in patients defined by the NCEP ATP III criteria (odds ratio [OR] 2.72; 95% confidence interval [CI] 1.07-8.16; P = 0.023). The X allele of the LPL S447X polymorphism was observed less frequently in metabolic syndrome patients (OR 0.52; 95% CI 0.34-0.78; P = 0.0009). Several genotypes, including the LPL S447X, APO E3/E3, and the CETP Taq1 B2B2, were associated with favorable lipid profiles. CONCLUSION: Dyslipidemia occurred with similar frequency in young Asian Indian patients with AMI and the metabolic syndrome, irrespective of the definition used. Significant associations were observed between LPL gene polymorphisms and the metabolic syndrome. Several lipid-associated genotypes exerted a favorable effect on lipid profiles. PMID- 19642913 TI - T-oligo induces apoptosis in advanced prostate cancer cells. AB - Prostate cancer is the most frequently diagnosed malignancy in men. As cancer progresses from an androgen-sensitive stage to hormone-refractory stage, it turns resistant to androgen ablation therapy. At this stage, effective newer therapies that induce apoptosis are needed for treatment of prostate cancer. DNA oligonucleotides homologous to the telomere 3' overhang (T-oligo) induce apoptosis in several human cancer cells. In the present study, we studied the effect of T-oligo on prostate cancer cells. Our studies showed that androgen independent DU-145 cells are sensitive to T-oligo in terms of inhibition of proliferation. Moreover, T-oligo induced DU-145 cells to undergo apoptosis. Therefore, our results are encouraging for further investigation in the potential application of T-oligo as a novel therapeutic approach for prostate cancer, especially the androgen-independent. PMID- 19642914 TI - Sequence and structural features of RNA aptamer against myasthenic autoantibodies. AB - Myasthenia gravis (MG) is mainly caused by autoantibodies to postsynaptic nicotinic acetylcholine receptors (AChRs). Previously, we isolated an RNA aptamer with 2'-amino pyrimidines that inhibited both a rat monoclonal antibody, which recognizes the main immunogenic region on the AChR, and MG patient autoantibodies from down-modulating AChRs on human cells. In this study, secondary configuration and binding motif of the aptamer were characterized, and moreover, various mutant aptamer forms were generated to figure out sequence and structure requirements of the aptamer. Then, we found that intrinsic structure formation and sequence composition of the selected RNA aptamer specific to the antibody are required for the aptamer activity to inhibit the myasthenic autoantibody-mediated destruction of cell surface AChRs. Noticeably, we identified 47-mer minimized aptamer version, which can efficiently protect cells from the effects of the autoantibodies and could be optimally applicable for MG therapy. PMID- 19642915 TI - Investigation of toxin genes by polymerase chain reaction in Staphylococcus aureus strains isolated from bovine mastitis in Turkey. AB - Staphylococcus aureus causes a number of diseases in humans and animals, and it is the most common etiological agent of contagious bovine mastitis. The agent produces several virulence factors such as coagulase (coa), clumping factor, protein A, exfoliative toxins, staphylococcal enterotoxins (SEs), and toxic shock syndrome toxin-1. The aim of the present study was to characterize coa-positive S. aureus strains (n = 92) isolated from bovine subclinical mastitis in Turkey by polymerase chain reaction (PCR) amplification of exfoliative toxin (eta and etb) and toxic shock syndrome toxin-1 (tsst) genes. In addition, a multiplex PCR was employed to investigate the presence of SE genes sea, seb, sec, sed, see, seg, seh, sej, and sei. By PCR amplification, while eta and etb were not detected, only three isolates (3.3%) were positive for tsst. Twenty-seven (29.3%) isolates harbored one or more SE genes, and sei was the most common pattern by multiplex PCR. None of the isolates harbored the genes encoding sea, see, and seh. The application of this multiplex PCR assay could enable more samples to be rapidly characterized for enterotoxin production of S. aureus isolates from milk for epidemiological studies. PMID- 19642916 TI - Salmonella enterica subclinical infection: bacteriological, serological, pulsed field gel electrophoresis, and antimicrobial resistance profiles--longitudinal study in a three-site farrow-to-finish farm. AB - The aim of this surveillance was to study both Salmonella spp. shedding patterns and the time course of serological response in farrow-to-finish reared pigs from a subclinically infected farm. Antimicrobial resistance profile, molecular subtyping, and the relationship among the isolates were determined by pulsed field gel electrophoresis (PFGE). A farrow-to-finish farm of 6000 sows, with a history of Salmonella Typhimurium septicemia, was selected. A longitudinal bacteriological and serological study was conducted in 25 sows before farrowing (M/S1) and in 50 offspring at 21 (M/S2), 35 (M/S3), 65 (M/S4), 86 (M/S5), 128 (M/S6), and 165 (M/S7) days of age. Serum antibodies were tested using Herdcheck((R)) Swine Salmonella antibody test kit (Idexx Laboratories, ME). Bacteria were isolated from pooled fecal samples. Suspected isolates were confirmed by conventional biochemical assays, and those identified as Salmonella spp. were serotyped. A variation between seropositive percentages and positive fecal samples was observed. Serologically positive pigs decreased from S1 to S4, and subsequently increased from S4 to S7. The percentages of fecal positive culture increased from M1 to M3, and then declined in M4, increased in M5, and were negative in M6 and M7. In the study three serovars, Salmonella 3,10:e,h:-, Salmonella Muenster, and Salmonella Bovismorbificans, were identified with low pathogenicity for swine. Three multidrug resistance strains (one belonged to Salmonella 3,10:e,h:- and two belonged to Salmonella Muenster) were found. PFGE results showed three different but closely related patterns among the 13 isolates of Salmonella Bovismorbificans, and two patterns for the three Salmonella Muenster and Salmonella 3,10:e,h:- isolates. This longitudinal study established critical points of Salmonella spp. infection in the farm and the production stages, where appropriate control measures must be taken. PFGE showed clonal relationships in each serovar. Antibiotic resistance profiles should be periodically included due to public health concerns. PMID- 19642917 TI - Commensal fecal Escherichia coli diversity in dairy cows at high and low risk for incurring subacute ruminal acidosis. AB - Subacute ruminal acidosis (SARA) is a common digestive disorder in dairy cows characterized by prolonged periods of undesirably low rumen pH (<5.8) and is caused by the accumulation of volatile fatty acids in rumen. This disorder damages the ruminal mucosa, causes diarrhea, reduces dry matter intake (DMI), and can result in anorexia and death. In this study, nonlactating dairy cows were fed diets predisposing them to a high risk (HR; n = 6) or a low risk (LR; n = 6) for experiencing SARA. The goal was to investigate differences in antimicrobial resistance selection, proliferation, and characterization of Escherichia coli strain types among the two treatment groups. Fecal samples were used to isolate total, tetracycline-resistant (Tet(r)), and ampicillin-resistant E. coli, and selected isolates were examined. We found reduced total (1.2-fold) and Tet(r) (1.4-fold) E. coli in HR cows. Low ampicillin-resistant E. coli shedding was detected from both HR (0.22 colony forming unit/g) and LR (0.46 colony forming unit/g) cows. Overall, 39 pulsed-field gel electrophoresis (PFGE) profiles and 13 antibiotic resistance profiles (phenotypes) were identified from the total isolates examined (n = 144). The LR cows exhibited diverse genotypes (22 PFGE profiles) clustering into seven restriction endonuclease digestion pattern clusters (REPCs) within total and Tet(r) E. coli. In comparison, isolates from HR animals showed increased genotypic relatedness (16 PFGE profiles and 13 REPC with comparable phenotypes). From both HR and LR cows, no significant differences in the detection of a particular phenotype were observed (p > 0.05), and tet(A) allele was frequently detected among isolates from HR (45.2%) and tet(B) from LR (36.6%) cows. Changes in fecal E. coli genotypes should be explored further for its usefulness as an indicator for SARA since dairy cows are a reservoir of diverse E. coli strain types. Our results elucidate phenotypic and genotypic differences in fecal E. coli shed between HR and LR cows. PMID- 19642918 TI - Prevalence and diversity of integrons and associated resistance genes in Escherichia coli isolates from poultry meat in Tunisia. AB - Fifty-five Escherichia coli isolates were acquired from chicken and turkey meat obtained from two slaughterhouses in Tunis. Eighty-nine percent, 80%, 78%, 67%, 45%, 27%, 7%, 4%, and 2% of these isolates showed resistance to tetracycline, trimethoprim/sulfamethoxazole, streptomycin, nalidixic acid, ampicillin, chloramphenicol, ciprofloxacin, colistine, and gentamicin, respectively. No resistance was detected to cefotaxime, ceftazidime, or amikacin. bla(TEM) gene was found in 22 of 25 ampicillin-resistant isolates, and 1 isolate harbored bla(OXA-1) gene. Tetracycline resistance was predominately mediated by the tetA gene. The sul1, sul2, and sul3 genes, alone or combined, were detected in 46 of 48 sulfonamide-resistant isolates, and sul1 and sul3 were included in class 1 integrons in some cases. Sixty percent of isolates harbored integrons (class 1, 30 isolates; class 2, 5 isolates). Class 2 integrons contained in all cases the dfrA1-sat1-aadA1-orfX gene cassette arrangement. Nine gene cassette arrangements have been detected among class 1 integrons, containing different alleles of dfrA (five alleles) and aadA (2 alleles) genes, which encode trimethoprim and streptomycin resistance, respectively. An uncommon gene cassette array (sat-psp aadA2-cmlA1-aadA1-qacH-IS440-sul3) has been identified in three class 1 integron positive isolates, and one additional isolate had this same structure with the insertion of IS26 inside the aadA1 gene (included in GenBank with accession no. FJ160769). The 55 studied isolates belong to the four phylogenic groups of E. coli, and phylogroups A and D were the most prevalent ones. At least one virulence-associated gene (fimA, papC, or aer) was detected in 44 of the 55 (80%) studied isolates. E. coli isolates of poultry origin could be a reservoir of antimicrobial-resistance genes and of integrons, and its evolution should be tracked in the future. PMID- 19642919 TI - sigma(B) and sigma(L) contribute to Listeria monocytogenes 10403S response to the antimicrobial peptides SdpC and nisin. AB - The ability of the foodborne pathogen Listeria monocytogenes to survive antimicrobial treatments is a public health concern; therefore, this study was designed to investigate genetic mechanisms contributing to antimicrobial response in L. monocytogenes. In previous studies, the putative bacteriocin immunity gene lmo2570 was predicted to be regulated by the stress responsive alternative sigma factor, sigma(B). As the alternative sigma factor sigma(L) controls expression of genes important for resistance to some antimicrobial peptides, we hypothesized roles for lmo2570, sigma(B), and sigma(L) in L. monocytogenes antimicrobial response. Results from phenotypic characterization of a L. monocytogenes lmo2570 null mutant suggested that this gene does not contribute to resistance to nisin or to SdpC, an antimicrobial peptide produced by some strains of Bacillus subtilis. While lmo2570 transcript levels were confirmed to be sigma(B) dependent, they were sigma(L) independent and were not affected by the presence of nisin under the conditions used in this study. In spot-on-lawn assays with the SdpC-producing B. subtilis EG351, the L. monocytogenes DeltasigB, DeltasigL, and DeltasigB/DeltasigL strains all showed increased sensitivity to SdpC, indicating that both sigma(B) and sigma(L) regulate genes contributing to SdpC resistance. Nisin survival assays showed that sigma(B) and sigma(L) both affect L. monocytogenes sensitivity to nisin in broth survival assays; that is, a sigB null mutant is more resistant than the parent strain to nisin, while a sigB null mutation in DeltasigL background leads to reduced nisin resistance. In summary, while the sigma(B)-dependent lmo2570 does not contribute to resistance of L. monocytogenes to nisin or SdpC, both sigma(B) and sigma(L) contribute to the L. monocytogenes antimicrobial response. PMID- 19642920 TI - Anisakis pegreffi etiological agent of gastric infections in two Italian women. AB - Two cases of gastric anisakiasis have been documented in two Italian women who had consumed raw anchovies (Engraulis encrasicolus). The first patient was a 49 year-old woman presenting with epigastric pain and bloody vomiting after ingestion of marinated (vinegar) raw anchovies. During the esophagogastroduodenoscopy (EGDS) a white color worm was detected and extracted from cardia by means of biopsy forceps. The second patient was a 59-year-old woman with irritable bowel syndrome and gastritis, who underwent to periodical EGDSs. In the course of the last EGDS, a white color round worm on antrum and a small polyp on the fundus of the stomach were observed. The two nematodes have been identified as L3 larvae of the genus Anisakis by a light microscope, and as Anisakis pegreffi by polymerase chain reaction-restriction fragment length polymorphism. The molecular identification of the etiological agent at the species level allows to identify what Anisakidae species play a zoonotic role and which are the fish host species. PMID- 19642922 TI - Molecular mechanisms in lymphatic function and disease. PMID- 19642921 TI - An evidence-based review of treatment-related determinants of patients' nonadherence to HIV medications. AB - Patients' adherence to antiretroviral medications is a primary determinant of both the effectiveness of treatment and the clinical course of HIV/AIDS. This empirical review is intended to compare the relative importance of patient and treatment characteristics on nonadherence behavior and the impact of nonadherence on treatment failure. Articles cited in PubMed and published between 2006 and June 2008 (n = 200) were reviewed to select those that address patient or treatment characteristics associated with nonadherence. Twenty-two articles were selected that provided odds ratio or hazard ratio statistics that quantified predictors of patients' level of nonadherence (e.g., <80%, 80%-95% and >95%). Results were summarized using random effects meta-analytic models. Predictors of nonadherence were divided into four predictive clusters (clinical predictors, comorbid predictors, treatment competence predictors, and dosing predictors). The summary odds ratios (ORs) of nonadherence for each cluster (in order of strength) were treatment competence 2.0 (95% confidence interval [CI]: 1.6-2.6), clinical predictors 1.6 (95% CI: 1.4-1.8), comorbid predictors 1.6 (95% CI: 1.4-1.8), and dosing predictors 1.5 (95% CI: 1.3-1.7). The effect of nonadherence on treatment failure supported the findings of two prior empirical reviews (OR 2.0, 95% CI: 1.6-2.5). Within dosing predictors, a pill burden of more versus less than 10 pills per day was associated with a much higher odds of nonadherence than twice versus once daily dosing or small differences in the number of types of antiretroviral treatments in a regimen. These results provide insight into the relative importance of various determinants of patient nonadherence that may inform the design of patient educational initiatives and initiatives to simplify treatment regimens. PMID- 19642924 TI - Progress in vascular anomalies and in lymphatic biology and disease. PMID- 19642927 TI - Lymphatic research: a global concern. PMID- 19642930 TI - T cell memory response to pneumococcal protein antigens in an area of high pneumococcal carriage and disease. AB - BACKGROUND: Streptococcus pneumoniae is a leading cause of vaccine-preventable disease worldwide. Pneumococcal protein antigens are currently under study as components of potential vaccines that offer protection against multiple serotypes. We have therefore characterized T cell pneumococcal immunity acquired through asymptomatic carriage. METHODS: Peripheral blood mononuclear cells from 40 healthy Gambian adults were stimulated with supernatants derived from S. pneumoniae strain (D39), 2 isogenic mutant strains lacking either pneumolysin or choline binding protein A, and recombinant pneumolysin. Immune responses were measured by cellular proliferation and by interleukin-10 (IL-10) and interferon gamma (IFN-gamma) enzyme-linked immunosorbent spot and bioplex cytokine assays. Nasopharyngeal swabs were cultured to determine carriage rates. RESULTS: S. pneumoniae nasopharyngeal carriage was detected in 60% of individuals. Both effector and resting (or central) CD4(+) T cell memory were frequently present to a range of pneumococcal antigens. However, the level of the effector memory response did not relate to current nasopharyngeal carriage. Pneumolysin was not immunodominant in these T cell responses but induced a distinct proinflammatory profile (high IFN-gamma, IL-12[p40], and L-17 levels and low IL-10 and IL-13 levels). CONCLUSIONS: In this population, T cell-mediated immunological memory potentially capable of pathogen clearance and immune surveillance is common but is not associated with the absolute interruption of pneumococcal carriage. How this naturally acquired immune memory influences pneumococcal vaccine efficacy remains to be determined. PMID- 19642931 TI - Prion protein expression and release by mast cells after activation. AB - In this study, we compared hematopoietic stem cells and mast cells, using microarray expression analysis, and identified the cellular prion protein (PrP(C)) as a potentially novel marker of mast cells. On further investigation, we found that PrP(C) is expressed on the surface of human and mouse mast cells, is rapidly released by mast cells upon activation, and is released in response to mast cell-dependent allergic inflammation in vivo. Because mast cells are long lived and traffic to the brain and central nervous system, our observations could have important implications for the transmission and pathology of prion diseases. PMID- 19642932 TI - Solving the puzzle of breast cancer-associated lymphedema: the role of imaging. PMID- 19642935 TI - Molecular mechanisms in lymphatic function and disease. PMID- 19642937 TI - Embracing vascular anomalies. PMID- 19642940 TI - Syndromic lymphedema: keys to the kingdom of lymphatic structure and function? PMID- 19642943 TI - Lymphatic investigation: from the endothelium to in vivo imaging. PMID- 19642947 TI - Wild European starlings (Sturnus vulgaris) adjust to captivity with sustained sympathetic nervous system drive and a reduced fight-or-flight response. AB - Although research on wild species typically involves capture, handling, and some degree of captivity, few studies examine how these actions affect and/or alter the animal's underlying stress physiology. Furthermore, we poorly understand the immediate changes that occur as wild animals adjust to captive conditions. Most studies to date have investigated relatively long-term changes in the glucocorticoid response to an acute stressor, but immediate changes in the fight or-flight response are relatively understudied in wild-caught species. In this study, we investigated changes to the cardiovascular stress response during the first 10 d of captivity of freshly captured wild European starlings (Sturnus vulgaris). We demonstrated that (1) baseline heart rate (HR) remains elevated for several days following transport into captivity, (2) the normal balance between sympathetic nervous system (SNS) and parasympathetic nervous system regulation of HR is disrupted, with the SNS exerting relatively greater control over baseline HR for the first days of captivity, and (3) the HR response to startle, a mild stressor, becomes significantly reduced compared to that of starlings maintained in captivity for several months and remains below the control response for at least 10 d. These data are the first to show that successive acute stressors and introduction to a captive setting significantly alter the physiology and responsiveness of the cardiovascular stress response system. PMID- 19642948 TI - What factors drive prolactin and corticosterone responses to stress in a long lived bird species (snow petrel Pagodroma nivea)? AB - Life-history theory predicts that individuals should adapt their parental investment to the costs and benefits of the current reproductive effort. This could be achieved by modulating the hormonal stress response, which may shift energy investment away from reproduction and redirect it toward survival. In birds, this stress response consists of a release of corticosterone that may be accompanied by a decrease in circulating prolactin, a hormone involved in the regulation of parental care. We lack data on the modulation of the prolactin stress response. In this study, we tested the hypothesis that individuals should modulate their prolactin stress response according to the fitness value of the current reproductive effort relative to the fitness value of future reproduction. Specifically, we examined the influence of breeding status (failed breeders vs. incubating birds) and body condition on prolactin and corticosterone stress responses in a long-lived species, the snow petrel Pagodroma nivea. When facing stressors, incubating birds had higher prolactin levels than failed breeders. However, we found no effect of body condition on the prolactin stress response. The corticosterone stress response was modulated according to body condition but was not affected by breeding status. We also performed an experiment using injections of adrenocorticotropic hormone (ACTH) and found that the modulation of the corticosterone stress response was probably associated with a reduction in ACTH release by the pituitary and a decrease in adrenal sensitivity to ACTH. In addition, we examined whether prolactin and corticosterone secretion were functionally linked. We found that these two hormonal stress responses were not correlated. Moreover, injection of ACTH did not affect prolactin levels, demonstrating that short-term variations in prolactin levels are not governed directly or indirectly by ACTH release. Thus, we suggest that the corticosterone and prolactin responses to short-term stressors are independent and may therefore mediate some specific components of parental investment in breeding birds. With mounting evidence, we suggest that examining both corticosterone and prolactin stress responses could be relevant to parental investment in vertebrates. PMID- 19642949 TI - Metabolic similarity despite striking behavioral divergence: aerobic performance in low- and high-density forms of the Mormon cricket. AB - Mormon crickets, large flightless katydids from western North America, occur in two forms that differ dramatically in population density and daily movement distances. The low-density form is small and cryptic and moves <1 m/d, while the high-density form is large and dark colored and travels up to 1-2 km/d in migratory bands. We determined daytime body temperatures and measured resting metabolic rate (RMR) and maximal aerobic metabolic rate (MMR) in forced exercise across a 10 degrees - 40 degrees C temperature range. Field body temperatures were 15 degrees - 20 degrees C in the morning and 25 degrees - 35 degrees C during most of the day, and they never exceeded 40.6 degrees C in either form. Mass-adjusted RMR and MMR were positively correlated across temperatures (significantly in some comparisons), indicating repeatability. Similarly, RMR was always positively and sometimes significantly correlated with MMR, suggesting a functional linkage between minimal and maximal aerobic performance. Factorial aerobic scopes (MMR/RMR) were highest at 10 degrees C and declined at higher temperatures, but absolute scope (MMR - RMR) was highest between 30 degrees and 40 degrees C. Given the ca. 1,000-fold contrast in daily movement distances, we expected higher MMR and aerobic scope in the migratory high-density form. However, there were no differences between forms in RMR, MMR, aerobic scope, or ventilation patterns. The forms were also similar in metabolic response to temperature (Q(10)) and in the mass scaling of metabolic rate. The absence of metabolic divergence among low- and high-density forms shows that large differences in locomotor behavior may not require concomitant changes in aerobic physiology. PMID- 19642950 TI - Retaspimycin hydrochloride (IPI-504): a novel heat shock protein inhibitor as an anticancer agent. AB - Heat shock proteins are vital to cell survival under conditions of stress. They bind client proteins to assist in protein stabilization, translocation of polypeptides across cell membranes and recovery of proteins from aggregates. Heat shock protein inhibitors are a diverse group of novel agents that have been demonstrated to have pro-apoptotic effects on malignant cells through inhibition of ATP binding on the ATP/ADP-binding pocket of the heat shock protein. Initial development of heat shock protein 90 inhibitors, geldanamycin and 17-AAG, were limited by hepatotoxicity and the need for solvent carrying agents. In contrast, retaspimycin, or IPI-504, a derivative of geldanamycin and 17-AAG, is highly soluble in water and generally well tolerated. In Phase I/II trials, retaspimycin has shown activity in NSCLC and gastrointestinal stromal tumor. The most promising activity was observed in gastrointestinal stromal tumors. Phase I/II trials are currently underway to evaluate the dosing schedules and activity of IPI-504 in breast cancer. Given the in vitro activity in diffuse large B-cell lymphoma, mantle cell lymphoma, melanoma, leukemia and pancreatic cancer, current and future trials are of clinical interest. This article reviews IPI-504 and its utility in a wide variety of cancer phenotypes. PMID- 19642952 TI - Rosiglitazone maleate + metformin hydrochloride extend: review of an emerging compound. AB - Clinical practice guidelines from around the world have continued to highlight the importance of glycemic control in the prevention of diabetes complications. Despite the many tools available to achieve these targets, it remains a constant challenge for healthcare providers and patients alike. Rosiglitazone maleate + metformin hydrochloride extend is a new compound that has the advantage of the clinical experience and knowledge about the current version and the added benefit of being a once daily, single pill option. The existing version of rosiglitazone + metformin has been shown to effectively lower hemoglobin A1C, improve insulin sensitivity and minimize weight gain. It is expected that the new compound will also have similar features, with the added benefit of improved patient adherence given its once daily formulation. PMID- 19642953 TI - The Oxford Health Alliance gives young people a voice on chronic disease. PMID- 19642951 TI - Novel targets in esophageal and gastric cancer: beyond antiangiogenesis. AB - Cancers of the stomach, gastroesophageal junction and esophagus are a major cause of cancer-related deaths worldwide. In Western countries, adenocarcinomas of the distal esophagus, gastroesophageal junction and proximal stomach have been increasing in frequency more rapidly than other malignancies. The majority of newly diagnosed patients present with advanced disease and the overall survival remains dismal at approximately 10% at 5 years. Better understanding of tumor biology has led to the development of promising novel therapeutic strategies. There is therefore increasing optimism that some of these approaches will improve the outcomes in these increasingly common cancers. Given the success of antiangiogenesis as a therapeutic strategy in various types of cancer, there are ongoing efforts to investigate the utility of other targeted therapies in the treatment of gastric and esophageal cancers. This review will focus on novel therapeutic targets other than angiogenesis and provide a rationale for the further clinical evaluation of these agents in patients with upper gastrointestinal tract cancers. PMID- 19642954 TI - Concepts and new frontiers for development - What role should health promoters play in lifestyle-based diabetes prevention programs in Australia? AB - ISSUE ADDRESSED: As the prevalence of many chronic diseases, particularly type 2 diabetes continues to increase, Australia's health system must be able to respond in an appropriate and cost-effective way. These efforts have been enhanced recently by a number of Council of Australian Governments' initiatives that have seen an increased focus on lifestyle-based secondary prevention of chronic disease, in particular for diabetes. This paper aims to stimulate interest and debate in relation to the role that health promotion practitioners can play in shaping lifestyle-based diabetes prevention programs in Australia. The paper briefly describes the chronic disease prevention policy context in Australia and defines primary, secondary, and tertiary prevention. It also examines effectiveness and cost-effectiveness of diabetes prevention interventions and describes how the field can use its expertise in the areas of equity, diffusion of innovation, partnership development, participant empowerment and advocacy in order to shape the design, implementation and evaluation of lifestyle-based diabetes prevention programs in Australia. CONCLUSIONS: State and national governments have substantially increased their investment in lifestyle-based diabetes prevention programs in Australia. If they are found to be effective and cost effective they are likely to attract additional investment and make up an increasing proportion of the prevention budget and accordingly, should not be ignored by the field of health promotion. PMID- 19642955 TI - Australia's national men's health policy: masculinity matters. AB - ISSUE ADDRESSED: The development of Australia's first national men's health policy provides an important opportunity for informed discussions of health and gender. It is therefore a concern that the stated policy appears to deliberately exclude hegemonic masculinity and other masculinities, despite evidence of their major influence on men's health-related values, beliefs, perspectives, attitudes, motivations and behaviour. METHODS: We provide an evidence-based critique of the proposed approach to a national men's health policy which raises important questions about whether the new policy can achieve its aims if it fails to acknowledge 'masculinity' as a key factor in Australian men's health. CONCLUSIONS: The national men's health policy should be a means to encourage gender analysis in health. This will require recognition of the influence of hegemonic masculinity, and other masculinities, on men's health. Recognising the influence of 'masculinity' on men's health is not about 'blaming' men for 'behaving badly', but is crucial to the development of a robust, meaningful and comprehensive national men's health policy. PMID- 19642956 TI - A focus on health promotion and prevention through the development of the national men's health policy. AB - ISSUES ADDRESSED: The Australian Government announced its intention to develop a national men's health policy in June 2008. A focus on prevention was identified as a foundation principle that would underpin the development of this policy. This brief report provides a descriptive account of the key discussion points relating to health promotion and prevention during a National Men's Health Roundtable held in Canberra in March 2009. METHODS: Invitations to the Roundtable were extended to peak professional organisations and national health bodies with an interest in men's health. Presentations from the National Preventative Health Taskforce, the National Primary Health Care External Reference Group and National Men's Health Ambassadors were used to provoke discussion relating to men's health. RESULTS: The most salient issues that were raised at the Roundtable and that were specific to health promotion and prevention contexts included the need to clearly define key terms that relate to health promotion and prevention (to support a joined-up and health-in-all-policies approach); acknowledge that gender intersects with other social determinants of health; recognise that men's engagement though health promotion and primary healthcare services can be improved by using settings-based approaches more widely; a greater focus on men's health literacy; a universal funding system to support men's health promotion; clarity about the roles and responsibilities that various health professionals play in improving the status of men's health; and the need to build health equity between and within specific populations of men through action on the social determinants of health. CONCLUSION: Recognising the place of health promotion and illness prevention in a national men's health policy will provide the necessary platform to build critical health literacy among men, promote equitable access to primary healthcare services and better support men's engagement within the health system. PMID- 19642957 TI - Prevalence and determinants of sunburn in Queensland. AB - ISSUE ADDRESSED: Australia records the highest incidence of skin cancer in the world. In response to this, public education campaigns have incorporated messages about reducing sun exposure and avoiding sunburn. This study sought to describe the prevalence of and factors associated with sunburn in Queensland residents. METHODS: The Queensland Cancer Risk Study was a population-based, cross-sectional survey of 9,298 respondents conducted via computer-assisted telephone interview during 2004. Sunburn prevalence and its association with socio-demographics and skin cancer risk variables were examined. RESULTS: More than two-thirds (70.4%) of respondents reported at least one episode of sunburn in the past 12 months, and one in 10 respondents reported at least one episode of severe sunburn in the past 12 months. Experiences of sunburn on two or more occasions were reported more frequently by males than females (57.6% versus 46.5%, p<0.001), and by nearly two-thirds (65.8%) of those aged 20-39 years compared to 48.0% of 40-59 year olds, and 26.7% of 60-75 year olds (p<0.001). Episodes of sunburn were strongly associated with being male (OR=2.20 95%CI 1.84-2.63) and being aged 20 to 39 years compared to 60 to 75 years (OR=9.79, 95%CI=7.66-12.50). CONCLUSIONS: Sunburn remains highly prevalent among Queensland residents particularly among men and in the younger age groups. PMID- 19642958 TI - Similarity of sun protection attitudes and behaviours within north Queensland peer groups. AB - ISSUE ADDRESSED: The study investigates whether the perceived sun protective practices of the peer group during a day-time recreational boat trip were associated with the sun protective attitudes and behaviours of individuals on the same boat. METHODS: Cross-sectional survey of recreational boat users conducted in Townsville, North Queensland, during the summer of 2003. One hundred and twenty-four of 134 boat users returning from a day trip agreed to participate, with 10 later excluded from analysis due to either being the sole person on the boat or because they were in the sun for less than an hour between 9 am and 3 pm (n=114, response rate=92%). RESULTS: The more positively respondents perceived the sun protective behaviours of other people on the boat, the more likely they were to report that they: did not enjoy exposing their unprotected skin to the sun (p=0.004); believed an occasional sunburn is not an acceptable risk (p=0.006); wore sunglasses on the trip (p=0.002); wore a wide-brimmed hat together with a long-sleeved shirt and sunscreen (p=0.006); and did not report reasons for neglecting to use sun protection (p=0.019). CONCLUSIONS: The perceived sun protection practices of the peer group majority were significantly associated with the sun protection practices of the observer. PMID- 19642959 TI - Tooty Fruity Vegie in Preschools: an obesity prevention intervention in preschools targeting children's movement skills and eating behaviours. AB - ISSUE ADDRESSED: This paper outlines the implementation strategies and evaluation methods of the Tooty Fruity Vegie (TFV) in Preschools program in NSW Australia which addressed diet, movement skills and overweight indicators. METHODS: The TFV program was a one-year intervention conducted during 2006 and 2007 in 18 preschools (matched with 13 control preschools). The study had a quasi experimental design with pre- and postintervention evaluation of nutrition and physical activity variables as well as anthropometric measures. Details of the program's methodological aspects such as the recruitment process, intervention strategies and evaluation instruments are described. PMID- 19642960 TI - Promoting a team ball game (Lifeball) to older people: who does this game attract and who continues? AB - ISSUE ADDRESSED: To describe the demographic and health-related characteristics (physical activity, self-reported health status, quality of life and falls history) of older people who enrol in a team-based game, Lifeball, and examine associations between continuation and participant characteristics. Reasons for stopping, participants' perceptions of the game and changes in health-related characteristics over 12 months were examined. METHODS: Telephone surveys were conducted with a cohort of Lifeball players at: baseline, soon after commencing playing and 12 months later. RESULTS: At baseline, participants were aged 40 to 96 years (mean 67). Most were female (84%), in good to excellent health (86%) and reported being sufficiently (>150 minutes per week) physically active (69%). Almost half (43%) were still playing 12 months later (continuers). Continuers were more likely to perceive Lifeball had helped them to: feel fitter and healthier (91%); improve their social life (73%); and be more active (53%). No significant changes in continuers' physical activity, self-reported health status and quality of life measures were reported. The main reason for stopping playing was illness/injury unrelated to Lifeball. CONCLUSIONS: Lifeball mainly appealed to healthy, active older people. PMID- 19642961 TI - Through the eyes of children: engaging primary school-aged children in creating supportive school environments for physical activity and nutrition. AB - ISSUES ADDRESSED: This paper presents a qualitative study of physical activity, eating and drinking experiences of children at Wellington Public School, NSW. The study was designed and implemented to inform school programs and policies with a goal of fostering a supportive and healthy environment at the school. METHODS: The study involved use of focus groups, drawings and photovoice with 37 students from Kindergarten to Year 6 to determine problems, underlying causes and possible student-led interventions to enhance the school physical activity and nutritional environment. RESULTS: Students considered play as related to fun games with friends. Sport was associated with structured, competitive types of physical activity. Infants class students preferred play, while primary students reported a preference for semi-structured and structured activities. Suggestions to improve school playing areas mirrored these preferences. The children suggested strategies for increasing fruit, vegetable and water consumption during the school day. CONCLUSION: The students were keen to explore ways to increase physical activity opportunities and develop a supportive nutritional environment at school. Simple, easy to implement suggestions were among the outcomes of the study, reinforcing the importance of including students' views in healthy school program and policy development. PMID- 19642962 TI - Qualitative data analysis: conceptual and practical considerations. AB - Qualitative inquiry requires that collected data is organised in a meaningful way, and this is referred to as data analysis. Through analytic processes, researchers turn what can be voluminous data into understandable and insightful analysis. This paper sets out the different approaches that qualitative researchers can use to make sense of their data including thematic analysis, narrative analysis, discourse analysis and semiotic analysis and discusses the ways that qualitative researchers can analyse their data. I first discuss salient issues in performing qualitative data analysis, and then proceed to provide some suggestions on different methods of data analysis in qualitative research. Finally, I provide some discussion on the use of computer-assisted data analysis. PMID- 19642963 TI - Revealing the wood and the trees: reporting qualitative research. AB - Qualitative research methodologies, which are oriented to better understanding of the context, meaning and experiences of people's lives, have much to contribute to health promotion. For researchers trained in quantitative methods, writing up qualitative research for a peer-reviewed journal can be a challenge, especially keeping within the prescribed word limits. How well you explain and disseminate your research will influence how others evaluate its quality; this has implications not only for what you write and the terminology you use but for how you structure your article. This paper provides a general guide to presenting qualitative research for publication in a way that has meaning for authors and readers, is acceptable to editors and reviewers, and meets criteria for high standards of qualitative research reporting across the board. We discuss the writing of all sections of an article, placing particular emphasis on how you might best present your findings, illustrating our points with examples drawn from previous issues of this Journal. Overall, we emphasise that reporting qualitative research involves sharing both the process and the findings, that is, revealing both the wood and the trees. PMID- 19642964 TI - "We would have got it by now if we were going to get it ..." An analysis of asthma awareness and beliefs in older adults. AB - ISSUE ADDRESSED: Asthma affects more than two million Australians, and of growing concern for the Australian health system is asthma in the over 65+ age group. Between 1997 and 2001, 61% of all deaths attributable to asthma occurred in people aged over 65 and mortality in this group remains higher than the rate for all other groups. METHODS: An investigation of older Australians' perceptions of asthma prevalence and impact was conducted in the Illawarra region of New South Wales. Eight focus groups with the target audience were conducted to explore their attitudes, knowledge and skills with regard to asthma symptoms, prevalence, diagnosis and treatment. Additionally, 12 in-depth interviews were conducted with a broad range of health professionals to ascertain their opinion of the target audience's asthma knowledge and understanding. RESULTS: Results indicate that these older Australians are unaware of the prevalence and severity of asthma in their age group, have limited understanding of symptoms and treatments, and associate the condition with children. Health professionals reported that older people minimise respiratory symptoms as a natural part of ageing. CONCLUSIONS: Qualitative analysis using the Health Belief Model, suggests that heightened knowledge and awareness is necessary to bring about voluntary behaviour change in order to reduce asthma mortality and morbidity in the 65+ age group. PMID- 19642965 TI - Building capacity for evidence-based practice in the health promotion workforce: evaluation of a train-the-trainer initiative in NSW. AB - ISSUE ADDRESSED: Evidence-based practice (EBP) is essential for effective health promotion practice, but not all health promotion staff have the required skills. In New South Wales this issue was addressed by implementing an EBP train-the trainer (TTT) program to build workforce capacity. METHODS: The success of the program was assessed through surveys completed by EBP-TTT participants and AHS participants of the disseminated EBP training activities. RESULTS: Ten formal EBP training activities were delivered in five of the eight NSW Areas, reaching a total of 133 practitioners. Participants reported significant improvements in their EBP knowledge and skills, and that these had been incorporated into their practice. A range of informal activities were also conducted. Barriers to delivery of training activities in the three remaining areas included resource restrictions, staff movement and organisational change, and insufficient confidence. CONCLUSIONS: The EBP-TTT program was an effective means of disseminating EBP knowledge and skills when the local 'training-team' felt sufficiently prepared and the Area Health Service was able to support local training activities. PMID- 19642966 TI - Making men's health policy relevant for the 21st century. PMID- 19642967 TI - In silico drug discovery approaches on grid computing infrastructures. AB - The first step in finding a "drug" is screening chemical compound databases against a protein target. In silico approaches like virtual screening by molecular docking are well established in modern drug discovery. As molecular databases of compounds and target structures are becoming larger and more and more computational screening approaches are available, there is an increased need in compute power and more complex workflows. In this regard, computational Grids are predestined and offer seamless compute and storage capacity. In recent projects related to pharmaceutical research, the high computational and data storage demands of large-scale in silico drug discovery approaches have been addressed by using Grid computing infrastructures, in both; pharmaceutical industry as well as academic research. Grid infrastructures are part of the so called eScience paradigm, where a digital infrastructure supports collaborative processes by providing relevant resources and tools for data- and compute intensive applications. Substantial computing resources, large data collections and services for data analysis are shared on the Grid infrastructure and can be mobilized on demand. This review gives an overview on the use of Grid computing for in silico drug discovery and tries to provide a vision of future development of more complex and integrated workflows on Grids, spanning from target identification and target validation via protein-structure and ligand dependent screenings to advanced mining of large scale in silico experiments. PMID- 19642968 TI - Stem/progenitor cells in liver injury repair and regeneration. AB - Morbidity and mortality from cirrhosis is increasing rapidly in the world. Currently, orthotopic liver transplantation is the only definitive therapeutic option. However, its clinical use is limited, because of poor long-term graft survival, donor organ shortage and high costs associated with the procedure. Stem cell replacement strategies are therefore being investigated as an attractive alternative approach to liver repair and regeneration. In this review we discuss recent preclinical and clinical investigations that explore the therapeutic potential of stem cells in repair of liver injuries. Several types of stem cells. including embryonic stem cells, haematopoietic stem cells and mesenchymal stem cells, can be induced to differentiate into hepatocyte-like cells by defined culture conditions in vitro. Stem cell transplantation has been shown to significantly improve liver function and increase animal survival in experimentally-induced liver-injury models. Moreover, several pilot clinical studies have reported encouraging therapeutic effects in patients treated with stem cells. Although there remain many unresolved issues, the available data support the notion that stem cell technology may lead to the development of effective clinical modalities for human liver diseases. PMID- 19642969 TI - Potential use of liposomal diallyl sulfide in the treatment of experimental murine candidiasis. AB - In the present study, we evaluated the potential of a liposomal formulation of the garlic oil component DAS (diallyl sulfide) in treating disseminated infection caused by the intracellular opportunistic pathogen Candida albicans in experimental mice. The PC (phosphatidylcholine) liposomal formulation of DAS was evaluated for size, zeta-potential, entrapment efficiency and release kinetics, toxicity etc. For therapeutic studies, mice were challenged with intravenous infection dosage of 10(7) blastospores of C. albicans followed by treatment with various doses of DAS formulations [12 and 6 mg/kg b.w. (body mass)] three times, on alternative days. The antifungal efficacy of liposomal DAS was assessed on the basis of survival of treated mice as well as the residual fungal load in vital organs like liver and spleen of mice. The results of the present study showed that treatment with DAS-bearing liposomes (12 mg/kg b.w.) resulted in the highest survival rate in animals. Liposomal DAS also significantly decreased residual fungal load in vital organs of experimental animals compared with the free form of DAS. The liposomal DAS was also found to be free of toxic manifestations as revealed by the erythrocyte lysis test and liver/kidney function tests. The results of the present study established that the antifungal activity of DAS, a poorly soluble compound, can be enhanced by the incorporation of it into liposomes. Further studies and optimizations are needed to build upon the promising findings of this study to enable the development of an effective plant derived antifungal formulation that can provide an alternative to currently available antifungal drugs. PMID- 19642970 TI - Transcranial Doppler ultrasonography predicts cardiovascular events after TIA. AB - BACKGROUND: Transient ischemic attack (TIA) patients are at high vascular risk. We assessed the value of extracranial (ECD) and transcranial (TCD) Doppler and duplex ultrasonography to predict clinical outcome after TIA. METHODS: 176 consecutive TIA patients admitted to the Stroke Unit were recruited in the study. All patients received diffusion-weighted imaging, standardized ECD and TCD. At a median follow-up of 27 months, new vascular events were recorded. RESULTS: 22 (13.8%) patients experienced an ischemic stroke or TIA, 5 (3.1%) a myocardial infarction or acute coronary syndrome, and 5 (3.1%) underwent arterial revascularization. ECD revealed extracranial > or = 50% stenosis or occlusions in 34 (19.3%) patients, TCD showed intracranial stenosis in 15 (9.2%) and collateral flow patterns due to extracranial stenosis in 5 (3.1%) cases. Multivariate analysis identified these abnormal ECD and TCD findings as predictors of new cerebral ischemic events (ECD: hazard ratio (HR) 4.30, 95% confidence interval (CI) 1.75 to 10.57, P = 0.01; TCD: HR 4.73, 95% CI 1.86 to 12.04, P = 0.01). Abnormal TCD findings were also predictive of cardiovascular ischemic events (HR 18.51, 95% CI 3.49 to 98.24, P = 0.001). CONCLUSION: TIA patients with abnormal TCD findings are at high risk to develop further cerebral and cardiovascular ischemic events. PMID- 19642971 TI - Demographic analysis reveals gradual senescence in the flatworm Macrostomum lignano. AB - Free-living flatworms ("Turbellaria") are appropriate model organisms to gain better insight into the role of stem cells in ageing and rejuvenation. Ageing research in flatworms is, however, still scarce. This is partly due to culture difficulties and the lack of a complete set of demographic data, including parameters such as median lifespan and age-specific mortality rate. In this paper, we report on the first flatworm survival analysis. We used the species Macrostomum lignano, which is an emerging model for studying the reciprocal influence between stem cells, ageing and rejuvenation. This species has a median lifespan of 205 +/- 13 days (average +/- standard deviation [SD]) and a 90th percentile lifespan of 373 +/- 32 days. The maximum lifespan, however, is more than 745 days, and the average survival curve is characterised by a long tail because a small number of individuals lives twice as long as 90% of the population. Similar to earlier observations in a wide range of animals, in M. lignano the age-specific mortality rate increases exponentially, but levels off at the oldest ages. To compare the senescence of M. lignano with that of other ageing models, we determined the mortality rate doubling time, which is 0.20 +/- 0.02 years. As a result, we can conclude that M. lignano shows gradual senescence at a rate similar to the vertebrate ageing models Rattus norvegicus and Mus musculus. We argue that M. lignano is a suitable model for ageing and rejuvenation research, and especially for the role of stem cells in these processes, due to its accessible stem cell system and regeneration capacity, and the possibility of combining stem cell studies with demographic analyses. PMID- 19642972 TI - Adolescents' experience of comments about their weight - prevalence, accuracy and effects on weight misperception. AB - BACKGROUND: Weight comments are commonly received by adolescents, but the accuracy of the comments and their effects on weight misperception are unclear. We assessed the prevalence and accuracy of weight comments received by Chinese adolescents from different sources and their relation to weight misperception. METHODS: In the Hong Kong Student Obesity Surveillance (HKSOS) project 2006-07, 22612 students aged 11-18 (41.5% boys) completed a questionnaire on obesity. Students responded if family members, peers and professionals had seriously commented over the past 30 days that they were "too fat" or "too thin" in two separate questions. The accuracy of the comments was judged against the actual weight status derived from self-reported height and weight. Self-perceived weight status was also reported and any discordance with the actual weight status denoted weight misperception. Logistic regression yielded adjusted odd ratios for weight misperception by the type of weight comments received. RESULTS: One in three students received weight comments, and the mother was the most common source of weight comments. Health professional was the most accurate source of weight comments, yet less than half the comments were correct. Adolescents receiving incorrect comments had increased risk of having weight misperception in all weight status groups. Receiving conflicting comments was positively associated with weight misperception among normal weight adolescents. In contrast, underweight and overweight/obese adolescents receiving correct weight comments were less likely to have weight misperception. CONCLUSION: Weight comments, mostly incorrect, were commonly received by Chinese adolescents in Hong Kong, and such incorrect comments were associated with weight misperception. PMID- 19642973 TI - The tumor suppressor gene TRC8/RNF139 is disrupted by a constitutional balanced translocation t(8;22)(q24.13;q11.21) in a young girl with dysgerminoma. AB - BACKGROUND: RNF139/TRC8 is a potential tumor suppressor gene with similarity to PTCH, a tumor suppressor implicated in basal cell carcinomas and glioblastomas. TRC8 has the potential to act in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control and has been identified in families with hereditary renal (RCC) and thyroid cancers. Haploinsufficiency of TRC8 may facilitate development of clear cell-RCC in association with VHL mutations, and may increase risk for other tumor types. We report a paternally inherited balanced translocation t(8;22) in a proposita with dysgerminoma. METHODS: The translocation was characterized by FISH and the breakpoints cloned, sequenced, and compared. DNA isolated from normal and tumor cells was checked for abnormalities by array-CGH. Expression of genes TRC8 and TSN was tested both on dysgerminoma and in the proposita and her father. RESULTS: The breakpoints of the translocation are located within the LCR-B low copy repeat on chromosome 22q11.21, containing the palindromic AT-rich repeat (PATRR) involved in recurrent and non-recurrent translocations, and in an AT-rich sequence inside intron 1 of the TRC8 tumor-suppressor gene at 8q24.13. TRC8 was strongly underexpressed in the dysgerminoma. Translin is underexpressed in the dysgerminoma compared to normal ovary.TRC8 is a target of Translin (TSN), a posttranscriptional regulator of genes transcribed by the transcription factor CREM-tau in postmeiotic male germ cells. CONCLUSION: A role for TRC8 in dysgerminoma may relate to its interaction with Translin. We propose a model in which one copy of TRC8 is disrupted by a palindrome-mediated translocation followed by complete loss of expression through suppression, possibly mediated by miRNA. PMID- 19642974 TI - Iliotibial band release as an adjunct to the surgical management of patellar stress fracture in the athlete: a case report and review of the literature. AB - Stress fracture of the patella is rare. In this report, a case of patellar stress fracture occurring in an amateur athlete is presented, and an operative adjunct to the surgical management of this condition is proposed.A review of the English literature identified 21 previous cases of stress fracture of the patella, the majority in young athletes. None of these reports discussed treatment addressing the pathological process contributing to patellar stress fracture.The subject of this case report is a young male netballer who presented with a transverse stress fracture in the inferior third of his patella, on a background of patellofemoral overload. The patient underwent open reduction and internal fixation of his patella, combined with release of the iliotibial band. He returned to training after 6 weeks.The previous literature suggests that operative fixation is indicated for the treatment of displaced patellar stress fractures. Iliotibial band release, as a surgical adjunct to this treatment, may address the pathology of these fractures, and facilitate a return to sport at the highest level. PMID- 19642976 TI - Chloroquine-resistant Plasmodium vivax malaria in Serbo town, Jimma zone, south west Ethiopia. AB - BACKGROUND: Ethiopia has the highest proportion of vivax malaria, approximately 40% of all malaria infections, in contrast to African countries. Chloroquine (CQ) is the drug of choice for the treatment of Plasmodium vivax infection in the country, although CQ resistant P. vivax (CRPv) has started to challenge the efficacy of the drug. The present study was conducted to assess the current status of CRPv at Serbo, Jimma zone, south-west Ethiopia. METHODS: A 28-day in vivo therapeutic efficacy test was conducted from October 2007 to January 2008. Recurrence of parasitaemia and the clinical condition of patients were assessed on each visit during the follow-up. The levels of haemoglobin (Hb) in the study participants were determined. The patients' blood drug levels were measured using HPLC. Data was analysed using SPSS for windows version 10.0. HPLC data was computed using Chem Station for LC 3D systems software. RESULTS: Of the total 84 patients included in the study, 78 completed their 28-day follow-up, six of whom being excluded for different reasons. In three children (aged 7, 12 and 13 years), parasitaemia reappeared within the 28-days follow-up in spite of adequate absorption of the drug and absence of malaria symptom. In addition, on the day of recurrence of parasitaemia the levels of chloroquine-desethylchloroquine (CQ-DCQ) were above the minimum effective concentration (>or=100 etag/ml) in all the three cases, showing that treatment failure could not be attributed to low level of drug in the patients blood. CONCLUSION: Reappearance of the parasite within the 28 days of follow-up is due to parasite resistance to CQ. The 3.6% (95% CI = 0.038 - 0.0758) prevalence of CRPv malaria in the study area signals the need for launching monitory activities for CQ resistant P. vivax. Moreover, as former report from the same country, Debrezeit, also showed the occurrence of CRPv, survey on CRPv malaria should be made in P. vivax endemic areas in order to estimate the level of burden across the country. PMID- 19642975 TI - 14-3-3sigma gene silencing during melanoma progression and its role in cell cycle control and cellular senescence. AB - BACKGROUND: The family of 14-3-3 proteins plays an important role in cancer biology by interfering with intracellular signalling pathways and cell cycle checkpoints. The 14-3-3sigma isoform acts as a tumor suppressor and is often inactivated during tumor development. RESULTS: Here, we demonstrate enhanced CpG methylation of the 14-3-3sigma gene in lymph node and cutaneous melanoma metastases compared with primary tumors, associated with dramatically reduced mRNA expression. In line with this, treatment of different metastatic melanoma cell lines with 5-aza-2'-deoxycytidine (5-Aza-CdR), a potent inhibitor of cytosine methylation, significantly induces 14-3-3sigma protein expression. Additional treatment with histone deacetylase inhibitor 4-phenylbutyric acid (Pba) further enhances 14-3-3sigma expression. Induction of 14-3-3sigma expression by 5-Aza-CdR/Pba treatment leads to almost complete inhibition of cell proliferation, with cells predominantly arrested in G2-M. The antiproliferative effect of 5-Aza-CdR/Pba was reversed in 14-3-3sigma knockdown cells. Similarly, melanoma cell lines stably overexpressing 14-3-3sigma show dramatically reduced cell proliferation rates. Moreover, synchronous 14-3-3sigma stably overexpressing cells do not progress through cell cycle, but display a permanent increase in the population of 4n DNA containing cells. Interestingly, overexpression of 14-3 3sigma induces senescence of melanoma cells and is involved in melanoma cell senescence under genotoxic stress. Finally, 14-3-3sigma knockdown supports migratory capacity of melanoma cells in vitro, while 14-3-3sigma overexpression has opposing effects. CONCLUSION: Taken together, the present report indicates that epigenetic silencing of 14-3-3sigma might contribute to tumor progression in malignant melanoma via loss of cell cycle control, impaired cellular senescence program and support of migratory capacity. PMID- 19642977 TI - Adherence to the Mediterranean diet moderates the association of aminotransferases with the prevalence of the metabolic syndrome; the ATTICA study. AB - BACKGROUND: Elevated liver enzymes are markers of liver steatosis and metabolic syndrome. We aimed to investigate the association of Mediterranean diet on the relationship between aminotransferases (i.e., AST, ALT, gGT) and the metabolic syndrome. METHODS: The ATTICA study has randomly enrolled 1514 adult males (18-87 yrs) and 1528 females (18-89 yrs) from the greater area of Athens. Adherence to Mediterranean diet was assessed through the MedDietScore. According to NCEP III criteria, participants were classified into those with or without the metabolic syndrome. RESULTS: Women with metabolic syndrome had higher gammaGT (p = 0.02) and lower AST/ALT levels (p = 0.018) than those without, and men with metabolic had a lower AST/ALT ratio (p = 0.01) compared to those without metabolic syndrome. The AST/ALT ratio was also positively correlated with MedDietScore (rho = 0.17, p < 0.001), while higher MedDietScore was associated with lower likelihood of having the metabolic syndrome in a multi-adjusted analysis (OR = 0.34, 95% CI: 0.16-0.73). Stratified analysis by the level of adherence to the Mediterranean diet, revealed that only in subjects away or with moderate adherence to the Mediterranean diet, an increase in the AST/ALT ratio was associated with lower likelihood of having the metabolic syndrome (OR = 0.33, p < 0.05 and OR = 0.34, p < 0.09, respectively); however, when we focused in those with greater adherence to the Mediterranean diet, AST/ALT ratio was not associated with the presence of the syndrome (OR = 0.51, p = 0.55). These findings remained similar in both genders, and even when the quantity of alcohol drinking was taken into account. CONCLUSION: Aminotransferases ratio constitutes a marker of the metabolic syndrome among healthy adults; however, this relationship is moderated when individuals are close to the Mediterranean dietary pattern. PMID- 19642978 TI - Discovery: an interactive resource for the rational selection and comparison of putative drug target proteins in malaria. AB - BACKGROUND: Up to half a billion human clinical cases of malaria are reported each year, resulting in about 2.7 million deaths, most of which occur in sub Saharan Africa. Due to the over-and misuse of anti-malarials, widespread resistance to all the known drugs is increasing at an alarming rate. Rational methods to select new drug target proteins and lead compounds are urgently needed. The Discovery system provides data mining functionality on extensive annotations of five malaria species together with the human and mosquito hosts, enabling the selection of new targets based on multiple protein and ligand properties. METHODS: A web-based system was developed where researchers are able to mine information on malaria proteins and predicted ligands, as well as perform comparisons to the human and mosquito host characteristics. Protein features used include: domains, motifs, EC numbers, GO terms, orthologs, protein-protein interactions, protein-ligand interactions and host-pathogen interactions among others. Searching by chemical structure is also available. RESULTS: An in silico system for the selection of putative drug targets and lead compounds is presented, together with an example study on the bifunctional DHFR-TS from Plasmodium falciparum. CONCLUSION: The Discovery system allows for the identification of putative drug targets and lead compounds in Plasmodium species based on the filtering of protein and chemical properties. PMID- 19642979 TI - Transcriptional profiling avian beta-defensins in chicken oviduct epithelial cells before and after infection with Salmonella enterica serovar Enteritidis. AB - BACKGROUND: Salmonella enterica serovar Enteritidis (SE) colonizes the ovary and oviduct of chickens without causing overt clinical signs which can lead to SE contamination of the content and membrane of shell-eggs as well as hatchery eggs. The organism utilizes the Salmonella Pathogenicity Island-2 encoded type III secretion system (T3SS-2) to promote persistence in the oviduct of laying hens. In this study, reverse transcriptase-polymerase chain reaction (RT-PCR) was carried out to determine the expression profiles of 14 known avian beta defensins (AvBDs) in primary chicken oviduct epithelial cells (COEC) before and after infections with a wild type SE strain and T3SS mutant SE strains carrying an inactivated sipA or pipB gene. RESULTS: Based on the expression levels in uninfected COEC, AvBDs can be loosely grouped into three categories with AvBD4-5 and AvBD9-12 being constitutively expressed at high levels; AvBD1, AvBD3, and AvBD13-14 at moderate levels; and AvBD2 and AvBD6-8 at minimal levels. Infection with the wild type SE strain temporarily repressed certain highly expressed AvBDs and induced the expression of minimally expressed AvBDs. The pipB mutant, compared to the wild type strain, had reduced suppressive effect on the expression of highly expressed AvBDs. Moreover, the pipB mutant elicited significantly higher levels of the minimally expressed AvBDs than the wild type SE or the sipA mutant did. CONCLUSION: Chicken oviduct epithelial cells express most of the known AvBD genes in response to SE infection. PipB, a T3SS-2 effector protein, plays a role in dampening the beta-defensin arm of innate immunity during SE invasion of chicken oviduct epithelium. PMID- 19642980 TI - The mRNA expression of SATB1 and SATB2 in human breast cancer. AB - BACKGROUND: SATB1 is a nuclear protein that has been recently reported to be a 'genome organizer' which delineates specific epigenetic modifications at target gene loci, directly up-regulating metastasis-associated genes while down regulating tumor-suppressor genes. In this study, the level of mRNA expression of SATB1 and SATB2 were assessed in normal and malignant breast tissue in a cohort of women with breast cancer and correlated to conventional clinico-pathological parameters. MATERIALS AND METHODS: Breast cancer tissues (n = 115) and normal background tissues (n = 31) were collected immediately after excision during surgery. Following RNA extraction, reverse transcription was carried out and transcript levels were determined using real-time quantitative PCR and normalized against beta-actin expression. Transcript levels within the breast cancer specimens were compared to the normal background tissues and analyzed against TNM stage, nodal involvement, tumour grade and clinical outcome over a 10 year follow up period. RESULTS: The levels of SATB1 were higher in malignant compared with normal breast tissue (p = 0.0167). SATB1 expression increased with increasing TNM stage (TNM1 vs. TNM2 p = 0.0264), increasing tumour grade (grade1 vs. grade 3 p = 0.017; grade 2 vs. grade 3 p = 0.0437; grade 1 vs. grade 2&3 p = 0.021) and Nottingham Prognostic Index (NPI) (NPI-1 vs. NPI-3 p = 0.0614; NPI-2 vs. NPI-3 p = 0.0495). Transcript levels were associated with oestrogen receptor (ER) positivity (ER(-) vs. ER(+) p = 0.046). SABT1 expression was also significantly correlated with downstream regulated genes IL-4 and MAF-1 (Pearson's correlation coefficient r = 0.21 and r = 0.162) and SATB2 (r = 0.506). After a median follow up of 10 years, there was a trend for higher SATB1 expression to be associated with shorter overall survival (OS). Higher levels of SATB2 were also found in malignant compared to background tissue (p = 0.049). SATB2 expression increased with increasing tumour grade (grade 1 vs. grade 3 p = 0.035). SATB2 was associated with ER positivity (ER(-) vs. ER(+) p = 0.0283) within ductal carcinomas. Higher transcript levels showed a significant association with poorer OS (p = 0.0433). CONCLUSION: SATB1 mRNA expression is significantly associated with poor prognostic parameters in breast cancer, including increasing tumour grade, TNM stage and NPI. SATB2 mRNA expression is significantly associated with increasing tumour grade and poorer OS. These results are consistent with the notion that SATB1 acts as a 'master genome organizer' in human breast carcinogenesis. PMID- 19642982 TI - The relation between athletic sports and prevalence of amenorrhea and oligomenorrhea in Iranian female athletes. AB - BACKGROUND: In 1992, the concept of female athlete triad was introduced to describe the interrelated problems of amenorrhea, eating disorders and osteoporosis seen in female athletes. To gain a clearer picture of amenorrhea/oligomenorrhea in Iran, one of the main components of the female athlete triad, we therefore established this study on the prevalence of amenorrhea/oligomenorrhea in elite Iranian female athletes, also evaluating the risk factors of these disorders in the same population. METHODS: This study performed as a cross-sectional study. All elite Iranian female athletes of 34 sports federation, including female athletes in national teams and medalists of Tehran were invited to participate. A total of 788 (95% response rate) returned the questionnaires and were examined. Younger athletes under the age of menarche were excluded. Each athlete completed a self-administered questionnaire, which covered the following questions about participant's demographic information, athletic history, history of injuries and menstrual pattern. In order to diagnose the causes of amenorrhea/Oligomenorrhea including polycystic ovary syndrome(PCOS), participants with amenorrhea/Oligomenorrhea underwent further investigation. They were evaluated by following Para clinic investigation, and an ultrasonographic study of ovary. RESULTS: The age ranged from 13-37 (mean = 21.1, SD = 4.5). Seventy one (9.0%) individuals had amenorrhea/oligomenorrhea, among those, 11 (15.5%) had PCOS.There was also a positive association between amenorrhea/oligomenorrhea and the following: age under 20 OR; 2.67, 95%CI(1.47 - 4.85), weight class sports OR; 2.09, 95%CI(1.15 - 3.82), endurance sports OR; 2.89, 95%CI(1.22 - 6.84), late onset of menarche OR; 3.32 95%CI(1.04-10.51), and use of oral contraceptive pills OR; 6.17, 95%CI(3.00 - 12.69). Intensity of training sport or BMI were not risk factors. CONCLUSION: These findings support the previous findings in the literature that the prevalence of amenorrhea/oligomenorrhea is high in athletes. Furthermore, we provided the first report on the prevalence of PCOS in female athletes with amenorrhea/oligomenorrhea. Athletes would be greatly benefited by greater general awareness about the complications of amenorrhea/oligomenorrhea.To increase awareness of exercise-associated menstrual cycle irregularities, it is necessary to design complete and comprehensive education programs for female athletes, their parents, their coaches, and the relevant authorities. PMID- 19642981 TI - Different modulation by dietary restriction of adipokine expression in white adipose tissue sites in the rat. AB - BACKGROUND: White adipose tissue (WAT) is a disperse organ acting as energy storage depot and endocrine/paracrine controlling factor in the management of energy availability and inflammation. WAT sites response under energy-related stress is not uniform. In the present study we have analyzed how different WAT sites respond to limited food restriction as a way to better understand the role of WAT in the pathogenesis of the metabolic syndrome. METHODS: Overweight male rats had their food intake reduced a 40% compared with free-feeding controls. On day ten, the rats were killed; circulating glucose, insulin, leptin, adiponectin, triacylglycerols and other parameters were measured. The main WAT sites were dissected: mesenteric, retroperitoneal, epididymal and subcutaneous inguinal, which were weighed and frozen. Later all subcutaneous WAT was also dissected and weighed. Samples were used for DNA (cellularity) analysis and mRNA extraction and semiquantitarive RT-PCR analysis of specific cytokine gene expressions. RESULTS: There was a good correlation between serum leptin and cumulative WAT leptin gene mRNA, but not for adiponectin. Food restriction reduced WAT size, but not its DNA content (except for epididymal WAT). Most cytokines were correlated to WAT site weight, but not to DNA. There was WAT site specialization in the differential expression (and probably secretion) of adipokines: subcutaneous WAT showed the highest concentration for leptin, CD68 and MCP-1, mesenteric WAT for TNFalpha (and both tissues for the interleukins 1beta and 6); resistin was highly expressed in subcutaneous and retroperitoneal WAT. CONCLUSION: Food restriction induced different patterns for mesenteric and the other WAT sites, which may be directly related to both the response to intestine-derived energy availability, and an inflammatory-related response. However, retroperitoneal WAT, and to a lower extent, subcutaneous and epididymal, reacted decreasing the expression of inflammatory markers and the signaling of decreased energy availability in their stores. The varying cytokine expression patterns highlight the fact that WAT sites show different inflammatory and signaling responses to energy availability; they are too much different to simply extend to the whole-body WAT the findings of one or even a couple of sites. PMID- 19642983 TI - Assessment of the effect of betaine on p16 and c-myc DNA methylation and mRNA expression in a chemical induced rat liver cancer model. AB - BACKGROUND: The development and progression of liver cancer may involve abnormal changes in DNA methylation, which lead to the activation of certain proto oncogenes, such as c-myc, as well as the inactivation of certain tumor suppressors, such as p16. Betaine, as an active methyl-donor, maintains normal DNA methylation patterns. However, there are few investigations on the protective effect of betaine in hepatocarcinogenesis. METHODS: Four groups of rats were given diethylinitrosamine (DEN) and fed with AIN-93G diets supplemented with 0, 10, 20 or 40 g betaine/kg (model, 1%, 2%, and 4% betaine, respectively), while the control group, received no DEN, fed with AIN-93G diet. Eight or 15 weeks later, the expression of p16 and c-myc mRNA was examined by Real-time PCR (Q PCR). The DNA methylation status within the p16 and c-myc promoter was analyzed using methylation-specific PCR. RESULTS: Compared with the model group, numbers and areas of glutathione S-transferase placental form (GST-p)-positive foci were decreased in the livers of the rats treated with betaine (P < 0.05). Although the frequency of p16 promoter methylation in livers of the four DEN-fed groups appeared to increase, there is no difference among these groups after 8 or 15 weeks (P > 0.05). Betaine supplementation attenuated the down-regulation of p16 and inhibited the up-regulation of c-myc induced by DEN in a dose-dependent manner (P < 0.01). Meanwhile, increases in levels of malondialdehyde (MDA) and glutathione S-transferase (GST) in model, 2% and 4% betaine groups were observed (P < 0.05). Finally, enhanced antioxidative capacity (T-AOC) was observed in both the 2% and 4% betaine groups. CONCLUSION: Our data suggest that betaine attenuates DEN-induced damage in rat liver and reverses DEN-induced changes in mRNA levels. PMID- 19642984 TI - Evaluation of an online Diabetes Needs Assessment Tool (DNAT) for health professionals: a randomised controlled trial. AB - BACKGROUND: Continuous medical education is traditionally reliant to a large extent on self-directed learning based on individuals' perceived learning priorities. Evidence suggests that this ability to self-assess is limited, and more so in the least competent. Therefore, it may be of benefit to utilise some form of external assessment for this purpose. Many diabetes educational programmes have been introduced, but few have been assessed for their benefit in a systematic manner. As diabetes is an increasingly prevalent disease, methods for the dissemination and understanding of clinical guidelines need to be explored for their effectiveness. This paper describes the study design of a randomised controlled trial to evaluate the effectiveness of using an interactive online Diabetes Needs Assessment Tool (DNAT), that builds a learning curriculum based on identified knowledge gaps, compared with conventional self-directed learning. The study assesses the effect of these interventions on health professionals' knowledge of diabetes management, evaluates the acceptability of this process of learning and self-reported changes in clinical practice as a result of this novel educational process. METHODS: Following a baseline assessment, participants will be randomised to undergo a 4-month learning period where they will either be given access to the diabetes learning modules alone (control group) or a Diabetes Needs Assessment Tool (DNAT) plus the diabetes learning modules (intervention group). On completion of the DNAT, a personalized learning report will be created for each participant identifying needs alongside individualised recommendations of the most appropriate learning modules to meet those requirements. All participants will complete a Diabetes Knowledge Test before and immediately after the allocated learning and the primary outcome will be the state of knowledge at 4 months. Learners will also be surveyed immediately after the learning period to assess the acceptability of the learning formats and the perceived usefulness and usability of the materials. After a further month, all learners will receive a series of questions to evaluate self-reported changes in clinical practice as a result of this educational experience and asked to include specific examples of any changes in their diabetes care practice. TRIAL REGISTRATION: Current Controlled Trials ISRCTN67215088. PMID- 19642987 TI - Primary ovarian leiomyoma associated with endometriotic cyst presenting with symptoms of acute appendicitis: a case report. AB - BACKGROUND: Ovarian leiomyoma is a rare benign tumor that accounts for 0.5 to 1% of all benign ovarian tumors. It probably arises from smooth muscle cells in the ovarian hilar blood vessels but there are other possible origins including cells in the ovarian ligament, smooth muscle cells or multipotential cells in the ovarian stroma, undifferentiated germ cells, or cortical smooth muscle metaplasia. Additionally, smooth muscle metaplasia of endometriotic stroma, smooth muscle present in mature cystic teratomas, and smooth muscle in the walls of mucinous cystic tumor may explain their occurrence in the ovary in some cases. CASE PRESENTATION: A 31-year-old woman was admitted to our surgical emergency service with a one-day history of appendicitis-like symptoms. Upon laparotomy, there was a solid, oval left-sided ovarian tumor located behind the uterus. The tumor was sent to the pathology department. A diagnosis of primary ovarian leiomyoma associated with an endometriotic cyst was established. CONCLUSION: The origin of ovarian leiomyoma is still unresolved. In our case, the tumor probably arose from smooth muscle cells derived from myofibroblasts that originate from metaplastic ovarian stromal cells present in the rim of the endometriotic cyst. Despite its rarity, ovarian leiomyoma should be considered in the differential diagnosis of ovarian spindle cell tumors. Appropriate diagnosis may require additional immunohistochemical analysis in some cases. PMID- 19642986 TI - Proteomic profiling of glucocorticoid-exposed myogenic cells: Time series assessment of protein translocation and transcription of inactive mRNAs. AB - BACKGROUND: Prednisone, one of the most highly prescribed drugs, has well characterized effects on gene transcription mediated by the glucocorticoid receptor. These effects are typically occurring on the scale of hours. Prednisone also has a number of non-transcriptional effects (occurring on minutes scale) on protein signaling, yet these are less well studied. We sought to expand the understanding of acute effects of prednisone action on cell signaling using a combination of SILAC strategy and subcellular fractionations from C2C12 myotubes. RESULTS: De novo translation of proteins was inhibited in both SILAC labeled and unlabeled C2C12 myotubes. Unlabeled cells were exposed to prednisone while SILAC labeled cells remained untreated. After 0, 5, 15, and 30 minutes of prednisone exposure, labeled and unlabeled cells were mixed at 1:1 ratios and fractionated into cytosolic and nuclear fractions. A total of 534 proteins in the cytosol and 626 proteins in the nucleus were identified and quantitated, using 3 or more peptides per protein with peptide based probability < or = 0.001. We identified significant increases (1.7- to 3.1- fold) in cytoplasmic abundance of 11 ribosomal proteins within 5 minutes of exposure, all of which returned to baseline by 30 min. We hypothesized that these drug-induced acute changes in the subcellular localization of the cell's protein translational machinery could lead to altered translation of quiescent RNAs. To test this, de novo protein synthesis was assayed after 15 minutes of drug exposure. Quantitative fluorography identified 16 2D gel spots showing rapid changes in translation; five of these were identified by MS/MS (pyruvate kinase, annexin A6 isoform A and isoform B, nasopharyngeal epithelium specific protein 1, and isoform 2 of Replication factor C subunit 1), and all showed the 5' terminal oligopyrimidine motifs associated with mRNA sequestration to and from inactive mRNA pools. CONCLUSION: We describe novel approaches of subcellular proteomic profiling and assessment of acute changes on a minute-based time scale. These data expand the current knowledge of acute, non-transcriptional activities of glucocorticoids, including changes in protein subcellular localization, altered translation of quiescent RNA pools, and PKC-mediated cytoskeleton remodeling. PMID- 19642985 TI - A novel hydroxyfuroic acid compound as an insulin receptor activator. Structure and activity relationship of a prenylindole moiety to insulin receptor activation. AB - BACKGROUND: Diabetes Mellitus is a chronic disease and many patients of which require frequent subcutaneous insulin injection to maintain proper blood glucose levels. Due to the inconvenience of insulin administration, an orally active insulin replacement has long been a prime target for many pharmaceutical companies. Demethylasterriquinone (DMAQ) B1, extracted from tropical fungus, Pseudomassaria sp., has been reported to be an orally effective agent at lowering circulating glucose levels in diabetic (db/db) mice; however, the cytotoxicity associated with the quinone moiety has not been addressed thus far. METHODS: A series of hydroxyfuroic acid compounds were synthesized and tested for their efficacies at activating human insulin receptor. Cytotoxicity to Chinese hamster ovary cells, selectivities over insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), and fibroblast growth factor (FGF) receptors were examined in this study. RESULT AND CONCLUSION: This study reports a new non-quinone DMAQ B1 derivative, a hydroxyfuroic acid compound (D-410639), which is 128 fold less cytotoxic as DMAQ B1 and as potent as compound 2, a DMAQ B1 synthetic derivative from Merck, at activating human insulin receptor. D-410639 has little activation potential on IGF-1 receptor but is a moderate inhibitor to EGF receptor. Structure and activity relationship of the prenylindole moiety to insulin receptor activation is discussed. PMID- 19642989 TI - Reliability and validity of pendulum test measures of spasticity obtained with the Polhemus tracking system from patients with chronic stroke. AB - BACKGROUND: Spasticity is a common impairment accompanying stroke. Spasticity of the quadriceps femoris muscle can be quantified using the pendulum test. The measurement properties of pendular kinematics captured using a magnetic tracking system has not been studied among patients who have experienced a stroke. Therefore, this study describes the test-retest reliability and known groups and convergent validity of the pendulum test measures obtained with the Polhemus tracking system. METHODS: Eight patients with chronic stroke underwent pendulum tests with their affected and unaffected lower limbs, with and without the addition of a 2.2 kg cuff weight at the ankle, using the Polhemus magnetic tracking system. Also measured bilaterally were knee resting angles, Ashworth scores (grades 0-4) of quadriceps femoris muscles, patellar tendon (knee jerk) reflexes (grades 0-4), and isometric knee extension force. RESULTS: Three measures obtained from pendular traces of the affected side were reliable (intraclass correlation coefficient > or = .844). Known groups validity was confirmed by demonstration of a significant difference in the measurements between sides. Convergent validity was supported by correlations > or = .57 between pendulum test measures and other measures reflective of spasticity. CONCLUSION: Pendulum test measures obtained with the Polhemus tracking system from the affected side of patients with stroke have good test-retest reliability and both known groups and convergent validity. PMID- 19642988 TI - Sequence diversity on four ORFs of citrus tristeza virus correlates with pathogenicity. AB - The molecular characterization of isolates of citrus tristeza virus (CTV) from eight locations in Mexico was undertaken by analyzing five regions located at the opposite ends of the virus genome. Two regions have been previously used to study CTV variability (coat protein and p23), while the other three correspond to other genomic segments (p349-B, p349-C and p13). Our comparative nucleotide analyses included CTV sequences from different geographical origins already deposited in the GenBank databases. The largest nucleotide differences were located in two fragments located at the 5' end of the genome (p349-B and p349-C). Phylogenetic analyses on those five regions showed that the degree of nucleotide divergence among strains tended to correlate with their pathogenicity. Two main groups were defined: mild, with almost no noticeable effects on the indicator plants and severe, with drastic symptoms. Mild isolates clustered together in every analyzed ORF sharing a genetic distance below 0.022, in contrast with the severe isolates, which showed a more disperse distribution and a genetic distance of 0.276. Analyses of the p349-B and p349-C regions evidenced two lineages within the severe group: severe common subgroup (most of severe isolates) and severe divergent subgroup (T36-like isolates). This study represents the first attempt to analyze the genetic variability of CTV in Mexico by constructing phylogenetic trees based on new genomic regions that use group-specific nucleotide and amino acid sequences. These results may be useful to implement specific assays for strain discrimination. Moreover, it would be an excellent reference for the CTV situation in Mexico to face the recent arrival of brown citrus aphid. PMID- 19642990 TI - Achieving progress in maternal and neonatal health through integrated and comprehensive healthcare services - experiences from a programme in northern Tanzania. AB - BACKGROUND: An integrated and comprehensive hospital/community based health programme is presented, aimed at reducing maternal and child mortality and morbidity. It is run as part of a general programme of health care at a rural hospital situated in northern Tanzania. The purpose was through using research and statistics from the programme area, to illustrate how a hospital-based programme with a vision of integrated healthcare may have contributed to the lower figures on mortality found in the area. Such an approach may be of interest to policy makers, in relation to the global strategy that is now developed in order to meet the MDGs 4 and 5. PROGRAMME SETTING: The hospital provides reproductive and child health services, PMTCT-plus, comprehensive emergency obstetric care, ambulance, radio and transport services, paediatric care, an HIV/AIDS programme, and a generalised healthcare service to a population of approximately 500 000. PROGRAMME DESCRIPTION AND OUTCOMES: We describe these services and their potential contribution to the reduction of the maternal and neonatal mortality ratios in the study area. Several studies from this area have showed a lower maternal mortality and neonatal mortality ratio compared to other studies from Tanzania and the national estimates. Many donor-funded programmes focusing on maternal and child health are vertical in their framework. However, the hospital, being the dominant supplier of health services in its catchment area, has maintained a horizontal approach through a comprehensive care programme. The total cost of the comprehensive hospital programme described is 3.2 million USD per year, corresponding to 6.4 USD per capita. CONCLUSION: Considering the relatively low cost of a comprehensive hospital programme including outreach services and the lower mortality ratios found in the catchment area of the hospital, we argue that donor funds should be used for supporting horizontal programmes aimed at comprehensive healthcare services. Through a strengthening of the collaboration between government and voluntary agency facilities, with clinical, preventive and managerial capabilities of the health facilities, the programmes will have a more sustainable impact and will achieve greater progress in the reduction of maternal and neonatal mortality, as opposed to vertical and segregated programmes that currently are commonly adopted for averting maternal and child deaths. Thus, we conclude that horizontal and comprehensive services of the type described in this article should be considered as a prerequisite for sustainable health care delivery at all policy and decision making levels of the local, national and international health care delivery pyramid. PMID- 19642991 TI - Age and gender differences in seven tests of functional mobility. AB - BACKGROUND: The objective of this study was to examine age and gender differences in seven tests of functional mobility. METHODS: The study included 50 young participants aged 20 to 39 years, and 684 older participants aged 75 to 98 years. Functional mobility measures included the coordinated stability test, the near tandem balance test, the six metre walk test, the sit to stand test with five repetitions, the alternate step test and the stair ascent and descent tests. RESULTS: Older participants performed significantly worse than the younger participants in all of the functional mobility tests (p < 0.001), with the older women performing worse than the older men in all of the tests (p < 0.05). Significant correlations were found within the older group among all the functional mobility tests scores (r = 0.24-0.87, p < 0.001), and between functional mobility performance and age (r = 0.14-0.35, p < 0.001). People with arthritis and stroke performed worse than people without these conditions in these tests. CONCLUSION: This study provides a normative database for performance of young and older community-dwelling people in a battery of validated and reliable functional mobility tests. The results confirm age-related differences in functional mobility between young and older adults. PMID- 19642993 TI - Pattern of mental ill health morbidities following hysterectomy for benign gynaecological disorders among Nigerian women. AB - OBJECTIVE: to compare the pre and post hysterectomy mental ill health (MIH) status and also, to determine whether there is any association with the surgical indication. METHODOLOGY: An observational study, conducted among women scheduled for hysterectomy at the University College Hospital, Ibadan from January till June 2005. The MIH morbidities were assessed using a validated general health questionnaire (GHQ) before and after the surgery by trained research assistant. The score of 4 and above was used as the cut off. Cross tabulations were performed to detect any association and also to compare pre and post hysterectomy mental health status. The level of statistical significance was set at P < 0.05. RESULTS: Of the 50 women recruited, 45 participated in the study. The age range of the participants was 35 to 63 years with a mean of 48.6 (SD = 0.6) years. Anxiety related disorder was present in 20 (44.4%), and depression in 3 (6.7%) before hysterectomy. Post surgery, there was significant increase in those with anxiety by 6.8% and a reduction in the proportion of depressive illness by 2.3%. Uterine fibroid as a preoperative diagnosis, had significant association among those with anxiety related disorder (68.4%) and depression (10.5%). CONCLUSION: This study suggests that mental ill health may complicates hysterectomy for benign uterine pathology among Nigerian women, and that anxiety related disorders increases after operation with the highest proportion in those with clinical diagnosis of Uterine Fibroid. We recommend adequate preoperative counseling using properly trained psychologists when affordable to minimize these morbidities. PMID- 19642992 TI - Reminiscence groups for people with dementia and their family carers: pragmatic eight-centre randomised trial of joint reminiscence and maintenance versus usual treatment: a protocol. AB - BACKGROUND: The growing number of people with dementia, and the increasing cost of care, provides a major incentive to develop and test methods of supporting them in the community for longer. Most attention has been given to pharmacological interventions, but there is increasing recognition that psychosocial interventions may be equally effective, even preferable where medication has negative side-effects. Reminiscence groups, run by professionals and volunteers, which use photographs, recordings and other objects to trigger personal memories are probably the most popular therapeutic approach to working with people with dementia, but there is little evidence for their effectiveness and cost-effectiveness. The recent inclusion of family carers in groups with people with dementia, notably in our own pilot studies, has generated informal evidence that this joint approach improves relationships between people with dementia and their carers, and benefits both. DESIGN AND METHODS: This multi centre, pragmatic randomised controlled trial (RCT) to assess the effectiveness and cost-effectiveness of joint reminiscence groups for people with dementia and their family care-givers has two parallel arms--an intervention group and a control group who receive care as usual. The intervention consists of joint reminiscence groups held weekly for twelve consecutive weeks, followed by monthly maintenance sessions for a further seven months.The primary outcome measures are the quality of life of people with dementia, as assessed by QoL-AD, and their care-givers' mental health as assessed by the GHQ-28. Secondary outcomes include: the autobiographical memories of people with dementia; the quality of the relationship between them and their care-givers; and the levels of depression and anxiety felt by them and their care-giver. Using a 5% significance level, comparison of 200 pairs attending joint reminiscence groups with 200 pairs receiving usual treatment will yield 80% power to detect a standardised difference of 0.38 in the QoL-AD rated by the person with dementia and 0.28 in the GHQ-28 or carer-rated QoL-AD. The trial will include a cost-effectiveness analysis from a public sector perspective. DISCUSSION: Our Cochrane review (2005) on reminiscence therapy for people with dementia did not identify any rigorous trials or economic analyses in this field. TRIAL REGISTRATION: ISRCTN42430123. PMID- 19642994 TI - Contamination of equipment in emergency settings: an exploratory study with a targeted automated intervention. AB - BACKGROUND: Despite standard manual decontamination, hospital equipment remains contaminated with microorganisms, contributing to nosocomial transmission and hospital acquired infections. This has the potential to negate the effects of healthcare workers' hand-washing protocols. In order to decrease the likelihood of equipment contamination, there has been a rise in the use of disposable pieces of equipment, especially non-critical disposables. However, these carry a significant cost, both a direct financial cost (running into billions of dollars), as well as a cost to the environment. This is important because we hope to contain the cost of healthcare, one way to do that, is to look to the hospitals themselves, for innovative solutions that maintain the standard of care. OBJECTIVE: To develop and evaluate the effectiveness of an simple decontamination device for use with portable hospital equipment, by comparing rates of residual contamination after use of the novel device versus those seen with standard manual decontamination methods. METHODS: The Self-cleaning Unit for the Decontamination of Small instruments (SUDS) is a user-friendly, automated instrument developed via multi-disciplinary collaboration for decontamination in the clinical area. Pre- and post- utilization of portable medical equipment in an emergency department (ED) setting were cultured. To evaluate durability of the decrease in antimicrobial contamination, objects were re-cultured 48 hours after SUDS cleaning and following re-introduction into the clinical setting. RESULTS: After manual decontamination, 25% (23/91) of the tested objects in the ED were found to be culture positive with clinically significant microorganisms(CSO). Fifteen percent (ED) of non-critical equipment tested had multiple organisms. Following the use of SUDS, the colonization rate decreased to 0%. Following SUDS treatment and re-introduction into the clinical settings, after 48 hours the contamination rates as reflected by the cultures remained 0%. CONCLUSION: Standard non-critical equipment is contaminated with clinically significant microorganisms. The SUDS device allows for effective and durable decontamination of hospital equipment of varying sizes in the clinical area without disrupting patient care. PMID- 19642996 TI - Superior dislocation of the patella: a case report. AB - BACKGROUND: Superior dislocation of the patella is an uncommon condition that mainly occurs in knees with a high patella and medial femorotibial degenerative arthritis. There are no previous reports of this condition occurring in association with tibial valgus osteotomy. CASE REPORT: We report the case of a patient in whom vertical dislocation recurred twice at 4 months after tibial valgus osteotomy. To avert additional recurrence or new dislocations, the patient was treated surgically to remove the existing osteophytes. CONCLUSIONS: An arthroscopic approach was decided because of the lower associated morbidity and good results with this technique compared to open surgery. PMID- 19642995 TI - Plasmodium falciparum enolase: stage-specific expression and sub-cellular localization. AB - BACKGROUND: In an earlier study, it was observed that the vaccination with Plasmodium falciparum enolase can confer partial protection against malaria in mice. Evidence has also build up to indicate that enolases may perform several non-glycolytic functions in pathogens. Investigating the stage-specific expression and sub-cellular localization of a protein may provide insights into its moonlighting functions. METHODS: Sub-cellular localization of P. falciparum enolase was examined using immunofluorescence assay, immuno-gold electron microscopy and western blotting. RESULTS: Enolase protein was detected at every stage in parasite life cycle examined. In asexual stages, enolase was predominantly (>or=85-90%) present in soluble fraction, while in sexual stages it was mostly associated with particulate fraction. Apart from cytosol, enolase was found to be associated with nucleus, food vacuole, cytoskeleton and plasma membrane. CONCLUSION: Diverse localization of enolase suggests that apart from catalyzing the conversion of 2-phosphoglycericacid into phosphoenolpyruvate in glycolysis, enolase may be involved in a host of other biological functions. For instance, enolase localized on the merozoite surface may be involved in red blood cell invasion; vacuolar enolase may be involved in food vacuole formation and/or development; nuclear enolase may play a role in transcription. PMID- 19642997 TI - A homoharringtonine-based induction regimen for the treatment of elderly patients with acute myeloid leukemia: a single center experience from China. AB - BACKGROUND AND PURPOSE: The response to remission induction in elderly patients with acute myeloid leukemia (AML) remains poor. The purpose of this paper is to evaluate the efficacy and toxicity of a plant alkaloid, homoharringtonine, in combination with cytarabine as an induction therapy for AML in elderly patients (> or =60 years). RESULTS: Twenty-three patients were treated with the HA regimen consisting of homoharringtonine (2 mg/m2/day for 7 days) and cytarabine (Ara-C, 100 mg/m2/day for 7 days). The overall response rate was 56.5% with complete remission (CR) rate of 39.1% and partial remission of 17.4%. There was no early death in this cohort of patients. The estimated median overall survival (OS) time of all patients was (12.0 +/- 3.0) months. The estimated OS time of the CR patients was 15 months. The estimated one-year OS rate of all patients treated with HA protocol was (49.3 +/- 13.5) %. The estimated one-year OS rate of the CR patients was (62.5 +/- 17.1) %. CONCLUSION: HA is a suitable induction regimen for elderly patients with AML, with relatively low toxicity and reasonable response rate. PMID- 19642998 TI - ABT-869, a promising multi-targeted tyrosine kinase inhibitor: from bench to bedside. AB - Tyrosine Kinase Inhibitors (TKI) have significantly changed the landscape of current cancer therapy. Understanding of mechanisms of aberrant TK signaling and strategies to inhibit TKs in cancer, further promote the development of novel agents.ABT-869, a novel ATP-competitive receptor tyrosine kinase inhibitor is a potent inhibitor of members of the vascular endothelial growth factor (VEGF) and platelet derived growth factor (PDGF) receptor families. ABT-869 showed potent antiproliferative and apoptotic properties in vitro and in animal cancer xenograft models using tumor cell lines that were "addicted" to signaling of kinases targeted by ABT-869. When given together with chemotherapy or mTOR inhibitors, ABT-869 showed at least additive therapeutic effects. The phase I trial for ABT-869 was recently completed and it demonstrated respectable efficacy in solid tumors including lung and hepatocellular carcinoma with manageable side effects. Tumor cavitation and reduction of contrast enhancement after ABT-869 treatment supported the antiangiogenic activity. The correlative laboratory studies conducted with the trial also highlight potential biomarkers for future patient selection and treatment outcome.Parallel to the clinical development, in vitro studies on ABT-869 resistance phenotype identified novel resistance mechanism that may be applicable to other TKIs. The future therapeutic roles of ABT-869 are currently been tested in phase II trials. PMID- 19642999 TI - All-trans retinoic acid promotes neural lineage entry by pluripotent embryonic stem cells via multiple pathways. AB - BACKGROUND: All-trans retinoic acid (RA) is one of the most important morphogens with pleiotropic actions. Its embryonic distribution correlates with neural differentiation in the developing central nervous system. To explore the precise effects of RA on neural differentiation of mouse embryonic stem cells (ESCs), we detected expression of RA nuclear receptors and RA-metabolizing enzymes in mouse ESCs and investigated the roles of RA in adherent monolayer culture. RESULTS: Upon addition of RA, cell differentiation was directed rapidly and exclusively into the neural lineage. Conversely, pharmacological interference with RA signaling suppressed this neural differentiation. Inhibition of fibroblast growth factor (FGF) signaling did not suppress significantly neural differentiation in RA-treated cultures. Pharmacological interference with extracellular signal regulated kinase (ERK) pathway or activation of Wnt pathway effectively blocked the RA-promoted neural specification. ERK phosphorylation was enhanced in RA treated cultures at the early stage of differentiation. CONCLUSION: RA can promote neural lineage entry by ESCs in adherent monolayer culture systems. This effect depends on RA signaling and its crosstalk with the ERK and Wnt pathways. PMID- 19643000 TI - Hydrogen bonding and packing density are factors most strongly connected to limiting sites of high flexibility in the 16S rRNA in the 30S ribosome. AB - BACKGROUND: Conformational flexibility in structured RNA frequently is critical to function. The 30S ribosomal subunit exists in different conformations in different functional states due to changes in the central part of the 16S rRNA. We are interested in evaluating the factors that might be responsible for restricting flexibility to specific parts of the 16S rRNA using biochemical data obtained from the 30S subunit in solution. This problem was approached taking advantage of the observation that there must be a high degree of conformational flexibility at sites where UV photocrosslinking occurs and a lack of flexibility inhibits photoreactivity at many other sites that are otherwise suitable for reaction. RESULTS: We used 30S x-ray structures to quantify the properties of the nucleotide pairs at UV- and UVA-s4U-induced photocrosslinking sites in 16S rRNA and compared these to the properties of many hundreds of additional sites that have suitable geometry but do not undergo photocrosslinking. Five factors that might affect RNA flexibility were investigated - RNA interactions with ribosomal proteins, interactions with Mg2+ ions, the presence of long-range A minor motif interactions, hydrogen bonding and the count of neighboring heavy atoms around the center of each nucleobase to estimate the neighbor packing density. The two factors that are very different in the unreactive inflexible pairs compared to the reactive ones are the average number of hydrogen bonds and the average value for the number of neighboring atoms. In both cases, these factors are greater for the unreactive nucleotide pairs at a statistically very significant level. CONCLUSION: The greater extent of hydrogen bonding and neighbor atom density in the unreactive nucleotide pairs is consistent with reduced flexibility at a majority of the unreactive sites. The reactive photocrosslinking sites are clustered in the 30S subunit and this indicates nonuniform patterns of hydrogen bonding and packing density in the 16S rRNA tertiary structure. Because this analysis addresses inter-nucleotide distances and geometry between nucleotides distant in the primary sequence, the results indicate regional and global flexibility of the rRNA. PMID- 19643001 TI - Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection. AB - BACKGROUND: Epidemiological studies showed that physical exercise, specifically moderate lifelong training, is protective against cardiovascular morbidity and mortality. Most experimental work has focused into the effects and molecular mechanisms underlying intense, rather than mild exercise, by exploring the acute effect of training. Our study aims at investigating the cardioprotective effect of mild chronic exercise training and the gene expression profile changes at 48 hrs after the exercise cessation. Rats were trained at mild intensity on a treadmill: 25 m/min, 10%incline, 1 h/day, 3 days/week, 10 weeks; about 60% of the maximum aerobic power. By Affymetrix technology, we investigated the gene expression profile induced by exercise training in the left ventricle (LV) of trained (n = 10) and control (n = 10) rats. Cardioprotection was investigated by ischemia/reperfusion experiments (n = 10 trained vs. n = 10 control rats). RESULTS: Mild exercise did not induce cardiac hypertrophy and was cardioprotective as demonstrated by the decreased infarct size (p = 0.02) after ischemia/reperfusion experiments in trained with respect to control rats. Ten genes and 2 gene sets (two pathways) resulted altered in LV of exercised animals with respect to controls. We validated by real-time PCR the increased expression of four genes: similar to C11orf17 protein (RGD1306959), caveolin 3, enolase 3, and hypoxia inducible factor 1 alpha. Moreover, caveolin 3 protein levels were higher in exercised than control rats by immunohistochemistry and Western Blot analysis. Interestingly, the predicted gene similar to C11orf17 protein (RGD1306959) was significantly increased by exercise. This gene has a high homology with the human C11orf17 (alias: protein kinase-A interacting protein 1 or breast cancer associated gene 3). This is the first evidence that this gene is involved in the response to the exercise training. CONCLUSION: Our data indicated that few, but significant, genes characterize the gene expression profile of the rat LV, when examined 48 hrs since the last training section and that mild exercise training determines cardioprotection without the induction of hypertrophy. PMID- 19643003 TI - Impact of falls on early mortality from severe traumatic brain injury. AB - BACKGROUND: The causes of severe traumatic brain injury (TBI) vary by age and other demographic characteristics. Mortality after trauma is higher for elderly than younger patients. This study is based on 2779 patients with severe TBI treated at 24 trauma centers enrolled in a New York State quality improvement program. The prospectively collected database includes information on age, sex, mechanism of injury, initial Glasgow Coma Scale score, blood pressure, pupillary assessment, and CT scan findings. This multi-center study was conducted to explore the impact of falls on early mortality from severe TBI among the elderly. RESULTS: After exclusion criteria were applied, a total of 2162 patients were eligible for analysis. Falls contributed to 21% of all severe TBI, 12% occurring from > 3 meters and 9% from < 3 meters. Two-week mortality ranged from 18% due to injuries other than falls to 31% due to falls from < 3 meters (p =< 0.0001). Mortality after a severe TBI is much greater among older people, reaching 58% for people 65 years and older sustaining a fall from < 3 meters. CONCLUSION: Among those 65 and older, falls contributed to 61% of all injuries and resulted in especially high mortality among individuals experiencing low falls. Preventive efforts directed toward older people to avoid falls from < 3 meters could have a significant impact on mortality. PMID- 19643002 TI - The efficacy of a comprehensive lifestyle modification programme based on yoga in the management of bronchial asthma: a randomized controlled trial. AB - BACKGROUND: There is a substantial body of evidence on the efficacy of yoga in the management of bronchial asthma. Many studies have reported, as the effects of yoga on bronchial asthma, significant improvements in pulmonary functions, quality of life and reduction in airway hyper-reactivity, frequency of attacks and medication use. In addition, a few studies have attempted to understand the effects of yoga on exercise-induced bronchoconstriction (EIB) or exercise tolerance capacity. However, none of these studies has investigated any immunological mechanisms by which yoga improves these variables in bronchial asthma. METHODS: The present randomized controlled trial (RCT) was conducted on 57 adult subjects with mild or moderate bronchial asthma who were allocated randomly to either the yoga (intervention) group (n = 29) or the wait-listed control group (n = 28). The control group received only conventional care and the yoga group received an intervention based on yoga, in addition to the conventional care. The intervention consisted of 2-wk supervised training in lifestyle modification and stress management based on yoga followed by closely monitored continuation of the practices at home for 6-wk. The outcome measures were assessed in both the groups at 0 wk (baseline), 2, 4 and 8 wk by using Generalized Linear Model (GLM) repeated measures followed by post-hoc analysis. RESULTS: In the yoga group, there was a steady and progressive improvement in pulmonary function, the change being statistically significant in case of the first second of forced expiratory volume (FEV1) at 8 wk, and peak expiratory flow rate (PEFR) at 2, 4 and 8 wk as compared to the corresponding baseline values. There was a significant reduction in EIB in the yoga group. However, there was no corresponding reduction in the urinary prostaglandin D2 metabolite (11beta prostaglandin F2alpha) levels in response to the exercise challenge. There was also no significant change in serum eosinophilic cationic protein levels during the 8-wk study period in either group. There was a significant improvement in Asthma Quality of Life (AQOL) scores in both groups over the 8-wk study period. But the improvement was achieved earlier and was more complete in the yoga group. The number-needed-to-treat worked out to be 1.82 for the total AQOL score. An improvement in total AQOL score was greater than the minimal important difference and the same outcome was achieved for the sub-domains of the AQOL. The frequency of rescue medication use showed a significant decrease over the study period in both the groups. However, the decrease was achieved relatively earlier and was more marked in the yoga group than in the control group. CONCLUSION: The present RCT has demonstrated that adding the mind-body approach of yoga to the predominantly physical approach of conventional care results in measurable improvement in subjective as well as objective outcomes in bronchial asthma. The trial supports the efficacy of yoga in the management of bronchial asthma. However, the preliminary efforts made towards working out the mechanism of action of the intervention have not thrown much light on how yoga works in bronchial asthma. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00815962. PMID- 19643004 TI - Dental pain, oral impacts and perceived need for dental treatment in Tanzanian school students: a cross-sectional study. AB - BACKGROUND: Dental caries, dental pain and reported oral problems influence people's oral quality of life and thus their perceived need for dental care. So far there is scant information as to the psychosocial impacts of dental diseases and the perceived treatment need in child populations of sub-Saharan Africa. OBJECTIVES: Focusing on primary school students in Kilwa, Tanzania, a district deprived of dental services and with low fluoride concentration in drinking water, this study aimed to assess the prevalence of dental pain and oral impacts on daily performances (OIDP), and to describe the distribution of OIDP by socio demographics, dental caries, dental pain and reported oral problems. The relationship of perceived need estimates with OIDP was also investigated. METHODS: A cross-sectional study was conducted in 2008. A total of 1745 students (mean age 13.8 yr, sd = 1.67) completed an extensive personal interview and under went clinical examination. The impacts on daily performances were assessed using a Kiswahili version of the Child-OIDP instrument and caries experience was recorded using WHO (1997) criteria. RESULTS: A total of 36.2% (41.3% urban and 31.4% rural, p < 0.001) reported at least one OIDP. The prevalence of dental caries was 17.4%, dental pain 36.4%, oral problems 54.1% and perceived need for dental treatment 46.8% in urban students. Corresponding estimates in rural students were 20.8%, 24.4%, 43.3% and 43.8%. Adjusted OR for reporting oral impacts if having dental pain ranged from 2.5 (95% CI 1.8-3.6) (problem smiling) to 4.7 (95% CI 3.4-6.5) (problem sleeping),--if having oral problems, from 1.9 (95% CI 1.3-2.6) (problem sleeping) to 3.8 (95% CI 2.7-5.2) (problem eating) and if having dental caries from 1.5 (95% CI 1.1-2.0) (problem eating) to 2.2 (95% CI 1.5-2.9) (problem sleeping). Students who perceived need for dental care were less likely to be females (OR = 0.8, 95% CI 0.6-0.9) and more likely to have impacts on eating (OR = 1.9, 95% CI 1.4-2.7) and tooth cleaning (OR = 1.6, 95% CI 1.6-2.5). CONCLUSION: Substantial proportions of students suffered from untreated dental caries, oral impacts on daily performances and perceived need for dental care. Dental pain and reported oral problems varied systematically with OIDP across the eight impacts considered. Eating and tooth cleaning problems discriminated between subjects who perceived need for dental treatment and those who did not. PMID- 19643005 TI - The health of Arab-Americans living in the United States: a systematic review of the literature. AB - BACKGROUND: Despite substantial attention paid to Arab-Americans (AAs) in the media and in public discourse, there is limited research about the health of AAs in the United States (US) in the public health literature. This review aims to synthesize the extant peer-reviewed literature concerned with the health of AAs living in the US. METHODS: We summarize existing research on the prevalence, relative burden compared to other ethnic and racial groups, and determinants of diseases within each morbidity cluster among AAs living in the US. RESULTS: Available evidence suggests that the health of AAs may differ from that of other ethnic and racial groups in the US, and that exposures specific to this ethnic group, such as immigration, acculturation, and discrimination may be important in the etiology of several diseases among AAs. CONCLUSION: Given the growth of this ethnic group and its marginalization in the current sociopolitical climate, more research about the health of AAs in the US seems warranted. We summarize relevant methodological concerns and suggest avenues for future research. PMID- 19643006 TI - UK pneumonectomy outcome study (UKPOS): a prospective observational study of pneumonectomy outcome. AB - BACKGROUND: In order to assess the short term risks of pneumonectomy for lung cancer in contemporary practice a one year prospective observational study of pneumonectomy outcome was made. Current UK practice for pneumonectomy was observed to note patient and treatment factors associated with major complications. METHODS: A multicentre, prospective, observational cohort study was performed. All 35 UK thoracic surgical centres were invited to submit data to the study. All adult patients undergoing pneumonectomy for lung cancer between 1 January and 31 December 2005 were included. Patients undergoing pleuropneumonectomy, extended pneumonectomy, completion pneumonectomy following previous lobectomy and pneumonectomy for benign disease, were excluded from the study.The main outcome measure was suffering a major complication. Major complications were defined as: death within 30 days of surgery; treated cardiac arrhythmia or hypotension; unplanned intensive care admission; further surgery or inotrope usage. RESULTS: 312 pneumonectomies from 28 participating centres were entered. The major complication incidence was: 30-day mortality 5.4%; treated cardiac arrhythmia 19.9%; unplanned intensive care unit admission 9.3%; further surgery 4.8%; inotrope usage 3.5%. Age, American Society of Anesthesiologists physical status >or= P3, pre-operative diffusing capacity for carbon monoxide (DLCO) and epidural analgesia were collectively the strongest risk factors for major complications. Major complications prolonged median hospital stay by 2 days. CONCLUSION: The 30 day mortality rate was less than 8%, in agreement with the British Thoracic Society guidelines. Pneumonectomy was associated with a high rate of major complications. Age, ASA physical status, DLCO and epidural analgesia appeared collectively most associated with major complications. PMID- 19643009 TI - Sending money home: a mixed-methods study of remittances by migrant nurses in Ireland. AB - BACKGROUND: This paper presents data on the remittances sent by migrant nurses to their families "back home". It gives voice to the experiences of migrant nurses and illustrates the financial obligations they maintain while working overseas. Although the international economic recession has decreased global remittance flows, they remain resilient. Drawing on the experiences of migrant nurses in Ireland, this paper indicates how and why migrants strive to maintain remittance flows, even in an economic downturn. METHODS: A mixed-methods approach was employed, and the paper draws on data from qualitative in-depth interviews undertaken with 21 migrant nurses in addition to a quantitative survey of 336 migrant nurses in Ireland. RESULTS: The survey of migrant nurses revealed that 87% (293) of the sample sent remittances on a regular basis. According to respondents, remittances made a huge difference in the lives of their family members back home. Remittances were used to ensure that family members could obtain access to health and education services. They were also used to provide an income source for family members who were unemployed or retired. As remittances played an essential role in supporting family members back home, respondent migrant nurses were reluctant to reduce the level of their remittances, despite the onset of a global recession. Respondents noted that an increased demand for remittances from their families coincided with a reduction in their own net salaries--as a result of increased taxes and reduced availability of overtime- and this was a cause for concern for Ireland's migrant nurses. CONCLUSION: This paper provides insights into the importance of remittances in funding social support for family members in home countries. It also illustrates the sacrifices made by migrant nurses to ensure continuation of the remittances, particularly in the context of an economic recession. PMID- 19643007 TI - Treatment of advanced, recurrent, resistant to previous treatments basal and squamous cell skin carcinomas with a synergistic formulation of interferons. Open, prospective study. AB - BACKGROUND: Aggressive non-melanoma skin cancer (deeply infiltrating, recurrent, and morphea form lesions) are therapeutically challenging because they require considerable tissue loss and may demand radical disfiguring surgery. Interferons (IFN) may provide a non-surgical approach to the management of these tumors. The aim of this work was to evaluate the effect of a formulation containing IFNs alpha and -gamma in synergistic proportions on patients with recurrent, advanced basal cell (BCC) or squamous cell skin carcinomas (SCSC). METHODS: Patients with extensive, recurrent, resistant to other procedures BCC or SCSC received the IFN formulation peri- and intralesionally, three times per week for 3 weeks. They had been previously treated with surgery and/or radiotherapy or chemotherapy. Thirteen weeks after the end of treatment, the original lesion sites were examined for histological evidence of remaining tumor. RESULTS: Sixteen elder (median 70 years-old) patients were included. They beared 12 BCC and 4 SCSC ranging from 1.5 to 12.5 cm in the longest dimension. At the end of treatment 47% CR (complete tumor elimination), 40% PR (>30% tumor reduction), and 13% stable disease were obtained. None of the patients relapsed during the treatment period. The median duration of the response was 38 months. Only one patient with complete response had relapsed until today. Principal adverse reactions were influenza like symptoms well known to occur with interferon therapy, which were well tolerated. CONCLUSION: The peri- and intralesional combination of IFNs-alpha and gamma was safe and showed effect for the treatment of advanced, recurrent and resistant to previous treatments of BCC and SCSC in elder patients. This is the first report of such treatment in patients with advance non-melanoma skin cancer. The encouraging result justifies further confirmatory trials. TRIAL REGISTRATION: Current Controlled Trials RPCEC00000052. PMID- 19643008 TI - Bioassay guided purification of the antimicrobial fraction of a Brazilian propolis from Bahia state. AB - BACKGROUND: Brazilian propolis type 6 (Atlantic forest, Bahia) is distinct from the other types of propolis especially due to absence of flavonoids and presence of other non-polar, long chain compounds, but presenting good in vitro and in vivo antimicrobial activity. Several authors have suggested that fatty acids found in this propolis might be responsible for its antimicrobial activity; however, so far no evidence concerning this finding has been reported in the literature. The goals of this study were to evaluate the antibacterial activity of the main pure fatty acids in the ethanolic extract and fractions and elucidate the chemical nature of the bioactive compounds isolated from Brazilian propolis type 6. METHODS: Brazilian propolis type 6 ethanolic extract (EEP), hexane fraction (H-Fr), major fatty acids, and isolated sub-fractions were analyzed using high performance liquid chromatography (HPLC), high resolution gas chromatography with flame ionization detection (HRGC-FID), and gas chromatography mass spectrometry (GC-MS). Three sub-fractions of H-Fr were obtained through preparative HPLC. Antimicrobial activity of EEP, H-Fr, sub-fractions, and fatty acids were tested against Staphyloccus aureus ATCC 25923 and Streptococcus mutans Ingbritt 1600 using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). RESULTS: EEP and H-Fr inhibited the growth of the microorganisms tested; nevertheless, no antimicrobial activity was found for the major fatty acids. The three sub-fractions (1, 2, and 3) were isolated from H Fr by preparative HPLC and only sub-fraction 1 showed antimicrobial activity. CONCLUSION: a) The major fatty acids tested were not responsible for the antimicrobial activity of propolis type 6; b) Sub-fraction 1, belonging to the benzophenone class, was responsible for the antimicrobial activity observed in the present study. The identification of the bioactive compound will improve the development of more efficient uses of this natural product. PMID- 19643010 TI - A comparison between the APACHE II and Charlson Index Score for predicting hospital mortality in critically ill patients. AB - BACKGROUND: Risk adjustment and mortality prediction in studies of critical care are usually performed using acuity of illness scores, such as Acute Physiology and Chronic Health Evaluation II (APACHE II), which emphasize physiological derangement. Common risk adjustment systems used in administrative datasets, like the Charlson index, are entirely based on the presence of co-morbid illnesses. The purpose of this study was to compare the discriminative ability of the Charlson index to the APACHE II in predicting hospital mortality in adult multisystem ICU patients. METHODS: This was a population-based cohort design. The study sample consisted of adult (>17 years of age) residents of the Calgary Health Region admitted to a multisystem ICU between April 2002 and March 2004. Clinical data were collected prospectively and linked to hospital outcome data. Multiple regression analyses were used to compare the performance of APACHE II and the Charlson index. RESULTS: The Charlson index was a poor predictor of mortality (C = 0.626). There was minimal difference between a baseline model containing age, sex and acute physiology score (C = 0.74) and models containing either chronic health points (C = 0.76) or Charlson index variations (C = 0.75, 0.76, 0.77). No important improvement in prediction occurred when the Charlson index was added to the full APACHE II model (C = 0.808 to C = 0.813). CONCLUSION: The Charlson index does not perform as well as the APACHE II in predicting hospital mortality in ICU patients. However, when acuity of illness scores are unavailable or are not recorded in a standard way, the Charlson index might be considered as an alternative method of risk adjustment and therefore facilitate comparisons between intensive care units. PMID- 19643012 TI - CCR5 signalling, but not DARC or D6 regulatory, chemokine receptors are targeted by herpesvirus U83A chemokine which delays receptor internalisation via diversion to a caveolin-linked pathway. AB - BACKGROUND: Herpesviruses have evolved chemokines and chemokine receptors, which modulate the recruitment of human leukocytes during the inflammatory response to infection. Early post-infection, human herpesvirus 6A (HHV-6A) infected cells express the chemokine receptor U51A and chemokine U83A which have complementary effects in subverting the CC-chemokine family thereby controlling anti-viral leukocyte recruitment. Here we show that, to potentiate this activity, the viral chemokine can also avoid clearance by scavenger chemokine receptors, DARC and D6, which normally regulate an inflammatory response. Conversely, U83A delays internalisation of its signalling target receptor CCR5 with diversion to caveolin rich membrane domains. This mechanism can redirect displaced human chemokines to DARC and D6 for clearance of the anti-viral inflammatory response, leaving the viral chemokine unchecked. METHODS: Cell models for competitive binding assays were established using radiolabeled human chemokines and cold U83A on CCR5, DARC or D6 expressing cells. Flow cytometry was used to assess specific chemotaxis of CCR5 bearing cells to U83A, and internalisation of CCR5 specific chemokine CCL4 after stimulation with U83A. Internalisation analyses were supported by confocal microscopy of internalisation and co-localisation of CCR5 with caveosome marker caveolin-1, after virus or human chemokine stimulation. RESULTS: U83A displaced efficiently human chemokines from CCR5, with a high affinity of 0.01nM, but not from DARC or D6. Signalling via CCR5 resulted in specific chemoattraction of primary human leukocytes bearing CCR5. However, U83A effective binding and signalling to CCR5 resulted in delayed internalisation and recycling up to 2 hours in the absence of continual re-stimulation. This resulted in diversion to a delayed caveolin-linked pathway rather than the rapid clathrin mediated endocytosis previously shown with human chemokines CCL3 or CCL4. CONCLUSION: U83A diverts human chemokines from signalling, but not regulatory or scavenger, receptors facilitating their clearance, while occupying signalling receptors at the cell surface. This can enhance virus specific inflammation, facilitating dissemination to replication sensitive leukocytes while evading clearance; this has implications for linked neuro-inflammatory pathologies. PMID- 19643011 TI - Inequality in treatment use among elderly patients with acute myocardial infarction: USA, Belgium and Quebec. AB - BACKGROUND: Previous research has provided evidence that socioeconomic status has an impact on invasive treatments use after acute myocardial infarction. In this paper, we compare the socioeconomic inequality in the use of high-technology diagnosis and treatment after acute myocardial infarction between the US, Quebec and Belgium paying special attention to financial incentives and regulations as explanatory factors. METHODS: We examined hospital-discharge abstracts for all patients older than 65 who were admitted to hospitals during the 1993-1998 period in the US, Quebec and Belgium with a primary diagnosis of acute myocardial infarction. Patients' income data were imputed from the median incomes of their residential area. For each country, we compared the risk-adjusted probability of undergoing each procedure between socioeconomic categories measured by the patient's area median income. RESULTS: Our findings indicate that income-related inequality exists in the use of high-technology treatment and diagnosis techniques that is not justified by differences in patients' health characteristics. Those inequalities are largely explained, in the US and Quebec, by inequalities in distances to hospitals with on-site cardiac facilities. However, in both Belgium and the US, inequalities persist among patients admitted to hospitals with on-site cardiac facilities, rejecting the hospital location effect as the single explanation for inequalities. Meanwhile, inequality levels diverge across countries (higher in the US and in Belgium, extremely low in Quebec). CONCLUSION: The findings support the hypothesis that income-related inequality in treatment for AMI exists and is likely to be affected by a country's system of health care. PMID- 19643014 TI - Needle and syringe sharing among Iranian drug injectors. AB - OBJECTIVE: The role of needle and syringe sharing behavior of injection drug users (IDUs) in spreading of blood-borne infections - specially HIV/AIDS - is well known. However, very little is known in this regard from Iran. The aim of our study was to determine the prevalence and associates of needle and syringe sharing among Iranian IDUs. METHODS: In a secondary analysis of a sample of drug dependents who were sampled from medical centers, prisons and streets of the capitals of 29 provinces in the Iran in 2007, 2091 male IDUs entered. Socio demographic data, drug use data and high risk behaviors entered to a logistic regression to determine independent predictors of lifetime needle and syringe sharing. RESULTS: 749(35.8%) reported lifetime experience of needle and syringe sharing. The likelihood of lifetime needle and syringe sharing was increased by female gender, being jobless, having illegal income, drug use by family members, pleasure/enjoyment as causes of first injection, first injection in roofless and roofed public places, usual injection at groin, usual injection at scrotum, lifetime experience of nonfatal overdose, and history of arrest in past year and was decreased by being alone at most injections. CONCLUSION: However this data has been extracted from cross-sectional design and we can not conclude causation, some of the introduced variables with association with needle and syringe sharing may be used in HIV prevention programs which target reducing syringe sharing among IDUs. PMID- 19643013 TI - Electric toothbrush application is a reliable and valid test for differentiating temporomandibular disorders pain patients from controls. AB - BACKGROUND: Current methods for identifying patients with pain hypersensitivity are sufficiently complex to limit their widespread application in clinical settings. We assessed the reliability and validity of a simple multi-modal vibrotactile stimulus, applied using an electric toothbrush, to evaluate its potential as a screening tool for central sensitization. METHODS: Fourteen female temporomandibular disorders (TMD) subjects with myofascial pain (RDC/TMD Ia or Ib) and arthralgia (RDC/TMD IIIa) were compared to 13 pain-free controls of matched age and gender. Vibrotactile stimulus was performed with an electric toothbrush, applied with 1 pound pressure for 30 seconds in four locations: over the lateral pole of the temporomandibular joint, masseter, temporalis, and mid ventral surface of forearm. Pain intensity (0-10) was recorded following the stimulus at 0, 15, 30, and 60 seconds. Test-retest reliability was assessed with measurements from 8 participants, taken 2-12 hours apart. Case versus control differentiation involved comparison of area under the curve (AUC). A receiver operating characteristic (ROC) curve was used to determine cutoff AUC scores for maximum sensitivity and specificity for this multi-modal vibrotactile stimulus. RESULTS: Test-retest reliability resulted in an ICC of 0.87 for all 4 pooled sites. ROC-determined AUC cutoff scores resulted in a sensitivity of 57% and specificity of 92% for all 4 pooled sites. CONCLUSION: The electric toothbrush stimulus had excellent test-retest reliability. Validity of the scores was demonstrated with modest sensitivity and good specificity for differentiating TMD pain patients from controls, which are acceptable properties for a screening test. PMID- 19643016 TI - Psychotrauma and effective treatment of post-traumatic stress disorder in soldiers and peacekeepers. AB - Psychotrauma occurs as a result to a traumatic event, which may involve witnessing someone's actual death or personally experiencing serious physical injury, assault, rape and sexual abuse, being held as a hostage, or a threat to physical or psychological integrity. Post-traumatic stress disorder (PTSD) is an anxiety disorder and was defined in the past as railway spine, traumatic war neurosis, stress syndrome, shell shock, battle fatigue, combat fatigue, or post traumatic stress syndrome (PTSS). If untreated, post-traumatic stress disorder can impair relationships of those affected and strain their families and society. Deployed soldiers are especially at a high risk to be affected by PTSD but often receive inadequate treatment. Reviews to date have focused only on a single type of treatment or groups of soldiers from only one country. The aim of the current review was to evaluate characteristics of therapeutic methods used internationally to treat male soldiers' PTSD after peacekeeping operations in South Eastern Europe and the Gulf wars.This systematic literature review returned results pertaining to the symptoms, diagnosis, timing and effectiveness of treatment. Sample groups and controls were relatively small and, therefore, the results lack generalizability. Further research is needed to understand the influence and unique psychological requirements of each specific military operation on the internationally deployed soldiers. PMID- 19643017 TI - Using Medical Emergency Teams to detect preventable adverse events. AB - INTRODUCTION: Medical Emergency Teams (METs), also known as Rapid Response Teams, are recommended as a patient safety measure. A potential benefit of implementing an MET is the capacity to systematically assess preventable adverse events, which are defined as poor outcomes caused by errors or system design flaws. We describe how we used MET calls to systematically identify preventable adverse events in an academic tertiary care hospital, and describe our surveillance results. METHODS: For four weeks we collected standard information on consecutive MET calls. Within a week of the MET call, a multi-disciplinary team reviewed the information and rated the cause of the outcome using a previously developed rating scale. We classified the type and severity of the preventable adverse event. RESULTS: We captured information on all 65 MET calls occurring during the study period. Of these, 16 (24%, 95% confidence interval [CI] 16%-36%) were felt to be preventable adverse events. The most common cause of the preventable adverse events was error in providing appropriate therapy despite an accurate diagnosis. One service accounted for a disproportionate number of preventable adverse events (n = 5, [31%, 95% CI 14%-56%]). CONCLUSIONS: Our method of reviewing MET calls was easy to implement and yielded important results. Hospitals maintaining an MET can use our method as a preventable adverse event detection system at little additional cost. PMID- 19643015 TI - Differential response of C57BL/6J mouse and DBA/2J mouse to optic nerve crush. AB - BACKGROUND: Retinal ganglion cell (RGC) death is the final consequence of many blinding diseases, where there is considerable variation in the time course and severity of RGC loss. Indeed, this process appears to be influenced by a wide variety of genetic and environmental factors. In this study we explored the genetic basis for differences in ganglion cell death in two inbred strains of mice. RESULTS: We found that RGCs are more susceptible to death following optic nerve crush in C57BL/6J mice (54% survival) than in DBA/2J mice (62% survival). Using the Illumina Mouse-6 microarray, we identified 1,580 genes with significant change in expression following optic nerve crush in these two strains of mice. Our analysis of the changes occurring after optic nerve crush demonstrated that the greatest amount of change (44% of the variance) was due to the injury itself. This included changes associated with ganglion cell death, reactive gliosis, and abortive regeneration. The second pattern of gene changes (23% of the variance) was primarily related to differences in gene expressions observed between the C57BL/6J and DBA/2J mouse strains. The remaining changes in gene expression represent interactions between the effects of optic nerve crush and the genetic background of the mouse. We extracted one genetic network from this dataset that appears to be related to tissue remodeling. One of the most intriguing sets of changes included members of the crystallin family of genes, which may represent a signature of pathways modulating the susceptibility of cells to death. CONCLUSION: Differential responses to optic nerve crush between two widely used strains of mice were used to define molecular networks associated with ganglion cell death and reactive gliosis. These results form the basis for our continuing interest in the modifiers of retinal injury. PMID- 19643018 TI - Postal survey of physicians and laboratories: practices and perceptions of molecular oncology testing. AB - BACKGROUND: Molecular oncology testing (MOT) to detect genomic alterations underlying cancer holds promise for improved cancer care. Yet knowledge limitations regarding the delivery of testing services may constrain the translation of scientific advancements into effective health care. METHODS: We conducted a cross-sectional, self-administered, postal survey of active cancer physicians in Ontario, Canada (N = 611) likely to order MOT, and cancer laboratories (N = 99) likely to refer (i.e., referring laboratories) or conduct (i.e., testing laboratories) MOT in 2006, to assess respondents' perceptions of the importance and accessibility of MOT and their preparedness to provide it. RESULTS: 54% of physicians, 63% of testing laboratories and 60% of referring laboratories responded. Most perceived MOT to be important for treatment, diagnosis or prognosis now, and in 5 years (61% - 100%). Yet only 45% of physicians, 59% of testing labs and 53% of referring labs agreed that patients in their region were receiving MOT that is indicated as a standard of care. Physicians and laboratories perceived various barriers to providing MOT, including, among 70% of physicians, a lack of clear guidelines regarding clinical indications, and among laboratories, a lack of funding (73% - 100%). Testing laboratories were confident of their ability to determine whether and which MOT was indicated (77% and 82% respectively), and perceived that key elements of formal and continuing education were helpful (75% - 100%). By contrast, minorities of physicians were confident of their ability to assess whether and which MOT was indicated (46% and 34% respectively), and while majorities considered various continuing educational resources helpful (68% - 75%), only minorities considered key elements of formal education helpful in preparing for MOT (17% - 43%). CONCLUSION: Physicians and laboratory professionals were enthusiastic about the value of MOT for cancer care but most did not believe patients were gaining adequate access to clinically necessary testing. Further, our results suggest that many were ill equipped as individual stakeholders, or as a coordinated system of referral and interpretation, to provide MOT. These challenges should inspire educational, training and other interventions to ensure that developments in molecular oncology can result in optimal cancer care. PMID- 19643021 TI - Rethinking global health research: towards integrative expertise. AB - The Bamako Call for Action on Research for Health stresses the importance of inter-disciplinary, inter-ministerial and inter-sectoral working. This challenges much of our current research and postgraduate research training in health, which mostly seeks to produce narrowly focused content specialists. We now need to compliment this type of research and research training, by offering alternative pathways that seek to create expertise, not only in specific narrow content areas, but also in the process and context of research, as well as in the interaction of these different facets of knowledge. Such an approach, developing 'integrative expertise', could greatly facilitate better research utilisation, helping policy makers and practitioners work through more evidence-based practice and across traditional research boundaries. PMID- 19643020 TI - Phase II assessment of talabostat and cisplatin in second-line stage IV melanoma. AB - BACKGROUND: Metastatic melanoma is an incurable disease with an average survival of less than one year. Talabostat is a novel dipeptidyl peptidase inhibitor with immunostimulatory properties. METHODS: This phase II, open label, single arm study was conducted to evaluate the safety and efficacy of 75-100 mg/m2 cisplatin combined with 300-400 mcg talabostat bid for 6, 21-day cycles. The primary endpoint was overall response. The rate of complete responses, duration of overall objective response, progression-free survival (PFS), and overall survival were the secondary endpoints. RESULTS: Six objective partial responses were recorded in the 74 patients (8.1%) in the intention-to-treat population. Five of these responses involved the 40 evaluable patients (12.5%). Thirty-one percent of patients reported SAEs to the combination of talabostat and cisplatin. CONCLUSION: Acceptable tolerability was observed in the intention-to-treat population and antitumor activity was observed in 12.5% of evaluable patients, which is not greater than historical expectation with cisplatin alone. PMID- 19643022 TI - Medial patellofemoral ligament injury patterns and associated pathology in lateral patella dislocation: an MRI study. AB - BACKGROUND: Lateral Patella dislocations are common injuries seen in the active and young adult populations. Our study focus was to evaluate medial patellofemoral ligament (MPFL) injury patterns and associated knee pathology using Magnetic Resonance Imaging studies. METHODS: MRI studies taken at one imaging site between January, 2007 to January, 2008 with the final diagnosis of patella dislocation were screened for this study. Of the 324 cases that were found, 195 patients with lateral patellar dislocation traumatic enough to cause bone bruises on the lateral femoral trochlea and the medial facet of the patella were selected for this study. The MRI images were reviewed by three independent observers for location and type of MPFL injury, osteochondral defects, loose bodies, MCL and meniscus tears. The data was analyzed as a single cohort and by gender. RESULTS: This study consisted of 127 males and 68 females; mean age of 23 yrs. Tear of the MPFL at the patellar attachment occurred in 93/195 knees (47%), at the femoral attachment in 50/195 knees (26%), and at both the femoral and patella attachment sites in 26/195 knees (13%). Attenuation of the MPFL without rupture occurred in 26/195 knees (13%). Associated findings included loose bodies in 23/195 (13%), meniscus tears 41/195 (21%), patella avulsion/fracture in 14/195 (7%), medial collateral ligament sprains/tears in 37/195 (19%) and osteochondral lesions in 96/195 knees (49%). Statistical analysis showed females had significantly more associated meniscus tears than the males (27% vs. 17%, p = 0.04). Although not statistically significant, osteochondral lesions were seen more in male patients with acute patella dislocation (52% vs. 42%, p = 0.08). CONCLUSION: Patients who present with lateral patella dislocation with the classic bone bruise pattern seen on MRI will likely rupture the MPFL at the patellar side. Females are more likely to have an associated meniscal tear than males; however, more males have underlying osteochondral lesions. Given the high percentage of associated pathology, we recommend a MRI of the knee in all patients who present with acute patella dislocation. PMID- 19643019 TI - Hepatitis C Virus entry: the early steps in the viral replication cycle. AB - Approximately 170 million are infected with the hepatitis C virus (HCV) world wide and an estimated 2.7 million are HCV RNA positive in the United States alone. The acute phase of the HCV infection, in majority of individuals, is asymptomatic. A large percentage of those infected with HCV are unable to clear the virus and become chronically infected. The study of the HCV replication cycle was hampered due to difficulties in growing and propagating the virus in an in vitro setting. The advent of the HCV pseudo particle (HCVpp) and HCV cell culture (HCVcc) systems have made possible the study of the HCV replication cycle, in vitro. Studies utilizing the HCVpp and HCVcc systems have increased our insight into the early steps of the viral replication cycle of HCV, such as the identification of cellular co-receptors for binding and entry. The aim of this article is to provide a review of the outstanding literature on HCV entry, specifically looking at cellular co-receptors involved and putting the data in the context of the systems used (purified viral envelope proteins, HCVpp system, HCVcc system and/or patient sera) and to also give a brief description of the cellular co-receptors themselves. PMID- 19643023 TI - Small intestinal bacterial overgrowth mimicking acute flare as a pitfall in patients with Crohn's Disease. AB - BACKGROUND: Small intestinal bacterial overgrowth (SIBO) is characterized by excessive proliferation of colonic bacterial species in the small bowel. Potential causes of SIBO include fistulae, strictures or motility disturbances. Hence, patients with Crohn's Disease (CD) are especially predisposed to develop SIBO. As result, CD patients may experience malabsorption and report symptoms such as weight loss, watery diarrhea, meteorism, flatulence and abdominal pain, mimicking acute flare in these patients. METHODS: One-hundred-fifty patients with CD reporting increased stool frequency, meteorism and/or abdominal pain were prospectively evaluated for SIBO with the Hydrogen Glucose Breath Test (HGBT). RESULTS: Thirty-eight patients (25.3%) were diagnosed with SIBO based on positive findings at HGBT. SIBO patients reported a higher rate of abdominal complaints and exhibited increased stool frequency (5.9 vs. 3.7 bowel movements/day, p = 0.003) and lower body weight (63.6 vs 70.4 kg, p = 0.014). There was no correlation with the Crohn's Disease Activity Index. SIBO was significantly more frequent in patients with partial resection of the colon or multiple intestinal surgeries; there was also a clear trend in patients with ileocecal resection that did not reach statistical significance. SIBO rate was also higher in patients with affection of both the colon and small bowel, while inflammation of the (neo)terminal ileum again showed only tendential association with the development of SIBO. CONCLUSION: SIBO represents a frequently ignored yet clinically relevant complication in CD, often mimicking acute flare. Because symptoms of SIBO are often difficult to differentiate from those caused by the underlying disease, targeted work-up is recommended in patients with corresponding clinical signs and predisposing factors. PMID- 19643024 TI - Analysis of Individual Social-ecological Mediators and Moderators and Their Ability to Explain Effect of a Randomized Neighborhood Walking Intervention. AB - BACKGROUND: Using data from the SHAPE trial, a randomized 6-month neighborhood based intervention designed to increase walking activity among older adults, this study identified and analyzed social-ecological factors mediating and moderating changes in walking activity. METHODS: Three potential mediators (social cohesion, walking efficacy, and perception of neighborhood problems) and minutes of brisk walking were assessed at baseline, 3-months, and 6-months. One moderator, neighborhood walkability, was assessed using an administrative GIS database. The mediating effect of change in process variables on change in brisk walking was tested using a product-of-coefficients test, and we evaluated the moderating effect of neighborhood walkability on change in brisk walking by testing the significance of the interaction between walkability and intervention status. RESULTS: Only one of the hypothesized mediators, walking efficacy, explained the intervention effect (product of the coefficients (95% CI) = 8.72 (2.53, 15.56). Contrary to hypotheses, perceived neighborhood problems appeared to suppress the intervention effects (product of the coefficients (95% CI = -2.48, -5.6, -0.22). Neighborhood walkability did not moderate the intervention effect. CONCLUSION: Walking efficacy may be an important mediator of lay-lead walking interventions for sedentary older adults. Social-ecologic theory-based analyses can support clinical interventions to elucidate the mediators and moderators responsible for producing intervention effects. PMID- 19643026 TI - Mosquito immune responses and compatibility between Plasmodium parasites and anopheline mosquitoes. AB - BACKGROUND: Functional screens based on dsRNA-mediated gene silencing identified several Anopheles gambiae genes that limit Plasmodium berghei infection. However, some of the genes identified in these screens have no effect on the human malaria parasite Plasmodium falciparum; raising the question of whether different mosquito effector genes mediate anti-parasitic responses to different Plasmodium species. RESULTS: Four new An. gambiae (G3) genes were identified that, when silenced, have a different effect on P. berghei (Anka 2.34) and P. falciparum (3D7) infections. Orthologs of these genes, as well as LRIM1 and CTL4, were also silenced in An. stephensi (Nijmegen Sda500) females infected with P. yoelii (17XNL). For five of the six genes tested, silencing had the same effect on infection in the P. falciparum-An. gambiae and P. yoelii-An. stephensi parasite vector combinations. Although silencing LRIM1 or CTL4 has no effect in An. stephensi females infected with P. yoelii, when An. gambiae is infected with the same parasite, silencing these genes has a dramatic effect. In An. gambiae (G3), TEP1, LRIM1 or LRIM2 silencing reverts lysis and melanization of P. yoelii, while CTL4 silencing enhances melanization. CONCLUSION: There is a broad spectrum of compatibility, the extent to which the mosquito immune system limits infection, between different Plasmodium strains and particular mosquito strains that is mediated by TEP1/LRIM1 activation. The interactions between highly compatible animal models of malaria, such as P. yoelii (17XNL)-An. stephensi (Nijmegen Sda500), is more similar to that of P. falciparum (3D7)-An. gambiae (G3). PMID- 19643025 TI - Breast-cancer-associated metastasis is significantly increased in a model of autoimmune arthritis. AB - INTRODUCTION: Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. METHODS: To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. RESULTS: We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor-alpha (TNF-alpha) may contribute to the increased metastasis. Treatment with anti-IL17 + celecoxib, an anti-inflammatory drug completely abrogated the development of metastasis and significantly reduced the primary tumor burden. CONCLUSIONS: The data clearly has important clinical implications for patients diagnosed with metastatic breast cancer, especially with regards to the prognosis and treatment options. PMID- 19643027 TI - Gene expression profiles in mouse embryo fibroblasts lacking stathmin, a microtubule regulatory protein, reveal changes in the expression of genes contributing to cell motility. AB - BACKGROUND: Stathmin (STMN1) protein functions to regulate assembly of the microtubule cytoskeleton by destabilizing microtubule polymers. Stathmin over expression has been correlated with cancer stage progression, while stathmin depletion leads to death of some cancer cell lines in culture. In contrast, stathmin-null mice are viable with minor axonopathies and loss of innate fear response. Several stathmin binding partners, in addition to tubulin, have been shown to affect cell motility in culture. To expand our understanding of stathmin function in normal cells, we compared gene expression profiles, measured by microarray and qRT-PCR, of mouse embryo fibroblasts isolated from STMN1+/+ and STMN1-/- mice to determine the transcriptome level changes present in the genetic knock-out of stathmin. RESULTS: Microarray analysis of STMN1 loss at a fold change threshold of > or = 2.0 revealed expression changes for 437 genes, of which 269 were up-regulated and 168 were down-regulated. Microarray data and qRT PCR analysis of mRNA expression demonstrated changes in the message levels for STMN4, encoding RB3, a protein related to stathmin, and in alterations to many tubulin isotype mRNAs. KEGG Pathway analysis of the microarray data indicated changes to cell motility-related genes, and qRT-PCR plates specific for focal adhesion and ECM proteins generally confirmed the microarray data. Several microtubule assembly regulators and motors were also differentially regulated in STMN1-/- cells, but these changes should not compensate for loss of stathmin. CONCLUSION: Approximately 50% of genes up or down regulated (at a fold change of > or = 2) in STMN1-/- mouse embryo fibroblasts function broadly in cell adhesion and motility. These results support models indicating a role for stathmin in regulating cell locomotion, but also suggest that this functional activity may involve changes to the cohort of proteins expressed in the cell, rather than as a direct consequence of stathmin-dependent regulation of the microtubule cytoskeleton. PMID- 19643028 TI - The association of levels of physical activity with metabolic syndrome in rural Australian adults. AB - BACKGROUND: Physical activity (PA) reduces risk factors related to metabolic syndrome. Rurality influences the way people incorporate physical activity into daily life. The aim of this study is to determine the association of PA level with metabolic syndrome in a rural Australian population. The influence of adiposity on these associations is also investigated. METHODS: Three cross sectional population health surveys were conducted in south-east Australia during 2004-2006 using a random population sample (n = 1563, participation rate 49%) aged 25-74 years. PA was assessed via a self-administered questionnaire, and components of the metabolic syndrome via anthropometric measurements taken by specially trained nurses and laboratory tests. RESULTS: Approximately one-fifth of participants were inactive in leisure-time and over one-third had metabolic syndrome (men 39%, women 33%; p = 0.022). There was an inverse association between level of PA and metabolic syndrome (p < 0.001). Men who were inactive in leisure-time were more than twice as likely and women more than three times as likely to have metabolic syndrome compared with those having high PA. Body mass index (BMI) is a mediating factor in the association between level of PA and metabolic syndrome. CONCLUSION: Some PA is better than none if adults, particularly women, are to reduce their risk of metabolic syndrome and associated vascular diseases. Specialised interventions that take rurality into consideration are recommended for adults who are inactive. PMID- 19643029 TI - Primer fabrication using polymerase mediated oligonucleotide synthesis. AB - BACKGROUND: Custom solid phase oligonucleotide synthesis is an important foundation supporting nearly every aspect of current genomics. In spite of the demand for oligonucleotide primers, their synthesis remains relatively expensive, time consuming and in many circumstances a wasteful process. In this methodology, described as polymerase mediated oligonucleotide synthesis (PMOS), a DNA polymerase is used to increase the hybridization affinity of one oligonucleotide by using another as a template for DNA synthesis. This self-assembly process provides an opportunity to instantly generate a very large number of useful gene specific primers from a small library of simple precursors. PMOS can be used to generate primers directly in the end-users laboratory within the context of any DNA polymerase chemistry such as in PCR or sequencing reactions RESULTS: To demonstrate the utility of PMOS, a universal 768-member oligonucleotide library (UniSeq) was designed, fabricated and its performance optimized and evaluated in a range of PCR and DNA sequencing reactions. This methodology used to derive specific 11-mers, performed well in each of these activities and produced the desired amplification or sequencing analysis with results comparable to primers made by time consuming and expensive custom synthesis. CONCLUSION: On the basis of these experiments, we believe this novel system would be broadly applicable and could in many circumstances replace the need for conventional oligonucleotide synthesis. PMID- 19643030 TI - Mass spectrometry analysis of the variants of histone H3 and H4 of soybean and their post-translational modifications. AB - BACKGROUND: Histone modifications and histone variants are of importance in many biological processes. To understand the biological functions of the global dynamics of histone modifications and histone variants in higher plants, we elucidated the variants and post-translational modifications of histones in soybean, a legume plant with a much bigger genome than that of Arabidopsis thaliana. RESULTS: In soybean leaves, mono-, di- and tri-methylation at Lysine 4, Lysine 27 and Lysine 36, and acetylation at Lysine 14, 18 and 23 were detected in HISTONE H3. Lysine 27 was prone to being mono-methylated, while tri-methylation was predominant at Lysine 36. We also observed that Lysine 27 methylation and Lysine 36 methylation usually excluded each other in HISTONE H3. Although methylation at HISTONE H3 Lysine 79 was not reported in A. thaliana, mono- and di methylated HISTONE H3 Lysine 79 were detected in soybean. Besides, acetylation at Lysine 8 and 12 of HISTONE H4 in soybean were identified. Using a combination of mass spectrometry and nano-liquid chromatography, two variants of HISTONE H3 were detected and their modifications were determined. They were different at positions of A31F41S87S90 (HISTONE variant H3.1) and T31Y41H87L90 (HISTONE variant H3.2), respectively. The methylation patterns in these two HISTONE H3 variants also exhibited differences. Lysine 4 and Lysine 36 methylation were only detected in HISTONE H3.2, suggesting that HISTONE variant H3.2 might be associated with actively transcribing genes. In addition, two variants of histone H4 (H4.1 and H4.2) were also detected, which were missing in other organisms. In the histone variant H4.1 and H4.2, the amino acid 60 was isoleucine and valine, respectively. CONCLUSION: This work revealed several distinct variants of soybean histone and their modifications that were different from A. thaliana, thus providing important biological information toward further understanding of the histone modifications and their functional significance in higher plants. PMID- 19643032 TI - Impact of supplementary private health insurance on stomach cancer care in Korea: a cross-sectional study. AB - BACKGROUND: Korea achieved universal health insurance coverage in only 12 years; however, insufficient government funding has resulted in high out-of-pocket payments and, in turn, a demand for supplementary private health insurance (PHI). Supplementary PHI provides a fixed amount of benefits in the event of critical illness (e.g., cancer or stroke), surgery, or hospitalization. In this study, we tried to identify factors that influence the decision to purchase supplementary PHI and investigate the impacts of PHI on various aspects of cancer care. METHODS: In a cross-sectional study of 391 patients with gastric cancer, we collected data on demographic and clinical variables, coverage by PHI at the time of diagnosis, and patients' cancer care experiences from surgery databases and patient questionnaires. Two separate multivariate logistic regression models were used 1) to determine whether various sociodemographic and clinical variables influence the purchase of supplementary PHI, and 2) to determine if there is a difference in various outcome measures between individuals with and without PHI. RESULTS: We studied 187 subjects (49.6%) who were covered under PHI at the time of diagnosis. Subjects who purchased PHI tended to be younger (aOR = 5.01, 95% C.I. = 2.05 - 12.24), and more educated (aOR = 2.67, 95% C.I. = 1.04 - 6.86). Supplementary PHI coverage was significantly associated with financial independence (aOR = 2.07, 95% CI = 1.19 - 3.61), but not with other aspects of cancer care, such as access to healthcare, quality of care, communication and patient autonomy. CONCLUSION: Our findings demonstrate that supplementary PHI neither serves as a safety net for vulnerable patients nor improves cancer care experience, except for maintaining the financial independence of beneficiaries. PMID- 19643031 TI - Understanding, beliefs and perspectives of Aboriginal people in Western Australia about cancer and its impact on access to cancer services. AB - BACKGROUND: Despite a lower overall incidence, Aboriginal Australians experience poorer outcomes from cancer compared with the non-Aboriginal population as manifested by higher mortality and lower 5-year survival rates. Lower participation in screening, later diagnosis of cancer, poor continuity of care, and poorer compliance with treatment are known factors contributing to this poor outcome. Nevertheless, many deficits remain in understanding the underlying reasons, with the recommendation of further exploration of Aboriginal beliefs and perceptions of cancer to help understand their care-seeking behavior. This could assist with planning and delivery of more effective interventions and better services for the Aboriginal population. This research explored Western Australian (WA) Aboriginal peoples' perceptions, beliefs and understanding of cancer. METHODS: A total of 37 Aboriginal people from various geographical areas within WA with a direct or indirect experience of cancer were interviewed between March 2006 and September 2007. Interviews were audio-recorded, transcribed verbatim and coded independently by two researchers. NVivo7 software was used to assist data management and analysis. A social constructionist framework provided a theoretical basis for analysis. Interpretation occurred within the research team with member checking and the involvement of an Aboriginal Reference Group assisting with ensuring validity and reliability. RESULTS: Outcomes indicated that misunderstanding, fear of death, fatalism, shame, preference for traditional healing, beliefs such as cancer is contagious and other spiritual issues affected their decisions around accessing services. These findings provide important information for health providers who are involved in cancer-related service delivery. CONCLUSION: These underlying beliefs must be specifically addressed to develop appropriate educational, screening and treatment approaches including models of care and support that facilitate better engagement of Indigenous people. Models of care and support that are more culturally-friendly, where health professionals take account of both Indigenous and Western beliefs about health and the relationship between these, and which engage and include Indigenous people need to be developed. Cultural security, removing system barriers and technical/scientific excellence are all important to ensure Indigenous people utilise healthcare to realise the benefits of modern cancer treatments. PMID- 19643033 TI - Educational intervention to improve physician reporting of adverse drug reactions (ADRs) in a primary care setting in complementary and alternative medicine. AB - BACKGROUND: Recent studies have shown that adverse drug reactions (ADRs) are underreported. This may be particularly true of ADRs associated with complementary and alternative medicine (CAM). Data on CAM-related ADRs, however, are sparse.Objective was to evaluate the impact of an educational intervention and monitoring programme designed to improve physician reporting of ADRs in a primary care setting. METHODS: A prospective multicentre study with 38 primary care practitioners specialized in CAM was conducted from January 2004 through June 2007. After 21 month all physicians received an educational intervention in terms of face-to-face training to assist them in classifying and reporting ADRs. The study centre monitored the quantity and quality of ADR reports and analysed the results.To measure changes in the ADR reporting rate, the median number of ADR reports and interquartile range (IQR) were calculated before and after the educational intervention. The pre-intervention and post-intervention quality of the reports was assessed in terms of changes in the completeness of data provided for obligatory items. Interrater reliability between the physicians and the study centre was calculated using Cohen's kappa with a 95% confidence interval (CI). We used Mann Whitney U-test for testing continuous data and chi-square test was used for categorical data. The level of statistical significance was set at P < 0.05. RESULTS: A total of 404 ADRs were reported during the complete study period. An initial 148% increase (P = 0.001) in the number of ADR reports was observed after the educational intervention. Compared to baseline the postinterventional number of ADR reportings was statistically significant higher (P < 0.005) through the first 16 months after the intervention but not significant in the last 4-month period (median: 8.00 (IQR [2.75; 8.75]; P = 0.605). The completeness of the ADR reports increased from 80.3% before to 90.7% after the intervention. The completeness of the item for classifying ADRs as serious or non-serious increased significantly (P < 0.001) after the educational intervention. The quality of ADR reports increased from kappa 0.15 (95% CI: 0.08; 0.29) before to 0.43 (95% CI: 0.23; 0.63) after the intervention. CONCLUSION: The results of the present study demonstrate that an educational intervention can increase physician awareness of ADRs. Participating physicians were able to incorporate the knowledge they had gained from face-to-face training into their daily clinical practice. However, the effects of the intervention were temporary. PMID- 19643035 TI - Biomedicinal implications of high-density lipoprotein: its composition, structure, functions, and clinical applications. AB - High-density lipoprotein (HDL) is a proven biomarker for the monitoring of changes in antioxidant and anti-inflammation capability of body fluids. The beneficial virtues of HDL are highly dependent on its lipids and protein compositions, and their ratios. In normal state, the HDL particle is enriched with lipids and several HDL-associated enzymes, which are responsible for its antioxidant activity. Lower HDL-cholesterol levels (40 mg/dL) have been recognized as an independent risk factor for coronary artery disease, as well as being a known component of metabolic syndrome. Functional and structural changes of HDL have been recognized as factors pivotal to the evaluation of HDL-quality. In this review, I have elected to focus on the functional and structural correlations of HDL and the roles of HDL-associated apolipoproteins and enzymes. Recent clinical applications of HDL have also been reviewed, particularly the therapeutic targeting of HDL metabolism and reconstituted HDL; these techniques represent promising emerging strategies for the treatment of cardiovascular disease, for drug or gene therapy. PMID- 19643034 TI - Disruption of chromosome 11 in canine fibrosarcomas highlights an unusual variability of CDKN2B in dogs. AB - BACKGROUND: In dogs in the western world neoplasia constitutes the most frequently diagnosed cause of death. Although there appear to be similarities between canine and human cancers, rather little is known about the cytogenetic and molecular alterations in canine tumours. Different dog breeds are susceptible to different types of cancer, but the genetic basis of the great majority of these predispositions has yet to be discovered. In some retriever breeds there is a high incidence of soft tissue sarcomas and we have previously reported alterations of chromosomes 11 and 30 in two poorly differentiated fibrosarcomas. Here we extend our observations and present a case report on detail rearrangements on chromosome 11 as well as genetic variations in a tumour suppressor gene in normal dogs. RESULTS: BAC hybridisations on metaphases of two fibrosarcomas showed complex rearrangements on chromosome 11, and loss of parts of this chromosome. Microsatellite markers on a paired tumour and blood DNA pointed to loss of heterozygosity on chromosome 11 in the CDKN2B-CDKN2A tumour suppressor gene cluster region. PCR and sequencing revealed the homozygous loss of coding sequences for these genes, except for exon 1beta of CDKN2A, which codes for the N-terminus of p14ARF. For CDKN2B exon 1, two alleles were observed in DNA from blood; one of them identical to the sequence in the dog reference genome and containing 4 copies of a 12 bp repeat found only in the canine gene amongst all species so far sequenced; the other allele was shorter due to a missing copy of the repeat. Sequencing of this exon in 141 dogs from 18 different breeds revealed a polymorphic region involving a GGC triplet repeat and a GGGGACGGCGGC repeat. Seven alleles were recorded and sixteen of the eighteen breeds showed heterozygosity. CONCLUSION: Complex chromosome rearrangements were observed on chromosome 11 in two Labrador retriever fibrosarcomas. The chromosome alterations were reflected in the loss of sequences corresponding to two tumour suppressor genes involved in cell-cycle progression. Sequencing of CDKN2B across many different breeds revealed a widespread polymorphism within the first exon of the gene, immediately before the ankyrin coding sequences. PMID- 19643037 TI - Multiple hTAF(II)31-binding motifs in the intrinsically unfolded transcriptional activation domain of VP16. AB - Transcriptional activation domain (TAD) in virion protein 16 (VP16) of herpes simplex virus does not have any globular structure, yet exhibits a potent transcriptional activity. In order to probe the structural basis for the transcriptional activity of VP16 TAD, we have used NMR spectroscopy to investigate its detailed structural features. Results show that an unbound VP16 TAD is not merely "unstructured" but contains four short motifs (residues 424 433, 442-446, 465-467 and 472-479) with transient structural order. Pre structured motifs in other intrinsically unfolded proteins (IUPs) were shown to be critically involved in target protein binding. The 472-479 motif was previously shown to bind to hTAF(II)31, whereas the hTAF(II)31-binding ability of other motifs found in this study has not been addressed. The VP16 TAD represents another IUP whose prestructured motifs mediate promiscuous binding to various target proteins. PMID- 19643036 TI - Targeted chiral lipidomics analysis of bioactive eicosanoid lipids in cellular systems. AB - We have developed a targeted lipidomics approach that makes it possible to directly analyze chiral eicosanoid lipids generated in cellular systems. The eicosanoids, including prostaglandins (PGs), thromboxanes (TXs), leukotrienes (LTs) and alcohols (HETEs), have been implicated as potent lipid mediators of various biological processes. Enzymatic formations of eicosanoids are regioselective and enantioselective, whereas reactive oxygen species (ROS) mediated formation proceeds with no stereoselectivity. To distinguish between enzymatic and non-enzymatic pathways of eicosanoid formation, it is necessary to resolve enantiomeric forms as well as regioisomers. High sensitivity is also required to analyze the eicosanoid lipids that are usually present as trace amounts (pM level) in biological fluids. A discovery of liquid chromatography electron capture atmospheric pressure chemical ionization/mass spectrometry (LCECAPCI/MS) allows us to couple normal phase chiral chromatography without loss of sensitivity. Analytical specificity was obtained by the use of collision induced dissociation (CID) and tandem MS (MS/MS). With combination of stable isotope dilution methodology, complex mixtures of regioisomeric and enantiomeric eicosanoids have been resolved and quantified in biological samples with high sensitivity and specificity. Targeted chiral lipidomics profiles of bioactive eicosanoid lipids obtained from various cell systems and their biological implications have been discussed. PMID- 19643038 TI - Effects of epitope sequence tandem repeat and proline incorporation on polyclonal antibody production against cytochrome 1A2 and 3A4. AB - We describe a method for producing polyclonal antibodies against peptide antigen cytochrome P450 1A2 and 3A4 using a tandem repeat of the epitope region and incorporation of proline residue between the repeated sequences. An ELISA assay revealed more efficient generation of polyclonal antibodies to tandem repeat peptide antigens than mono-epitope peptides. The incorporation of proline residues further stimulated antibody production. PMID- 19643039 TI - Transcriptional activation of an anti-oxidant mouse Pon2 gene by dexamethasone. AB - Glucocorticoids regulate multiple physiological processes such as metabolic homeostasis and immune response. Mouse Pon2 (mPon2) acts as an antioxidant to reduce cellular oxidative stress in cells. In this present study, we investigated the transcriptional regulation of mPon2 by glucocorticoids. In the presence of glucocorticoid analogue dexamethasone, the expression of mPon2 mRNA in cells was increased, whereas the expression was inhibited by a transcription inhibitor actinomycin D. Glucocorticoid receptors bound to the putative glucocorticoid response elements located between -593 bp and -575 bp of the mPon2 promoter. Transcriptional activity was completely blocked when the putative element was mutated. Taken together, these results suggest that the expression of the mPon2 gene is directly regulated by glucocorticoid-glucocorticoid receptor complexes. PMID- 19643040 TI - Static tensional forces increase osteogenic gene expression in three-dimensional periodontal ligament cell culture. AB - Orthodontic tooth movement results from the combinational process of both bone resorption and formation in the compressive and tension sides, respectively. However, the genes responsible for new bone formation in tension sides have not been determined. In this study, we used DNA microarray and real-time RT-PCR to identify genes in human periodontal ligament (PDL) cells that undergo significant changes in expression in response to static tensional forces (2 or 12 hours). The genes found were alkaline phospatase (ALP), matrix metalloproteinases (MMPs), vascular endothelial growth factor (VEGF), and several collagen genes. Furthermore, an ELISA evaluating the expression of VEGF, type IV collagen and MMP 2 found levels significantly increased after 24 and 72 hours (P 0.05). ALP activity was also increased after 24 hours (P 0.05). Collectively, we found the genes up-regulated in our study by the static tensional force are related to osteogenic processes such as matrix synthesis and angiogenesis. PMID- 19643041 TI - Proteome analysis of the m. longissimus dorsi between fattening stages in Hanwoo steer. AB - The objective of this study was to identify proteins in the m. longissimus dorsi between early (12 months of age) and late (27 months of age) fattening stages of Hanwoo (Korean cattle) steers. Using two-dimensional electrophoresis and mass spectrometry, 8 proteins of 11 differentially expressed spots between the 12 and 27 month age groups were identified in the loin muscle. Among those that were differentially expressed, zinc finger 323 and myosin light chain were highly expressed in late-fattening stage, and two catabolic enzymes, triosephosphate isomerase (TPI) and succinate dehydrogenase (SDH) were expressed more in the early versus the late-fattening stage. In particular, the quantification of TPI and SDH by immunoblotting correlated well with fat content. Our data suggested that TPI and SDH are potential candidates as markers and their identification provides new insight into the molecular mechanisms and pathways associated with intramuscular fat contents of bovine skeletal muscle. PMID- 19643042 TI - Differential expression of a poplar SK2-type dehydrin gene in response to various stresses. AB - Dehydrins are group II, late embryogenesis abundant proteins that act putatively as chaperones in stressed plants. To elucidate the function of dehydrins in poplar, we isolated the SK(2)-type dehydrin gene Podhn from Populus alba x P. tremula var. glandulosa suspension cells and analyzed its expression following treatments of abiotic stress, wounding and plant growth regulator. Sequence homology and phylogenetic analyses indicate Podhn encodes an acidic dehydrin (pI 5.14, 277 amino acids, predicted size 25.6 kDa) containing two lysine-rich "K segments" and a 7-serine residue "S-segment", both characteristic of SK(2)-type dehydrins. Southern blots show Podhn genes form a small gene family in poplar. Podhn was expressed in all tissues examined under unstressed conditions, but most strongly in cell suspensions (especially in the stationary phase). Drought, salt, cold and exogenous abscisic acid (ABA) treatments enhanced Podhn expression, while wounding and jasmonic acid caused its reduction. Therefore, Podhn might be involved in ABA or stress response. PMID- 19643043 TI - Cytosolic prion protein induces apoptosis in human neuronal cell SH-SY5Y via mitochondrial disruption pathway. AB - Different neurodegenerative disorders like prion disease, is caused by protein misfolding conformers. Reverse-transfected cytosolic prion protein (PrP) and PrP expressed in the cytosol have been shown to be neurotoxic. To investigate the possible mechanism of neurotoxicity due to accumulation of PrP in cytosol, a PrP mutant lacking the signal and GPI (CytoPrP) was introduced into the SH-SY5Y cell. MTT and trypan blue assays indicated that the viability of cells expressing CytoPrP was remarkably reduced after treatment of MG-132. Obvious apoptosis phenomena were detected in the cells accumulated with CytoPrP, including loss of mitochondrial transmembrane potential, increase of caspase-3 activity, more annexin V/PI-double positive-stained cells and reduced Bcl-2 level. Moreover, DNA fragmentation and TUNEL assays also revealed clear evidences of late apoptosis in the cells accumulated CytoPrP. These data suggest that the accumulation of CytoPrP in cytoplasm may trigger cell apoptosis, in which mitochondrial relative apoptosis pathway seems to play critical role. PMID- 19643044 TI - Proteome analysis of chloroplast proteins in stage albinism line of winter wheat (triticum aestivum) FA85. AB - The "stage albinism line of winter wheat" FA85 was a specific natural mutant strain on leaf color. This physiological mutation was controlled by cytogene. In order to reveal the genetic and biochemical mechanism of albinism, 2-DE was used to investigate the difference of chloroplast protein expression pattern between FA85 and its parent wheat Aibian 1. From the results of 2-DE gels analysis, approximately 683 spots were detected on each gel, and 57 spots were expressed differently at least two-fold. Using MALDI-TOF/TOF MS, 14 of 57 spots were identified, which could be categorized into four classes: carbon metabolism, energy metabolism, defense/stress response and signal transduction. Compared with the parent wheat, the expression of ATPase-gamma and GP1-alpha was up-regulated in FA85, and of other proteins was down-regulated. Together, we concluded that the expression of chloroplast proteins had changed obviously in FA85, which might be related to the leaf color mutant. PMID- 19643045 TI - Proteomic characterization of differentially expressed proteins associated with no stress in retinal ganglion cells. AB - Proteomic analyses of differentially expressed proteins in rat retinal ganglion cells (RGC-5) following S-nitrosoglutathione (GSNO), an NO donor, treatment were conducted. Of the approximately 314 protein spots that were detected, 19 were differentially expressed in response to treatment with GSNO. Of these, 14 proteins were up-regulated and 5 were down- regulated. Notably, an increase in GAPDH expression following GSNO treatment was detected in RGC-5 cells through Western blotting as well as proteomics. The increased GAPDH expression in response to GSNO treatment was accompanied by an increase in Herc6 protein, an E3 ubiquitin ligase. Moreover, GSNO treatment resulted in the translocation of GADPH from the cytosol to the nucleus and its subsequent accumulation. These results suggest that NO stress-induced apoptosis may be associated with the nuclear translocation and accumulation of GAPDH in RGC-5 cells. PMID- 19643046 TI - Effects of protein concentration and detergent on endotoxin reduction by ultrafiltration. AB - Lipopolysaccharide (LPS), found in the outer membrane of Gram negative bacteria, only exerts its toxic effects when in free form. LPS has three major parts, lipid A, the toxic component, along with a core polysaccharide and O-specific polysaccharide. LPS monomers are known to have molecular masses between 10 to 30 kDa. Under physiological conditions, LPS exists in equilibrium between monomer and vesicle forms. LPS removal by 100 kDa ultrafiltration was more efficient (99.6% of LPS removed) with a low concentration of protein (2.0 mg/ml) compared to a high concentration (20.1 mg/ml). In the presence of different detergents (0.5% Tween 20, 1.0% taurodeoxycholate and 1.0% Triton X-100), LPS removal was more efficient at low protein concentrations (2.0 mg/ml) compared to high protein concentrations (20.1 mg/ml). PMID- 19643049 TI - Europe's initial experience with pandemic (H1N1) 2009 - mitigation and delaying policies and practices. AB - Europe has experienced more than two months of the first transmissions and outbreak of the 2009 pandemic of A(H1N1)v. This article summarises some of the experience to date and looks towards the expected autumn increases of influenza activity that will affect every country. To date the distribution of transmission has been highly heterogenous between and within countries, with one country the United Kingdom (UK) experiencing the most cases and the highest transmission rates. Most infections are mild but there are steadily increasing numbers of people needing hospital care and more deaths are being reported. An initial difference in practice between Europe and North America was over case-finding and treatment with some authorities in Europe using active case-finding, contact tracing and treatment/prophylaxis with antivirals to try and delay transmission. This article details the history of this practice in the past two months and explains how and why countries are moving to mitigation, especially treating with antivirals those at higher risk of experiencing severe disease. PMID- 19643050 TI - An outbreak of viral gastroenteritis linked to municipal water supply, Lombardy, Italy, June 2009. AB - We report an outbreak of viral gastroenteritis linked to municipal drinking water in a town in northern Italy in June 2009. Over one month we identified 299 probable cases of whom 30 were confirmed for at least one of the following viruses: norovirus, rotavirus, enterovirus or astrovirus. Water samples and filters from the water system also tested positive for norovirus and enterovirus. Control measures included treating the water system with chlorine dioxide and filters with peracetic acid, while providing temporary alternative sources of drinking water to the population. PMID- 19643051 TI - A case of verocytotoxin-producing Escherichia coli O157 from a private barbecue in South East England. AB - The following case report describes a cluster of Escherichia coli O157 cases in the United Kingdom related to undercooked beef at a barbecue, resulting in an intensive care admission in France with haemolytic uraemic syndrome and highlighting the need to cook beef properly. PMID- 19643052 TI - Clinical features of cases of influenza A (H1N1)v in Osaka prefecture, Japan, May 2009. AB - This report describes the clinical characteristics of influenza A(H1N1)v virus infection in Osaka. By the end of May, 171 cases had been reported in Osaka. Most patients were from one school. No patient had a serious underlying medical condition.Clinical symptoms were mild and resembled those of seasonal influenza. The sensitivity of the rapid antigen test was 77%. Antivirals were given to the majority of the cases. Early antiviral treatment may have shortened the duration of fever. PMID- 19643054 TI - Modified surveillance of influenza A(H1N1)v virus infections in France. AB - Up to early July 2009, surveillance of H1N1 cases in France was based on the identification of all possible cases in order to implement, around each of them, control measures aimed at delaying the spread of the virus. The global dissemination of the virus and the starting community transmission in France led us to shift to a population-based surveillance relying mainly on the identification and investigation of clusters of influenza-like illness, on the identification and individual follow-up of confirmed hospitalised cases as well as on the monitoring, through various sentinel systems, of the use of ambulatory and hospital care for influenza-like symptoms. PMID- 19643053 TI - Enhanced surveillance of influenza A(H1N1)v in Greece during the containment phase. AB - Following the emergence of a novel influenza virus (influenza A(H1N1)v) with pandemic potential in late April 2009, public health measures were put in place in an effort to contain disease spread in Greece. These included enhanced surveillance of infections due to influenza A(H1N1)v virus, in order to continuously ascertain the situation and guide further public health action. On 15 July, Greece moved to mitigation phase. This report summarises surveillance findings in Greece during the delaying (or containment) phase, from 30 April to 14 July 2009. PMID- 19643058 TI - How the media reported the first days of the pandemic (H1N1) 2009: results of EU wide media analysis. AB - The European Centre for Disease Prevention and Control (ECDC) commissioned an in depth review of European media coverage of the opening days of the pandemic (H1N1) 2009. A total of 3,979 articles were collected from 31 European countries in the period 27 April until 3 May 2009. National and international public health authorities were by far the leading source of information on the new virus. They were identified as the main source of information in 75% of the articles analysed. 94% of the articles were either neutral, relaying factual information (70%), or expressing support for the authorities handling of the situation (24%). These results seem to vindicate the communication strategy adopted by the public health authorities. PMID- 19643056 TI - European Antibiotic Awareness Day, 2008 - the first Europe-wide public information campaign on prudent antibiotic use: methods and survey of activities in participating countries. AB - Antibiotic resistance is a major European and global public health problem and is, for a large part, driven by misuse of antibiotics. Hence, reducing unnecessary antibiotic use, particularly for the treatment of certain respiratory tract infections where they are not needed, is a public health priority. The success of national awareness campaigns to educate the public and primary care prescribers about appropriate antibiotic use in Belgium and France stimulated a European initiative coordinated by the European Centre for Disease Prevention and Control (ECDC), and named European Antibiotic Awareness Day (EAAD), to take place each year on 18 November. Specific campaign materials, including key messages, logos, slogans and a media toolkit, were developed and made available for use in European countries. The focus of the first EAAD campaign was about not taking antibiotics for viral infections such as colds and flu. A post-campaign survey was conducted in January 2009. Thirty-two European countries participated in the first EAAD, producing information materials and implementing activities to mark EAAD. Media coverage peaked on 18 and 19 November. At EU level, EAAD was launched at a scientific meeting in the European Parliament, Strasbourg. The event received EU political engagement through support from the EU Commissioner for Health, the Slovenian and French EU Presidencies, and Members of the European Parliament. Critical factors that led to the success of the first EAAD were good cooperation and process for building the campaign, strong political and stakeholder support and development of campaign materials based on scientific evidence. Countries indicated wide support for another EAAD in 2009. For this purpose, ECDC is developing several TV spots as well as a second set of EAAD campaign materials targeting primary care prescribers. PMID- 19643057 TI - Validity of routine surveillance data: a case study on Swedish notifications of methicillin-resistant Staphylococcus aureus. AB - Surveillance of communicable diseases is a public health corner stone. Routine notification data on communicable diseases are used as a basis for public health action as well as for policy making. While there are agreed standards for evaluating the performance of surveillance systems, it is rarely possible to analyse the validity of the data entered into these systems. In this study we compared data on all Swedish cases of methicillin-resistant Staphylococcus aureus (MRSA) routinely notified between 2000 and 2003 with follow-up information collected for each of these cases as part of a public health project. The variables Reason for testing (clinical sample, contact tracing, screening of risk group), Clinical presentation (disease, colonisation), Transmission setting (healthcare-acquired, community-acquired), Country of acquisition (Sweden, abroad) and Risk-occupation (yes, no) were analysed for sensitivity, positive predictive value and completeness of answers. The sensitivity varied between 23% and 83%, the positive predictive values were generally higher (55% to 97%), while missing answers varied from 11% to 59%. The proportion of community-acquired cases was markedly higher when excluding either cases of MRSA colonisation or cases found through public health-initiated activities (contact tracing or screening of risk groups). We conclude that the quality of routine surveillance data may be inadequate for in-depth epidemiological analyses. This should be taken into account when interpreting routine surveillance figures. Whether or not the case definition includes cases of MRSA colonisation may have a significant impact on population-wide estimates of MRSA occurrence. PMID- 19643059 TI - Epidemiologic analysis of the laboratory-confirmed cases of influenza A(H1N1)v in Colombia. AB - From 2 May to 16 July 2009, a total of 183 laboratory-confirmed cases of influenza A(H1N1)v were reported in Colombia, 117 (63.9%) of these had travelled outside the country. Hospital admission was necessary in 26 (14.21%) cases and seven patients died (fatality-case ratio: 3.8%). The infection affected younger age-groups and the symptoms most frequently reported were cough, fever and sore throat. Our findings are consistent with recent reports from other countries. PMID- 19643060 TI - Pandemic influenza A(H1N1)v viruses currently circulating in New Zealand are sensitive to oseltamivir. AB - New Zealand, like other southern hemisphere countries with a temperate climate, has been in the winter period with seasonal influenza activity. New Zealand has also experienced a dramatic increase in the number of cases of pandemic influenza A(H1N1)v virus. Early reports from the northern hemisphere at the beginning of the pandemic showed that the virus was sensitive to the antiviral drug oseltamivir. In this study we report that pandemic influenza A(H1N1)v viruses currently circulating in New Zealand are sensitive to oseltamivir, but seasonal influenza A(H1N1) viruses - the co-circulating predominant seasonal strain, is resistant to oseltamivir. PMID- 19643062 TI - Oseltamivir adherence and side effects among children in three London schools affected by influenza A(H1N1)v, May 2009 - an internet-based cross-sectional survey. AB - This report describes the results of a cross-sectional anonymised online survey on adherence to, and side effects from oseltamivir when offered for prophylaxis, among pupils from one primary and two secondary schools with confirmed cases of influenza A(H1N1)v in London in April-May 2009. Of 103 respondents (response rate 40%), 95 were estimated to have been offered oseltamivir for prophylaxis, of whom 85 (89%) actually took any. Less than half (48%) of primary schoolchildren completed a full course, compared to three-quarters (76%) of secondary schoolchildren. More than half (53%) of all schoolchildren taking prophylactic oseltamivir reported one or more side effects. Gastrointestinal symptoms were reported by 40% of children and 18% reported a mild neuropsychiatric side effect. The results confirmed anecdotal evidence of poor adherence, provided timely information with which to assist decision-making, and formed part of the body of growing evidence that contributed to policy changes to restrict widespread use of prophylaxis for school contacts of confirmed cases of influenza A(H1N1)v. PMID- 19643061 TI - Compliance and side effects of prophylactic oseltamivir treatment in a school in South West England. AB - School closure along with mass prophylactic oseltamivir treatment of pupils have been used in England and elsewhere to contain school outbreaks of influenza A(H1N1)v. We evaluated the protective effect, compliance with and side effects of oseltamivir chemoprophylactic treatment with a ten-day course of 1x 75mg given to 11-12-year-old pupils in one school year in a secondary school in South West England closed for ten days in response to a symptomatic laboratory-confirmed pupil. We distributed a questionnaire to pupils in the affected school year in class after the school had re-opened. Questions included symptoms of flu-like illness, compliance with chemoprophylaxis and side effects. All present on the day, 248 (93.2%) participated. Compliance with chemoprophylaxis was high, 77% took the full course, 91% took at least seven days. Fifty-one percent experienced symptoms such as feeling sick (31.2%), headaches (24.3%) and stomach ache (21.1%). Although some children were ill with flu-like symptoms, those tested did not have A(H1N1)v infection. Compliance with oseltamivir chemoprophylaxis was high, although likely side effects were common. The burden of side effects needs to be considered when deciding on mass oseltamivir chemoprophylaxis in children especially given that the symptoms of A(H1N1)v influenza are generally mild. PMID- 19643063 TI - Regulation and function of pyridoxal phosphate in CNS. AB - Pyridoxal phosphate and pyridoxamine phosphate, the catalytically active forms of vitamin B(6), influence brain function by participating at stages in metabolism of proteins, lipids, carbohydrates, other coenzymes and hormones. Vitamin B(6) participates in the metabolism of amino acids in the form of decarboxylation, transamination, deamination, racemization and desulfhydration reactions. The crucial roles that these coenzymes play in the maintenance of functional integrity of the brain become evident when one realizes that some compounds implicated as neurotransmitters are synthesized and/or metabolized by the aid of the vitamin B(6)-dependent enzymatic reactions. These include dopamine, norepinephrine and serotonin, tyramine, tryptamine, taurine, histamine, gamma aminobutyric acid, and even acetylcholine indirectly. In recent years, the above mentioned biogenic amines have become of considerable interest to neurobiologists who are investigating the etiology and the pathological manifestations of many disorders of the central nervous system such as Parkinsonism, Huntington's chorea, minimal brain disfunction, schizophrenia, depression, sleep disorders and seizure disorders. Vitamin B(6) deficiency in these cases is characterized by anemia, growth retardation and alteration in neuronal function, including neuropathies, hyperirritability, hyperexcitability and convulsions. The importance of vitamin B(6) in the study of brain function assumes still greater significance when one considers the effects of nutritional deficiencies on growth and development of the brain and mental processes and in the involvement of vitamin B(6) in some inborn errors of metabolism which result in mental retardation. Vitamin B(6) deficiency results in a lowered concentration of Coenzyme A in blood, in reduced absorption and storage of vitamin B(12), and in increased excretion of vitamin C. Furthermore, vitamin B(6) acts synergistically with vitamin E to control metabolism of unsaturated fats, with vitamin C in tyrosine metabolism and with niacin in its action and participates in niacin synthesis. In addition, vitamin B(6) deficiency results in insufficiency of insulin and in alteration of the functions of adrenal and pituitary glands, since it is involved in the synthesis of growth hormone, follicle-stimulating hormone, luteinizing hormone, aldosterone, glucagon, cortisol, estradiol, testosterone and epinephrine. It is hoped that by understanding the factors that regulate the synthesis, binding, storage and degradation of pyridoxal phosphate in the brain, a better insight into the role of vitamin B(6) in neurobiology may be gained. PMID- 19643064 TI - Regulation and function of pyridoxal phosphate in CNS. PMID- 19643065 TI - Galactosyl ceramides of the myelin sheath: thermal studies. AB - The thermal properties of several hydrated glycosyl ceramides have been investigated by differential scanning calorimetry in relation to the role of galactosyl ceramides in the myelin sheath of central nerve tissue. Myelin galactosyl ceramides are characterised by the presence of a large proportion of alpha-hydroxy fatty acids which lower the phase transition of this lipid class in comparison to galactosyl ceramides with normal fatty acids of similar chain length. Alteration of the sugar headgroup from galactose to glucose produced no significant change in the transition temperature of the lipid. The presence of a disaccharide headgroup lowered the transition temperature and altered the structure of the endotherm. Increasing concentrations of cholesterol in aqueous dispersions of galactosyl ceramide progressively decreased the enthalpy of the phase transition until, in the presence of 34 mole % cholesterol, it was no longer detectable. Examination of the effects of a range of phospholipids on the phase transition of galactosyl ceramides suggest that the phase behaviour of phospholipid-galactosyl ceramide mixtures is complex. However, only a single endotherm was observed in all the phospholipid-galactosyl ceramide systems examined. This tends to indicate that segregated phases enriched in galactosyl ceramides do not occur in the intact myelin membrane. PMID- 19643066 TI - Effects of lesions on (3)H-apomorphine and (3)H-spiperone stereospecific binding sites in subcellular fractions of rat striatum. AB - (3)H-spiperone and (3)H-apomorphine showed saturable stereospecific binding to membranes of both a microsomal and a mitochondrial fraction of rat striatum. For each ligand, the K(D)-values were similar in both subcellular fractions, but the microsomal fraction contained a 2 times higher binding site density than the mitochondrial fraction. In both subcellular preparations the number of (3)H spiperone stereospecific binding sites was about two times higher than the number of (3)H-apomorphine stereospecific binding sites. Unilateral striatal kainic acid lesions caused a reduction of 67% of (3)H-spiperone and of 71% of (3)H apomorphine stereospecific binding in the microsomal fraction. In the mitochondrial fraction the reduction in stereospecific binding sites was only 33% and 40% for the (3)H-ligands respectively. Scatchard plots of (3)H-spiperone stereospecific binding were linear in the two subcellular fractions of both lesioned and control striata, and binding affinities were similar throughout. Scatchard plots of (3)H-apomorphine stereospecific binding appeared to be non linear in conditions where non-specific binding exceeded stereospecific binding i.e. in the mitochondrial fractions and in the microsomal fraction of the lesioned striata. To allow clear analysis of the data, original experimental measurements of total binding and non-specific binding are reported. The impact of variations in blank values on the final outcome of the analysis of specific binding is discussed. Unilateral cortical ablation caused a 22% reduction of both (3)H-spiperone and (3)H-apomorphine stereospecific binding in the microsomal fraction, but did not affect the binding in the mitochondrial fraction. (3)H spiperone and (3)H-apomorphine stereospecific binding sites appear to occur concomitantly and to be affected in parallel by the lesions. Binding sites recovered in the striatal microsomal and mitochondrial fraction show the same binding characteristics but are apparently of different cellular origin. Dopamine receptors on intrastriatal neurones and cortical striatal afferents are mostly recovered in the microsomal fraction, and are likely to be localized on plasma membranes or associated with small subcellular transport particles. The origin of dopamine receptors recovered in the mitochondrial fraction is unknown. The presently reported findings corroborate the hypothesis that (3)H-spiperone and (3)H-apomorphine label the same unitary dopamine receptor complex, but probably interact with different sub-unit sites of the receptor. PMID- 19643067 TI - The effect of solubilization on the properties and molecular forms of rat brain acetylcholinesterase. AB - Attempts were made to solubilize acetylcholinesterase from Wistar rat brains by extraction with dilute buffer, Triton X-100 and proteolytic digestion. About 13% of the total enzyme activity could be solubilized with 30 mM sodium phosphate buffer (pH 7) and the remainder brought into solution with 1% w/v Triton X-100. Storage of the brains in dry toluene for 3-6 months followed by extraction did not improve the yield and resulted in the loss of about half of the enzyme activity. Digestion with trypsin or collagenase was totally ineffective in solubilizing the enzyme from fresh or toluene-stored brains. The enzyme in the buffer and detergent extracts of fresh and toluene-stored brains was very stable when stored at -20 degrees C for several months although some activity was found in a 100,000 g pellet obtained by centrifugation of the thawed extracts. All enzyme preparations showed inhibition by excess substrate and an optimum substrate concentration of 2 mM acetylcholine. The Km of the crude tissue suspension was 80 microM acetylcholine while that of the buffer-soluble enzyme was 91 microM and that of the detergent-solubilized enzyme was 250 microM. Storage of the brains in toluene had little effect on these values. Starch-block electrophoresis and polyacrylamide gel electrophoresis showed up to five bands with different net charge while gradient gel electrophoresis revealed up to eleven forms with molecular weights ranging from 39,000 to 450,000. The electrophoretic pattern obtained depended on the preparation and extraction of the tissue as well as the temperature and the presence of salt, mercaptoethanol and inhibitors. Storage of the tissue in toluene does affect the yield and the properties of acetylcholinesterase obtained from rat brain thus emphasising the need to clearly define the methods and conditions of solubilization when reporting the presence of multiple molecular forms of acetylcholinesterase. PMID- 19643068 TI - Effects of m-chlorophenylpiperazine on receptor binding and brain metabolism of monoamines in rats. AB - m-Chlorophenylpiperazine (mCPP) was studied for its ability to displace the binding of (3)H-ligands for monoamines to brain membranes and its effect on monoamine metabolism in various brain areas of the rat. mCPP displaced (3)H serotonin binding to cortex membranes (Ki = 10(-7) M) but had virtually no effect on (3)H-spiroperidol binding to striatal membranes used as ligand for dopamine receptors (Ki > 10(-5) M). mCPP showed Ki values very similar to those of noradrenaline in displacing the binding of (3)H-WB 4101 (2-2,6-dimethoxy-phenoxy ethylaminomethylbenzodioxan) and (3)H-DHA ((3)H-dihydroalprenolol), used as ligands for alpha(1) and beta adrenergic receptors respectively. At 0.3 and 1 mg/kg, mCPP preferentially reduced serotonin metabolism (decrease of 5-hydroxy indoleacetic acid level) in various brain areas but at 3 and 10 mg/kg it raised homovanillic levels in the striatum and nucleus accumbens and 3-methoxy-4 hydroxyphenylethylene glycol sulphate levels in the brain as well. The data are compatible with the hypothesis that at lower doses mCPP preferentially acts by mimicking the action of serotonin on postsynaptic receptors. It is suggested that the effects on dopamine metabolism observed with higher doses might be mediated by the action of mCPP on brain serotonin, whereas direct action on central noradrenaline-containing neurons could contribute to the increase of noradrenaline metabolism. PMID- 19643069 TI - Purification and characterization of an ATP-binding protein from brain membranes. AB - An ATP-binding protein was purified from pig cerebral cortex. Extraction of a crude membrane fraction with distilled water, differential acetone fractionation and sequential column chromatography on Sephadex G 200, DEAE-Sephacel and an ATP affinity Sepharose led to a 310-fold purification. ATPase, phosphodiesterase, adenylate cyclase and protein kinase were separated during the preparation. ATP binding was studied by a filtration technique. Specific binding of ATP exhibited a biphasic time course and was pH and temperature dependent. Scatchard plots of equilibrium binding data were nonlinear suggesting the existence of two different binding sites for ATP. The dissociation constants (K(d)) were 4.1 x 10(-8) and 2.0 x 10(-7) M and the maximal number of binding sites (B(max)) 0.68 and 1.0 nmol ATP bound per mg of purified protein. Several related compounds were studied for their ability to inhibit ATP-binding. Only ADP, GTP and CTP, but not adenosine, AMP, cyclic AMP and cyclic GMP, were potent in displacing ATP from its binding sites. Specific binding of ATP was strictly dependent on the presence of divalent cations, Mg(2+), Mn(2+) and Ca(2+) being equipotent. PMID- 19643070 TI - Guanylate cyclase in synaptosomal soluble fraction from rat brain: possible involvement of free radical acceptor in endogenous activation mechanisms. AB - Guanylate cyclase (GTP pyrophosphate-lyase (cyclizing); EC 4.6.1.2), in the crude synaptosomal soluble (P(2)-soluble) fraction obtained by hypo-osmotic treatment and subsequent centrifugation of crude synaptosomal (P(2)) fraction from the rat brain, showed a significantly high activity when assayed in the presence of high concentration of Mn(2+). The basal activity was markedly inhibited by various compounds reacting with free radicals. Guanylate cyclase in the P(2)-soluble fraction treated with acetone exhibited a low activity and was not activated by nitrosoguanidine. The responsiveness to nitrosoguanidine was restored, however, by the addition of low concentration hemin. On the other hand, the preincubation (37 degrees C, 10 min) of P(2)-soluble fraction with membranous fraction of P(2) similarly induced a marked decrease of guanylate cyclase activity, but this enzyme was strongly stimulated by nitrosoguanidine. The responsiveness of the enzyme to nitrosoguanidine was also eliminated by acetone-treatment or gel filtration on Sepharose 6B, but was partially restored by the addition of hemin. These results suggest that guanylate cyclase in the P(2)-soluble fraction from rat brain may be activated endogenously by free radical(s) through a free radical acceptor which is replaceable by hemin. PMID- 19643071 TI - Analysis of fluctuations in the activity of rat pineal tyrosine hydroxylase. AB - Tyrosine hydroxylase was measured in pineals removed from light-adapted and dark adapted rats. The animals were adapted to the appropriate light situation for approximately 5 h before removal of the pineals. Bilateral ganglionectomy confirmed that all detectable enzyme activity in the pineal appears present in sympathetic fibers originating in the superior cervical ganglia. An analysis of tyrosine hydroxylase at subsaturating cofactor concentrations in dark-adapted rats revealed activity which was 60% higher than in appropriate light control animals. Further kinetic analysis showed that the K(m) for the synthetic cofactor, 6-methyltetrahydropterin, for dark-adapted animals was 0.8 + or - 0.1 mM which was significantly lower than a K(m) value of 1.4 + or - 0.2 mM for light adapted animals. Thus the rate of norepinephrine synthesis in vivo could increase due to an alteration in the enzyme molecule, which affects its interaction with substrate. These findings support previously documented results which show both an increased turnover and an increase in the concentration of norepinephrine in the pineals of dark-adapted rats. PMID- 19643072 TI - Profiling of gene-dependent translational progress in cell-free protein synthesis by real-space imaging. AB - In general, gene-dependent translational progress affects the efficiency of protein expression. To evaluate the translational progress of protein synthesis, it is necessary to trace the time course of translation as well as the quantity of products. Here we present a new method for tracking translation steps in cell free protein synthesis using atomic force microscopy (AFM). The cell-free protein synthesis system is useful to track the inherent translational progress of a target gene, whereas conventional UV absorption measurement coupled with density gradient fractionation is difficult to analyze such small sample quantities. Because the high resolution of AFM enables us to clearly count the number of ribosomes included in polysomes, polysome profiles can be obtained directly without complicated fractionation. With this method, we could elucidate the detailed polysome profile with only 1 microl of sample solution. We observed the translational progress of green fluorescent protein synthesis, a model of high expression protein, as well as human retinoid X receptor. Detailed polysome profiles showed different patterns of translational progress and were clearly associated with the results of time-dependent protein expression. Our study suggests the possibility for comprehensive character analysis of inherent gene dependent translational progress. PMID- 19643073 TI - Proteome analysis of a single zebrafish embryo using three different digestion strategies coupled with liquid chromatography-tandem mass spectrometry. AB - Zebrafish is a powerful model to analyze vertebrate embryogenesis and organ development. Although a number of genes have been identified to specify embryonic development processes, only a few large-scale proteomic analyses have been reported in regard to these events to date. Here the total proteins of a single embryo were analyzed by urea-, sodium deoxycholate (SDC)-, and performic acid (PA)-assisted trypsin digestion strategies coupled to capillary liquid chromatography-tandem mass spectrometry (CapLC-MS/MS) identification. In total, 509 and 210 proteins were detected from the embryos at 72 and 120 hours postfertilization (hpf), respectively, with a false identification rate of less than 1%. Approximately 95% of those proteins could be observed by combining the urea- and SDC-assisted digestion strategies, suggesting that these two methods are more effective than the PA-assisted method. Compared with 0.5% SDC, 1% SDC was more effective to identify proteins in zebrafish embryos. In addition, removal of the predominant yolk proteins could significantly improve protein identification efficiency. Our study represents the first overview of the protein expression profile of a single zebrafish embryo at 72 or 120 hpf. More important, this single individual proteome methodology could be applied to multiple development stages of wide-type or mutant embryos, providing a simple and powerful way to further our understanding of embryonic development. PMID- 19643074 TI - A gas chromatography-mass spectrometry method for the quantitation of N nitrosoproline and N-acetyl-S-allylcysteine in human urine: application to a study of the effects of garlic consumption on nitrosation. AB - Biomarkers in urine can provide useful information about the bioactivation of chemical carcinogens and can be used to investigate the chemoprotective properties of dietary nutrients. N-Nitrosoproline (NPRO) excretion has been used as an index for endogenous nitrosation. In vitro and animal studies have reported that compounds in garlic may suppress nitrosation and inhibit carcinogenesis. We present a new method for extraction and sensitive detection of both NPRO and N acetyl-S-allylcysteine from urine. The latter is a metabolite of S-allylcysteine, which is found in garlic. Urine was acidified and the organic acids were extracted by reversed-phase extraction (RP-SPE) and use of a polymeric weak anion exchange (WAX-SPE) resin. NPRO was quantified by isotope dilution gas chromatography-mass spectrometry (GC-MS) using [13C5]NPRO and N nitrosopipecolinic acid (NPIC) as internal standards. This method was used to analyze urine samples from a study that was designed to test whether garlic supplementation inhibits NPRO synthesis. Using this method, 2.4 to 46.0 ng NPRO/ml urine was detected. The method is straightforward and reliable, and it can be performed with readily available GC-MS instruments. N-Acetyl-S allylcysteine was quantified in the same fraction and detectable at levels of 4.1 to 176.4 ng/ml urine. The results suggest that 3 to 5 g of garlic supplements inhibited NPRO synthesis to an extent similar to a 0.5-g dose of ascorbic acid or a commercial supplement of aged garlic extract. Urinary NPRO concentration was inversely associated with the N-acetyl-S-allylcysteine concentration. It is possible that allyl sulfur compounds found in garlic may inhibit nitrosation in humans. PMID- 19643075 TI - Characterization and complementation of a psbR mutant in Arabidopsis thaliana. AB - In this communication we have characterized an Arabidopsis thaliana mutant which lacks the PsbR protein of Photosystem II and complemented its phenotype by introduction and expression of a C-terminally His(6)-tagged PsbR protein. Absence of the PsbR protein leads to decreased levels of the PsbP, PsbQ and D2 proteins associated with Photosystem II membranes. Functional defects in the mutant were localized principally to the reducing-side of the photosystem and included slowing of electron transfer from Q(A)(-) to Q(B). These defects were almost fully corrected in transgenic plants containing the C-terminally His(6)-tagged PsbR protein. We hypothesize that the functional defects observed in the mutant were due to defective assembly and/or binding of the PsbP and PsbQ components to Photosystem II in the absence of the PsbR protein. PMID- 19643077 TI - A novel functional element in the N-terminal region of Arum concinnatum alternative oxidase is indispensable for catalytic activity of the enzyme in HeLa cells. AB - Alternative oxidase (AOX) is a quinol-oxygen oxidoreductase, which is known to possess a dicarboxylate diiron reaction center held in structurally postulated alpha-helical bundle. However, little is known about the structural or functional features of its N-terminal region in any organism, with the exception of a regulatory cysteine residue (CysI) in angiosperm plants. Here, we show that transcripts of two AOX1 isozymes (AcoAOX1a and AcoAOX1b) are coexpressed in thermogenic appendices of Arum concinnatum, while their enzymatic activities seem to be distinct. Namely, AcoAOX1a, an abundantly expressed transcript in vivo, shows an apparent cyanide-insensitive and n-propyl gallate-sensitive respiration during ectopic expression of the protein in HeLa cells, whereas AcoAOX1b exhibits a lower transcript expression, and appears to be totally inactive as AOX at the protein level. Our functional analyses further reveal that an E83K substitution in AcoAOX1b, which is located far upstream of CysI in the N-terminal region, is the cause of this loss of function. These results suggest the presence of a naturally occurring inactive AOX homologue in thermogenic plants. Accordingly, our results further imply that the N-terminal region of the AOX protein functionally contributes to the dynamic activities of respiratory control within the mitochondria. PMID- 19643076 TI - Flavin-dependent thymidylate synthase: a novel pathway towards thymine. AB - For several decades only one chemical pathway was known for the de novo biosynthesis of the essential DNA nucleotide, thymidylate. This reaction catalyzed by thyA or TYMS encoded thymidylate synthases is the last committed step in the biosynthesis of thymidylate and proceeds via the reductive methylation of uridylate. However, many microorganisms have recently been shown to produce a novel, flavin-dependent thymidylate synthase encoded by the thyX gene. Preliminary structural and mechanistic studies have shown substantial differences between these deoxyuridylate-methylating enzymes. Recently, both the chemical and kinetic mechanisms of FDTS have provided further insight into the distinctions between thyA and thyX encoded thymidylate synthases. Since FDTSs are found in several severe human pathogens their unusual mechanism offers a promising future for the development of antibiotic and antiviral drugs with little effect on human thymidylate biosynthesis. PMID- 19643078 TI - D1 protein variants in Photosystem II from Thermosynechococcus elongatus studied by low temperature optical spectroscopy. AB - In Photosystem II (PSII) from Thermosynechococcus elongatus, high-light intensity growth conditions induce the preferential expression of the psbA(3) gene over the psbA(1) gene. These genes encode for the D1 protein variants labeled D1:3 and D1:1, respectively. We have compared steady state absorption and photo-induced difference spectra at <10 K of PSII containing either D1:1 or D1:3. The following differences were observed. (i) The pheophytin Q(x) band was red-shifted in D1:3 (547.3 nm) compared to D1:1 (544.3 nm). (ii) The electrochromism on the Pheo(D1) Q(x) band induced by Q(A)(-) (the C550 shift) was more asymmetric in D1:3. (iii) The two variants differed in their responses to excitation with far red (704 nm) light. When green light was used there was little difference between the two variants. With far red light the stable (t(1/2)>50 ms) Q(A)(-) yield was approximately 95% in D1:3, and approximately 60% in D1:1, relative to green light excitation. (iv) For the D1:1 variant, the quantum efficiency of photo-induced oxidation of side-pathway donors was lower. These effects can be correlated with amino acid changes between the two D1 variants. The effects on the pheophytin Q(x) band can be attributed to the hydrogen bond from Glu130 in D1:3 to the 13(1) keto of Pheo(D1), which is absent for Gln130 in D1:1. The reduced yield with red light in the D1:1 variant could be associated with either the Glu130Gln change, and/or the four changes near the binding site of P(D1), in particular Ser153Ala. Photo-induced Q(A)(-) formation with far red light is assigned to the direct optical excitation of a weakly absorbing charge transfer state of the reaction centre. We suggest that this state is blue-shifted in the D1:1 variant. A reduced efficiency for the oxidation of side-pathway donors in the D1:1 variant could be explained by a variation in the location and/or redox potential of P+. PMID- 19643079 TI - A possible role of lysophospholipids produced by calcium-independent phospholipase A(2) in membrane-raft budding and fission. AB - Phospholipase A(2) (PLA(2)) not only plays a role in the membrane vesiculation system but also mediates membrane-raft budding and fission in artificial giant liposomes. This study aimed to demonstrate the same effects in living cells. Differentiated Caco-2 cells were cultured on filter membranes. MDCK cells were challenged with Influenza virus. The MDCK cultures were harvested for virus titration with a plaque assay. Alkaline phosphatase (ALP), a membrane-raft associated glycosylphosphatidylinositol (GPI)-anchored protein, was 70% released by adding 0.2 mmol/l lysophosphatidylcholine, which was abolished by treatment with a membrane-raft disrupter, methyl-beta-cyclodextrin. Activation of calcium independent PLA(2) (iPLA(2)) by brefeldin A increased the apical release of ALP by approximately 1.5-fold (p<0.01), which was blocked by PLA(2) inhibitor bromoenol lactone (BEL). BEL also reduced Influenza virus production into the media (<10%) in the MDCK culture. These results suggest that cells utilize inverted corn-shaped lysophospholipids generated by PLA(2) to modulate plasma membrane structure and assist the budding of raft-associated plasma membrane particles, which virus utilizes for its budding. Brush borders are enriched with membrane-rafts and undergo rapid turnover; thus, PLA(2) may be involved in the regulatory mechanism in membrane dynamism. Further, iPLA(2) may provide a therapeutic target for viral infections. PMID- 19643080 TI - DNA-binding specificity of the Lon protease alpha-domain from Brevibacillus thermoruber WR-249. AB - Lon protease has been well studied in many aspects; however, the DNA-binding specificity of Lon in prokaryotes has not been clearly identified. Here we examined the DNA-binding activity of Lon protease alpha-domains from Brevibacillus thermoruber (Bt), Bacillus subtilis (Bs), and Escherichia coli (Ec). MALDI-TOF mass spectroscopy showed that the alpha-domain from Bt-Lon binds to the duplex nucleotide sequence 5'-CTGTTAGCGGGC-3' (ms1) and protected it from DNase I digestion. Surface plasmon resonance showed that the Bt-Lon alpha-domain binds with ms1 double-stranded DNA tighter than Bs- and Ec-Lon alpha-domains, whereas the Bt-Lon alpha-domain has dramatically lower affinity for double stranded DNA with 0 and 50% identity to the ms1 binding sequence. Our results indicated that Bt-Lon alpha-domain plays a critical role with ms1 sequence in the DNA-binding specificity. PMID- 19643081 TI - Salvianolic acid B-vitamin C synergy in cardiac differentiation from embryonic stem cells. AB - Inefficient cardiomyocyte differentiation limits the therapeutic use of embryonic stem (ES) cell-derived cardiomyocytes. While large collections of proprietary chemicals had been screened to improve ES cell differentiation into cardiomyocytes, the natural product library remained unexplored. Using a mouse ES cell line transfected with a cardiomyocyte-specific alpha-myosin heavy chain promoter-driven enhanced green fluorescent protein (EGFP) reporter, we screened 24 natural products with known cardioprotective actions. Salvianolic acid B (saB), while produced minimal effect on its own, concentration-dependently synergized with vitamin C in inducing cardiomyocyte differentiation, as demonstrated by an increase in EGFP(+) cells, beating area in embryoid bodies, and expression of cardiomyocyte maturity markers. This synergy is specific to cardiomyocyte differentiation, and is involved with collagen synthesis. The present study demonstrates the saB-vitamin C synergy in inducing ES cell differentiation into matured and functional cardiomyocytes, and this may lead to a practicable cocktail approach to generate ES cell-derived cardiomyocytes for cardiac stem cell therapy. PMID- 19643083 TI - HIF-1alpha is necessary to support gluconeogenesis during liver regeneration. AB - Coordinated recovery of hepatic glucose metabolism is prerequisite for normal liver regeneration. To examine roles of hypoxia inducible factor-1alpha (HIF 1alpha) for hepatic glucose homeostasis during the reparative process, we inactivated the gene in hepatocytes in vivo. Following partial hepatectomy (PH), recovery of residual liver weight was initially retarded in the mutant mice by down-regulation of hepatocyte proliferation, but occurred comparably between the mutant and control mice at 72h after PH. At this time point, the mutant mice showed lowered blood glucose levels with enhanced accumulation of glycogen in the liver. The mutant mice exhibited impairment of hepatic gluconeogenesis as assessed by alanine tolerance test. This appeared to result from reduced expression of PGK-1 and PEPCK since 3-PG, PEP and malate were accumulated to greater extents in the regenerated liver. In conclusion, these findings provide evidence for roles of HIF-1alpha in the regulation of gluconeogenesis under liver regeneration. PMID- 19643082 TI - Sirtuin 1 overexpression mice show a reference memory deficit, but not neuroprotection. AB - Sirtuin 1 (SIRT1) is the closest mammalian homologue of yeast silent information regulator 2 (Sir2) and has a role in lifespan modulation. Reportedly, SIRT1 is also linked to neurodegenerative diseases. However, there are limited studies that report the relation between SIRT1 and neurodegenerative diseases using in vivo transgenic (Tg) methods. In the present study, we generated neuron-specific enolase (NSE) SIRT1 Tg mice that overexpress human SIRT1 in neurons. We examined possible neuroprotective effects of SIRT1 overexpression and compared their higher brain functions with those of wild-type (WT) mice. Overexpression of SIRT1 did not have any neuroprotective effects against the neuronal damage induced by ischemia or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, SIRT1 Tg mice exhibited a reference memory deficit. These findings suggest that an excessive expression of SIRT1 might induce the memory deficit in mice, but not neuroprotective effects. PMID- 19643084 TI - Endothelial cells promote the proliferation of lymphocytes partly through the Wnt pathway via LEF-1. AB - The function of T cells and B cells is to recognize specific "non-self" antigens, during a process known as antigen presentation. Once they have identified an invader, the cells generate specific responses that are tailored to maximally eliminate specific pathogens or pathogen-infected cells. Endothelial cells (ECs) can trigger the activation of T cells through their class I and class II MHC molecules. In this study, we examined the effect of ECs on the proliferation of lymphocytes. We report that the proliferation of T and B cells can be improved by interaction with ECs. LEF-1 is one of the main molecular mediators in this process, and the inhibition of LEF-1 induces apoptosis. These results suggest that LEF-1 modulates positively the proliferation of lymphocytes induced by their interaction with ECs. PMID- 19643085 TI - Structural basis for the Helicobacter pylori-carcinogenic TNF-alpha-inducing protein. AB - Stomach cancer is strongly associated with infection by Helicobacter pylori. In 2005, we identified a new H. pylori gene encoding a TNF-alpha inducing protein (Tipalpha) that acts as a carcinogenic factor. Tipalpha is secreted from H. pylori as a homodimer whose subunits are linked by disulfide bonds. We also characterized a Tipalpha deletion mutant (del-Tipalpha) that lacks the N-terminal six amino acid residues (LQACTC), including two cysteines (C5 and C7) that form disulfide bonds, but nonetheless shows a weak ability to induce TNF-alpha expression. Here we report that del-Tipalpha has a novel elongated structure containing a 40-A-long alpha helix, and forms a heart-shaped homodimer via non covalent bonds. Moreover, their circular dichroism spectra strongly suggest that the structures of the del-Tipalpha and Tipalpha homodimers are very similar. del Tipalpha's unique mode of dimer formation provides important insight into protein protein interactions and into the mechanism underlying the carcinogenicity of H. pylori infection. PMID- 19643086 TI - Functional elements in the minimal promoter of the human proton-coupled folate transporter. AB - The proton-coupled folate transporter (PCFT) is the dominant intestinal folate transporter, however, its promoter has yet to be revealed. Hence, we here cloned a 3.1kb fragment upstream to the first ATG of the human PCFT gene and generated sequential deletion constructs evaluated in luciferase reporter assay. This analysis mapped the minimal promoter to 157bp upstream to the first ATG. Crucial GC-box sites were identified within the minimal promoter and in its close vicinity which substantially contribute to promoter activity, as their disruption resulted in 94% loss of luciferase activity. We also identified upstream enhancer elements including YY1 and AP1 which, although distantly located, prominently transactivated the minimal promoter, as their inactivation resulted in 50% decrease in reporter activity. This is the first functional identification of the minimal PCFT promoter harboring crucial GC-box elements that markedly contribute to its transcriptional activation via putative interaction with distal YY1 and AP1 enhancer elements. PMID- 19643087 TI - Effective neuropathic pain relief through sciatic nerve administration of GAD65 expressing rAAV2. AB - Recently, we demonstrated that the administration of GAD65-expressing rAAV2 to DRG attenuates peripheral neuropathy by inducing GABA release in the spinal cord. However, the direct injection to DRG is invasive and may therefore cause nerve injury and other side effects. To circumvent this surgical intervention, we explored the potential of a much simpler and less invasive route of sciatic nerve administration. Using a neuropathic pain model, we introduced rAAV2-GAD65 through sciatic nerve and examined its therapeutic potency in pain-related behavior tests. Both GFP and GAD65 expression indicated that effective transgene delivery to the DRG can be accomplished via sciatic nerve administration. Equally importantly, the GABA concentration in the spinal cord increased significantly after GAD65 introduction, and pain symptoms were dramatically reduced and persistently controlled. The implication is that the sciatic nerve is a highly promising route for delivering rAAV2 to the DRG, and thus represents a much less invasive, clinically viable gene therapy option. PMID- 19643088 TI - Antiproliferative and antiangiogenic effects of the benzophenanthridine alkaloid sanguinarine in melanoma. AB - This study was aimed at evaluating the potential application of benzophenanthridine alkaloids, sanguinarine and cheleritrine, in the therapy of melanoma cancer. In vitro antiproliferative activity of sanguinarine was higher than that of cheleritrine against the B16 melanoma 4A5 cells. Both agents were able to produce DNA breaks, and the DNA unwinding assay showed that they act as DNA intercalating agents. Sanguinarine was selected for determination of its in vivo preclinical efficacy. Oral treatment with sanguinarine reduced the tumor burden in a transplantable murine tumor grown in a syngeneic host (B16 melanoma 4A5 in C57BL/6 mice), and in a human tumor xenograft grown in immunodeficient mice (A375 human melanoma in athymic nude mice). In A375 tumors a significant decrease in the proliferation marker Ki67, and a reduction in the activated mitogen-activated protein kinases (p-p44/42 MAPK), and in protein kinase B (pAKT) were also observed. Three out of eleven A375-bearing treated mice were tumor-free at the end of treatment, and did not develop any tumor after a further, treatment free, observation period of 60 days. Sanguinarine also showed a striking antiangiogenic activity in mice. Data from the present study support the concept that sanguinarine can be effective in melanoma skin cancer. PMID- 19643089 TI - Useful pharmacological parameters for G-protein-coupled receptor homodimers obtained from competition experiments. Agonist-antagonist binding modulation. AB - Many G-protein-coupled receptors (GPCRs) are expressed on the plasma membrane as dimers. Since drug binding data are currently fitted using equations developed for monomeric receptors, the interpretation of the pharmacological data are equivocal in many cases. As reported here, GPCR dimer models account for changes in competition curve shape as a function of the radioligand concentration used, something that cannot be explained by monomeric receptor models. Macroscopic equilibrium dissociation constants for the agonist and homotropic cooperativity index reflecting the intramolecular communication within the dopamine D1 or adenosine A2A receptor homodimer as well as hybrid equilibrium dissociation constant, which reflects the antagonist/agonist modulation may be calculated by fitting binding data from antagonist/agonist competition experiments to equations developed from dimer receptor models. Comparing fitting the data by assuming a classical monomeric receptor model or a dimer model, it is shown that dimer receptor models provide more clues useful in drug discovery than monomer-based models. PMID- 19643090 TI - Characterization of transgenic mice with neuron-specific expression of soluble epoxide hydrolase. AB - Soluble epoxide hydrolase (sEH) is the major enzyme responsible for the metabolism and inactivation of epoxyeicosatrienoic acids (EETs). EETs are produced by the cytochrome P450 (CYP) epoxygenase pathway of arachidonic acid (AA) metabolism and tend to be anti-hypertensive, anti-inflammatory and protective against ischemic injury. Since the metabolism of EETs by sEH reduces or eliminates their bioactivity, inhibition of sEH has become a therapeutic strategy for hypertension and inflammation. sEH is found in nearly all tissues so the systemic application of inhibitors is likely to affect more than blood pressure and inflammation. In the central nervous system, EETs are thought to play a role in the regulation of local blood flow, protection from ischemic injury, inhibition of inflammation, the release of peptide hormones and modulation of fever. However, little is known about region- and cell-specific expression of sEH in the brain. In the mouse brain, expression of sEH was found widely in cortical and hippocampal astrocytes and also in a few specific neuron types in the cortex, cerebellum, and medulla. To assess the functional significance of neuronal sEH, we generated a transgenic mouse model, which over expresses sEH specifically in neurons. Transgenic mice showed increased neuron labeling in cortex and hippocampus with little change in labeling of other brain regions. Despite a 3-fold increase in sEH activity in the brain, there was no change in arterial pressure. This data provides new information required for studying the central roles of the cytochrome P450 epoxygenase pathway. PMID- 19643091 TI - Acute brown adipose tissue temperature response to cold in monosodium glutamate treated Siberian hamsters. AB - Neonatal monosodium glutamate (MSG) administration increases adiposity, decreases energy expenditure and is associated with arcuate nucleus (Arc) destruction. Disrupted brown adipose tissue (BAT) thermogenesis underlies some of these effects, although, interscapular BAT temperature (T(IBAT)) has not been measured. Therefore, we tested the effects of neonatal MSG or vehicle administration in Siberian hamsters and, when they were adults, measured T(IBAT) during acute cold exposure. The Arc and its projection to the hypothalamic paraventricular nucleus (PVH) are both components of the CNS outflow circuits to IBAT, with the latter implicated in BAT thermogenesis that could be compromised by MSG treatment. Using a viral transneuronal tract tracer, pseudorabies virus (PRV), we also tested whether the components of these circuits were intact. As adults, MSG-treated hamsters had significantly increased body mass and some white fat pad masses, markedly reduced Arc Nissl and neuropeptide staining, and PVH neuropeptide fiber staining. Cold-exposed (18 h at 5 degrees C) MSG- and vehicle-treated hamsters initially maintained T(IBAT), but the ability of the former waned after 2 h being significantly decreased by 18 h. PRV immunoreactive fibers/cells were not altered by neonatal MSG treatment despite substantial Arc and PVH destruction. MSG- and vehicle-treated hamsters given an exogenous norepinephrine challenge showed identical increases in the duration and peak of T(IBAT). Thus, the inability of MSG-treated animals to sustain T(IBAT) in the cold is not due to any obvious MSG induced deletions of central sympathetic outflow circuits to IBAT, but appears to be extrinsic to the tissue nevertheless. PMID- 19643092 TI - Neuregulin 1 transgenic mice display reduced mismatch negativity, contextual fear conditioning and social interactions. AB - INTRODUCTION: Neuregulin-1 (NRG1) is one of susceptibility genes for schizophrenia and plays critical roles in glutamatergic, dopaminergic and GABAergic signaling. Using mutant mice heterozygous for Nrg1 (Nrg1(+/-)) we studied the effects of Nrg1 signaling on behavioral and electrophysiological measures relevant to schizophrenia. EXPERIMENTAL PROCEDURE: Behavior of Nrg1(+/-) mice and their wild type littermates was evaluated using pre-pulse inhibition, contextual fear conditioning, novel object recognition, locomotor, and social choice paradigms. Event-related potentials (ERPs) were recorded to assess auditory gating and novel stimulus detection. RESULTS: Gating of ERPs was unaffected in Nrg1(+/-) mice, but mismatch negativity in response to novel stimuli was attenuated. The Nrg1(+/-) mice exhibited behavioral deficits in contextual fear conditioning and social interactions, while locomotor activity, pre-pulse inhibition and novel object recognition were not impaired. SUMMARY: Nrg1(+/-) mice had impairments in a subset of behavioral and electrophysiological tasks relevant to the negative/cognitive symptom domains of schizophrenia that are thought to be influenced by glutamatergic and dopaminergic neurotransmission. These mice are a valuable tool for studying endophenotypes of schizophrenia, but highlight that single genes cannot account for the complex pathophysiology of the disorder. PMID- 19643095 TI - Preconditioning with 4-aminopyridine protects cerebellar granule neurons against excitotoxicity. AB - Preconditioning by excitatory stimuli such as N-methyl-d-aspartate (NMDA) offers good neuroprotection against excitotoxic insults, but is potentially limited by the risk of damage associated with the treatment. We report here the potential of an alternative strategy, tested on rat neonatal cerebellar granule neurons, which involves a 48-hour preconditioning step using the potassium channel blocker 4 aminopyridine (4-AP), at a low (50 microM) and at a higher (2500 microM) concentration (in the presence or absence of the GABA(A) receptor antagonist, bicuculline). 4-Aminopyridine gave extensive protection against a number of stressors (glutamate, NMDA and 3-nitropropionic acid) applied 24 h following the end of the preconditioning period. Blockade of neuronal depolarisation by tetrodotoxin during preconditioning attenuated but did not eliminate protection, whilst co-application with the NMDA receptor blocker MK-801 increased protection. Western blot analysis showed that CREB phosphorylation was significantly increased by the 4-AP preconditioning, although bcl-2 expression was not stimulated. Glutamate induced cell death without significant activation of caspase-3, suggesting that 4-AP preconditioning is effective primarily against necrotic excitotoxicity. Since 4-AP preconditioning affords extensive protection against a range of neurotoxic insults we propose that it could provide the basis for a novel neuroprotective therapy worthy of further investigation. PMID- 19643093 TI - Spatial learning and memory deficits following exposure to 24 h of sleep fragmentation or intermittent hypoxia in a rat model of obstructive sleep apnea. AB - Obstructive sleep apnea is primarily characterized by hypoxemia due to frequent apneic episodes and fragmentation of sleep due to the brief arousals that terminate the apneic episodes. Though neurobehavioral deficits frequently accompany sleep apnea, the relative roles of hypoxia versus sleep fragmentation are difficult to separate in apneic patients. Here, we assessed cognitive function as measured by water maze in the Fischer/Brown Norway (FBN) rat, comparing 24 h of sleep interruption (SI) to 24 h of intermittent hypoxia (IH), in order to dissociate their relative contributions to cognitive impairment. For SI, automated treadmills were used to induce brief ambulation in rats every 2 min, either prior to, or after, initial water maze acquisition training. IH was simulated by cycling environmental oxygen levels between 6% and 19% every 2 min, again either prior to, or after, acquisition. Twenty-four hours of IH exposure had no significant effect on either acquisition or retention, irrespective of whether IH occurred prior to, or after, acquisition. To replicate previous work, another group of rats, exposed to 3 days of IH (10 h/day) prior to acquisition, had impaired performance during acquisition. A comparison of the 24 h IH and 3 day IH findings suggests that a minimum amount of IH exposure is necessary to produce detectable spatial memory impairments. Although SI before acquisition had no effect on acquisition or later retention of the hidden platform location, SI after acquisition robustly impaired retention, indicating that spatial memory consolidation is more susceptible to the effects of sleep disruption than is the acquisition (learning) of spatial information. PMID- 19643094 TI - Leptin "gates" thermogenic action of thyrotropin-releasing hormone in the hindbrain. AB - Leptin, acting as a measure of metabolic fuel availability, exerts a powerful permissive influence on neurogenic thermogenesis. During starvation and an absence of leptin, animals cannot produce thermogenic reactions to cold stress. However, thermogenesis is rescued by restoring leptin. We have previously observed (Hermann, G.E., Barnes, M.J., Rogers, R.C., 2006. Leptin and thyrotropin releasing hormone: cooperative action in the hindbrain to activate brown adipose thermogenesis. Brain Res. 1117, 118-124.) a highly cooperative interaction between leptin and thyrotropin-releasing hormone [TRH] to activate hindbrain generated thermogenic responses. Specifically, exposure to both leptin and TRH elicited a 3.5 degrees C increase in brown adipose tissue [BAT] thermogenesis, while leptin alone did not evoke any change, and TRH alone caused only approximately 1 degrees C increase. The present study shows that the leptin-TRH synergy in controlling brown adipose [BAT] thermogenesis is order-specific and dependent on the feeding status of the animal. That is, fourth ventricular [4V] application of leptin to the food-deprived animal, before TRH injection, yields a substantial increase in BAT; while the reverse order yields a significantly smaller effect. If the animal were fed within minutes of anesthesia, then exogenous leptin was not necessary for TRH to yield a large increase in BAT temperature. The leptin-TRH synergy was uncoupled by pretreatment with the phosphoinositol-tris phosphate kinase [PI3K] inhibitor, wortmannin and the Src SH2 antagonist, PP2. The TRH transduction mechanism utilizes phospholipase C [PLC] potently regulated by the SH2 site. Previous work in culture systems suggests that the product of PI3K activity [PIP3] potently upregulates PLC by activating the SH2 domain of the PLC complex. Perhaps leptin "gates" the thermogenic action of TRH in the hindbrain by invoking this same mechanism. PMID- 19643096 TI - Neuroprotective effects of (arylthio)cyclopentenone derivatives on manganese induced apoptosis in PC12 cells. AB - Parkinson's disease is characterized by degeneration of dopaminergic neurones in the substantia nigra. Chronic manganese poisoning shares many features of Parkinson's disease, and also induces extrapyramidal syndromes that resemble those of Parkinson's disease due to dopamine depletion in the central nervous system. This study was undertaken to develop novel neuroprotective drugs via the identification of compounds that inhibit manganese-induced apoptosis. Here, we report that (arylthio)cyclopentenone derivatives, which are synthetic analogs of cyclopentenone prostaglandins, prevent manganese-induced apoptosis in PC12 cells. A highly sensitive assay of caspase-3/7 activity was used for screening newly synthesized prostaglandin analogs. The results showed that some cyclopentenone derivatives (GIF-0642, GIF-0643, GIF-0644, GIF-0745, and GIF-0747) inhibit manganese-induced caspase-3/7 activation in a concentration-dependent manner. Effective compounds all have an arylthio group, indicating that this structure plays an important role in the anti-apoptotic effects of (arylthio)cyclopentenone derivatives. The anti-apoptotic effects of these compounds were confirmed by verifying their ability to inhibit the DNA fragmentation and caspase-9 activation induced by manganese. Furthermore, GIF-0747 prevented manganese-induced cytochrome c release from mitochondria. These results suggest that (arylthio)cyclopentenone derivatives may be good candidates for treating neurodegenerative diseases. PMID- 19643097 TI - Effect of internal carotid artery reperfusion in combination with Tenecteplase on clinical scores and hemorrhage in a rabbit embolic stroke model. AB - In the present study, we used a modification of the rabbit small clot embolic stroke model (RSCEM), a multiple infarct ischemia model to achieve reperfusion (REP) through the internal carotid artery (ICA) following small clot embolization. We determined if increasing regional cortical blood flow (RCBF) following an embolic stroke is beneficial to neurological outcome. We compared this to cerebral reperfusion induced by the administration of the thrombolytic Tenecteplase (TNK, 1.5 mg/kg, IV bolus) in the presence or absence of REP. In this study, we also measured the incidence of ICH following REP and thrombolytic treatment. Following embolization, RCBF was reduced to 48-55% of baseline. When REP was induced by removal of a CCA ligature, RCBF initially increased to 185% of baseline. REP (P(50)=1.18+/-0.43 mg) had no effect on embolization-induced behavior measured 24 h following embolization compared to control (P(50)=1.01+/ 0.48 mg). However, TNK treatment (2-hours post-embolization) in the absence or presence of REP (initiated 2 h following embolization) significantly (p<0.05) increased the group P(50) to 2.92+/-0.55 mg and 2.42+/-0.40 mg, respectively. In addition, ICH was increased in the REP (42%, p<0.05) and REP-TNK (35%, p>0.05) group compared to either the control group (5.5%) or TNK group (10%). This study show that reperfusion of ICA can increase RCBF following embolization, but this is not associated with improved neurological outcome measured using quantal analysis. However, TNK administration significantly increased behavioral outcome when given 2 h following embolization; an increase that is not affected by combining TNK with REP. PMID- 19643098 TI - Age-related cognitive decline and nesting behavior in an APPswe/PS1 bigenic model of Alzheimer's disease. AB - A large series of 3-, 6-, 9-, and 12-month-old bigenic mice (N=240) with Swedish APP and A246E PS1 mutations was investigated in nest-building, spontaneous alternation, and two learning tasks. Progressive cognitive impairment was observed in APPswe/PS1 mice relative to controls for nest-building, spontaneous alternation, the reversal phase of left-right discrimination learning in a water filled T-maze, and in retention of passive avoidance learning. The behavioral deficits in transgenic mice start at 6 months, appearing to offer an opportunity for assessing potential therapeutic agents in attenuating or preventing Alzheimer's disease. PMID- 19643099 TI - Vasorelaxant effect in rat aortic rings through calcium channel blockage: a preliminary in vitro assessment of a 1,3,4-oxadiazole derivative. AB - The study was undertaken on the basis of several reports in the literature that relaxation of vascular smooth muscles is a good treatment strategy in hypertension, angina and other cardiovascular disorders. Oxadiazoles have been reported to have effect on vascular smooth muscles and calcium influx. The goals of our current in vitro study were to investigate the effect of a 1,3,4 oxadiazole derivative on vascular smooth muscles in rat aorta, and to elucidate the associated signaling pathway. NOX-1 induced a relaxation of vascular smooth muscles in both endothelium intact and denuded rat aortic rings precontracted with norepinephrine or phenylephrine or KCl. NOX-1 also significantly antagonized cumulative dose-response effect of norepinephrine, phenylephrine, KCl or calcium with reduction in submaximal contractions. Verapamil, an L-type of calcium channel blocker, effectively attenuated phenylephrine and calcium induced contractions in aortic rings. Incubation with NOX-1 and verapamil did not significantly alter the dose-response curve of phenylephrine or calcium compared to verapamil treatment alone indicating L-type Ca2+ channel blockage leads to loss of NOX-1 activity. Hence it can be concluded NOX-1 exhibited vasorelaxant action by inhibiting calcium influx from extracellular space to intracellular space through L-type of calcium channels. PMID- 19643100 TI - Performance characteristics of beta-2-microglobulin measurements on a Beckman Immage analyzer with the DakoCytomation reagent kit. AB - OBJECTIVE: Evaluation of serum beta-2-microglobulin (beta2M) in an automated analyzer. DESIGN AND METHODS: The DakoCytomation beta2M kit is an antibody based reagent intended for quantitative determination of beta2M in serum and plasma by rate nephelometry. RESULTS: The limit of blank is 0.16 mg/L. The method is linear up to 17.9 mg/L. The imprecision ranged from 2.1% to 7.9% at the concentrations of 1.77 and 7.19 mg/L, respectively. Method comparison yielded slope=1.009, r=0.998. No interference was observed from hemolytic or icteric specimens. Reference interval of a healthy population was 1.13 mg/L to 3.04 mg/L. CONCLUSION: The DakoCytomation reagent is acceptable to measure serum beta2M. PMID- 19643101 TI - Drugs of abuse testing by tandem mass spectrometry: a rapid, simple method to replace immunoassays. AB - PRIMARY OBJECTIVE: To replace immunoassay screening for drugs of abuse (DOA) with a cost-effective tandem mass spectrometry method. SECONDARY OBJECTIVE: To substantially expand the drugs of abuse assay menu. DESIGN AND METHODS: The requirement was to perform high throughput DOA screening for 200 urine specimens/day for 40 drugs/metabolites. The total analysis time had to be <5 min. We used UPLC chromatography, small particle size LC columns and fast scanning tandem mass spectrometry. Urine samples were hydrolyzed enzymatically, diluted and injected with isotopically labeled internal standards. The data produced was transferred by exporting reports as text files to a LIMS system followed by auto certification of the results. RESULTS: 40 different drugs were separated by UPLC (ultra pressure liquid chromatography) with a run time of 5.2 min. Detection limits were below our cut-off values. Individual drug species instead of drug classes were identified; correlation with GC/MS was excellent. A high throughput, robust assay with acceptable accuracy, precision and specificity was developed. The procedure can also be used as a quantitative method with simple modifications. CONCLUSIONS: An improved, high throughput, cost-effective method for drugs of abuse screening has been implemented. GC/MS confirmations were reduced or eliminated. The new procedure is a viable alternative to our previous immunoassay method. Acceptable turn around times, an expanded menu, simplified sample preparation and analytical reliability makes this method a desirable option in the clinical laboratory setting. PMID- 19643102 TI - Evolution of early embryogenesis in rhabditid nematodes. AB - The cell-biological events that guide early-embryonic development occur with great precision within species but can be quite diverse across species. How these cellular processes evolve and which molecular components underlie evolutionary changes is poorly understood. To begin to address these questions, we systematically investigated early embryogenesis, from the one- to the four-cell embryo, in 34 nematode species related to C. elegans. We found 40 cell-biological characters that captured the phenotypic differences between these species. By tracing the evolutionary changes on a molecular phylogeny, we found that these characters evolved multiple times and independently of one another. Strikingly, all these phenotypes are mimicked by single-gene RNAi experiments in C. elegans. We use these comparisons to hypothesize the molecular mechanisms underlying the evolutionary changes. For example, we predict that a cell polarity module was altered during the evolution of the Protorhabditis group and show that PAR-1, a kinase localized asymmetrically in C. elegans early embryos, is symmetrically localized in the one-cell stage of Protorhabditis group species. Our genome-wide approach identifies candidate molecules-and thereby modules-associated with evolutionary changes in cell-biological phenotypes. PMID- 19643103 TI - Origin of the prechordal plate and patterning of the anteroposterior regional specificity of the involuting and extending archenteron roof of a urodele, Cynops pyrrhogaster. AB - We analyzed the notochord formation, formation of the prechordal plate, and patterning of anteroposterior regional specificity of the involuting and extending archenteron roof of a urodele, Cynops pyrrhogaster. The lower (LDMZ) and upper (UDMZ) domains of the dorsal marginal zone (DMZ) of the early gastrula involuted and formed two distinct domains: the anterior fore-notochordal endodermal roof and the posterior domain containing the prospective notochord. Cygsc is expressed in the LDMZ from the onset of gastrulation, and the Cygsc expressing LDMZ planarly induces the notochord in the UDMZ at the early to mid gastrula stages. At the mid to late gastrula stages, part of the Cygsc-expressing LDMZ is confined to the prechordal plate. On the other hand, Cybra expression only begins at mid gastrula stage, coincident with notochord induction at this stage. Anteroposterior regional specificity of the neural plate was patterned by the posterior domain of the involuting archenteron roof containing the prospective notochord at the mid to late gastrula stages. Cynops gastrulation thus differs significantly from Xenopus gastrulation in that the regions of the DMZ are specified from the onset of gastrulation, while the equivalent state of specification does not occur in Cynops until the middle of gastrulation. Thus we propose that Cynops gastrulation is divided into two phases: a notochord induction phase in the early to mid gastrula, and a neural induction phase in the mid to late gastrula. PMID- 19643104 TI - Jak-STAT regulation of male germline stem cell establishment during Drosophila embryogenesis. AB - Germline stem cells (GSCs) in Drosophila are descendants of primordial germ cells (PGCs) specified during embryogenesis. The precise timing of GSC establishment in the testis has not been determined, nor is it known whether mechanisms that control GSC maintenance in the adult are involved in GSC establishment. Here, we determine that PGCs in the developing male gonad first become GSCs at the embryo to larval transition. This coincides with formation of the embryonic hub; the critical signaling center that regulates adult GSC behavior within the stem cell microenvironment (niche). We find that the Jak-STAT signaling pathway is activated in a subset of PGCs that associate with the newly-formed embryonic hub. These PGCs express GSC markers and function like GSCs, while PGCs that do not associate with the hub begin to differentiate. In the absence of Jak-STAT activation, PGCs adjacent to the hub fail to exhibit the characteristics of GSCs, while ectopic activation of the Jak-STAT pathway prevents differentiation. These findings show that stem cell formation is closely linked to development of the stem cell niche, and suggest that Jak-STAT signaling is required for initial establishment of the GSC population in developing testes. PMID- 19643105 TI - Two Hox cofactors, the Meis/Hth homolog UNC-62 and the Pbx/Exd homolog CEH-20, function together during C. elegans postembryonic mesodermal development. AB - The TALE homeodomain-containing PBC and MEIS proteins play multiple roles during metazoan development. Mutations in these proteins can cause various disorders, including cancer. In this study, we examined the roles of MEIS proteins in mesoderm development in C. elegans using the postembryonic mesodermal M lineage as a model system. We found that the MEIS protein UNC-62 plays essential roles in regulating cell fate specification and differentiation in the M lineage. Furthermore, UNC-62 appears to function together with the PBC protein CEH-20 in regulating these processes. Both unc-62 and ceh-20 have overlapping expression patterns within and outside of the M lineage, and they share physical and regulatory interactions. In particular, we found that ceh-20 is genetically required for the promoter activity of unc-62, providing evidence for another layer of regulatory interactions between MEIS and PBC proteins. PMID- 19643106 TI - Review on enzyme-linked immunosorbent assays for sulfonamide residues in edible animal products. AB - The current status of enzyme-linked immunosorbent assays (ELISAs) for sulfonamides in edible animal products is reviewed. The attention was focused on the design and synthesis of haptens, conjugation to carrier protein, production of antibody, application of homologous and heterologous systems, as well as the molecular modeling of the haptens and sulfonamides. Researches have shown that sulfonamides seem to be particularly resistant to attempts to produce broad specificity antibodies. By summarizing the available research on sulfonamide ELISAs, it is hoped that it can be considered as a basis for further investigation aimed at developing the most efficient approaches for detection. PMID- 19643107 TI - Does the onset of sexual maturation terminate the expression of migratory behaviour in moths? A study of the oriental armyworm, Mythimna separata. AB - It is generally accepted that in most insects adults are sexually immature when they initiate migration and that migratory behaviour terminates with the onset of sexual maturation. However, a few studies examining the mating status of field collected moths have suggested that sexually mature individuals may continue migrating, but in these cases it was impossible to completely eliminate the possibility that the mated females captured came from local, non-migrant populations. In this study we examined the ovarian development of Mythimna separata females captured using a vertical pointing searchlight trap on Beihuang Island in the Bohai Gulf, China, a site >40km from land. Moths were collected from May to October from 2003 to 2008 in order to test the hypothesis that the onset of sexual maturation resulted in the termination of migratory behaviour. While females at the end of the summer had little ovarian development and were unmated, a significant proportion of those migrating northward in the early summer had developed ovaries and often had at least one spermatophore. Given that theses insects were captured while flying up to 500m above sea level, at a site with no local populations, the findings would not support the hypothesis and suggest that both ovarian development and mating may occur during migration. PMID- 19643108 TI - Tarsal morphology and attachment ability of the codling moth Cydia pomonella L. (Lepidoptera, Tortricidae) to smooth surfaces. AB - Despite several studies on the attachment ability of different insect taxa, little is known about this phenomenon in adult Lepidoptera. In this study we combined morphological and experimental analyses of tarsal adhesive devices and the attachment ability of the codling moth Cydia pomonella (L.) (Lepidoptera, Tortricidae) to smooth surfaces. Pretarsi of C. pomonella attach to smooth substrates by means of their smooth, flexible and well developed arolia. Using the centrifugal force measurement technique, friction forces of males and females were assessed on hydrophobic and hydrophilic glass surfaces. Adults of both sexes generated similar forces in spite of the noticeable difference in their body masses. That is why males showed significantly higher safety factors (attachment force divided by body weight) compared to those of females. Hydrophobicity of the substrate had no considerable effect on friction forces. For females, friction forces (sliding parallel to the substrate plane) were compared with adhesive forces (pulling off perpendicularly from the substrate plane) measured on Plexiglas surfaces. It can be concluded that the attachment system of C. pomonella is rather robust against physico-chemical properties of the substrate and is able to achieve a very good attachment on vertical and horizontal substrata. PMID- 19643110 TI - Stochastic tunneling in the colonization of mutualistic organisms: primary succession by mycorrhizal plants. AB - In mutualism under spatial structure, asynchrony between the dispersions of the interacting species can be a key determinant of their dynamics. We focused on the plant-mycorrhizal fungi system to theoretically analyze the colonization process by calculating the probability of colony establishment under environmental fluctuation. This can be considered a joint process of two sub-processes before and after the association between the host plant and the mycorrhizal fungi in a novel habitat. When colony growth undergoes environmental fluctuation, the dynamics of colony size can be considered a combination of the two stochastic sub processes that mediated the association event between the plant and the fungi. Therefore, properties of whole system are influenced by five parameters, means and variances of colony growth rates of two sub-systems, and a rate of association of plant and fungi. For the successful establishment of a colony, the second sub-process must start before the first sub-process finishes (i.e., extinction), which we refer to as "stochastic tunneling." Our analysis of the establishment probability of a plant colony based on this concept revealed that (1) the mean colony growth rates of the host alone and the symbiotic association affect establishment probability in different ways, (2) the variance of colony growth rate of the symbiotic association reduces the establishment probability, although the variance of growth rate of the host alone facilitates the establishment probability when the mean growth rate of the host alone is negative, and (3) a trade-off between the mean colony growth rates of the host alone and the symbiotic association could result in the evolution of either a symbiotic or parasitic relationship, based on a host decision. The model we present is widely applicable to the colonization processes of both positive and negative species relationships, where the interacting species disperse independently. PMID- 19643109 TI - Dynamic extended folding: modeling the RNA secondary structures during co transcriptional folding. AB - For RNA secondary structure prediction, it is an important issue that how to deal with co-transcriptional folding during the RNA synthesis in the cell. On one hand, co-transcriptional folding, leads to the correct final structure of the whole RNA molecule. On the other hand, it may form the recognition sites for the progress of the transcription. Considering the hurdles in the experimental determination of RNA folding structures, we proposed a so-called "dynamic extended folding simulation" approach. We used two human pre-mRNA samples, the first functional alpha-gene HBZ and the fifth beta-gene HBB, to "display" the co transcriptional folding images in detail. The modeling process starts from the prediction of a 30-nucleotide (nt) sequence, then in each update 30 nts was extended, say, 1-30, 1-60, 1-90, 1-120,..., 1-1651 nts (for HBB, 1-1606 nts). We selected the RNAstructure program to predict the folding secondary structures of all the segments. We defined "hairpin" as the unit of the secondary structure and analyzed the states of such unit during the sequential dynamic extended folding processes. We found that some hairpins are "conserved", i.e., after its appearance, it always is there in the followed foldings. Some hairpins present partially in the folding segments, and some hairpins appear for only once or twice. This phenomenon vividly depicts the generation and adjusting of the temporal structural units during the co-transcriptional folding process. It is these "hairpins" that support the thermodynamically stable structure at the end of the RNA synthesis. They may also play a role in RNA splicing process and even in the folding structure of the synthesized protein. PMID- 19643111 TI - Adaptive changes in prey vulnerability shape the response of predator populations to mortality. AB - Simple models are used to explore how adaptive changes in prey vulnerability alter the population response of their predator to increased mortality. If the mortality is an imposed harvest, the change in prey vulnerability also influences the relationship between harvest effort and yield of the predator. The models assume that different prey phenotypes share a single resource, but have different vulnerabilities to the predator. Decreased vulnerability is assumed to decrease resource consumption rate. Adaptive change may occur by phenotypic changes in the traits of a single species or by shifts in the abundances of a pair of coexisting species or morphs. The response of the predator population is influenced by the shape of the predator's functional response, the shape of resource density dependence, and the shape of the tradeoff between vulnerability and food intake in the prey. Given a linear predator functional response, adaptive prey defense tends to produce a decelerating decline in predator population size with increased mortality. Prey defense may also greatly increase the range of mortality rates that allow predator persistence. If the predator has a type-2 response with a significant handling time, adaptive prey defense may have a greater variety of effects on the predator's response to mortality, sometimes producing alternative attractors, population cycles, or increased mean predator density. Situations in which there is disruptive selection on prey defense often imply a bimodal change in yield as a function of harvesting effort, with a minimum at intermediate effort. These results argue against using single-species models of density dependent growth to manage predatory species, and illustrate the importance of incorporating anti-predator behavior into models in applied population ecology. PMID- 19643112 TI - P2X7 regenerative-loop potentiation of glutamate synaptic transmission by microglia and astrocytes. AB - P2X7 purinergic receptors have been implicated in chronic neuropathic and neuroinflammatory pain as well as in depression. These receptors are predominantly found in the central nervous system on microglial cells and on glutamatergic nerve terminals. Here, we develop hypotheses concerning mechanisms by which transient high-frequency impulse firing in glutamatergic terminals, such as occurs in nociceptor terminals accompanying neuropathic/neuroinflammatory pain, can lead to long-lasting changes in neural network function that is mediated by surrounding glial cells. The hypothesis consists of two parts. In the first, glutamate released by low-frequency (2Hz) terminal action potentials is insufficient to generate postsynaptic action potentials, but these are generated by brief high-frequency input bursts. Glutamate released by these bursts is partly removed by transporters on the enveloping astrocyte processes and also excites AMPA receptors on these processes, which then release ATP. This ATP is partly metabolised to adenosine, which acts on presynaptic A1 receptors to inhibit glutamate release. The remaining ATP acts on the presynaptic P2X7 receptors to facilitate glutamate release by both the high-frequency burst of action potentials as well as by a continuous low-frequency (2Hz) action potential firing that occurs in the absence of a neuropathic/neuroinflammatory insult. The positive feedback of terminal glutamate release, triggering astrocyte ATP release and leading to further glutamate release through activation of P2X7 receptors, is then sufficient to allow the normal low-frequency (2Hz) action potentials to now elicit postsynaptic action potentials after the insult is removed. In the second part of this model, the high concentration of ATP derived from astrocytes at the terminal attracts microglia by chemotaxis. The P2X7 receptors on these microglia are then engaged, resulting in microglia secreting the cytokine TNFalpha. This acts on postsynaptic TNF-R1 receptors to increase the number of AMPA receptors there, thus enhancing the efficacy of synaptic transmission. The TNFalpha also acts on presynaptic TNF-R1 to increase the amount of glutamate released by each nerve terminal impulse. Experimental tests can be made of this hypothesis that P2X7 receptors on the presynaptic terminal and those on the microglia synergistically act to ensure feedback pathways that reset to a high level the efficacy of synaptic transmission, thus ensuring chronic neuropathic/neuroinflammatory pain even when the initial insult has subsided. PMID- 19643113 TI - Predicting the fate of microRNA target genes based on sequence features. AB - MicroRNAs (miRNAs) are important post-transcriptional regulators that repress gene expression by binding to the 3'UTRs of their target mRNAs. There are two main outcomes for the transcripts targeted by miRNAs: mRNA degradation and translational repression. It is still unclear what factors determine whether a target transcript is degraded or translationally repressed. In this study, we collected two classes of genes that are targeted by miR-1, miR-155, miR-16, miR 30a, and let-7b and built new computational models with machine-learning methods to predict the fates of target genes based on sequence features. The prediction results indicate that the sequence context of the miRNA binding site at the 3'UTR of a target gene plays an important role in determining how an miRNA regulates the expression of its target. Further analysis shows that four out of the five studied miRNAs probably share similar regulatory mechanisms on their target genes. PMID- 19643114 TI - Morphogenesis by coupled regulatory networks: reliable control of positional information and proportion regulation. AB - Based on a non-equilibrium mechanism for spatial pattern formation we study how position information can be controlled by locally coupled discrete dynamical networks, similar to gene regulation networks of cells in a developing multicellular organism. As an example we study the developmental problems of domain formation and proportion regulation in the presence of noise, as well as in the presence of cell flow. We find that networks that solve this task exhibit a hierarchical structure of information processing and are of similar complexity as developmental circuits of living cells. Proportion regulation is scalable with system size and leads to sharp, precisely localized boundaries of gene expression domains, even for large numbers of cells. A detailed analysis of noise-induced dynamics, using a mean-field approximation, shows that noise in gene expression states stabilizes (rather than disrupts) the spatial pattern in the presence of cell movements, both for stationary as well as growing systems. Finally, we discuss how this mechanism could be realized in the highly dynamic environment of growing tissues in multicellular organisms. PMID- 19643115 TI - Hypoxia/reoxygenation up-regulates death receptor expression and enhances apoptosis in human biliary epithelial cells. AB - AIMS: To investigate whether ischemia/reperfusion (I/R)-induced apoptosis in the bile duct epithelium could be mediated by tumor necrosis factor-related apoptosis inducing ligand (TRAIL) receptors in biliary epithelial cells, we examined the effects of hypoxia/reoxygenation (H/R) on TRAIL cytotoxicity. MAIN METHODS: Using an H/R model, normal primary human intrahepatic biliary epithelial cells were exposed to hypoxia for 1 h, and then reoxygenated. Expressions of death receptor 4 (DR4) and DR5 mRNA and protein were measured. After 1 h of hypoxia, biliary epithelial cells were treated with TRAIL in different concentrations for 4 h. The death of biliary epithelial cells was confirmed by analysis of apoptosis and methylthiazolyl tetrazolium. The activities of caspase-3 and caspase-8 were determined by fluorometric assay. KEY FINDINGS: Compared with normoxic-cultured cells, the mRNA expressions of DR4 and DR5 were up-regulated from 0 min after reoxygenation, reaching a peak value at 60 min after reoxygenation. The protein expression of DR4 was most intense at 90 min after reoxygenation; the most intense expression of DR5 came at 120 min after reoxygenation. The apoptosis rate increased in the TRAIL treatment group and further increased in the TRAIL plus H/R group, and the effect of concentration-dependent TRAIL-mediated cell killing was more pronounced. Caspase-3 and caspase-8 enzymatic activities after H/R also increased with increased TRAIL concentration. SIGNIFICANCE: H/R up-regulated the expression of DR4 and DR5, and enhanced TRAIL-mediated apoptosis in normal human intrahepatic biliary epithelial cells. PMID- 19643117 TI - What's behind an inference? An EEG study with conditional arguments. AB - Conditional reasoning studies typically involve presenting a major conditional premise (If P then Q), a minor premise (P) and a conclusion (Q). We describe how most fMRI studies investigate reasoning and point out that these studies neglect to take into consideration the temporal sequence of cognitive steps generated by the interaction of the premises. The present study uses EEG to address this issue and compares the processing of the minor premise P when it is presented before vs. after the conditional statement (P; If P then Q vs. If P then Q; P). When the minor premise comes after the conditional statement and matches the antecedent its processing results in a P3b component, known to reflect the satisfaction of expectations, and in two later components, a PSW component and a CNV component. These two components are discussed in light of a conclusion generation phase and a maintenance phase. We also investigated the effect of violating expectations through the presentation of a minor premise that mismatches the antecedent of the conditional statement (If P then Q; R). The data indicate that the processing of such a premise yields an N2 component which is known to reflect perceptual conflict. PMID- 19643116 TI - Performance monitoring is altered in adult ADHD: a familial event-related potential investigation. AB - BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder that starts in childhood and frequently persists in adults. Electrophysiological studies in children with ADHD provide evidence for abnormal performance monitoring processes and familial association of these processes with ADHD. It is not yet known whether these processes show the same abnormalities and familial effects in adults. METHOD: We investigated event related potential (ERP) indices of performance monitoring in adults with ADHD compared to age matched control participants. We subsequently investigated whether the ERP indices showed a familial association with ADHD by investigating these processes in first degree relatives of children with ADHD. This was achieved using an arrow flanker task presented to 21 adults with ADHD, 20 fathers of children with ADHD and 20 control participants. RESULTS: Compared to the control group, both adults with ADHD and fathers of children with ADHD displayed significantly weaker error and conflict monitoring, as indexed by the smaller error negativity (Ne) and the N2 components. These two components were highly correlated within each of the three groups (r=0.53-0.65). The groups did not differ on the error positivity (Pe). CONCLUSIONS: These findings closely resemble those previously found in children with ADHD, suggesting that conflict monitoring and early error processing are also abnormal in adults with ADHD; and share familial influences with ADHD throughout the lifespan. The relationship between different indices of performance monitoring may suggest partly common underlying mechanisms or modulators. PMID- 19643118 TI - Dissociation of extrastriate body and biological-motion selective areas by manipulation of visual-motor congruency. AB - To date, several posterior brain regions have been identified that play a role in the visual perception of other people and their movements. The aim of the present study is to understand how these areas may be involved in relating body movements to their visual consequences. We used fMRI to examine the extrastriate body area (EBA), the fusiform body area (FBA), and an area in the posterior superior temporal sulcus (pSTS) that responds to patterns of human biological motion. Each area was localized in individual participants with independent scans. In the main experiment, participants performed and/or viewed simple, intransitive hand actions while in the scanner. An MR-compatible camera with a near-egocentric view of the participant's hand was used to manipulate the relationship between motor output and the visual stimulus. Participants' only view of their hands was via this camera. In the Compatible condition, participants viewed their own live hand movements projected onto the screen. In the Incompatible condition, participants viewed actions that were different from the actions they were executing. In pSTS, the BOLD response in the Incompatible condition was significantly higher than in the Compatible condition. Further, the response in the Compatible condition was below baseline, and no greater than that found in a control condition in which hand actions were performed without any visual input. This indicates a strong suppression in pSTS of the response to the visual stimulus that arises from one's own actions. In contrast, in EBA and FBA, we found a large but equivalent response to the Compatible and Incompatible conditions, and this response was the same as that elicited in a control condition in which hand actions were viewed passively, with no concurrent motor task. These findings indicate that, in contrast to pSTS, EBA and FBA are decoupled from motor systems. Instead we propose that their role is limited to perceptual analysis of body-related visual input. PMID- 19643120 TI - Changes in brain cortical activity measured by EEG are related to individual exercise preferences. AB - Exercise is well known to result in changes of brain cortical activity measured by EEG. The aim of this study was (1) to localise exercise induced changes in brain cortical activity using a distributed source localisation algorithm and (2) to show that the effects of exercise are linked to participants' physical exercise preferences. Electrocortical activity (5 min) and metabolical parameters (heart rate, lactate, peak oxygen uptake) of eleven recreational runners were recorded before and after incremental treadmill, arm crank and bicycle ergometry. Electroencephalographic activity was localised using standardised low resolution brain electromagnetic tomography (sLORETA). Results revealed an increase in frontal alpha activity immediately post exercise whereas increases after bike exercise were found to be localised in parietal regions. All three kinds of exercise resulted in an increase of beta activity in Brodmann area 7. Fifteen and thirty minutes post exercise a specific activation pattern (decrease in frontal brain activity-increase in occipital regions) was noticeable for treadmill and bike but not arm crank exercise. We conclude that specific brain activation patterns are linked to different kinds of exercise and participants' physical exercise preferences. PMID- 19643119 TI - Prefrontal contributions to rule-based and information-integration category learning. AB - Previous research revealed that the basal ganglia play a critical role in category learning [Ell, S. W., Marchant, N. L., & Ivry, R. B. (2006). Focal putamen lesions impair learning in rule-based, but not information-integration categorization tasks. Neuropsychologia, 44(10), 1737-1751; Maddox, W. T. & Filoteo, J. V. (2007). Modeling visual attention and category learning in amnesiacs, striatal-damaged patients and normal aging. In Advances in Clinical cognitive science: formal modeling and assessment of processes and symptoms (pp. 113-146). Washington DC: American Psychological Association] but less is known about the specific role of prefrontal cortical (PFC) regions in category learning. The current study examined rule-based (RB) and information-integration (II) category learning in 13 patients with damage primarily to ventral PFC regions. After 600 learning trials with feedback, patients were significantly less accurate than matched controls on both RB and II learning. Model-based analysis identified subgroups of patients whose impaired performance in each task was due to the use of sub-optimal learning strategies. Those patients impaired at either II or RB learning, performed significantly worse on the Wisconsin Card Sorting Test, a test of abstract rule formation and the ability to shift and maintain rules. Lesion analysis pointed to damage in a fairly circumscribed region of ventral medial prefrontal cortex as common to the impaired group of patients and those patients without ventral PFC damage mostly performed normally. These results provide further evidence that the ventromedial prefrontal cortex is critically important for the ability to monitor and integrate feedback in order to select and maintain optimal learning strategies. PMID- 19643121 TI - Non-steroidal anti-inflammatory drugs interact with testosterone glucuronidation. AB - Testosterone and epitestosterone are secreted mainly as glucuronide metabolites and the urinary ratio of testosterone glucuronide to epitestosterone glucuronide, often called T/E, serves as a marker for possible anabolic steroids abuse by athletes. UDP-glucuronosyltransferase (UGT) 2B17 is the most important catalyst of testosterone glucuronidation. The T/E might be affected by drugs that interact with UGT2B17, or other enzymes that contribute to testosterone glucuronidation. Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used by sportsmen and we have examined the effect of two NSAIDs, diclofenac and ibuprofen, on testosterone and epitestosterone glucuronidation in human liver microsomes. In parallel, we have studied the inhibitory effect of these NSAIDs on recombinant UGT2B17 and UGT2B15, as well as other human hepatic UGTs that revealed low but detectable testosterone glucuronidation activity, namely UGT1A3, UGT1A4, UGT1A9 and UGT2B7. Both diclofenac and ibuprofen inhibited testosterone glucuronidation in microsomes, as well as UGT2B15 and UGT2B17. Interestingly, UGT2B15 was more sensitive than UGT2B17 to the two drugs, particularly to ibuprofen. Human liver microsomes lacking functional UGT2B17 exhibited significantly higher sensitivity to ibuprofen, suggesting that UGT2B15 plays a major role in the residual testosterone glucuronidation activity in UGT2B17-deficient individuals. Nonetheless, a minor contribution of other UGTs, particularly UGT1A9, to testosterone glucuronidation in such individuals cannot be ruled out at this stage. The epitestosterone glucuronidation activity of human liver microsomes was largely insensitive to ibuprofen and diclofenac. Taken together, the results highlight potential interactions between NSAIDs and androgen glucuronidation with possible implications for the validity of doping tests. PMID- 19643122 TI - Low- and high-level motion perception deficits in anisometropic and strabismic amblyopia: evidence from fMRI. AB - Maximum motion displacement (Dmax) is the largest dot displacement in a random dot kinematogram (RDK) at which direction of motion can be correctly discriminated [Braddick, O. (1974). A short-range process in apparent motion. Vision Research, 14, 519-527]. For first-order RDKs, Dmax gets larger as dot size increases and/or dot density decreases. It has been suggested that this increase in Dmax reflects greater involvement of high-level feature-matching motion mechanisms and less dependence on low-level motion detectors [Sato, T. (1998). Dmax: Relations to low- and high-level motion processes. In T. Watanabe (Ed.), High-level motion processing, computational, neurobiological, and psychophysical perspectives (pp. 115-151). Boston: MIT Press]. Recent psychophysical findings [Ho, C. S., & Giaschi, D. E. (2006). Deficient maximum motion displacement in amblyopia. Vision Research, 46, 4595-4603; Ho, C. S., & Giaschi, D. E. (2007). Stereopsis-dependent deficits in maximum motion displacement. Vision Research, 47, 2778-2785] suggest that this "switch" from low-level to high-level motion processing is also observed in children with anisometropic and strabismic amblyopia as RDK dot size is increased and/or dot density is decreased. However, both high- and low-level Dmax were reduced relative to controls. In this study, we used functional MRI to determine the motion-sensitive areas that may account for the reduced Dmax in amblyopia In the control group, low-level RDKs elicited stronger responses in low-level (posterior occipital) areas and high-level RDKs elicited a greater response in high-level (extra-striate occipital-parietal) areas when activation for high-level RDKs was compared to that for low-level RDKs. Participants with anisometropic amblyopia showed the same pattern of cortical activation although extent of activation differences was less than in controls. For those with strabismic amblyopia, there was almost no difference in the cortical activity for low-level and high-level RDKs, and activation was reduced relative to the other groups. Differences in the extent of cortical activation may be related to amblyogenic subtype. PMID- 19643123 TI - Schizotypal personality traits influence idiosyncratic initiation of saccadic face exploration. AB - Visual face exploration is usually biased to the left half of a presented face. Recent findings now indicate that the first saccade in face exploration has a strong idiosyncratic component with around 30% of healthy individuals showing a consistent rightward bias. We investigated in a random sample of 64 right-handed healthy participants whether this rightward bias might relate to individual differences, i.e. a psychotic-like thinking style (schizotypy). Elevated positive (magical ideation) but not negative (physical anhedonia) schizotypy scores accounted for a pronounced left-face preference for first saccades. Furthermore, when using magical ideation and physical anheonia to group individuals according to their median scale scores into four groups (either both scores elevated or low, or mixed with one score elevated, one low), participants with both scores elevated exhibited the most pronounced left-face preference and participants with both scores low the least. The same participant groups did not differ with respect to their side preference in exploring fractals nor for other exploration parameters such as first fixation duration, number of saccades or scanpath length. These findings indicate pronounced right-hemispheric dominance for face exploration in healthy individuals with elevated positive schizotypal thought. These findings contrast with expectations from studies with schizophrenic patients, and point to the relevance of individual differences in lateralized face processing. PMID- 19643124 TI - Buspirone, chlordiazepoxide and diazepam effects in a zebrafish model of anxiety. AB - Zebrafish are becoming more widely used to study neurobehavioral pharmacology. We have developed a method to assess novel environment diving behavior of zebrafish as a model of stress response and anxiolytic drug effects. In a novel tank, zebrafish dwell in the bottom of the tank initially and then increase their swimming exploration to higher levels over time. We previously found that nicotine, which has anxiolytic effects in rodents and humans, significantly lessens the novel tank diving response in zebrafish. The specificity of the diving effect was validated with a novel vs. non-novel test tank. The novel tank diving response of zebrafish was tested when given three anxiolytic drugs from two different chemical and pharmacological classes: buspirone, chlordiazepoxide and diazepam. When the test tank was novel the diving response was clearly seen whereas it was significantly reduced when the test tank was not novel. Buspirone, a serotonergic (5HT(1A) receptor agonist) anxiolytic drug with some D(2) dopaminergic effect, had a pronounced anxiolytic-like effect in the zebrafish diving model at doses that did not have sedative effects. In contrast, chlordiazepoxide, a benzodiazepine anxiolytic drug, which is an effective agonist at GABA-A receptors, did not produce signs of anxiolysis in zebrafish over a broad dose range up to those that caused sedation. Diazepam another benzodiazepine anxiolytic drug did produce an anxiolytic effect at doses that did not cause sedation. The zebrafish novel tank diving task can be useful in discriminating anxiolytic drugs of several classes (serotonergic, benzodiazepines and nicotinic). PMID- 19643126 TI - Analysis of chemical components of shiitake polysaccharides and its anti-fatigue effect under vibration. AB - The shiitake polysaccharides were obtained from shiitake mushroom. Four fractions were isolated from the polysaccharides using a Sephadex G-100 gel column. Chemical components of the two main fractions were determined by thin layer chromatography (TLC), and high performance liquid chromatography (HPLC). F1 was composed of rhamnose, glucose, and mannose. F3 was composed of xylose, mannose, arabinose and galactose. The obtained results still showed that administration of shiitake polysaccharides could improve muscle's comfortability of animals under a long period of vibration. The above findings might be applicable to studies of vibration ergonomics. PMID- 19643125 TI - A multifaceted school-based intervention to reduce risk for type 2 diabetes in at risk youth. AB - OBJECTIVE: To evaluate the impact of a multifaceted, school-based intervention on inner city youth at high risk for type 2 diabetes mellitus (T2DM) and to determine whether the addition of coping skills training (CST) and health coaching improves outcomes. METHOD: 198 students in New Haven, CT at risk for T2DM (BMI>85th percentile and family history of diabetes) were randomized by school to an educational intervention with or without the addition of CST and health coaching. Students were enrolled from 2004 to 2007 and followed for 12 months. RESULTS: Students in both groups showed some improvement in anthropometric measures, lipids, and depressive symptoms over 12 months. BMI was not improved by the intervention. Students who received CST showed greater improvement on some indicators of metabolic risk than students who received education only. CONCLUSION: A multifaceted, school-based intervention may hold promise for reducing metabolic risk in urban, minority youth. PMID- 19643127 TI - In vitro antioxidant activities of a water-soluble polysaccharide derived from Dendrobium nobile Lindl. extracts. AB - A water-soluble polysaccharide (DNP), isolated from the aqueous extracts of the stem of Dendrobium nobile Lindl., was found to have an average molecular weight (Mw) of about 8.76 x 10(4)Da. Monosaccharides analysis revealed that DNP was composed of rhamnose, arabinose, xylose, mannose, glucose and galactose in a molar ratio of 1.00:2.80:2.20:30.76:117.96:31.76. The evaluation of antioxidant activity in vitro revealed that DNP is a novel potential antioxidant. The NMR spectra suggested that the main structure of DNP was possible as the predicted main structure of DNP from Dendrobium nobile, (fig. 5). PMID- 19643128 TI - Evaluation of free radicals scavenging and immunity-modulatory activities of Purslane polysaccharides. AB - In this study, antioxidant and immunity-modulatory activities of Purslane polysaccharide were estimated. The results revealed that in a dose-dependent manner, Purslane polysaccharides could significantly scavenge superoxide anion, 1,1-diphenyl-2-picrylhydrazyl (DPPH(-)), nitric oxide and hydroxyl radicals. Furthermore, the Purslane polysaccharides could still effectively inhibit the red blood cell (RBC) haemolysis, and increase spleen, thymocyte T and B lymphocyte proliferation, it could be concluded that Purslane polysaccharides could be of considerable preventive and therapeutic significance to some free radical associated health problems such as ovarian cancer, by scavenging accumulating free radicals and enhancing immunity functions. PMID- 19643129 TI - Physicochemical and bioactivity of cross-linked chitosan-PVA film for food packaging applications. AB - This work aimed to develop a novel antimicrobial coating based on chitosan and PVA to evaluate its effect on minimally processed tomato by means of microbiological analyses. In this report an antimicrobial film was prepared by blending chitosan (CS) and poly(vinyl alcohol) (PVA) with glutaraldehyde as the cross-linker. The miscibility and morphology of the film were investigated by X ray diffraction (XRD) and scanning electron microscopy (SEM). The thermal property of the chitosan-PVA film was examined by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The microbiological screening has demonstrated the antimicrobial activity of the film against food pathogenic bacteria viz. Escherichia coli, Staphylococcus aureus, and Bacillus subtilis. The obtained results indicate the film may be a promising material for food packaging applications. PMID- 19643130 TI - Characteristics of xanthan gum-based biodegradable superporous hydrogel. AB - A novel biopolymer-based superporous hydrogel (SPH) was synthesized through chemical crosslinking by graft copolymerization of 2-hydroxyethyl methacrylate (HEMA) and acrylic acid (AA) on to xanthan gum (XG) via redox initiator system of ammonium persulfate (APS) and N, N, N', N'-tetramethylethylenediamine (TMED), in the presence of N, N'-methylenebisacrylamide (MBA) crosslinking agent, sodium bicarbonate foaming agent, a triblock copolymer of polyoxyethylene/polyoxypropylene/polyoxyethylene as a foam stabilizer. Characterization of SPH was done by FT-IR, TGA, SEM, HPC and GCMS. The effects of pH and salinity on the swelling aptitude of the SPH were investigated along with its degradability in Streptococcus bovis medium. PMID- 19643131 TI - Sleepiness as a need for sleep: when is enough, enough? AB - This review considers the relationship between sleep need and sleepiness. In healthy adults, objective measures of sleepiness (e.g. Multiple Sleep Latency Test; Psychomotor Vigilance Test) and subjective indices (e.g. Stanford Sleepiness Scale) often poorly inter-correlate and have been seen as orthogonal dimensions. This is perhaps not surprising as the methodology of these tests is quite different in, for example, their duration, testing environment, whether they are experimenter versus participant-paced, and the understanding and expectancy of participants. It is argued, here, that 'sleepiness', the 'propensity to fall asleep' and the 'need for sleep' are not synonymous, but qualitatively different. They may represent different positions on a dimension ranging from essential to non-essential sleep/sleepiness, and the position on this dimension is detected to varying extents by the different measures. As these tests can detect - and perhaps induce - levels of sleepiness which would be undetectable by, and of little concern to people under everyday situations, they can reveal a sleepiness having the potential to be misinterpreted as sleep debt. PMID- 19643132 TI - Effect of manganese exposure on intracellular Ca2+ homeostasis and expression of NMDA receptor subunits in primary cultured neurons. AB - Overexposure to manganese (Mn) has been known to induce neuronal damage. However, the mechanisms of Mn-induced neuronal cell death are incompletely understood. The objective of this study is to explore mechanisms that contribute to Mn-induced neuronal apoptosis focusing on the alteration of intracellular Ca(2+) homeostasis and expression of NMDA receptor subunits in primary cultured neurons. Treatment of neuronal cells with Mn (0-400 microM) for 6-48 h resulted in the damages of primary cultured neurons concentration- and time-dependently, which were determined by methyl thiazolyl tetrazolium (MTT) and lactate dehydrogenase (LDH) release assay and supported by morphological examination. After neurons treated with Mn (25, 100, 400 microM) for 12 h, there was a significant increase in apoptosis rate [Ca(2+)](i) and decrease in Na(+)-K(+)-ATPase and Ca(2+)-ATPase activities in a concentration-dependent manner. Moreover, Mn could inhibit expression of NMDA receptor subunits in neuron and expression of NR2A mRNA and protein were much more sensitive to Mn than those of NR1 and NR2B. In conclusion, the present results showed that Mn-induced neuronal damage by increasing [Ca(2+)](i) and altering expression of NMDA receptor subunits mRNAs and proteins. PMID- 19643133 TI - Environmental contributors to the achievement gap. AB - Extensive research shows that blacks, those of low socioeconomic status, and other disadvantaged groups continue to exhibit poorer school performance compared with middle and upper-class whites in the United States' educational system. Environmental exposures may contribute to the observed achievement gap. In particular, childhood lead exposure has been linked to a number of adverse cognitive outcomes. In previous work, we demonstrated a relationship between early childhood lead exposure and end-of-grade (EOG) test scores on a limited dataset. In this analysis, data from the North Carolina Childhood Lead Poisoning Prevention Program surveillance registry were linked to educational outcomes available through the North Carolina Education Research Data Center for all 100 counties in NC. Our objectives were to confirm the earlier study results in a larger population-level database, determine whether there are differences in the impact of lead across the EOG distribution, and elucidate the impact of cumulative childhood social and environmental stress on educational outcomes. Multivariate and quantile regression techniques were employed. We find that early childhood lead exposure is associated with lower performance on reading EOG test scores in a clear dose-response pattern, with the effects increasingly more pronounced in moving from the high end to the low end of the test score distribution. Parental educational attainment and family poverty status also affect EOG test scores, in a similar dose-response fashion, with the effects again most pronounced at the low end of the EOG test score distribution. The effects of environmental and social stressors (especially as they stretch out the lower tail of the EOG distribution) demonstrate the particular vulnerabilities of socioeconomically and environmentally disadvantaged children. Given the higher average lead exposure experienced by African American children in the United States, lead does in fact explain part of the achievement gap. PMID- 19643134 TI - Synaptic plasticity and the analysis of the field-EPSP as well as the population spike using separate recording electrodes in the dentate gyrus in freely moving rats. AB - Commonly, synaptic plasticity events such as long-term potentiation (LTP) are investigated by using a stimulation electrode and a single, monopolar field recording electrode in the dentate gyrus in intact, freely moving rats. The recording electrode is mostly positioned in the granular cell layer, or the hilar region of the dentate gyrus, i.e. far away from the place of generation of monosynaptic postsynaptic excitatory potentials (EPSP). Since LTP is a synaptic phenomenon and field recordings far away from the activated synapses do not guarantee a specific interpretation of the overlaid, mixture of complex potentials of several different electrical fields it is often difficult or even impossible to interpret the data obtained by such a single recording electrode. Therefore, at least a separate or two recording electrodes should be used to record the EPSP as well as the spike, respectively, ideally at their places of generation. Here, we describe a method by implanting a chronic bipolar recording electrode which fulfils the above requirements by recording the field-EPSP as well as the population spike at their places of generation and describe the time course of LTP measured using this "double-recording" electrode. We show that different tetanization protocols resulted in EPSP- or population spike-LTP but only if the potentials were recorded by electrodes positioned within adequate places of potential generation. Interestingly, the commonly used recording in the hilus of a distinct part of a potential, mistakenly analyzed as an "EPSP" did not reveal any LTP. PMID- 19643135 TI - Detection of neural correlates of self-paced motor activity using empirical mode decomposition phase locking analysis. AB - Transient episodes of synchronisation of neuronal activity in particular frequency ranges are thought to underlie cognition. Empirical mode decomposition phase locking (EMDPL) analysis is a method for determining the frequency and timing of phase synchrony that is adaptive to intrinsic oscillations within data, alleviating the need for arbitrary bandpass filter cut-off selection. It is extended here to address the choice of reference electrode and removal of spurious synchrony resulting from volume conduction. Spline Laplacian transformation and independent component analysis (ICA) are performed as pre processing steps, and preservation of phase synchrony between synthetic signals, combined using a simple forward model, is demonstrated. The method is contrasted with use of bandpass filtering following the same pre-processing steps, and filter cut-offs are shown to influence synchrony detection markedly. Furthermore, an approach to the assessment of multiple EEG trials using the method is introduced, and the assessment of statistical significance of phase locking episodes is extended to render it adaptive to local phase synchrony levels. EMDPL is validated in the analysis of real EEG data, during finger tapping. The time course of event-related (de)synchronisation (ERD/ERS) is shown to differ from that of longer range phase locking episodes, implying different roles for these different types of synchronisation. It is suggested that the increase in phase locking which occurs just prior to movement, coinciding with a reduction in power (or ERD) may result from selection of the neural assembly relevant to the particular movement. PMID- 19643137 TI - Autoimmune diabetic patients undergoing allogeneic islet transplantation: are we ready for a regulatory T-cell therapy? AB - Regulatory T cells (Tregs) are thought to be pivotal in controlling both autoimmune and allogeneic undesired immune responses. Recently, an extensive effort has been devoted to design clinical trials with Tregs in T cell-mediated diseases (such as autoimmune diseases or transplantation). Theoretically, this approach can be used also in patients with autoimmunity (e.g., type 1 diabetes) undergoing allogeneic transplantation (e.g., pancreatic islet transplant). However, in this latter case Tregs must control two distinct effector immune responses: a pre-existing response towards self-antigens and a de novo response induced by the newly transplanted allogeneic cells. In this review we summarize results supporting the use of Tregs in controlling either autoimmunity or allo transplantation. We also provide our view on how Treg therapy can achieve the final goal of immunological tolerance in the extremely challenging clinical setting of type 1 diabetic subjects transplanted with allogeneic islets. PMID- 19643136 TI - Expression of Th2-skewed pathology mediators in monocyte-derived type 2 of dendritic cells (DC2). AB - The information conveyed from dendritic cells (DCs) to naive CD4(+) T cells has crucial influence on their differentiation toward effector T cells. In an effort to identify DC-derived molecules directly contributing to T cell differentiation, we searched for molecules distinctively expressed between two DC subtypes, which were differentiated from peripheral monocytes by cultivation with GM-CSF (for DC1) or IL-3 (for DC2) in the presence of IL-4 and had the ability to induce naive T cells to differentiate into Th1 or Th2 cells, respectively. As the first step to address this issue, we subtracted DC1 transcripts from those of DC2 and compiled the gene profile dominantly expressed in DC2, whose products are known to reside in other than the nucleus. Intriguingly, many of them were molecules involved in Th2-skewed disease pathologies, such as FN1, ITGAE, GPNMB, PLAUR, FPRL2, LILRB4, SERPINE1, ALOX15, TBXAS1, NCF2, CCL3, IL1RN, SPARC, and STAB1, suggesting that DCs function not only as antigen presenting cells but also as producers of Th2 pathology specific milieus leading to disease deteriorations. We also found that expressions of CYP27A1, PPAP2B, RSAD2, and ABCC3 were up regulated in DC2, implying their significant function in Th2-deviated states. The identification of differentially expressed genes between DC subtypes provides new insights into their functions and our comparative gene expression profile will be highly useful for the identification of DC-derived key molecules for T cell differentiation. PMID- 19643138 TI - Over-expression of integrin beta3 can partially overcome the defect of integrin beta3 signaling in transglutaminase 2 null macrophages. AB - Transglutaminase 2 (TG2) is a protein crosslinking enzyme with many additional biological functions. We have previously shown that in TG2(-/-) mice the in vivo clearance of apoptotic cells is defective leading to autoimmunity. TG2 contributes to the formation of phagocytic portals by binding to both integrin beta(3), a known phagocytic receptor, and its bridging molecule, MFG-E8. In TG2 null macrophages integrin beta(3) cannot accumulate around the apoptotic cells and its signaling is impaired. In the present study we describe a subline of TG2 null mice, in which a compensatory increase in integrin beta(3) expression, which resulted alone in a high receptor concentration around the apoptotic cells without the requirement for accumulation, partially corrected the defect in integrin beta(3) signaling. Our data provide a proof for the concept that the function of TG2 is to stabilize accumulated integrin beta(3) concentration in the phagocytic cup. PMID- 19643139 TI - Real-time quantitative PCR based sensitive detection and genotype discrimination of Pepino mosaic virus. AB - Over the last decade a new virus disease caused by Pepino mosaic virus (PepMV) has been threatening the tomato industry worldwide. Reliable detection is vitally important to aid disease control. Methods must be both sensitive and capable of detecting the range of distinct genotypes that have been identified. The development of five new reverse transcription real-time quantitative PCR (RT qPCR) assays is described, which allow the detection of all known PepMV genotypes. The performance of the assays was evaluated on Peruvian, European tomato, Ch2 and US1 PepMV genotypes and optimised for both two- and one-step RT qPCR detection formats. One-step RT-qPCR detected PepMV European tomato genotype particles at least two orders of magnitude more sensitively than ELISA. The method detected as little as one naturally infected seed among 5000 uninfected seeds. The genotype-specificity of the five assays was compared using PepMV isolates representing all of the different genotypes. The following genotype combinations were all discriminated successfully: European tomato-Peruvian, Ch2, and US1. In addition to its application for diagnostic purposes, the genotype specificity and the quantitative potential of the method, makes it very useful for epidemiological studies or for studies evaluating resistance of plants to virus infection. PMID- 19643140 TI - Establishment of an indicator cell line for monitoring bovine immunodeficiency virus infection and inhibitor susceptibility. AB - Indicator cell lines are useful biological tools for monitoring virus infection. In order to monitor infection with bovine immunodeficiency virus (BIV) in vitro, an indicator cell line derived from baby hamster kidney cells which contains integrated copies of an enhanced green fluorescent protein gene driven by the BIV long terminal repeat was constructed. The BIV indicator cell line, designated BIVE, can detect BIV infection more easily and effectively than the established method, which involves the observation of cell cytopathic effects. Furthermore, viral titration using an assay based on the indicator cells is 100 times more sensitive than the assay based on cytopathic effect. The finding that BIV can infect the hamster cell line expands the known host range of BIV in vitro. The BIV indicator cell line could also be used for the evaluation of the inhibitory effect of antiviral agents. The fusion inhibition effect of the heptad repeat 2 region of the BIV envelope protein could also be quantified. PMID- 19643142 TI - Colorimetric microwell plate reverse-hybridization assay for detection and genotyping of hepatitis C virus. AB - This study describes a colorimetric method for detecting and genotyping hepatitis C virus (HCV) in which four different oligonucleotide probes are fixed onto microwell plates and hybridized separately with biotinylated PCR amplification products derived from clinical samples. The first probe capable of hybridizing with all seven known HCV genotypes was used for overall detection, and the remaining probes were used to recognize specifically genotypes 1-3. When combined with an improved silica-based RNA extraction method, the sensitivity of the test was 50 IU/mL. Eighty-five of the 86 samples analyzed (98.8%) yielded results in agreement with reference detection methods. The remaining sample was HCV-RNA positive in the COBAS Amplicor qualitative assay, but was negative using the reverse-hybridization method. The usefulness of the new genotyping test was confirmed by comparison with direct sequencing of PCR products: 98% of samples tested (54/55) were in agreement using the two methods (21, 7 and 27 from genotypes 1-3, respectively). The single discrepancy might have been due to a mixed HCV infection. The new method is an alternative to the use of commercially available genotyping kits and should be particularly convenient in developing countries where genotypes 1-3 represent a high proportion of HCV isolates. PMID- 19643143 TI - Development of ELISA kits for antibodies against avian reovirus using the sigmaC and sigmaB proteins expressed in the methyltropic yeast Pichia pastoris. AB - Both the sigmaC and sigmaB proteins of avian reovirus (ARV) can induce type- and group-specific neutralizing antibodies, respectively. In this study, the full length of S1133 sigmaC, 1071-1 sigmaC, S1133 sigmaB, and S1133 sigmaC-sigmaB fusion genes of ARV were cloned into a secreted vector pPICZalphaA and then integrated into the chromosome of Pichia pastoris for induced expression. Western blot assay showed that ARV sigmaC, sigmaB, and sigmaC-sigmaB fusion proteins were expressed and secreted into the medium. Two types of ELISA kits using equal mixtures of 1071-1sigmaC and S1133 sigmaB and S1133 sigmaC-sigmaB fusion proteins as antigens were developed. After a checker board titration for optimal conditions, the cut-off values of positive results for the 1071-1sigmaC/S1133 sigmaB and S1133 sigmaC-sigmaB ELISA kits were 0.24 and 0.12, respectively. Forty four serum neutralization test-positive and twenty-eight serum neutralization negative samples from vaccinated and commercial farm chickens were tested by the new ELISA kits and by the conventional ELISA. The new ELISA kits have higher positive rates than the conventional ELISA. The results revealed that the correlation rates for the serum neutralization titer and the absorbance values with the new ELISA kits and the conventional ELISA were 100% and 95.8%, respectively. PMID- 19643141 TI - Simultaneous assessment of CD4 and MHC-I downregulation by Nef primary isolates in the context of infection. AB - The HIV-1 Nef protein plays a key role in pathogenesis, as demonstrated by strong selective pressure to maintain its open reading frame, and disease attenuation when it is deleted. Among myriad cellular effects attributed to Nef, downregulation of cell surface CD4 and major histocompatibility complex class I (MHC-I) proteins are the best documented. However, few data regarding primary isolate Nef functions are available, and most studies have been performed using transient transfections to express Nef driven by a non-physiologic promoter. A novel assay system to measure simultaneously the downregulation of CD4 and MHC-I by primary HIV-1 nef in a more physiologic viral genomic context is presented. Examination of plasma nef mixtures allowed comprehensive profiling of these Nef functions within the quasispecies in vivo. Subsets within the circulating nef population were observed that are either fully functional or non-functional. These data demonstrated that this assay system allows rapid characterization of bulk and clonal Nef functional profiles that can be used in pathogenesis studies to define further its important role in pathogenesis. PMID- 19643144 TI - Development of reverse-transcription loop-mediated isothermal amplification for the detection of infectious bursal disease virus. AB - To establish a reverse-transcription loop-mediated isothermal amplification (RT LAMP) method for rapid detection of infectious bursal disease virus (IBDV), four primers specific to six regions of the VP3 gene were designed; the VP3 region was selected because it is a conserved part of the IBDV genome. After amplification in an isothermal water bath for 70 min, samples containing IBDV generated the expected ladder-like products while other viruses generated no product. The sensitivity and specificity of the RT-LAMP assay were evaluated by comparison with reverse-transcription polymerase chain reaction (RT-PCR) and virus isolation. The assay was significantly more sensitive than normal gel-based RT PCR. Because it is specific and simple, the RT-LAMP assay can be widely applied in clinical laboratories for rapid detection of IBVD. PMID- 19643145 TI - The effects of foraging role and genotype on light and sucrose responsiveness in honey bees (Apis mellifera L.). AB - In honey bees, the sensory system can be measured by touching sugar water to the antennae, eliciting the extension of the proboscis. The proboscis extension response (PER) [6,13] is closely associated with complex behavioral traits involving foraging and learning [30-32,34-36,43-49]. Bees specializing in pollen foraging are more responsive to low concentrations of sucrose solution and, as a consequence, perform better in associative learning assays [4,43,46-48]. An important unanswered question is whether sensory-motor differences between pollen and nectar specialists are restricted to the gustatory modality or whether pollen foragers are in general more sensitive to sensory stimuli associated with foraging. We used an assay designed to test responsiveness to varying intensities of light [11] and tested responsiveness to varying concentrations of sucrose in wild-type pollen and non-pollen foragers and bees artificially-selected for differences in pollen-hoarding behavior [27]. Workers of the high pollen-hoarding strain are more likely to specialize on collecting pollen. In wild-type bees, pollen foragers were more responsive to sucrose and light than non-pollen foragers. In the selected strains, high pollen-hoarding pre-foragers were more responsive to sucrose and light than low pollen-hoarding pre-foragers. These PER and light assays demonstrate a positive relationship between the gustatory and visual sensory modalities with respect to foraging behavior and genotype. We propose that light responsiveness, in addition to sucrose responsiveness, is a component of a pollen-hoarding behavioral syndrome - a suite of traits that covary with hoarding behavior [51,52] - previously described for honey bees [14,37,41]. We suggest that the modulation of the sensory system may be partially constrained by the interdependent modulation of multiple sensory modalities associated with hoarding and foraging. PMID- 19643146 TI - Effects of unilateral amygdala dopamine depletion on behaviour in the elevated plus maze: role of sex, hemisphere and retesting. AB - A growing body of literature suggests that sex differences exist in both rodents and humans in terms of the central processing of stress and emotion, and an important factor in this regard may involve differential hemispheric specialization. The amygdala has been shown to be functionally asymmetrical in both rats and humans and its involvement in stress and emotion processing is well documented. Given that amygdala function is importantly modulated by dopamine (DA), the present study examined the effects of left vs. right unilateral DAergic depletion targeting the basolateral amygdala in male and female rats. We examined behaviour in the elevated plus maze over two consecutive days, and plasma adrenocorticotropic hormone (ACTH) levels in response to a separate 30min restraint stress. Overall, females showed significantly more exploration of open arms of the plus maze than males, while not differing in general activity reflected in closed arm entries. Significant SexxHemisphere interactions were observed for all measures related to open arm exploration, as right amygdala DA depletion produced an anxiolytic effect in males, increasing open arm exploration, but reduced this behaviour in females. Moreover, open arm exploration was greatly reduced on the second maze exposure in males, but unchanged in females. A SexxHemisphere interaction was also found for plasma ACTH levels. It is suggested that the role of amygdala DA on stress-related behaviour and physiology reflects inherent differences in amygdala function dependent on both sex and hemisphere. PMID- 19643147 TI - Diurnal rhythm and stress regulate dendritic architecture and spine density of pyramidal neurons in the rat infralimbic cortex. AB - The medial prefrontal cortex (mPFC) participates in several higher order cognitive functions and is involved in the regulation of the stress response. The infralimbic cortex (ILC), the most ventral part of the mPFC, receives a strong afferent input from the master circadian pacemaker, the suprachiasmatic nucleus. This fact raises the possibility that, similarly to stress, the diurnal rhythm may affect structural plasticity of neurons in the ILC. Here we investigated, whether diurnal changes in combination with immobilization stress have any impact on the dendritic morphology of layer III pyramidal neurons in the ILC. Prefrontal cortices were collected from control rats at two different time points of the diurnal cycle (12h apart), and from rats exposed to 1-week of daily restraint stress either during their active or resting period. Dendritic architecture and spine density of Golgi-Cox stained neurons were digitally reconstructed and analyzed. We found that in control rats during the active period, the basilar dendrites were always longer and more complex, and had more spines than during the resting period. Similar although less pronounced diurnal differences exist in the apical dendrites. Stress affected dendritic architecture in a way that the diurnal differences either disappeared or became reduced in their magnitude. Our findings indicate that the diurnal rhythm has a unique impact on the structural plasticity of pyramidal cells in the ILC and that stress interferes with this form of neuroplasticity. PMID- 19643148 TI - Epigallocatechin gallate ameliorates chronic fatigue syndrome in mice: behavioral and biochemical evidence. AB - Three decades after the coining of the term chronic fatigue syndrome, the diagnosis of this illness is still symptom based and the aetiology remains elusive. Chronic fatigue syndrome pathogenesis seems to be multifactorial and the possible involvement of immune system is supported. The present study was designed to evaluate the effects of the epigallocatechin gallate in a mouse model of immunologically induced chronic fatigue. On 19th day, after lipopolysaccharide/Brucella abortus administration, the mice showed significant increase in immobility period, post swim fatigue and thermal hyperalgesia. Behavioral deficits were coupled with enhanced oxidative-nitrosative stress as evident by increased lipid peroxidation, nitrite levels and decreased endogenous antioxidant enzymes (superoxide dismutase, reduced glutathione and catalase) and inflammation (increased levels of tumor necrosis factor-alpha and tissue growth factor-beta). Chronic treatment with epigallocatechin gallate restored these behavioral and biochemical alterations in mice. The present study points out towards the beneficial effect of epigallocatechin gallate in the amelioration of chronic fatigue syndrome and thus may provide a new, effective and powerful strategy to treat chronic fatigue syndrome. PMID- 19643149 TI - Medial prefrontal administration of MK-801 impairs T-maze discrimination reversal learning in weanling rats. AB - Several executive functions rely on the medial prefrontal cortex (mPFC) in the rat. Aspiration and neurotoxic lesions of the mPFC impair reversal learning in adult rats. Systemic administration of MK-801, an NMDA-receptor antagonist, impairs T-maze reversal learning in weanling rats but the role of mPFC NMDA receptor antagonism in this effect is not known in either adult or young animals. This set of studies showed that mPFC NMDA receptors are specifically involved in T-maze discrimination reversal in weanling rats. In Experiment 1, 26-day-old rats (P26) demonstrated a dose-dependent impairment following bilateral mPFC administration of either 2.5 or 5.0microg MK-801 or saline (vehicle) during the reversal training phase only. In Experiment 2, P26 rats were trained on the same task, but four groups of rats received bilateral mPFC infusions during acquisition only (MK-SAL), reversal only (SAL-MK), both phases (MK-MK), or neither phase (SAL-SAL). MK-801 impaired performance only when infused during reversal. This suggests that NMDA-receptor antagonism in the mPFC is selectively involved in reversal learning during development and this may account for the previously reported effects of systemic MK-801 on T-maze discrimination reversal in weanling rats. PMID- 19643150 TI - Molecular and functional characterisation of the heat shock protein 10 of Strongyloides ratti. AB - Strongyloides stercoralis and S. ratti are intestinal parasitic nematodes infecting rats and humans, respectively. Both present extraordinary life cycles comprising a free-living generation in addition to parasitic stages. In search of molecules possibly involved in parasite-host interaction, we performed mass spectrometry to identify excretory/secretory products of S. ratti. Amongst others we detected homologs of the heat shock proteins HSP10 and HSP60 (Sr-HSP10 and Sr HSP60). HSPs are well known as chaperones involved in stress responses of cells, but recent studies suggest additional roles of small HSPs for parasite biology including immune modulation. To characterise Sr-HSP10, we cloned its full-length cDNA, analysed the genomic organisation, tested its presumptive role as an interaction partner of Sr-HSP60, studied its transcription in the parasite, and expressed the protein to test its immune responses. The cDNA contains an open reading frame of 330bp encoding a polypeptide of 110 amino acids with an approximate molecular weight of 10kDa. The Sr-HSP10 protein is highly homologous to that of the human pathogen S. stercoralis with only eight amino acid substitutions. Analysis of the genomic organisation of the Sr-HSP10 locus revealed that the gene is linked head-to-head to the gene encoding Sr-HSP60, and both share a bidirectional promoter. RT-PCR experiments indicated potential independent expression of the Sr-HSPs genes. In situ hybridisation results demonstrate Sr-HSP10 transcription in the gut area. Mammalian and yeast two hybrid assays show dimerisation of Sr-HSP10, but no binding to recombinant Sr HSP60. Immunisation experiments finally revealed a strong immunogenicity of Sr HSP10 and provided evidence for a role in regulating the host-parasite interaction. PMID- 19643151 TI - Human brain response to visual stimulus between lower/upper visual fields and cerebral hemispheres. AB - We studied the human brain response to visual stimulation in which a square area was randomly presented in upper and lower visual fields (VFs). Seven normal volunteers carried out a contrast-based visual search task. Magnetic responses were detected in the bilateral parietal regions at 200-250 ms after stimulus onset. We compared the response latencies and strengths of the essential single sensor and root mean square (RMS) of the regions. The former evaluates the strength of neural activity with relatively high spatial resolution, while the latter evaluates the global neural activity. The single sensor and RMS latencies for the lower left VF were significantly longer than that for the upper left (paired t-test, P<0.05). The strengths did not differ between the upper and lower left VFs. There was no significant difference in latency or strength between the upper right and lower right VFs. These findings suggest that only left VF has different response properties in the upper versus lower VF, and that both local and global extrastriate activities are responsible for this anisotropy. PMID- 19643152 TI - Surface-functionalized electrospun nanofibers for tissue engineering and drug delivery. AB - Electrospun nanofibers with a high surface area to volume ratio have received much attention because of their potential applications for biomedical devices, tissue engineering scaffolds, and drug delivery carriers. In order to develop electrospun nanofibers as useful nanobiomaterials, surfaces of electrospun nanofibers have been chemically functionalized for achieving sustained delivery through physical adsorption of diverse bioactive molecules. Surface modification of nanofibers includes plasma treatment, wet chemical method, surface graft polymerization, and co-electrospinning of surface active agents and polymers. A variety of bioactive molecules including anti-cancer drugs, enzymes, cytokines, and polysaccharides were entrapped within the interior or physically immobilized on the surface for controlled drug delivery. Surfaces of electrospun nanofibers were also chemically modified with immobilizing cell specific bioactive ligands to enhance cell adhesion, proliferation, and differentiation by mimicking morphology and biological functions of extracellular matrix. This review summarizes surface modification strategies of electrospun polymeric nanofibers for controlled drug delivery and tissue engineering. PMID- 19643153 TI - Nanofibers in regenerative medicine and drug delivery. PMID- 19643155 TI - Electrospinning of polysaccharides for regenerative medicine. AB - Electrospinning techniques enable the production of continuous fibers with dimensions on the scale of nanometers from a wide range of natural and synthetic polymers. The number of recent studies regarding electrospun polysaccharides and their derivatives, which are potentially useful for regenerative medicine, is increasing dramatically. However, difficulties regarding the processibility of the polysaccharides (e.g., poor solubility and high surface tension) have limited their application. In this review, we summarize the characteristics of various polysaccharides such as alginate, cellulose, chitin, chitosan, hyaluronic acid, starch, dextran, and heparin, which are either currently being used or have potential to be used for electrospinning. The recent progress of nanofiber matrices electrospun from polysaccharides and their biomedical applications in tissue engineering, wound dressings, drug delivery, and enzyme immobilization are discussed. PMID- 19643154 TI - Electrospun silk biomaterial scaffolds for regenerative medicine. AB - Electrospinning is a versatile technique that enables the development of nanofiber-based biomaterial scaffolds. Scaffolds can be generated that are useful for tissue engineering and regenerative medicine since they mimic the nanoscale properties of certain fibrous components of the native extracellular matrix in tissues. Silk is a natural protein with excellent biocompatibility, remarkable mechanical properties as well as tailorable degradability. Integrating these protein polymer advantages with electrospinning results in scaffolds with combined biochemical, topographical and mechanical cues with versatility for a range of biomaterial, cell and tissue studies and applications. This review covers research related to electrospinning of silk, including process parameters, post treatment of the spun fibers, functionalization of nanofibers, and the potential applications for these material systems in regenerative medicine. Research challenges and future trends are also discussed. PMID- 19643156 TI - The application of nanofibrous scaffolds in neural tissue engineering. AB - The repairing process in the nervous system is complicated and brings great challenges to researchers. Tissue engineering scaffolds provide an alternative approach for neural regeneration. Sub-micron and nano-scale fibrous scaffolds which mimic the topography of natural extracellular matrix (ECM) can be potential scaffold candidates for neural tissue engineering. Two fiber-fabrication methods have been explored in the field of nerve regeneration: electrospinning and self assembly. Electrospinning produces fibers with diameters ranging from several micrometers to hundreds of nanometers. The fibrous nerve conduits can be introduced at lesion sites by implantation. Self-assembly fibers have diameters of tens of nanometers and can be injected for central nervous system (CNS) injury repair. Both fibrous scaffolds would enhance neurite extension and axon regrowth. These functional nanofibrous scaffolds can serve as powerful tools for neural tissue engineering. PMID- 19643157 TI - Influence of whole grain barley, whole grain wheat, and refined rice-based foods on short-term satiety and energy intake. AB - This study compared the effect of whole grain high-fiber barley, whole grain wheat and refined rice-based foods on energy intake and satiety. Forty-seven healthy subjects consumed a breakfast of hot cereal and a snack mix containing either barley, wheat, or refined rice, followed by an ad libitum smorgasbord lunch using a crossover design. Energy intake was measured at the lunch using plate waste. Hunger, fullness, desire to eat, amount of food consumed, and thirst were assessed using a modified Visual Analog Scale (VAS) before and after the breakfast, snack and lunch. Energy intake at lunch did not differ among products. There were no differences in the area under the time curve in modified VAS scores among products for any parameter. However, subjects reported significantly less hunger before lunch compared to their hunger before breakfast when consuming the barley, but there was no significant reduction in hunger before lunch after consumption of wheat or rice. In conclusion, intake of a whole grain high-fiber barley, whole grain wheat, or refined rice breakfast and snack did not decrease energy intake acutely, but consumption of whole grain high-fiber barley foods significantly decreased hunger whereas whole wheat and refined rice foods did not. PMID- 19643158 TI - Induction of liver preneoplastic foci in F344 rats subjected to 28-day oral administration of diheptyl phthalate and its in vivo genotoxic potential. AB - To investigate possible potential inducing preneoplastic lesions in liver and in vivo genotoxic potential of diheptyl phthalate (DHP), male F344 rats were subjected to repeated oral administration of DHP at 0, 2.5 or 5 g/kg/day for 28 days. In addition, F344 rats were subjected to once or 14 repeated oral administrations of 5 g/kg/day of DHP, and their livers were subjected to analysis in an alkaline single-cell gel electrophoresis (comet) assay. Furthermore, based on the results of these studies, partial hepatectomized male F344 rats given once, three times, and 14 repeated oral administration of 0, 2.5 or 5 g/kg body weight of DHP were examined by an in vivo liver initiation assay. In a 28-day repeated dose toxicity study, the number and area of glutathione-S-transferase placental form (GST-P) positive foci, a marker of hepatocellular preneoplastic lesions in rats, were significantly increased in DHP-treated groups compared with controls. At 24h after the 14 repeated administrations of DHP, DNA migration, a marker of DNA damage in the comet assay, was significantly induced in DHP-treated rat livers, whereas single treatment did not show such an alteration. In an in vivo liver initiation assay, a significant increase in the number and area of GST P positive foci was observed in DHP-treated groups subjected to 14 repeated oral administrations of DHP as compared with the control group. These results indicate that DHP may induce altered hepatocellular foci in liver of rats which suggests that DHP is a genotoxic carcinogen in the liver of rats. PMID- 19643159 TI - Molecular evidence for an involvement of organic anion transporters (OATs) in aristolochic acid nephropathy. AB - Aristolochic acid (AA), present in Aristolochia species, is the major causative agent in the development of severe renal failure and urothelial cancers in patients with AA nephropathy. It may also be a cause of Balkan endemic nephropathy. Epithelial cells of the proximal tubule are the primary cellular target of AA. To study whether organic anion transporters (OATs) expressed in proximal tubule cells are involved in uptake of AA, we used human epithelial kidney (HEK293) cells stably expressing human (h) OAT1, OAT3 or OAT4. AA potently inhibited the uptake of characteristic substrates, p-aminohippurate for hOAT1 and estrone sulfate for hOAT3 and hOAT4. Aristolochic acid I (AAI), the more cytotoxic and genotoxic AA congener, exhibited high affinity for hOAT1 (K(i)=0.6 microM) as well as hOAT3 (K(i)=0.5 microM), and lower affinity for hOAT4 (K(i)=20.6 microM). Subsequently, AAI-DNA adduct formation (investigated by (32)P postlabelling) was used as a measure of AAI uptake. Significantly higher levels of adducts occurred in hOAT-expressing cells than in control cells: this effect was abolished in the presence of the OAT inhibitor probenecid. In Xenopus laevis oocytes hOAT-mediated efflux of p-aminohippurate was trans-stimulated by extracellular AA, providing further molecular evidence for AA translocation by hOATs. Our study indicates that OATs can mediate the uptake of AA into proximal tubule cells and thereby participate in kidney cell damage by this toxin. PMID- 19643160 TI - The fourfold way of the genetic code. AB - We describe a compact representation of the genetic code that factorizes the table in quartets. It represents a "least grammar" for the genetic language. It is justified by the Klein-4 group structure of RNA bases and codon doublets. The matrix of the outer product between the column-vector of bases and the corresponding row-vector V(T)=(C G U A), considered as signal vectors, has a block structure consisting of the four cosets of the KxK group of base transformations acting on doublet AA. This matrix, translated into weak/strong (W/S) and purine/pyrimidine (R/Y) nucleotide classes, leads to a code table with mixed and unmixed families in separate regions. A basic difference between them is the non-commuting (R/Y) doublets: AC/CA, GU/UG. We describe the degeneracy in the canonical code and the systematic changes in deviant codes in terms of the divisors of 24, employing modulo multiplication groups. We illustrate binary sub codes characterizing mutations in the quartets. We introduce a decision-tree to predict the mode of tRNA recognition corresponding to each codon, and compare our result with related findings by Jestin and Soule [Jestin, J.-L., Soule, C., 2007. Symmetries by base substitutions in the genetic code predict 2' or 3' aminoacylation of tRNAs. J. Theor. Biol. 247, 391-394], and the rearrangements of the table by Delarue [Delarue, M., 2007. An asymmetric underlying rule in the assignment of codons: possible clue to a quick early evolution of the genetic code via successive binary choices. RNA 13, 161-169] and Rodin and Rodin [Rodin, S.N., Rodin, A.S., 2008. On the origin of the genetic code: signatures of its primordial complementarity in tRNAs and aminoacyl-tRNA synthetases. Heredity 100, 341-355], respectively. PMID- 19643161 TI - Molecular and structural basis of steroid hormone binding and release from corticosteroid-binding globulin. AB - Corticosteroid-binding globulin (CBG), a non-inhibitory member of the serine proteinase inhibitor (serpin) super-family, is the high-affinity transport protein for glucocorticoids in vertebrate blood. Plasma CBG is a glycoprotein with 30% of its mass represented by N-linked oligosaccharide chains. Its well characterized steroid-binding properties represent a "bench-mark data set" used extensively for in silico studies of protein-ligand interactions and drug design. Recent crystal structure analyses of intact rat CBG and cleaved human CBG have revealed the precise topography of the steroid-binding site, and shown that cortisol-bound CBG displays a typical stressed (S) serpin conformation with the reactive center loop (RCL) fully exposed from the central beta-sheet A, while proteolytic cleavage of the RCL results in CBG adopting a relaxed (R) conformation with the cleaved RCL fully inserted within the protein core. These crystal structures have set the stage for mechanistic studies of CBG function which have so far shown that helix D plays a key role in coupling RCL movement and steroid-binding site integrity, and provided evidence for an allosteric mechanism that modulates steroid binding and release from CBG. These studies have also revealed how the irreversible release of steroids occurs after proteolysis and re-orientation of the RCL within the R conformation. This recent insight into the structure and function of CBG reveals how naturally occurring genetic CBG mutations affect steroid binding, and helps understand how proteolysis of CBG enhances the targeted delivery of biologically active steroids to their sites of action. PMID- 19643162 TI - Suppressor of cytokine signalling-3 inhibits Tumor necrosis factor-alpha induced apoptosis and signalling in beta cells. AB - Tumor necrosis factor-alpha (TNFalpha) is a pro-inflammatory cytokine involved in the pathogenesis of several diseases including type 1 diabetes mellitus (T1DM). TNFalpha in combination with interleukin-1-beta (IL-1beta) and/or interferon gamma (IFNgamma) induces specific destruction of the pancreatic insulin-producing beta cells. Suppressor of cytokine signalling-3 (SOCS-3) proteins regulate signalling induced by a number of cytokines including growth hormone, IFNgamma and IL-1beta which signals via very distinctive pathways. The objective of this study was to investigate the effect of SOCS-3 on TNFalpha-induced signalling in beta cells. We found that apoptosis induced by TNFalpha alone or in combination with IL-1beta was suppressed by expression of SOCS-3 in the beta cell line INSr3#2. SOCS-3 inhibited TNFalpha-induced phosphorylation of the mitogen activated protein kinases ERK1/2, p38 and JNK in INSr3#2 cells and in primary rat islets. Furthermore, SOCS-3 repressed TNFalpha-induced degradation of IkappaB, NFkappaB DNA binding and transcription of the NFkappaB-dependent MnSOD promoter. Finally, expression of Socs-3 mRNA was induced by TNFalpha in rat islets in a transient manner with maximum expression after 1-2h. The ability of SOCS-3 to regulate signalling induced by the three major pro-inflammatory cytokines involved in the pathogenesis of T1DM makes SOCS-3 an interesting therapeutic candidate for protection of the beta cell mass. PMID- 19643164 TI - Genotype-phenotype associations in understanding the role of corticosteroid binding globulin in health and disease animal models. AB - Corticosteroid-binding globulin (CBG) is a plasma glycoprotein discovered more than 60 years ago for its high-affinity for glucocorticoids. Although its molecular structure and its biochemical properties have been described, its various biological roles and its importance are not yet fully understood. This review focuses first on studies that have used no-hypothesis-driven genetic approaches in animal models to reveal the higher than expected importance of CBG in particular in glucocorticoid stress responses. Then the dissection of some CBG physiological roles in an animal model of genetic CBG deficiency is reported. Finally, studies on the role of CBG genetic variability in human obesity traits are reviewed and discussed. PMID- 19643163 TI - Selective labeling of IRAP by the tritiated AT(4) receptor ligand [3H]Angiotensin IV and its stable analog [3H]AL-11. AB - 'AT(4) receptors' through which Angiotensin IV (Ang IV) improves memory acquisition, were recently identified as insulin regulated aminopeptidase (IRAP). Radioligand binding studies have hitherto been performed with iodinated Ang IV in the presence of divalent cation chelators EDTA and 1,10-phenanthrolin. Hence, they referred to the apo-form of IRAP. Presently, binding of [(3)H]Ang IV and [(3)H]AL-11, a stable Ang IV analog, was compared on Chinese hamster ovary (CHO K1) and mouse hippocampal (P40H1) cell membranes. With chelators, their high affinity sites showed the same pharmacological profile as for [(125)I]Ang IV binding. Without chelators, only high affinity binding was perceived for [(3)H]AL 11. The same pharmacological profile was recorded in both membrane preparations; it was different from the one in the presence of chelators and corresponded to catalytically active IRAP (despite the concurrent presence of aminopeptidase N (APN) in P40H1 cell membranes). This confirms that the active and apo-forms of IRAP have a distinct pharmacological profile. PMID- 19643165 TI - Genetically modified mouse models for premature ovarian failure (POF). AB - Premature ovarian failure (POF) is a complex disorder that affects approximately 1% of women. POF is characterized by the depletion of functional ovarian follicles before the age of 40 years, and clinically, patients may present with primary amenorrhea or secondary amenorrhea. Although some genes have been hypothesized to be candidates responsible for POF, the etiology of most of the cases is idiopathic, with the underlying causes still unidentified because of the heterogeneity of the disease. In this review, we consider some mutant mouse models that exhibit phenotypes which are comparable to human POF, and we suggest that the use of these mouse models may help us to gain a better understanding of the molecular mechanisms underlying POF in humans. PMID- 19643166 TI - Corticosteroid-binding globulin: the clinical significance of altered levels and heritable mutations. AB - Corticosteroid-binding globulin (CBG) is the specific high-affinity plasma transport glycoprotein for cortisol. Stress-induced falls in CBG levels may heighten hypothalamic-pituitary-adrenal axis responses and CBG:tissue interactions may allow targeted cortisol delivery. Three genetic variants of CBG have been identified that reduce cortisol binding affinity and/or CBG levels. These include the Leuven and Lyon mutations which reduce CBG:cortisol binding affinity 3- and 4-fold, respectively, and the null mutation resulting in a 50% (heterozygote) or 100% (homozygote) reduction in CBG levels. The three reported null homozygotes demonstrate that complete CBG deficiency is not lethal, although it may be associated with hypotension and fatigue. The phenotype of a CBG null murine model included fatigue and immune defects. One community-based study revealed that severe CBG mutations are rare in idiopathic fatigue disorders. The mechanisms by which CBG mutations may cause fatigue are unknown. There are preliminary data of altered CBG levels in hypertension and in the metabolic syndrome; however, the nature of these associations is uncertain. Further studies may clarify the functions of CBG, and clinical observations may validate and/or extend the phenotypic features of various CBG mutations. PMID- 19643167 TI - Is HSD17B1 a new sex reversal gene in human? PMID- 19643168 TI - Comparison of in vitro hormone activities of selected phthalates using reporter gene assays. AB - Phthalates are widely used in the plastic industry and food packaging, imparting softness and flexibility to normally rigid plastic medical devices and children's toys. Even though phthalates display low general toxicity, there is increasing concern on the effects of endocrine system induced by some of phthalate compounds. The hormone activity of dibutyl phthalate (DBP), mono-n-butyl phthalate (MBP) and di-2-ethylhexyl phthalate (DEHP) were assessed using the luciferase reporter gene assays. The results showed that DBP, MBP and DEHP, not only exhibited potent antiandrogenic activity, with IC(50) value of 1.05x10(-6), 1.22x10(-7)M and exceeding 1x10(-4)M respectively, but also showed the androgenic activity with EC(50) value of 6.17x10(-6), 1.13x10(-5)M and exceeding 1x10(-4)M. We also found that all the three related chemicals possessed thyroid receptor (TR) antagonist activity with IC(50) of 1.31x10(-5), 2.77x10(-6)M and exceeding 1x10(-4)M respectively, and none showed TR agonist activity. These results indicate that TR might be the targets of industrial chemicals. In the ER mediate reporter gene assay, three chemicals showed no agonistic activity except for DBP, which appeared weakly estrogenic at the concentration of 1.0x10(-4)M. Together, the findings demonstrate that the three phthalates could simultaneously disrupt the function of two or more hormonal receptors. Therefore, these phthalates should be considered in risk assessments for human health. PMID- 19643169 TI - Testicular gene expression profiling following 2-methoxyethanol and 2 ethoxyethanol exposure in male rats reveals abnormal expression of the actin binding protein cortactin in degenerating spermatocytes. AB - The glycol ether solvents 2-methoxyethanol (2-ME) and 2-ethoxyethanol (2-EE) produce testicular toxicity characterized by spermatocyte degeneration, while a similar glycol ether, 2-butoxyethanol (2-BE), has no testicular effects. The goal of the current study was to better understand the mechanism of glycol ether testicular toxicity through gene expression profiling and functional classification of differentially expressed genes. Male rats were administered 2 ME (150 and 50mg/kg/day), 2-EE (500 mg/kg/day), 2-BE (125 mg/kg/day), or vehicle for 3 days, and testes were collected for histopathological and gene expression analysis. Histopathological changes in the testes were observed only in animals given 150 mg/kg/day 2-ME, consisting of degeneration and necrosis of spermatocytes and reductions in spermatocyte numbers. Microarray analysis of testicular samples from these animals revealed a large number of differentially expressed genes from animals exposed to 2-EE or to 50mg/kg or 150 mg/kg 2-ME (>900 each at >1.5-fold changed), compared to 28 genes from 2-BE treated animals. Expression Analysis Systematic Explorer (EASE) analysis of these genes demonstrated statistical enrichment in genes in categories including protein transport, endocytosis, protein kinase activity, cell cycle, and meiosis. Quantitative PCR confirmation of select genes confirmed increased expression of the actin binding protein cortactin and the transcription factor Wilm's tumor 1 (Wt1) following 2-ME exposure. Increased localization of cortactin in abnormal spermatocytes was also observed by immunohistochemistry, consistent with a possible role for this protein in the mechanism of toxicity. PMID- 19643170 TI - Nanosized polyamidoamine (PAMAM) dendrimer-induced apoptosis mediated by mitochondrial dysfunction. AB - Nano-materials are currently being used in a variety of fields. One of the concerns associated with their use is their potential to harm human health. In an attempt to identify genes expressed differently in human lung cells (WI-26 VA4) exposed to nanosized (45 nm in diameter) PAMAM (polyamidoamine) dendrimers, we observed down-regulation of mitochondrial DNA-encoded genes involved in the maintenance of mitochondrial membrane potential. Down-regulation of gene expression was confirmed by semi-quantitative RT-PCR. Dendrimers were shown to colocalize with mitochondria and cause the release of cytochrome C. Mitochondrial membrane potential was disrupted and the viability of cells was decreased in the presence of dendrimers. Activation of caspases 3 and 9 was increased. Apoptosis was observed by annexin V/propidium iodide staining and DNA fragmentation. In summary, nanosized dendrimers damaged mitochondria resulting in apoptosis. PMID- 19643171 TI - Lanthanum chloride impairs memory, decreases pCaMK IV, pMAPK and pCREB expression of hippocampus in rats. AB - Surveys have reported that rare-earth elements (REEs) could impair cognitive functions of children. Experimental studies have shown the neurological adverse effects of REEs on animals. However, the mechanism underlying these impairments is unclear. Lanthanum is often selected to study the effects of REEs. The purpose of this study was to investigate the memory impairment induced by lanthanum chloride (LaCl3) exposure and the possible mechanism from the aspects of expression of CREB signal pathway and synaptic ultrastructure in the hippocampus. Lactational rats were exposed to 0%, 0.25%, 0.50%, and 1.0% LaCl3 in drinking water, respectively. Their offspring were exposed to LaCl3 by parental lactation for 3 weeks and then administrated with 0%, 0.25%, 0.50% and 1.0% LaCl3 in drinking water for 1 month. The results showed that 0.25%, 0.50%, and 1.0% LaCl3 exposure could significantly impair memory of young rats. Hippocampal pCaMK IV, pMAPK, pCREB, c-fos and egr1 expression were decreased significantly, and synaptic ultrastructure was negatively affected after LaCl3 exposure. These results indicate that LaCl3 exposure impairs memory of rats and this impairment may be attributed to the lower levels of pCaMK IV, pMAPK, pCREB, c-fos and egr1 expression and change of synaptic ultrastructure in hippocampus. PMID- 19643172 TI - Controlled transdermal iontophoresis of sulfosalicylic acid from polypyrrole/poly(acrylic acid) hydrogel. AB - A conductive polymer-hydrogel blend between sulfosalicylic acid-doped polypyrrole (PPy) and poly(acrylic acid) (PAA) was used as a carrier/matrix for the transdermal drug delivery under applied electrical field. PAA films and the blend films were prepared by solution casting with ethylene glycol dimethacrylate (EGDMA) as a cross-linking agent, followed by the blending of PPy particles and the PAA matrix. The effects of cross-linking ratio and electric field strength on the diffusion of the drug from PAA and PPy/PAA hydrogels were investigated using a modified Franz-diffusion cell with an acetate buffer of pH 5.5 and at 37 degrees C, for a period of 48h. The diffusion coefficient of the drug is calculated using the Higuchi equation, with and without an electric field, at various cross-linking ratios. The drug diffusion coefficient decreases with increasing drug size/mesh size ratio, irrespective of the presence of the conductive polymer as the drug carrier. The diffusion coefficient, at the applied electric field of 1.0V, becomes larger by an order of magnitude relative to those without the electric field. PMID- 19643173 TI - Glutathione S-transferase M1, T1, and P1 polymorphisms as susceptibility factors for noise-induced temporary threshold shift. AB - The generation of reactive oxygen species (ROS) is thought to be part of the mechanism underlying noise-induced hearing loss (NIHL). Glutathione is an important cellular antioxidant that limits cell damage by ROS. We aimed to determine the effect of genetic polymorphisms of glutathione S-transferase (GST) T1, GSTM1, and GSTP1, on temporary threshold shift (TTS) in 58 noise-exposed male workers from a steel factory. The pre-shift hearing impairment at high frequency (HF, average of 3, 4, and 6kHz) was 30.7dB HL (S.D.=19.3). The amount of daily noise exposure was 83.0dBA (S.D.=5.0). Noise-induced TTS at HF by pure-tone audiometry (PTA) was related to the daily noise exposure (p<0.05). Based on combinatory analysis, we found that individuals carrying all genotypes with GSTT1 null, GSTM1 null, and GSTP1 Ile(105)/Ile(105) were more susceptible to NIHL. These results suggest that pre-shift hearing impairment and daily noise exposure had impacts on TTS at HF by PTA. In addition, GST genetic polymorphisms may modify the susceptibility to noise-induced TTS. PMID- 19643174 TI - Different distributions of calbindin and calretinin immunostaining across the medial and dorsal divisions of the mouse medial geniculate body. AB - We studied the distributions of calretinin and calbindin immunoreactivity in subdivisions of the mouse medial geniculate body and the adjacent paralaminar nuclei. We found that the vast majority of labeled cells in the dorsal division of the medial geniculate body were immunoreactive for calbindin-only, whereas most of the remaining labeled cells were double-labeled. Very few calretinin+ only cells were observed. By contrast, we observed significant proportions of calbindin+ only, calretinin+ only and double-labeled cells in the medial division of the medial geniculate body. Further, the distributions of calbindin-only, calretinin-only and double-labeled cells did not differ between the medial division of the medial geniculate body, the suprageniculate nucleus, the peripeduncular nucleus and the posterior intralaminar nucleus. We found essentially no somatic staining for either calbindin or calretinin in the ventral division of the medial geniculate body. These data suggest that there are distinct neurochemical differences between the two non-lemniscal auditory thalamic nuclei. In addition, these data extend previous observations that the medial division of the medial geniculate body shares many properties with the paralaminar group of nuclei. PMID- 19643175 TI - Inhibitory effects of citrus extracts on the experimental pulmonary fibrosis. AB - AIM OF THE STUDY: A Chinese herbal formula, Hu-qi-yin possessed an anti-pulmonary fibrosis effect. Pericarp of Citrus reticulata, one of the herbal drugs contained in this formula showed the most potent inhibitory activity on the proliferation of human embryonic lung fibroblasts (HELF). The present study was designed to clarify the active principles responsible for the activity and further explore the anti-pulmonary fibrosis effect in vivo. MATERIALS AND METHODS: The water, 75% ethanol and flavonoids-enriched extracts of Citrus reticulata were prepared and screened for their anti-proliferation activity using HELF culture system. The ethanol extract was further administered orally at doses of 100 and 200 mg/(kg day) to bleomycin (BLM)-induced pulmonary fibrosis rats. The analyses of the rat body weight, hydroxyproline levels in serum and lung, scores of alveolitis and fibrosis, as well as the expression of transforming growth factor-beta(1) (TGF beta(1)) at the protein and the messenger ribonucleic acid (mRNA) levels in lung were performed. RESULTS: The ethanol extract showed the strongest inhibitory activity on HELF proliferation. Further research using BLM-induced rat model revealed that the ethanol extract at the doses of 100 and 200 mg/(kg day) caused a marked increase of body weight at first 7 days, significantly lowered the hydroxyproline levels in lung, greatly improved the pathologic scores, as well as inhibited the overexpressions of TGF-beta(1) protein and mRNA. CONCLUSIONS: The results suggest that the ethanol extract of Citrus reticulata has anti-pulmonary fibrosis effects and might have a great potential for the treatment of fibrosis of lung. PMID- 19643176 TI - Depression, cortisol, and suppressed cell-mediated immunity in metastatic breast cancer. AB - Cancer treatment is known to have significant immuno-suppressive/dysregulatory effects. Psychological distress and depression, which often accompany cancer diagnosis and treatment, can also suppress or dysregulate endocrine and immune function. Cell-mediated immunity (CMI) is critical for protection against a host of pathogens to which cancer patients may be particularly susceptible. CMI is also important for defense against some tumors. This study explored relationships among depressive symptoms, cortisol secretion, and CMI responses in 72 women with metastatic breast cancer. Depressive symptoms were assessed with the Center for Epidemiologic Studies-Depression Scale (CES-D). Saliva was sampled throughout the day over a 3-day period to obtain a physiologic index of diurnal cortisol concentrations and rhythmicity, which is associated with breast cancer survival time. CMI for specific antigens was measured following intradermal administration of seven commonly encountered antigens (tuberculin, tetanus, diphtheria, Streptococcus, Candida, Trichophyton, and Proteus). Analyses adjusting for relevant medical and treatment variables indicated that women reporting more depressive symptoms showed suppressed immunity as measured by lower average induration size. Women with higher mean diurnal cortisol concentrations also showed suppressed immunity as indicated by a decreased number of antigens to which positive reactions were measured. This study highlights the relationships among depression, stress, and immune function in the context of advanced breast cancer. PMID- 19643177 TI - Inhibition of dynamin prevents CCL2-mediated endocytosis of CCR2 and activation of ERK1/2. AB - The magnitude and duration of G protein-coupled receptor (GPCR) signals are regulated through desensitization mechanisms. In leukocytes, ligand binding to chemokine receptors leads to Ca2+ mobilization and ERK activation through pertussis toxin-sensitive G proteins, as well as to phosphorylation of the GPCR. After interaction with the endocytic machinery (clathrin, adaptin), the adaptor beta-arrestin recognizes the phosphorylated GPCR tail and quenches signaling to receptors. The molecular mechanisms that lead to receptor endocytosis are not universal amongst the GPCR, however, and the precise spatial and temporal events in the internalization of the CCR2 chemokine receptor remain unknown. Here we show that after ligand binding, CCR2 internalizes rapidly and reaches early endosomes, and later, lysosomes. Knockdown of clathrin by RNA interference impairs CCR2 internalization, as does treatment with the dynamin inhibitor, dynasore. Our results show that CCR2 internalization uses a combination of clathrin-dependent and -independent pathways, as observed for other chemokine receptors. Moreover, the use of dynasore allowed us to confirm the existence of a dynamin-sensitive element that regulates ERK1/2 activation. Our results indicate additional complexity in the link between receptor internalization and cell signaling. PMID- 19643178 TI - Klhl31 is associated with skeletal myogenesis and its expression is regulated by myogenic signals and Myf-5. AB - Klhl31 is an orthologue of Drosophila Kelch and belongs to a family of Kelch-like proteins in vertebrates. Members of this family contain multiple protein domains, including an amino-terminal broad complex/tram-track/bric-a-brac (BTB) or poxvirus and zinc finger (POZ) domain, carboxy-terminal Kelch repeats and a central linker region. We show that Klhl31 is highly expressed in the developing heart, the somite myotome and later in differentiated skeletal muscle and the myocardium. In developing somites expression of Klhl31 was initiated in the epaxial domain of the myotome, shortly after the skeletal muscle specific bHLH transcription factor, MyoD, was first expressed. Klhl31 remained expressed in skeletal muscle throughout embryonic and fetal development. Tissue ablations and rescue experiments that regulate myogenesis also govern expression of Klhl31 expression in somites. In particular, axial tissues, neural tube, floor plate and notochord, and surface ectoderm, provide combinatorial cues for myogenesis and the appropriate expression of Klhl31. We show that a combination of myogenic signals, Shh and either Wnt-1 or Wnt-6, are sufficient for Klhl31 expression in the dorsal somite. Furthermore, ectopic expression of Myf-5 led to expression of Klhl31 in the developing neural tube, indicating that Klhl31 is a novel and integral part of vertebrate myogenesis. PMID- 19643179 TI - The C-terminal domains of ADAMTS-4 and ADAMTS-5 promote association with N-TIMP 3. AB - We investigated whether the affinity of tissue inhibitor of metalloproteinases (TIMP)-3 for adamalysins with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 is affected by the non-catalytic ancillary domains of the enzymes. For this purpose, we first established a novel method of purifying recombinant FLAG-tagged TIMP-3 and its inhibitory N-terminal domain (N-TIMP-3) by treating transfected HEK293 cells with sodium chlorate to prevent heparan sulfate proteoglycan-mediated TIMP 3 internalization. TIMP-3 and N-TIMP-3 affinity for selected matrix metalloproteinases and forms of ADAMTS-4 and -5 lacking sequential C-terminal domains was determined. TIMP-3 and N-TIMP-3 displayed similar affinity for various matrix metalloproteinases as has been previously reported for E. coli expressed N-TIMP-3. ADAMTS-4 and -5 were inhibited more strongly by N-TIMP-3 than by full-length TIMP-3. The C-terminal domains of the enzymes enhanced interaction with N-TIMP-3 and to a lesser extent with the full-length inhibitor. For example, N-TIMP-3 had 7.5-fold better K(i) value for full-length ADAMTS-5 than for the catalytic and disintegrin domain alone. We propose that the C-terminal domains of the enzymes affect the structure around the active site, favouring interaction with TIMP-3. PMID- 19643181 TI - The physiological and pathophysiological role of PRMT1-mediated protein arginine methylation. AB - Post-translational modifications are well-known effectors in DNA damage signaling and epigenetic gene expression. Protein arginine methylation is a covalent modification that results in the addition of methyl groups to the nitrogen atoms of the arginine side chains and is catalyzed by a family of protein arginine methyltransferases (PRMTs). In the past, arginine methylation was mainly observed on abundant proteins such as RNA-binding proteins and histones, but recent advances have revealed a plethora of arginine-methylated proteins implicated in a variety of cellular processes including signal transduction, epigenetic regulation and DNA repair pathways. Herein, we discuss these recent advances, focusing on the role of PRMT1, the major asymmetric arginine methyltransferase, in cellular processes and its link to human diseases. PMID- 19643180 TI - Antitumor activities and pharmacokinetics of silatecans DB-67 and DB-91. AB - DB-67 and its lactone homolog DB-91 are derivatives of topoisomerase I inhibitor camptothecin (CPT) with silyl moiety, which may exhibit a slower inactivation process by changed kinetics of protein binding and/or hydrolysis of its lactone ring and result in increased antitumor activity and decreased toxicity. Pharmacokinetic properties and antitumor activities of the two silatecans were studied and compared. The lactone ring of DB-91 is more stable than those of all the other CPT derivatives in mouse plasma. Both silatecans were metabolized faster than CPT in mouse and human liver microsomes. Pharmacokinetic study revealed a plasma elimination half-life (t(1/2)) of 33 and 94min for DB-67 and DB 91, respectively; similar systemic exposure in plasma between DB-67 and DB-91; and similar volume of distribution at the steady state between DB-67 and DB-91, approximately 15-fold smaller than that of CPT. While DB-91 showed limited activities, DB-67 exhibited activities against the growth of in vivo-like histocultured human tumors and s.c. xenografted human tumors in nude mice. In conclusion, DB-67 is more effective, compared to DB-91, against human tumor growth in in vitro, in vivo-like and in vivo systems. Further pre-clinical and clinical investigations of DB-67 are warranted. PMID- 19643182 TI - A gas chromatography-mass spectrometry method to monitor detergents removal from a membrane protein sample. AB - In membrane protein biochemical and structural studies, detergents are used to mimic membrane environment and maintain functional, stable conformation of membrane proteins in the absence of lipid bilayers. However, detergent concentration, esp. molar ratio of membrane protein to detergent is usually unknown. Here, a gas chromatography-mass spectrometry selected ion monitoring (GC MS-SIM) method was developed to quantify four detergents which are frequently used in membrane protein structural studies. To remove excessive detergents, a filtered centrifugation using Centricon tubes was applied. A membrane protein Ig Beta fragment in four different detergent micelles was exemplified. Detergent concentrations in the upper and lower fraction of the Centricon tube were measured after each round of centrifugation. The results were very consistent to basic properties of detergent micelles in aqueous solvents. Therefore, coupling of GC-MS-SIM and detergent removal by Centricon tubes, detergents concentration, esp. molar ratio of membrane protein to detergent could be controlled, which will expedite membrane protein structural and biochemical studies. PMID- 19643184 TI - Increasing top-down suppression from prefrontal cortex facilitates tactile working memory. AB - Navigated transcranial magnetic stimulation (TMS) combined with diffusion weighted magnetic resonance imaging (DW-MRI) and tractography allows investigating functional anatomy of the human brain with high precision. Here we demonstrate that working memory (WM) processing of tactile temporal information is facilitated by delivering a single TMS pulse to the middle frontal gyrus (MFG) during memory maintenance. Facilitation was obtained only with a TMS pulse applied to a location of the MFG with anatomical connectivity to the primary somatosensory cortex (S1). TMS improved tactile WM also when distractive tactile stimuli interfered with memory maintenance. Moreover, TMS to the same MFG site attenuated somatosensory evoked responses (SEPs). The results suggest that the TMS-induced memory improvement is explained by increased top-down suppression of interfering sensory processing in S1 via the MFG-S1 link. These results demonstrate an anatomical and functional network that is involved in maintenance of tactile temporal WM. PMID- 19643183 TI - Brain structure changes visualized in early- and late-onset blind subjects. AB - We examined 3D patterns of volume differences in the brain associated with blindness, in subjects grouped according to early and late onset. Using tensor based morphometry, we mapped volume reductions and gains in 16 early-onset (EB) and 16 late-onset (LB) blind adults (onset <5 and >14 years old, respectively) relative to 16 matched sighted controls. Each subject's structural MRI was fluidly registered to a common template. Anatomical differences between groups were mapped based on statistical analysis of the resulting deformation fields revealing profound deficits in primary and secondary visual cortices for both blind groups. Regions outside the occipital lobe showed significant hypertrophy, suggesting widespread compensatory adaptations. EBs but not LBs showed deficits in the splenium and the isthmus. Gains in the non-occipital white matter were more widespread in the EBs. These differences may reflect regional alterations in late neurodevelopmental processes, such as myelination, that continue into adulthood. PMID- 19643186 TI - Simplified parametric methods for [18F]FDDNP studies. AB - The purpose of the present study was to evaluate the performance of various parametric methods for quantification of [(18)F]FDDNP studies. All parametric methods tested were based on the use of a reference tissue and they were compared with the simplified reference tissue model (SRTM), as previously it has been shown that SRTM is the method of choice for analysing [(18)F]FDDNP studies, even when an arterial plasma input function is available. The following parametric methods were evaluated: receptor parametric mapping (basis function implementation of SRTM; with and without fixing the reference tissue efflux rate constant k'(2)), reference Logan and several multi-linear reference tissue methods (again with and without fixing k'(2)). Simulations were used to assess the effects of variation in relative flow (R(1)), fractional blood volume (V(b)) and binding potential (BP(ND)) on precision and accuracy of estimated BP(ND). For clinical data, best performance was obtained using receptor parametric mapping (RPM2) and one of the multi-linear reference tissue models (MRTM2), with k'(2) being fixed in both methods. These models showed good correlation with SRTM, their BP(ND) results were less affected by noise and images showed good contrast. Furthermore, in simulations, RPM2 and MRTM2 provided the most accurate and precise BP(ND) estimates. RPM2 and MRTM2 are the methods of choice for parametric analysis of [(18)F]FDDNP studies. PMID- 19643185 TI - Anatomical atlas-guided diffuse optical tomography of brain activation. AB - We describe a neuroimaging protocol that utilizes an anatomical atlas of the human head to guide diffuse optical tomography of human brain activation. The protocol is demonstrated by imaging the hemodynamic response to median-nerve stimulation in three healthy subjects, and comparing the images obtained using a head atlas with the images obtained using the subject-specific head anatomy. The results indicate that using the head atlas anatomy it is possible to reconstruct the location of the brain activation to the expected gyrus of the brain, in agreement with the results obtained with the subject-specific head anatomy. The benefits of this novel method derive from eliminating the need for subject specific head anatomy and thus obviating the need for a subject-specific MRI to improve the anatomical interpretation of diffuse optical tomography images of brain activation. PMID- 19643187 TI - BOLD fMRI using a modified HASTE sequence. AB - For more than a decade, turbo spin echo (TSE) pulse sequences have been suggested as an alternative to echo planar imaging (EPI) sequences for fMRI studies. Recent development in parallel imaging has renewed the interest in developing more robust TSE sequences for fMRI. In this study, a modified half Fourier acquisition single-shot TSE (mHASTE) sequence has been developed with a three-fold GRAPPA to improve temporal resolution as well as a preparation time to enhance BOLD sensitivity. Using a classical flashing checkerboard block design, the BOLD signal characteristics of this novel method have been systematically analyzed as a function of several sequence parameters and compared to those of gradient-echo and spin-echo EPI sequences. Experimental studies on visual cortex of five volunteers have provided evidence suggesting that mHASTE can be more sensitive to extra-vascular BOLD effects around microvascular networks, which leads to more accurate function localization. The studies also show that the activation cluster size in mHASTE increases with the refocusing RF flip angle and TE while decreasing with the echo number (n(center)) used to sample the k-space center. Compared to spin-echo EPI, mHASTE incurs an approximately 50% reduction in activation cluster size and an approximately 20% decrease in BOLD contrast. However a higher signal-to-noise ratio and a spatially more uniform temporal stability have been observed in mHASTE as compared to the EPI sequences when the scan times are held constant. With further refinement and optimization, mHASTE can become a viable alternative for fMRI in situations where the conventional EPI sequences are limited or prohibitive. PMID- 19643189 TI - Surveillance in Barrett's esophagus: lessons from behavioral economics. PMID- 19643190 TI - Deciphering hepatocellular carcinoma: from bench to bedside and back. PMID- 19643191 TI - Developing irritable bowel syndrome guidelines through meta-analyses: does the emperor really have new clothes? PMID- 19643188 TI - Callosal atrophy in mild cognitive impairment and Alzheimer's disease: different effects in different stages. AB - Alzheimer's Disease (AD) is a neurodegenerative disorder that mainly affects grey matter (GM). Nevertheless, a number of investigations have documented white matter (WM) pathology associated with AD. The corpus callosum (CC) is the largest WM fiber bundle in the human brain. It has been shown to be susceptible to atrophy in AD mainly as a correlate of Wallerian degeneration of commissural nerve fibers of the neocortex. The aim of this study was to investigate which callosal regions are affected and whether callosal degeneration is associated with the stage of the disease. For this purpose, we analyzed high-resolution MRI data of patients with amnesic mild cognitive impairment (MCI) (n=20), mild AD (n=20), severe AD (n=10), and of healthy controls (n=20). Callosal morphology was investigated applying two different structural techniques: mesh-based geometrical modeling methods and whole-brain voxel-based analyses. Our findings indicate significant reductions in severe AD patients compared to healthy controls in anterior (genu and anterior body) and posterior (splenium) sections. In contrast, differences between healthy controls and mild AD patients or amnesic MCI patients were less pronounced and did not survive corrections for multiple comparisons. When correlating anterior and posterior WM density of the CC with GM density of the cortex in the severe AD group, we detected significant positive relationships between posterior sections of the CC and the cortex. We conclude that callosal atrophy is present predominantly in the latest stage of AD, where two mechanisms might contribute to WM alterations in severe AD: the Wallerian degeneration in posterior subregions and the myelin breakdown process in anterior subregions. PMID- 19643192 TI - Intestinal lipid absorption, GLP-2, and CD36: still more mysteries to moving fat. PMID- 19643194 TI - Working through polytomies: auklets revisited. AB - Polytomies, or phylogenetic "bushes", are the result of a series of internodes occurring in a short period of evolutionary time (which can result in data that do not contain enough information), or data that have too much homoplasy to resolve a bifurcating branching pattern. In this study we used the Aethia auklet polytomy to explore the effectiveness of different methods for resolving polytomies: mitochondrial DNA gene choice, number of individuals per species sampled, model of molecular evolution, and AFLP loci. We recovered a fully resolved phylogeny using NADH dehydrogenase subunit 2 (ND2) sequence data under two different Bayesian models. We were able to corroborate this tree under one model with an expanded mtDNA dataset. Effectiveness of additional intraspecific sampling varied with node, and fully 20% of the subsampled datasets failed to return a congruent phylogeny when we sampled only one or two individuals per species. We did not recover a resolved phylogeny using AFLP data. Conflict in the AFLP dataset showed that nearly all possible relationships were supported at low levels of confidence, suggesting that either AFLPs are not useful at the genetic depth of the Aethia auklet radiation (7-9% divergent in the mtDNA ND2 gene), perhaps resulting in too much homoplasy, or that the Aethia auklets have experienced incomplete lineage sorting at many nuclear loci. PMID- 19643193 TI - Finding and killing the CRABs of pancreatic cancer. PMID- 19643195 TI - Phylogeny of Spinicaudata (Branchiopoda, Crustacea) based on three molecular markers--an Australian origin for Limnadopsis. AB - Taxonomy and phylogeny within the branchiopod taxon Spinicaudata are still controversial. We analyzed sequences of three gene fragments (28S rRNA, 16S rRNA and COI) from up to 41 species of the Cyzicidae, Limnadiidae and Leptestheriidae to infer their phylogenetic relationships, focusing in particular on species from Australia and their phylogenetic position within Spinicaudata. Four major monophyletic lineages could be distinguished: Limnadiidae, Leptestheriidae, Eocyzicus and all Cyzicidae except Eocyzicus. A clear genetic distinction between Australian and non-Australian Cyzicidae is well supported (i.e. Caenestheria and Caenestheriella species from Australia and Caenestheriella and Cyzicus species from Europe, Asia and North America). In the genera Eocyzicus and Eulimnadia the Australian species were closely related to those from other continents. The species of the Australian endemic genus Limnadopsis and Australian Limnadia species form a monophylum. This suggests that the origin of Limnadopsis lies in Australia and that Limnadia is not monophyletic. PMID- 19643196 TI - Complex evolution in the Neotropics: the origin and diversification of the widespread genus Leptodeira (Serpentes: Colubridae). AB - Lineage diversification in the Neotropics is an interesting topic in evolutionary biology but is also one of the least understood. The abiotic and biotic complexity of the region precludes generalizations that can be drawn regarding the historical evolutionary processes responsible for the diversity observed. The snake genus Leptodeira provides an excellent opportunity to investigate such processes because it spans the entire Neotropical region. In this study, we infer the phylogenetic position of Leptodeira within Dipsadinae, estimate evolutionary relationships among and within Leptodeira species, and estimate the diversification time and biogeography of the genus. Three mitochondrial gene regions were sequenced for individuals representing all the Leptodeira species and most subspecies currently recognized. Additionally, two nuclear protein coding gene regions were sequenced for representatives of each species and several genera within the Dipsadinae. We infer that several Leptodeira species are either paraphyletic or polyphyletic as currently recognized, and that most recognized subspecies are not monophyletic lineages. Despite the taxonomic discordance with evolutionary relationships, clades appear to correspond very well to major biogeographic regions of Mexico, Central America and South America. Our results thus highlight the important role of the Miocene and Pliocene for lineage diversification in the Neotropics. Additionally, our time estimates suggest that recent intraspecific phylogeographic structure is likely the result of habitat and climatic fluctuations during the Pleistocene. Cumulatively, our inferences of lineage diversification within Leptodeira suggest a complex evolutionary scenario in the Mexican transition zone and a north to south expansion with a final colonization of the tropics in South America. PMID- 19643197 TI - Inactivation of the basolateral amygdala impairs the retrieval of recent and remote taste-potentiated odor aversion memory. AB - Memory reorganization as a time-dependent process can be investigated using various learning tasks such as the taste-potentiated odor aversion (TPOA). In this paradigm rats acquire a strong aversion to an olfactory cue presented simultaneously with a gustatory cue. Together these cues are paired with a delayed visceral illness. The basolateral amygdaloid nucleus (BLA) plays a key role in TPOA acquisition but its involvement in retrieval remains unclear. We investigated the involvement of the BLA in either recent or remote retrieval of TPOA. In each case, the number of licks observed in response to the presentation of either the odor or the taste was used to assess retrieval. Before the retrieval test, rats received a bilateral infusion of lidocaine to inactivate the BLA. We observed that both recent and remote TPOA retrieval tests induced by the odor presentation were disrupted in the lidocaine-injected rats. By contrast, the BLA inactivation had no effect upon the aversion towards the taste cue regardless of the time of retrieval. The present study provides evidence that BLA functioning is necessary for retrieval of aversive odor memory, even with a long post-acquisition delay. PMID- 19643198 TI - Heterokaryons and parasexual recombinants of Cryphonectria parasitica in two clonal populations in southeastern Europe. AB - Evidence for parasexuality in natural populations of haploid fungi requires the demonstration of diploids or heterokaryons and recombinant genotypes in the absence of sex. We studied clonal populations of the chestnut blight fungus, Cryphonectria parasitica, in southeastern Europe and found evidence of parasexuality in two locations. In Osoj, Macedonia, we found one isolate (Os05 66) that had two alleles at six codominant loci, giving a haplotype that was a composite of two clones in this population. Six single-conidial isolates from Os05-66 had two alleles at some loci, suggesting partial diploidy or aneuploidy, and we found four recombinant haplotypes among single-conidial isolates from hyphal-tip isolates of the same isolate. In Teano, Italy, we found two heterokaryon isolates that were partial composites of two dominant clones. Single conidial isolates from hyphal-tip isolates had recombinant haplotypes. These results provide evidence that is consistent with the hypothesis of parasexuality in C. parasitica in Europe, similar to an earlier report in a natural population in the USA. PMID- 19643199 TI - The dynamin-related protein Vps1 regulates vacuole fission, fusion and tubulation in the fission yeast, Schizosaccharomyces pombe. AB - Fission yeast cells lacking the dynamin-related protein (DRP) Vps1 had smaller vacuoles with reduced capacity for both fusion and fission in response to hypotonic and hypertonic conditions respectively. vps1Delta cells showed normal vacuolar protein sorting, actin organisation and endocytosis. Over-expression of vps1 transformed vacuoles from spherical to tubular. Tubule formation was enhanced in fission conditions and required the Rab protein Ypt7. Vacuole tubulation by Vps1 was more extensive in the absence of a second DRP, Dnm1. Both dnm1Delta and the double mutant vps1Delta dnm1Delta showed vacuole fission defects similar to that of vps1Delta. Over-expression of vps1 in dnm1Delta, or of dnm1 in vps1Delta failed to rescue this phenotype. Over-expression of dnm1 in wild-type cells, on the other hand, induced vacuole fission. Our results are consistent with a model of vacuole fission in which Vps1 creates a tubule of an appropriate diameter for subsequent scission by Dnm1. PMID- 19643200 TI - Restriction of Chlamydia pneumoniae replication in human dendritic cell by activation of indoleamine 2,3-dioxygenase. AB - Infection with Chlamydia pneumoniae, a human respiratory pathogen, has been associated with various chronic diseases such as asthma and atherosclerosis, possibly because the pathogen can exist in a persistent form. C. pneumoniae persistently infect DCs in a TNF-alpha dependent manner. The present study investigated whether C. pneumoniae infection can induce indoleamine 2,3 dioxygenase (IDO) activity in dendritic cells, and whether the restriction of chlamydial growth in the DCs by TNF-alpha is IDO dependent. Our data indicate that infection of DCs with C. pneumoniae resulted in the induction of IDO expression. Reporting on our use of anti-TNF-alpha antibody adalimumab and varying concentrations of TNF-alpha, we further demonstrate that IDO induction following infection of DCs with C. pneumoniae is TNF-alpha dependent. The anti chlamydial activity induced by TNF-alpha and the expression of chlamydial 16S rRNA gene, euo, groEL1, ftsk and tal genes were correlated with induction of IDO. Addition of excess amounts of tryptophan to the DC cultures resulted in abrogation of the TNF-alpha-mediated chlamydial growth restriction. These findings suggest that infection of DCs by C. pneumoniae induces production of functional IDO, which subsequently causes depletion of tryptophan. This may represent a potential mechanism for DCs to restrict bacterial growth in chlamydial infections. PMID- 19643201 TI - Modulation of cellular function by polyamines. AB - Polyamines (putrescine, spermidine and spermine) are essential for normal cell growth. The polyamine levels in cells are regulated by biosynthesis, degradation, and transport. Polyamines can modulate the functions of DNA, nucleotide triphosphates, proteins, and especially RNA because most polyamines exist in a polyamine-RNA complex in cells. Thus, the major focus on this review is on the role of polyamines in protein synthesis. In addition, effects of polyamines on B to Z conversion of DNA, transcription, phosphorylation of proteins, cell cycle progression, apoptosis and ion channels, especially NMDA receptors, are outlined. The function of eIF5A is also briefly discussed. Finally, a correlation between acrolein, produced from polyamines by polyamine oxidases, and chronic renal failure or brain stroke is summarized. Increased levels of polyamine oxidases and acrolein are good markers of chronic renal failure and brain stroke. PMID- 19643202 TI - Comparative and evolutionary aspects of macromolecular translocation across membranes. AB - Membrane barriers preserve the integrity of organelles of eukaryotic cells, yet the genesis and ongoing functions of the same organelles requires that their limiting membranes allow import and export of selected macromolecules. Multiple distinct mechanisms are used for this purpose, only some of which have been traced to prokaryotes. Some can accommodate both monomeric and also large heterooligomeric cargoes. The best characterized of these is nucleocytoplasmic transport. This synthesis compares the unidirectional and bidirectional mechanisms of macromolecular transport of the endoplasmic reticulum, mitochondria, peroxisomes and the nucleus, calls attention to the powerful experimental approaches which have been used for their elucidation, discusses their regulation and evolutionary origins, and highlights relatively unexplored areas. PMID- 19643204 TI - Ampullary carcinoid: diagnostic challenges and update on management. PMID- 19643203 TI - Two dissimilar AT(1) agonists distinctively activate AT(1) receptors located on the luminal membrane of coronary endothelium. AB - Diverse intracoronary agonists cause cardiac effects while acting on coronary endothelial luminal membrane (CELM) receptor. Our data show: a) the presence of AT(1)R in isolated CELM and in all cardiac cell types and b) sustained intracoronary infusions of Ang II-POL, a large sized molecule (approximately 15,000 kDa) confined to the vessel lumen that can only act on CELM's AT(1)R or Ang II (approximately 1 kDa); both exert the same maximum positive inotropic (PIE) and coronary constriction (CPP). The effects of these two agonists are blocked by Losartan and by Sar-POL; a large size antagonist (approximately 15,000 kDa) that acts only on CELM. Ang II effects are transient due to desensitization and cause tachyphylaxis to Ang II and toward Ang II-POL suggesting that both Ang II and Ang II-POL act on the same receptor group. In contrast, Ang II-POL effects are sustained and do not cause tachyphylaxis. The results show that intravascular Ang II and Ang II-POL act differentially by an unknown mechanism on CELM's AT(1)R and suggest that intravascular Ang II and Ang II-POL cause PIE and CCP by activation limited to CELM's AT(1)R through an unknown mechanism that is space confined to the CELM's AT(1)R. PMID- 19643206 TI - Bats and birds: Exceptional longevity despite high metabolic rates. AB - Bats and birds live substantially longer on average than non-flying mammals of similar body size. The combination of small body size, high metabolic rates, and long lifespan in bats and birds would not seem to support oxidative theories of ageing that view senescence as the gradual accumulation of damage from metabolic byproducts. However, large-scale comparative analyses and laboratory studies on a few emerging model species have identified multiple mechanisms for resisting oxidative damage to mitochondrial DNA and cellular structures in both bats and birds. Here we review these recent findings, and suggest areas in which additional progress on ageing mechanisms can be made using bats and birds as novel systems. New techniques for determining the age of free-living, wild individuals, and robustly supported molecular phylogenies, are under development and will improve the efforts of comparative biologists to identify ecological and evolutionary factors promoting long lifespan. In the laboratory, greater development of emerging laboratory models and comparative functional genomic approaches will be needed to identify the molecular pathways of longevity extension in birds and bats. PMID- 19643205 TI - Nucleotide sequence polymorphism at the apical membrane antigen-1 locus reveals population history of Plasmodium vivax in Thailand. AB - Apical membrane antigen-1 is a candidate for inclusion in a vaccine for the human malaria parasite Plasmodium vivax. We collected 231 complete sequences of the gene encoding this antigen (pvama-1) from three regions of Thailand, the most extensive collection to date of sequences at this locus. The domain II loop (previously mentioned as a potential vaccine component) was almost completely conserved, with a single amino acid variant (I313R) observed in a single sequence. The 3' portion of the gene (domain II through the stop codon) showed significantly lower nucleotide diversity than the 5' portion (start codon through domain I); and a given domain I sequence might be found in a haplotype with more than one domain II sequence. These results imply a hotspot of recombination between domains I and II. We found significant geographic subdivision among the three regions of Thailand (NW, East, and South) in which collections were made in 2007. Numbers of P. vivax infections have experienced overall declines since 1990 in all three regions; but the decline has been most recent in the NW, and there has been a rebound in numbers of infections in the South since 2000. Consistent with population history, amino acid sequence diversity was greatest in the NW. The South, which had by far the lowest sequence diversity of the three regions, showed signs of a population that has expanded from a small number of founders after a bottleneck. PMID- 19643207 TI - Dietary fatty acids in dementia and predementia syndromes: epidemiological evidence and possible underlying mechanisms. AB - Drugs currently used in the treatment of cognitive impairment and dementia have a very limited therapeutic value, suggesting the necessity to potentially individualize new strategies able to prevent and to slow down the progression of predementia and dementia syndromes. An increasing body of epidemiological evidence suggested that elevated saturated fatty acids (SFA) could have negative effects on age-related cognitive decline (ARCD) and mild cognitive impairment (MCI). Furthermore, a clear reduction of risk for cognitive decline has been found in population samples with elevated fish consumption, high intake of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), particularly n-3 PUFA. Epidemiological findings demonstrated that high PUFA intake appeared to have borderline non-significant trend for a protective effect against the development of MCI. Several hypotheses could explain the association between dietary unsaturated fatty acids and cognitive functioning, including mechanisms through the co-presence of antioxidant compounds in food groups rich in fatty acids, via atherosclerosis and thrombosis, inflammation, accumulation of b-amyloid, or via an effect in maintaining the structural integrity of neuronal membranes, determining the fluidity of synaptosomal membranes that thereby regulate neuronal transmission. However, recent findings from clinical trials with n-3 PUFA supplementation showed efficacy on depressive symptoms only in non apolipoprotein E (APOE) epsilon4 carriers, and on cognitive symptoms only in very mild Alzheimer's disease (AD) subgroups, MCI patients, and cognitively unimpaired subjects non-APOE epsilon4 carriers. These data together with epidemiological evidence support a possible role of fatty acid intake in maintaining adequate cognitive functioning and possibly for the prevention and management of cognitive decline and dementia, but not when the AD process has already taken over. PMID- 19643209 TI - Adsorption of tripeptide RGD on rutile TiO(2) nanotopography surface in aqueous solution. AB - Molecular dynamics simulations were carried out to investigate the adsorption mechanisms of tripeptide Arg-Gly-Asp (RGD) on the nanotopography and perfect rutile TiO(2) (110) surfaces in aqueous solution. It is shown that the amino groups (NH(2) and NH3+) and carboxyl group (COO(-)) of RGD are the main groups bonding to hydrophilic TiO(2) surface by electrostatic and van der Waals interactions. It is also demonstrated that RGD adsorbs much more rapidly and stably on the nanotopography surface than the perfect surface. On the hydrophilic TiO(2) surface, the water molecules occupy the adsorption sites to form hydration layers, which have a significant influence on RGD adsorption. On the perfect surface, since the fivefold titanium atom is surrounded by surface bridging oxygen atoms above it and has a water molecule bonding to it, the amino group NH(2) is the adsorption group. However, because the pit surface exposes more adsorption sites and has higher surface energy, RGD can adsorb rapidly on the surfaces by amino groups NH(2) and NH3+, and the carboxyl group COO(-) may edge out the adsorbed water molecules and bond to the surface titanium atom. Moreover, the surface with higher surface energy has more adsorption energy of RGD. PMID- 19643208 TI - Malignancies in systemic lupus erythematosus. AB - Systemic lupus erythematosus (SLE) is a prototypical systemic autoimmune disease, characterized by a wide array of symptoms and organ involvements, leading to varying disease courses and outcome, and ranging from mild to severe types. In patients with SLE, the incidence and risk of malignancy development is increased, and mostly non-Hodgkin's lymphoma (NHL), cervical cancer, as well as bronchial carcinomas occur. Besides others, the common genetic predisposition, chronic antigen stimulus, disproportional immune responses, as well as the chronic administration of immunosuppressive medications can contribute to the development of malignancies in lupus. In this review we present the molecular pathology, as well as the epidemiological and clinical aspects of malignancies in patients with SLE. PMID- 19643210 TI - Bioconverted products of essential fatty acids as potential antimicrobial agents. AB - This review deals with the recent findings on the microbial conversion of essential fatty acids (EFAs) through Pseudomonas aeruginosa PR3 NRRL-B-18602, and the antimicrobial properties of bioconverted EFAs, with particular emphasis on n 3 or n-6 fatty acids. The first section deals with the most recent and some background literature on which have been the latest developments with respect to bioconverted EFAs as potential antibacterial agents, in particular the inhibition of severe foodborne and food spoilage bacteria causing deleterious effects in food and human beings. The second section of the review deals with the inhibition of certain important plant pathogenic fungi through the bioconverted EFAs which cause drastic losses to food and agriculture industries. Also we have given emphasis through the literature on the importance of microbial bioconversion of EFAs along with their possible applications in various beneficial fields. PMID- 19643211 TI - Production and distribution of beta-glucosidase in a mutant strain Trichoderma viride T 100-14. AB - The characterization of beta-glucosidase's production and distribution in a mutant strain Trichoderma viride T 100-14 at extracellular and intracellular levels were studied in this paper. Three experiment groups were done automatically with pH controlled at 4.8 during fermentation process, with 1mg/ml 2-deoxy-d-glucose addition or without pH control and 2-deoxy-d-glucose addition (control). Activity assay and electron microscopic immunogold labeling experiments were performed at different culture periods (24, 48, 72, 96 and 120 hours). Under constant pH 4.8, high density of immunogold labeling particles, highest intracellular enzyme activity, total enzyme activity and specific activity were observed at 24 hours of fermentation. After 72 hours, the extracellular and total activities fluctuated little and the maximal activity in extracellular fraction was 2.7 times higher than control. By contrast, with 2 deoxy-d-glucose addition, the secreted and total beta-glucosidase activities achieved their maximum at 96 hours of fermentation, and the maximal secreted activity increased 2.05-fold than the control. Additionally, the secretion ratio (maximal secreted beta-glucosidase activity/maximal total activity) with pH control or 2-deoxy-d-glucose addition was elevated profoundly near to a level as the cellulase in fungi. PMID- 19643212 TI - Iron overload alters iron-regulatory genes and proteins, down-regulates osteoblastic phenotype, and is associated with apoptosis in fetal rat calvaria cultures. AB - Iron overload has been implicated in decreased bone mineral density. However, the effect of iron overload on osteoblast lineage cells remains poorly understood. The purpose of this study was to examine osteoblast differentiation, function, and apoptosis in iron-loaded cells from fetal rat calvaria. Cells were incubated with media supplemented with 0-10 microM ferrous sulfate (FeSO(4)) during differentiation (days 6-20). Intracellular iron status was assessed by measuring iron content in cell layers and changes in transferrin receptor (TrfR) and ferritin gene and protein expression. Osteoblast differentiation and function were evaluated by measuring osteoblast phenotypic gene markers and capacity of cultures to form mineralized bone nodules. Apoptotic hallmarks were evaluated by microscopy. A 2.3-fold increase in media iron concentration resulted in saturable accumulation of iron in the cell layer 20-fold higher than control (p<0.05) by mid-differentiation (day 15, D15). Iron accumulation resulted in rapid and sustained down-regulation of TrfR gene and protein levels (within 24 h) and up regulation of light and heavy chain ferritin protein levels at late differentiation (day 20, D20). Concurrently, osteoblast phenotype gene markers were suppressed by D15 and a decreased number of mineralized nodules at D20 were observed. Apoptotic events were observed within 24 h of iron loading. These results provide evidence that iron overload alters iron metabolism and suppresses differentiation and function of cells in the osteoblast lineage associated with increased apoptosis. PMID- 19643214 TI - Battling polio in Pakistan: breaking new ground. PMID- 19643213 TI - Vaccination of children in low-resource countries against Shigella is unlikely to present an undue risk of reactive arthritis. AB - Shigellosis is a major cause of morbidity and mortality among children in low resource countries. Promising vaccine strategies in development include genetically attenuated Shigella, killed whole cell vaccines, subcellular vaccines, and O-polysaccharide-protein conjugates. There is a concern that Shigella vaccines could either induce reactive arthritis or could prime vaccinees for arthritis after a subsequent exposure to the pathogen because shigellosis is associated with reactive arthritis, especially in patients expressing the HLA B27 histocompatibility antigen. Our understanding of the pathogenesis of reactive arthritis is incomplete, and even surrogate biomarkers of bacterial arthritogenic activity have not yet been identified. Nonetheless, all of the Shigella vaccine strategies currently in development are designed to limit inflammation and intracellular antigen persistence that could trigger arthritogenic sequelae. The relatively low occurrence of the HLA B27 phenotype in most Shigella endemic areas, and the rarity of reported reactive arthritis in these populations, suggests that vaccination with attenuated, killed, or subcellular vaccines may not increase the background incidence of arthritic sequelae. More importantly, incidence rates of shigellosis in children living in low-resource countries suggest that, during maturation, the entire pediatric population may be infected with Shigella-possibly with devastating consequences. Therefore, clinical trials of candidate Shigella vaccines should be pursued aggressively in the developing world, beginning with a Phase 1 in HLA B27-negative volunteers, but proceeding to Phase 2 and Phase 3 in unscreened volunteers. Post-vaccination monitoring for possible reactive arthritis should be included in all clinical protocols. PMID- 19643215 TI - Authors' reply to Prymula R. Re: "Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: potential implications for pneumococcal conjugate vaccines" [Vaccine 27 (2009) 4739-4740]. PMID- 19643216 TI - Cardio-respiratory coupling depends on the pons. AB - Cardio-respiratory coupling is reciprocal; it is expressed as respiratory modulated sympathetic nerve activity and pulse-modulated respiratory motor activity. In the brainstem, the neuraxis controlling cardio-respiratory functions forms a ventrolateral cell column which extends to the dorsolateral (dl) pons. Our general working hypothesis is that these control systems converge at points with the common purpose of gas exchange and that neural activity along this axis coordinates both arterial pulse pressure and breathing. Here, we review the data showing that pontine nuclei modulate heart rate, blood pressure and breathing, and present new results demonstrating a vagal influence on pontine activity modulated with both arterial pulse pressure and phrenic nerve activity in the decerebrate cat. Generally with the vagi intact, dl pontine activity was weakly modulated by both arterial pulse pressure and respiratory pattern. After bilateral vagotomy, the strength and consistency of respiratory modulation increased significantly, although the strength and consistency of arterial pulse pressure modulation did not change significantly for the group; a decrease in some (62%) was offset by an increase in others (36%) neurons. Thus, the vagus shapes the envelope of the cycle-triggered averages of neural activity for both the respiratory and cardiac cycles. These data provide insight into the neural substrate for the prominent vagal effect on the cardio-respiratory coupling pattern, in particular respiratory sinus arrhythmia. While these results support convergence of inputs to neural populations controlling breathing and cardiovascular functions, the physiologic role of balancing ventilation, vascular resistance, heart rate and blood flow for the benefit of tissue oxygenation, remains hypothetical. PMID- 19643217 TI - The neurochemistry of rule use. PMID- 19643218 TI - Increased brain size in autism--what it will take to solve a mystery. PMID- 19643219 TI - Resin-bonded fixed partial dentures with a new modified zirconia surface: a clinical report. AB - This report describes the clinical application of a new modified zirconia surface. Resin-bonded fixed partial dentures were fabricated for nonprepared abutments, cemented, and evaluated for retention and esthetics. Initial evaluation of this new modified zirconia surface reveals acceptable mechanical and esthetic properties. PMID- 19643220 TI - The service life of implant-retained overdenture attachment systems. AB - STATEMENT OF PROBLEM: Implant-retained overdentures are a treatment option for patients who are not satisfied with conventional complete dentures. Although implant-retained overdentures are widely used, little data are available or provided by implant manufacturers about retentive strength and wear of attachments. PURPOSE: The purpose of this study was to evaluate retentive strength and fatigue resistance of 4 overdenture bar-and-clip attachment systems. MATERIAL AND METHODS: Forty bar-and-clip attachment system specimens were tested (n=10): Conexao Bar Clip (polymer clip), Sterngold Hader Bar (polymer clip), 3i Gold Hader Type Clip (metal clip), or SIN Clipo (metal clip). Specimens immersed in artificial saliva were tested to 5500 cycles at 0.8 Hz using a servohydraulic universal testing machine. Retention strength values (N) were recorded initially and after 1100, 2200, 3300, 4400, and 5500 insertion and removal cycles during the tensile test using a speed of 1 mm/min and a load cell of 1 kN. Data were submitted to a 2-way repeated-measures ANOVA and the Tukey A post hoc test (alpha = .05). RESULTS: An increase in retention strength values was observed during the fatigue test after 5500 cycles of insertion and removal. No significant difference in retentive strength was observed in the groups using polymer clips (Conexao Bar Clip and Sterngold Hader Bar) (P=.729); the same occurred with metal clip systems (SIN Clipo and 3i Gold Hader Type Clip) (P=.068). The SIN Clipo system demonstrated the smallest retention strength values, which were significantly different from the other 2 attachment systems, the Sterngold Hader Bar (P<.01) and the Conexao Bar Clip (P<.01). Although the 3i Gold Hader Type Clip did not differ significantly, in terms of retentive strength, from the Sterngold Hader Bar (P=.258), its retentive strength was significantly lower than the retentive strength of the Conexao Bar Clip system (P=.030). CONCLUSIONS: The systems evaluated demonstrated satisfactory retention for all time periods tested, as retention strengths from 5 to 7 N should be sufficient to stabilize overdentures. No component fracture or compromise in retention was found for any of the systems tested. PMID- 19643221 TI - Influence of dental rotary instruments on the roughness and wettability of human dentin surfaces. AB - STATEMENT OF PROBLEM: Although it is known that different dental rotary instrument types produce distinct surface roughness of the axial walls which may contribute to the clinical performance of a cast restoration, the ideal roughness that produces optimum wetting at the adhesive interface is unclear. PURPOSE: The purpose of this study was to characterize the surface roughness and its influence on wettability of teeth prepared for complete veneer crowns with different dental rotary instruments. MATERIAL AND METHODS: Sixty standardized tooth preparations for complete crowns were completed using a modified milling machine on extracted human teeth with diamond, tungsten carbide finishing, and cross-cut carbide rotary instruments of similar shape (n=20). Morphological changes obtained were investigated with a surface texture analyzer. Two additional specimens from each group were treated and prepared for scanning electron microscopy. The contact angle of a drop of distilled water on each of the prepared surfaces was used as the measure of wettability with a goniometer microscope. The data were analyzed with 1-way ANOVA and Tukey's Honestly Significant Difference (HSD) test (alpha=.05). RESULTS: Surface preparation resulted in significant differences for surface topography and wettability (P<.001). The carbide burs had significantly higher mean roughness readings (SD) for all parameters: Ra (8.6 (1.9) microm), Rq (10.9 (2.2) microm), and Ry (41.1 (2.1) microm), except for the mean Rz (12.1 (3.1) microm) value, which was recorded for diamonds. The other roughness parameters for the diamond rotary instruments were intermediate. Teeth completed with carbide finishing burs produced a smoother surface Ra (1.2 (0.5) microm), Rq (1.6 (0.6) microm), Ry (6.4 (2.6) microm), and Rz (1.9 (0.6) microm). The highest mean contact angle (SD), 81.5 (9.1) degrees, was associated with diamond rotary instruments, and the lowest (75.3 (5.9) degrees) was recorded for finishing burs. The contact angle for teeth prepared with tungsten carbide burs was intermediate: 76.1 (5.9) degrees. CONCLUSIONS: The selection of dental rotary instruments for tooth preparation significantly affects surface roughness and wettability of dentin, which may influence the retention of cast restorations. PMID- 19643222 TI - Magnetic resonance imaging on TMJ disc thickness in TMD patients: a pilot study. AB - STATEMENT OF PROBLEM: Studies of temporomandibular joint (TMJ) discs removed from autopsy specimens and in surgery indicate that they are often thicker in patients with temporomandibular disorders (TMDs). Disc thickness may also change when the condyle moves in and out of the joint fossa during opening and closing. PURPOSE: The purpose of this pilot study was to test the hypothesis that the TMJ disc thickness is greater in TMD patients than in healthy subjects and is affected by the degree of jaw opening. MATERIAL AND METHODS: Magnetic resonance images (MRI) were made of the TMJs in young volunteers, 9 asymptomatic subjects and 9 TMD subjects, at closed and at 10-, 20-, and 30-mm open positions. The thickness of the anterior and posterior bands of the discs and the intermediate zones was measured and compared between TMD and control groups, and between closed and opened positions, using the repeated-measures method in general linear model (alpha=.05). RESULTS: The hypothesis that the disc was thicker in the TMD than in the control group was supported with respect to the anterior band and intermediate zone (P<.046), but not with respect to the posterior band. The hypothesis that the thickness is affected by the degree of jaw opening was only supported for the posterior band, where it increased during opening in both groups (P<.005). CONCLUSIONS: The results indicate that the anterior band and the intermediate zone of the TMJ discs are thicker in TMD patients than in healthy subjects. The posterior band thickness increases with mouth opening in both asymptomatic and TMD subjects. PMID- 19643223 TI - The relationship of facial anatomic landmarks with midlines of the face and mouth. AB - STATEMENT OF PROBLEM: The importance of the midline is well known to dentists. Currently, there are no verifiable guidelines that direct the choice of specific anatomic landmarks to determine the midline of the face or midline of the mouth. PURPOSE: The purpose of this study was to determine the hierarchy of facial anatomic landmarks closest to the midline of the face as well as midline of the mouth. MATERIAL AND METHODS: Three commonly used anatomic landmarks, nasion, tip of the nose, and tip of the philtrum, were marked clinically on 249 subjects (age range: 21-45 years). Frontal full-face digital images of the subjects in smile were then made under standardized conditions. A total of 107 subjects met the inclusion criteria. Upon applying exclusion criteria, images of 87 subjects were used for midline analysis using a novel concept called the Esthetic Frame. Deviations from the midlines of the face and mouth were measured for the 3 clinical landmarks; the existing dental midline was considered as the fourth landmark. The entire process of midline analysis was done by a single observer and repeated twice. Reliability analysis and 1-sample t tests were conducted at alpha values of .001 and .05, respectively. RESULTS: The results indicated that each of the 4 landmarks deviated uniquely and significantly (P<.001) from the midlines of the face as well as the mouth. CONCLUSIONS: Within the limitations of the study, the hierarchy of anatomic landmarks closest to the midline of the face in smile was as follows: the midline of the oral commissures, natural dental midline, tip of philtrum, nasion, and tip of the nose. The hierarchy of anatomic landmarks closest to the midline of the oral commissures was: natural dental midline, tip of philtrum, tip of the nose, and nasion. These relationships were the same for both genders and all ethnicities classified. PMID- 19643224 TI - Wear of two artificial tooth materials in vivo: a 12-month pilot study. AB - STATEMENT OF PROBLEM: Wear of methacrylate artificial teeth resulting in vertical loss is a problem for both dentists and patients. PURPOSE: The purpose of this study was to quantify wear of artificial teeth in vivo and to relate it to subject and tooth variables. MATERIAL AND METHODS: Twenty-eight subjects treated with complete dentures received 2 artificial tooth materials (polymethyl methacrylate (PMMA)/double-cross linked PMMA fillers; 35%/59% (SR Antaris DCL, SR Postaris DCL); experimental 48%/46%). At baseline and after 12 months, impressions of the dentures were poured with improved stone. After laser scanning, the casts were superimposed and matched. Maximal vertical loss (mm) and volumetric loss (mm(3)) were calculated for each tooth and log-transformed to reduce variability. Volumetric loss was related to the occlusally active surface area. Linear mixed models were used to study the influence of the factors jaw, tooth, and material on adjusted (residual) wear values (alpha=.05). RESULTS: Due to drop outs (n=5) and unmatchable casts (n=3), 69% of all teeth were analyzed. Volumetric loss had a strong linear relationship to surface area (P<.001); this was less pronounced for vertical loss (P=.004). The factor showing the highest influence was the subject. Wear was tooth dependent (increasing from incisors to molars). However, these differences diminished once the wear rates were adjusted for occlusal area, and only a few remained significant (anterior versus posterior maxillary teeth). Another influencing factor was the age of the subject. CONCLUSIONS: Clinical wear of artificial teeth is higher than previously measured or expected. The presented method of analyzing wear of artificial teeth using a laser-scanning device seemed suitable. PMID- 19643225 TI - Hardness and surface roughness of reline and denture base acrylic resins after repeated disinfection procedures. AB - STATEMENT OF PROBLEM: Microwave irradiation and immersion in chemical solutions have been recommended for denture disinfection. However, the effect of these procedures on the surface characteristics of denture base and reline resins has not been completely evaluated. PURPOSE: The purpose of this study was to evaluate the effect of microwave and chemical disinfection on the Vickers hardness (VHN) and surface roughness (Ra, microm) of 2 hard chairside reline resins (Kooliner, DuraLiner II), and 1 heat-polymerizing denture base resin (Lucitone 550). MATERIAL AND METHODS: Specimens (12 x 12 x 3 mm) were divided into 2 control and 4 test groups (n=8). Hardness and roughness measurements were performed after: polymerization and immersion in water (37 degrees C) for 7 days (controls), or repeated exposure to disinfection by immersion in sodium perborate (50 degrees C/10 min) or microwave irradiation (650 W/6 min). Measurements of surface roughness (Ra, microm) and hardness (kg/mm(2)) were analyzed using 3-way ANOVA and Tukey's Honestly Significant Difference (HSD) test (alpha=.05). RESULTS: Microwave and chemical disinfection increased the mean (SD) hardness of Kooliner (from 4.1 to 7.5 kg/mm(2)) and DuraLiner II (from 2.6 to 5.6 kg/mm(2)), whereas Lucitone 550 (14.4 kg/mm(2)) remained unaffected. Disinfection by immersion in sodium perborate increased the surface roughness of DuraLiner II (from 0.13 to 0.26 microm) and Kooliner (from 0.16 to 0.26 microm), regardless of the number of cycles. For Lucitone 550, an increase in roughness was observed after 2 cycles of chemical disinfection (from 0.12 to 0.26 microm). Two cycles of microwave disinfection increased the roughness of both reline resins (DuraLiner II: from 0.13 to 0.22 microm; Kooliner: from 0.16 to 0.24 microm), whereas repeated microwave disinfection increased the roughness of DuraLiner II (from 0.11 to 0.25 microm). CONCLUSIONS: Disinfection by immersion in sodium perborate or microwave irradiation did not adversely affect the hardness of all materials evaluated. The effect of both disinfection methods on the roughness varied among materials. PMID- 19643226 TI - Internally weighted mandibular denture fabrication using a processed denture base. AB - This article describes a method of fabricating a customized weighted metal base for the mandibular complete denture using a processed denture base and a plaster index of the tooth arrangement. PMID- 19643227 TI - Fabrication of a custom incisal guide table with vinyl polysiloxane. PMID- 19643228 TI - Topical anesthesia for prosthetic implant procedures. PMID- 19643229 TI - A simple cementation method to prevent material extrusion into the periimplant tissues. PMID- 19643230 TI - Vasectomy and vasectomy reversal: important issues. Preface. PMID- 19643231 TI - History of vasectomy. AB - Vasectomy as a medical term is a misnomer because only part of the vas deferens is excised during the procedure. Vas deferens as an anatomic structure was not a subject of significant clinical and research interest until the nineteenth century. It is difficult to find another surgical procedure as simple as vasectomy that has sparked so much medical and social controversies for more than a century. Vasectomy is a historical, social, philosophic, medical, demographic, and legal phenomenon. It is not surprising that the history of this procedure combines not only a constant quest for ideal technique and better results but also misconceptions, false beliefs, and erroneous indications. PMID- 19643232 TI - Demographics of vasectomy--USA and international. AB - Vasectomy is safer, simpler, less expensive, and equally as effective as female sterilization--yet it remains one of the least known and least used methods of contraception. Worldwide, an estimated 33 million of married women ages 15 to 49 (less than 3%) rely on their partner's vasectomy for contraception. PMID- 19643233 TI - Techniques of vasectomy. AB - Vasectomy remains a safe and effective method of contraception for men. Many variations in surgical technique currently are used by surgeons in the United States, each with its own benefits and drawbacks. Regardless of the surgical method used, the most important factor for successful vasectomy remains the experience and skill of the surgeon. The amount of evidence-based literature on the rationale for the different techniques for vasectomy remains limited. Careful study and innovation of vasectomy techniques will ensure that the most commonly performed urologic surgical procedure remain an excellent form of contraception in the future. PMID- 19643234 TI - Effectiveness of vasectomy techniques. AB - The effectiveness of various vasectomy techniques is reviewed, with a focus on methods used for vas occlusion. Spontaneous recanalization of the vas is more common than generally recognized and is often transient. Simple ligation and excision has an unacceptably high risk for failure. Techniques that include cautery seem to have a lower risk for failure than techniques that do not include cautery. There is insufficient evidence to recommend a particular standardized cautery technique, but adding fascial interposition to cautery seems to be associated with the lowest risk for failure. PMID- 19643235 TI - Risks and complications of vasectomy. AB - Vasectomy is a safe and effective procedure for permanent contraception. Vasectomy is 30 times less likely to fail and 20 times less likely to have postoperative complications than its gynecologic counterpart. Complications from vasectomy are rare and minor in nature. Immediate risks include infection, hematoma, and pain. Complications seldom lead to hospitalization or aggressive medical management. Technique is surgeon dependent; however, certain techniques, such as fascial interposition, seem to decrease rates of vasectomy failure. Despite myriad vasectomy techniques, failure rates are less than those seen with tubal ligation. Available data suggest that vasectomized men do not seem at increased risk for immune-complex diseases. PMID- 19643236 TI - Putative health risks associated with vasectomy. AB - Vasectomy is widely regarded as a safe method of contraception, but over the years there have been many reports suggesting putative health risks associated with the procedure. Concerns over the possible association of vasectomy with a number of medical conditions, including cardiovascular disease, testicular cancer, prostate cancer, psychologic distress, and a variety of immune complex mediated disease processes have been reported. Most recently, a manuscript from the neurology literature has described an association between vasectomy and primary progressive aphasia, a rare variety of frontotemporal dementia. This article reviews the literature surrounding each of these purported health concerns. Because the ultimate findings have important ramifications for both informed consent of vasectomy patients and for public health, the reported health risks in question should be critically evaluated. PMID- 19643237 TI - The law and vasectomy. AB - This article explores why the national court system has seen a steady influx of claims alleging practitioners' failure properly to perform vasectomy or ensure sterilization and the manner in which that influx has caused physicians to reassess their methods of practicing medicine in an increasingly litigious environment and make the appropriate and necessary accommodations. Through their experiences as medical malpractice litigators and through the analysis of reported cases, national jury verdicts, and insurance claims made and paid in lawsuits arising from claims regarding the performance of vasectomy, the authors enlighten the reader as to the legal theories and hurdles applicable to such claims and the medical theories most often elucidated and litigated by the patients who bring them. Also offered are suggestions as to the manner in which the practitioner may be proactive in both preventing and defending exposure to malpractice litigation. PMID- 19643238 TI - History of vasectomy reversal. AB - Vasectomy reversal has come a long way since the first anastomosis of the vas deferens and epididymis. Although its history is not as politically charged as that of vasectomy, the progress of reversal surgery has had its share of brilliant discoveries and missteps. In the early part of the twentieth century, vasovasostomy and vasoepididymostomy were esoteric procedures, but by the 1970s, a majority of urologists had some experience with reversal surgery. With the advent of microsurgical technique, reversal surgery has become once more a specialist's undertaking. The history of vasectomy reversal is an excellent case study in the evolution of surgery. PMID- 19643239 TI - Techniques for vasectomy reversal. AB - This article details the contemporary preoperative preparation, microsurgical techniques, and postoperative care recommended for vasectomy reversal. The two layer vasovasostomy and intussuscepted epididymovasostomy techniques are presented in detail. PMID- 19643240 TI - Factors predicting successful microsurgical vasectomy reversal. AB - A man who desires restoration of fertility after vasectomy has two main treatment options for having his genetic child: vasectomy reversal or sperm extraction with subsequent in vitro fertilization with intracytoplasmic sperm injection. Microsurgical reconstructive techniques and their widespread availability have made vasectomy reversal a realistic option for many couples; however, vasectomy reversal outcomes are varied because there are many factors that alter the chance of success. Some of these factors become known preoperatively, whereas others can only be ascertained at the time of surgery. Intraoperatively, the urologist must identify factors and understand how they will affect the decision to proceed. This article systematically reviews each of these phases of decision-making and management. PMID- 19643241 TI - Cost-effectiveness of vasectomy reversal. AB - In this era of cost-consciousness and containment, it is imperative to examine not only treatment outcomes but also cost of these treatments. With improvements of in vitro fertilization outcome and continued development of less-invasive sperm retrieval methods, physicians and couples must examine all options available after surgical sterilization. Vasectomy reversal remains the gold standard of treatment; however, certain situations may be present in which sperm acquisition/in vitro fertilization may be a better option. A physician's responsibility is to present all options with the pros and cons of each, including cost, to help arrive at an informed decision. PMID- 19643244 TI - Case studies in corporate compliance: putting the rubber to the road. AB - An interdisciplinary, proactive perspective allows providers to engage in productive, long-term collaborative relationships with corporations, while 1) maintaining patient care improvements; 2) maintaining legality; 3) enhancing technical and clinical innovation; and 4) providing fair compensation for work done. The case study approach is used to demonstrate an effective approach to compliant behavior. PMID- 19643245 TI - Extracts from the Cochrane Library: homeopathic medicines for adverse effects of cancer treatments. PMID- 19643246 TI - Functional outcomes after transoral robotic surgery for head and neck cancer. AB - OBJECTIVE: To evaluate functional outcomes following transoral robotic surgery for head and neck cancer. STUDY DESIGN: Case series with planned data collection. SETTING: Academic hospital. SUBJECTS AND METHODS: Between March 2007 and December 2008, 54 of 62 candidate patients underwent transoral robotic tumor resection. Outcomes include airway management, swallowing (MD Anderson Dysphagia Inventory), and enterogastric feeding. RESULTS: Tumors were most commonly oropharynx (61%) or larynx (22%) and T1 (35%) or T2 (44%). Many received radiotherapy (22% preoperatively, 41% postoperatively) and chemotherapy (31%). Endotracheal intubation was retained (22%) for up to 48 hours, tracheostomy less frequently (9%), and all were decannulated by 14 days. Most commenced oral intake prior to discharge (69%) or within two weeks (83%). A worse postoperative Dysphagia Inventory score was associated with retained feeding tube (P=0.020), age>60 (P=0.017), higher T stage (P=0.009), laryngeal site (P=0.017), and complications (P=0.035). At a mean 12 months' follow-up, 17 percent retained a feeding tube (9.5% among primary cases). Retained feeding tube was associated with preoperative tube requirement (P=0.017), higher T stage (P=0.043), oropharyngeal/laryngeal site (P=0.034), and recurrent/second primary tumor (P=0.008). Complications including airway edema (9%), aspiration (6%), bleeding (6%), and salivary fistula (2%) were managed without major sequelae. CONCLUSION: Transoral robotic surgery provides an emerging alternative for selected primary and salvage head and neck tumors with low morbidity and acceptable functional outcomes. Patients with advanced T stage, laryngeal or oropharyngeal site, and preoperative enterogastric feeding may be at increased risk of enterogastric feeding and poor swallowing outcomes. PMID- 19643247 TI - Importance of treatment institution in head and neck cancer radiotherapy. AB - OBJECTIVE: The treatment for head and neck cancer (HNC) often involves radiotherapy. Many HNC patients are treated at the academic center (AC) where the initial surgery or diagnosis was made. Because of the lengthy time course for radiotherapy, some patients are treated at community radiation facilities (non AC) rather than the AC despite potential AC advantages in terms of experience and technology. Our goal is to determine if these potential AC advantages correspond to a difference in treatment outcome. STUDY DESIGN: Historical cohort study. SETTING: University of Kansas Medical Center, Kansas City, Kansas. SUBJECTS AND METHODS: Review of records of patients with HNC cancers evaluated at the otolaryngology (ENT) department of an AC. Each patient's information and treatment characteristics were recorded, including radiotherapy treatment venue and treatment outcome. RESULTS: Three hundred seventy-four patients were analyzed, 263 were treated at an AC and 101 at a non-AC. Patients treated at a non-AC were more likely to present with earlier stage tumors, be treated with radiation alone rather than chemoradiotherapy, and be treated with adjuvant rather than primary radiotherapy. There was no difference in overall survival or recurrence rates between AC and non-AC. CONCLUSION: Patients treated at an AC are more likely to have advanced stage tumors and receive chemoradiotherapy as their primary treatment. In analyses of matching patient subsets, there was no significant difference in patient outcomes. Patients can be treated at a non-AC without affecting outcome compared with treatment at an AC. PMID- 19643248 TI - Head and neck squamous cell carcinoma targeted chemosensitization. AB - OBJECTIVE: The current treatment for advanced head and neck squamous cell carcinoma continues to result in poor outcomes. The purpose of this study is to investigate the benefit of fibroblast growth factor 2-targeted adenovirus mediated mutant-Rad50 (FGF2-Ad-Rad50) gene transfer in enhancing chemosensitization for head and neck squamous cell carcinoma and reducing chemotoxicity. STUDY DESIGN: Randomized controlled laboratory study. SETTING: University of Pennsylvania, Philadelphia, PA. SUBJECTS AND METHODS: Human head and neck squamous cell carcinoma tumor cells and a mouse model with human head and neck squamous cell carcinoma were used for this study. There were five mice in each study group. FGF2-fab' molecule was conjugated with an adenoviral mutant Rad50 construct. FGF2-targeted transgene expression efficiency was evaluated in vitro. Tumor cytotoxicity and growth inhibition were examined after combined FGF2 Ad-Rad50 with cisplatin treatment in vitro and in vivo. Anti-tumor mechanisms were investigated. RESULTS: FGF2-targeted gene transfer approach significantly improved transgene expression in head and neck squamous cell carcinoma tumor cells over a nontargeted approach (207.51+/-33.62 vs 51.44+/-8.28, respectively). FGF2-Ad-Rad50 with cisplatin demonstrated a superior tumor suppression effect (264.5+/-124.1 mm3 vs 567.1+/-267.6 mm3), increased DNA double-strand breaks (1349+/-51.67 vs 774+/-28.56), and anti-angiogenesis (%ROI: 0.76%+/-0.38% vs 2.10%+/-1.66%) in tumor cells over nontargeted adenovirus. CONCLUSION: Combination of FGF2-Ad-Rad50 with cisplatin significantly improves anti-tumor effect by targeting DNA repair systems and tumor angiogenesis. The great benefit of this strategy supports clinical trial for novel treatment of head and neck squamous cell carcinoma. PMID- 19643249 TI - A new porcine skull base model: fibrin glue improves strength of cerebrospinal fluid leak repairs. AB - OBJECTIVES: Fibrin glue is used in addition to grafts and flaps to repair cerebrospinal (CSF) leaks. We designed a porcine model to test the hypothesis that fibrin glue increases biomechanical strength. STUDY DESIGN: A randomized experimental animal study. METHODS: Ten pigs underwent craniotomy with creation of a fistula through the cribriform plate into the nasal cavity. CSF leaks were endoscopically confirmed and repaired using pericranial grafts. The animals were randomized into a fibrin glue group (n=5) and a control group (n=5). Seven days later, endoscopic examination assessed for CSF leaks. The skull bases were harvested and examined for the degree of graft adherence (graded I-V) and subjected to burst pressure testing and histopathological analysis. RESULTS: Eight animals survived, four in each group. There were no CSF leaks in the fibrin glue group and one in the control group. The fibrin glue group showed greater graft adherence (P=0.029) and higher burst pressures (13.8+/-5.4 vs 4.6+/-3.1 psi, P=0.021). Histopathological analysis revealed no difference in inflammation and bone remodeling. CONCLUSIONS: The porcine model is a good model for anterior skull base defects. The model confirmed that fibrin glue reduces the rate of CSF leak by improving graft adherence and strength of repair. PMID- 19643250 TI - Pectoralis myofascial flap during salvage laryngectomy prevents pharyngocutaneous fistula. AB - OBJECTIVE: To determine the rate of pharyngocutaneous fistula after salvage laryngectomy and assess if pectoralis myofascial flap reinforcement over primary pharyngeal closure prevents pharyngocutaneous fistula. STUDY DESIGN: Case series with chart review. SETTING: Tertiary-care public hospital. SUBJECTS AND METHODS: This study included 43 patients undergoing total laryngectomy between 2003 and 2008. Pectoralis myofascial flap reinforcement of the pharyngeal closure during salvage laryngectomy was performed on patients after June 2006. The main outcome measure was pharyngocutaneous fistula after primary laryngectomy, salvage laryngectomy, and salvage laryngectomy with pectoralis flap reinforcement. RESULTS: Of the 43 patients, 26 were treated with primary total laryngectomy while 17 received salvage laryngectomy. Seven of 26 patients (27%) undergoing primary total laryngectomy developed pharyngocutaneous fistula. All patients in this group were closed primarily with no flap reinforcement. For salvage laryngectomy, four of seven patients (57%) with primary pharyngeal closure developed pharyngocutaneous fistula; however, none of 10 patients (0%) undergoing salvage laryngectomy with pectoralis myofascial flap reinforcement developed fistula (P<0.02; 0%-23%; 95% CI). CONCLUSIONS: With pectoralis myofascial flap reinforcement, pharyngocutaneous fistula rate after salvage laryngectomy dropped to 0 percent in this study (0%-23%; 95% CI). This is a simple, reliable technique that prevents postoperative pharyngocutaneous fistula and its associated morbidity after salvage laryngectomy. PMID- 19643251 TI - Analysis of outcomes of vascularized flap reconstruction in patients with advanced mandibular osteoradionecrosis. AB - OBJECTIVE: To examine outcomes of vascularized bone flap reconstruction of end stage osteoradionecrosis of the mandible. STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary care academic hospital. SUBJECTS: Patients with end-stage radiation-induced osteoradionecrosis (ORN) refractory to conservative therapy with wound complications including chronic infections, fistula formation, and pathologic fracture were included. RESULTS: Outcomes of 33 patients were prospectively collected and analyzed, making this the largest series on this subject in the literature and the only one with planned data collection. Data on preoperative variables including radiation dose, sub-site location, treatment date, and prior therapy, along with intraoperative issues and postoperative outcomes, were tracked and are presented. ORN was seen to develop in a bimodal distribution based on the timing of interval surgical intervention. The extent of local soft tissue injury often required the use of contralateral recipient vessels. Local wound complication rates were higher than that seen in primary reconstructions. CONCLUSIONS: Successful reconstruction was achieved in all of the patients in this series. Long-term resolution of infectious complication and disease resolution was seen in 91 percent of the patients in this series. PMID- 19643252 TI - Submental flap for reconstructing tongue defect with V-Y advancement flap for repairing submental defect. AB - OBJECTIVE: To assess the reliability of the facial-submental artery island flap for reconstructing tongue defects and the aesthetic benefits of using two V-Y islanded flaps for repairing the resulting submental defect. STUDY DESIGN: Case series with chart review. SETTING: Patient with tongue cancer, younger patient, cosmetic outcome. SUBJECTS AND METHODS: Thirty-three tongue defects were repaired with facial-submental artery island flaps, and the submental defects were repaired with two V-Y advancement flaps. The ages of the patients ranged from 28 to 57 years; 19 were men and 14 were women. All of the lesions were tongue squamous cell carcinoma. The size of the facial-submental artery island flap ranged from 3.5x7.0 to 5.0x8.0 cm. The size of the V-Y advancement flaps ranged from 3.0x3.0 to 4.0x4.0 cm. Direct closure was achieved at all donor sites. RESULTS: The facial-submental artery island flaps and V-Y advancement flaps survived in 93.9 percent and 97.0 percent, respectively. The patients were followed for 12 to 26 months. The functional results in terms of speech and swallowing were good, and the aesthetic outcomes using two V-Y advancement flaps to repair the submental defects were satisfactory. Two patients with extracapsular lymph node spread developed local recurrence: One is alive with disease and the other is dead. CONCLUSIONS: The facial-submental artery island flap is a simple, reliable flap that is preferred for reconstructing tongue defects. Using two V-Y advancement flaps for repairing the donor site defect improves the cosmetic outcome in the submental region. PMID- 19643253 TI - Emerging concepts in airway infantile hemangioma assessment and management. AB - OBJECTIVE: The purpose of this study was to evaluate changes in airway infantile hemangioma treatment. STUDY DESIGN: Retrospective. SUBJECTS: Airway hemangioma patients, tertiary pediatric hospital. METHODS: Data collected included age at diagnosis, evaluation methods, hospitalizations, airway size, and interventions. Patients were divided into group A (1981-1993) and group B (1994-2005) and were analyzed using descriptive statistics, the Fisher exact test, and the Student t test. RESULTS: Thirty-two subjects were identified. Nasopharyngoscopy was used more in group B (11/16 [69%]) than group A (4/16 [25%], P=0.032). CT angiography (3/16 [19%]) and laryngeal distractors (11/16 [69%]) were only used in group B; these techniques showed airway hemangiomas to be "transglottic," not just "subglottic." Intralesional steroids alone (3/16 [19%]) and primary hemangioma excision (2/16 [13%]) were new treatments used in group B. Frequent direct laryngoscopies (>six) correlated with tracheotomy (5/32 [16%], P=0.015). Presenting age (<2 months) impacted treatment more than airway hemangioma size. CONCLUSIONS: New methods of airway infantile hemangioma assessment changed our concept of airway hemangiomas and their primary treatment. PMID- 19643254 TI - Differential expression of SKI oncogene protein in hemangiomas. AB - OBJECTIVE: The pathogenesis for benign tumorigenesis in hemangiomas is unknown. Oncogene proteins may be influential in this process. SKI proteins have been previously described in various malignancies. We investigated the differential expression of the SKI (sarcoma viral oncogene) protein in hemangiomas. STUDY DESIGN: Prospective basic science study. SUBJECTS AND METHODS: Paraffin-embedded hemangioma tissues were obtained from the senior author from 2005 to 2006. We created the first vascular tissue array composed of 12 hemangioma specimens at various stages of growth and anatomic location. Two cores were taken from each sample. Controls were also included. Immunohistochemical studies were performed using SKI, CD31, and Ki67. RESULTS: All 12 hemangioma tissues overexpressed the SKI protein. The staining pattern was perinuclear within the endothelial cells. The intensity of staining was inversely proportional to the growth stage. The endothelial cells that were SKI-positive were involved in active cell division. CONCLUSION: SKI oncogene protein is differentially and specifically expressed in hemangioma tissues. SKI acts as a transcriptional co-repressor and inhibits the TGF-beta pathway, thus leading to uncontrolled cellular proliferation and transformation. All vascular controls were negative for SKI staining. CLINICAL SIGNIFICANCE OF STUDY: The SKI oncogene protein is upregulated by hemangiomas and may play a role in hemangioma tumorigenesis. PMID- 19643255 TI - Percutaneous treatment of lymphatic malformations. AB - OBJECTIVE: The aim of this study is to investigate a new treatment regimen for macrocystic and microcystic lymphatic malformations (LM) of the head and neck. STUDY DESIGN: The study represents a retrospective review of outcomes from new percutaneous treatments for lymphatic malformations. SUBJECTS AND METHODS: Thirty one patients (age range, 2 days to 51 years of age) underwent percutaneous treatment for LM of the head and neck from 2001 to 2007. The LM involved the orbit, ear, parotid gland, face, and neck. Twenty-seven patients underwent primary treatment of LM; 4 were treated for recurrence after operative resection. Macrocysts (>or=1 cm) were treated with dual-drug chemoablation (sequential intracystic sodium tetradecyl sulfate and ethanol); doxycycline was used for microcysts. Macrocysts and microcysts were treated after complete cyst aspiration with sonographic guidance. Fifty-four macrocysts and 125 microcysts were treated. The goal of treatment was complete cyst ablation documented by sonography or MR imaging. RESULTS: Mean number of treatments was 1.7 per patient; mean number of treatments for macrocysts was 1.1; mean treatments for microcysts was 1.7. Ablation efficacy was 179 of 179 (100%) cysts. Effective cyst ablation achieved effective clinical control with resolution of the external mass appearance. Treatments included massive head and neck mixed LM and cysts surrounding the facial nerve and brachial plexus. Infection occurred in 2 (6%) of 31 patients. No patient experienced postprocedural pain, skin necrosis, neuropathy, skin retraction, or myoglobinuria. CONCLUSION: Percutaneous sclerotherapy provides effective treatment for macrocystic and microcystic LM as primary treatment or for recurrence after surgical resection. PMID- 19643256 TI - Partial cricotracheal resection in children: potential pitfalls and avoidance of complications. AB - OBJECTIVES: To delineate the various factors contributing to failure or delay in decannulation after partial cricotracheal resection (PCTR) in children. STUDY DESIGN: Case series. SETTING: Academic tertiary medical center. SUBJECTS AND METHODS: A retrospective case review of 100 children who underwent PCTR between 1978 and 2008 for severe subglottic stenosis using an ongoing database. RESULTS: Ninety of 100 (90%) patients were decannulated. Six patients needed secondary tracheostomy. The results of the preoperative evaluation showed grade II stenosis in four patients, grade III in 64 patients, and grade IV in 32 patients. The overall decannulation rate was 100 percent in grade II, 95 percent in grade III, and 78 percent in grade IV stenosis. Fourteen (14%) patients required revision open surgery. The most common cause of revision surgery was posterior glottic stenosis. Partial anastomotic dehiscence was seen in four patients. Delayed decannulation (>1 year) occurred in nine patients. Overall mortality rate in the whole series was 6 percent. No deaths were directly related to the surgery. No iatrogenic recurrent laryngeal nerve injury was present in the entire series. CONCLUSION: Comorbidities and associated syndromes should be addressed before PCTR is planned to improve the final postoperative outcome in terms of decannulation. Perioperative morbidity due to anastomotic dehiscence, to a certain extent, can be avoided by intraoperative judgment in the selection of double-stage surgery when more than five tracheal rings need to be resected. Subglottic stenosis with glottic involvement continues to pose a difficult challenge to pediatric otolaryngologists, often necessitating revision procedures. PMID- 19643257 TI - Analysis of residual symptoms after treatment in benign paroxysmal positional vertigo using questionnaire. AB - OBJECTIVES: Canalith repositioning procedure (CRP) provides rapid and long lasting relief of symptoms in most patients with benign paroxysmal positional vertigo. However, some patients express nonspecific symptoms such as anxiety or discomfort after treatment, even after the disappearance of nystagmus and vertigo. The purpose of this study was to assess the residual symptoms after CRP in patients with benign paroxysmal positional vertigo using the Dizziness Handicap Inventory (DHI) in a questionnaire format. STUDY DESIGN AND SETTING: Controlled, prospective study. SUBJECTS AND METHODS: CRP was performed in 135 patients until nystagmus and vertigo disappeared. Patients were asked to complete the questionnaire before and 5 to 7 days after treatment. A control group of 135 normal volunteers was selected and cross-matched according to the age and sex of the patient group. The data were compared for the pre-CRP, post-CRP, and control groups. RESULTS: There was a significant improvement in the DHI scores when comparing the pre- and post-CRP groups (P=0.000), although six items showed incomplete improvement. Subsequent comparison of DHI scores between the control group and the post-CRP group still showed a difference in some items so that the improvement was incomplete. CONCLUSION: Even after successful CRPs, Dizziness Handicap Inventory scores indicated that residual subjective symptoms may remain. Thus, additional follow-up and management are important for these patients. PMID- 19643258 TI - Long-term results of endolymphatic mastoid shunt surgery in patients with intractable Meniere's disease. AB - OBJECTIVE: To evaluate changes in vertigo and hearing from patients with Meniere's disease managed by endolymphatic mastoid shunt (EMS). STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center. SUBJECTS AND METHODS: Data from 16 patients were analyzed using 1995 AAO-HNS criteria. RESULTS: Among 16 patients, six had class A vertigo control two years after treatment, five had class B, one class C, three class D, and one class F. At four years after surgery, seven patients had class A, four class B, three class C, and two class F. The mean functional level before surgery was 4.8 and improved to 2.9 and 2.6 at two years and four years after surgery, respectively. The bone conduction pure-tone averages (four frequencies) were 43.3 before surgery and improved to 33.5 dB HL and 35.5 dB HL at three and six months after surgery, respectively. At two years of follow-up, the hearing level was 38.6 dB HL and was not different from the preoperative hearing level. Two years after surgery, the hearing level gradually decreased and was 42.0 dB HL at five years of follow-up. CONCLUSION: EMS appears to be beneficial in the short term for the symptomatic patients. PMID- 19643259 TI - Incudostapedial rebridging ossiculoplasty with bone cement. AB - OBJECTIVE: The purpose of this study is to evaluate hearing results of our experience with ionomeric bone cement repair of ossicular discontinuity between incus and stapes. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center. SUBJECTS AND METHODS: One hundred thirty-six patients who underwent incudostapedial rebridging ossiculoplasty with ionomeric bone cement were included in the study. Preoperative and postoperative audiologic results of incudostapedial rebridging ossiculoplasty with bone cement were evaluated. One year of follow-up is provided. RESULTS: The postoperative air-bone gap was less than 20 dB in 81.6 percent after one year. The mean preoperative and postoperative pure-tone avarages of the patients were 52.82+/-5.59 and 32.81+/ 7.18 dB, respectively (P<0.01). The mean preoperative and postoperative air-bone gaps were 35.83+/-4.73 and 16.54+/-5.01, respectively (P<0.01). There were no statistically significant differences among the hearing results of different types of surgeries (P>0.05). No complications in the middle ear related to bone cements were encountered. CONCLUSIONS: Incudostapedial rebridging ossiculoplasty with ionomeric bone cement is a reliable method for ossicular reconstruction that is cost effective and offers satisfactory hearing results in selected patients. PMID- 19643260 TI - Histopathologic assessment of fibrosis and new bone formation in implanted human temporal bones using 3D reconstruction. AB - OBJECTIVE: To evaluate new bone formation and fibrosis in implanted human temporal bones and relate that to neurosensory elements preservation. STUDY DESIGN: Human temporal bone histopathology study. SETTING: Temporal bone laboratory. SUBJECTS AND METHODS: Ten human temporal bones from eight patients with multichannel cochlear implants and one single-electrode implant were examined under light microscopy and reconstructed with AMIRA 4.1 3D reconstruction software. Volumes of new bone formation, fibrosis, and patent area were calculated in each bone. RESULTS: The amount of fibrosis and new bone formation postimplantation varied among bones. There were no statistically significant relationships between age at implantation or duration of implantation and the overall amount of new tissue in the implanted ear. There was a relationship between total amount of new tissue and preservation of neurosensory elements only in segment I of the cochlea (Rho=-0.75, P18 years old, type I Fujita, body mass index (BMI)<33, Friedman clinical stage II, with apnea-hypopnea index (AHI) from 1.0 to 30.0. The mean follow-up time was 33.5 months. The procedure involved an anterior soft palatal advancement technique with or without removal of the tonsils. The procedure was done under general or local anesthesia. RESULTS: There were 69 men and eight women; the mean age was 39.3 years old; and mean BMI was 24.9 (range 20.7-26.8). There were 38 snorers and 39 OSA patients. The AHI improved in patients with OSA, 25.3+/-12.6 to 11.0+/-9.9 (P<0.05). The overall success rate for this OSA group was 71.8 percent (at mean 33.5 months). The mean snore scores (visual analog score) improved from 8.4 to 2.5 (for all 77 patients). Lowest oxygen saturation also improved in all OSA patients. Subjectively, all patients felt less tired. CONCLUSION: This technique has been shown to be effective in the management of patients with snoring and mild-moderate OSA. PMID- 19643262 TI - Upper airway reconstructive surgery long-term quality-of-life outcomes compared with CPAP for adult obstructive sleep apnea. AB - OBJECTIVE: To measure long-term quality-of-life (QOL) improvement following contemporary multilevel upper airway reconstruction surgery, compared with continuous positive airway pressure (CPAP) therapy. Secondary aims were to investigate factors determining clinical effectiveness and QOL impact of reported side effects. DESIGN: Cohort study. SUBJECTS AND METHODS: Consecutive, simultaneously treated adult patients with moderate-severe obstructive sleep apnea (OSA) having upper airway surgery (N=77) or CPAP (N=89) therapy were studied by questionnaire. Glasgow Benefit Inventory (GBI), change in snoring status and Epworth Sleepiness Scale (ESS), subjective CPAP compliance, and side effects in both groups were measured at mean+/-SEM 44.12+/-5.78 months (3.68+/ 0.48 years) after commencement of therapy. RESULTS: No significant difference was seen between surgical outcomes for GBI, snoring, or ESS and CPAP controls. Multivariate analysis showed reduction in Respiratory Disturbance Index (RDI) predicted postoperative snoring and ESS, but not GBI outcomes. Snoring control and GBI were related to CPAP compliance (P<0.001). CPAP side effects (reported in 26%) significantly reduced the QOL benefit of treatment, independent of compliance. Surgical complications (occurring in 44%) did not affect QOL treatment benefit. CONCLUSION: Patients with poor CPAP compliance and/or significant side effects of CPAP therapy (45% of cases in this series) should be evaluated for contemporary upper airway reconstructive surgery. PMID- 19643263 TI - Association of heartburn and laryngopharyngeal symptoms with endoscopic reflux esophagitis, smoking, and drinking. AB - OBJECTIVES: This study was conducted to investigate the association of laryngopharyngeal symptoms and heartburn with endoscopic esophagitis, smoking, and drinking. The clinical importance of the Reflux Symptom Index (RSI) in predicting endoscopic esophagitis was also evaluated. STUDY DESIGN: Case series with planned data collection. SUBJECTS AND METHODS: From November 2006 to February 2007, 156 adults received a whole-body physical check-up. They filled out the RSI questionnaire and were dichotomized into either a "no problem group" or a "possible patients group" according to their scores on the RSI. All subjects received an esophagoscopy. The relationship between RSI score and endoscopic esophagitis, smoking, and drinking was analyzed. RESULTS: Voice change, but not heartburn, was significantly associated with endoscopic reflux esophagitis. Based on the RSI scores, some items in addition to voice change were significantly associated with smoking or drinking but not with endoscopic esophagitis. CONCLUSIONS: While screening patients for reflux esophagitis by using the RSI questionnaire, there is little value in using heartburn to predict endoscopic esophagitis in Taiwanese people. On the other hand, a husky voice might be a good clinical indicator of patients at risk of having reflux esophagitis. PMID- 19643264 TI - The effect of arytenoid resection on functional results of cricohyoidopexy. AB - OBJECTIVE: The aim of this study was to evaluate the influence of arytenoid resection on voice and swallowing function in patients who undergo supracricoid laryngectomy with cricohyoidopexy. STUDY DESIGN: A case series with chart review. According to the arytenoid number, patients were divided into two groups: 11 patients with two arytenoids and 9 patients with one arytenoid. The decannulation, nasogastric tube removal, and hospitalization times were noted. Maximum phonation time, average fundamental frequency, percent jitter, percent shimmer, and noise-to-harmonic ratio were measured. Grade, roughness, breathiness, asthenicity and strain scale (for the perceptual evaluation of vocal quality), Voice Handicap Index (for self-assessment of the voice), and dysphagia score were used. RESULTS: The mean decannulation, nasogastric tube removal, and hospitalization time was 18.4, 40.2, and 32.7 days in patients with one arytenoid, whereas 8.8, 20.8, and 25.3 days in patients with two arytenoids, respectively. The differences were statistically significant. For all of the parameters that are associated with voice function and dysphagia, there was no statistically significant difference between one arytenoid and two arytenoids. CONCLUSION: Arytenoid resection may affect the swallowing function in the early postoperative period, but for voice and deglutition functions there was no difference between cricohyoidopexy with one arytenoid and two over the course of time. PMID- 19643265 TI - Detection of human papillomavirus and adenovirus in benign and malignant lesions of the larynx. AB - OBJECTIVE: To investigate the role of human papillomavirus (HPV) and adenovirus (AdV) infections in the oncogenesis of squamous cell carcinomas of the larynx and of laryngeal dysplasia. STUDY DESIGN: Cross-sectional study with planned data collection. SETTING: Department of Otorhinolaryngology G. Ferreri and Department of Experimental Medicine and Pathology-Section of Virology, Sapienza University of Rome. SUBJECTS AND METHODS: Biopsy samples were taken from 68 patients with benign and malignant lesions of the larynx. All tissue samples were analyzed by means of polymerase chain reaction with two groups of primers for HPV and with a pair of primers for AdV. RESULTS: All cases of carcinomas and dysplasia as well as all control cases were negative for both viruses. Four of the five cases of laryngeal papillomas were positive for only HPV, confirming the role of these viral types in the origin of papillomas. CONCLUSION: The absence of viral genomes in laryngeal carcinomas as in the other cases studied suggests the existence of other factors that play a more important role than viral infection in the carcinogenesis of these lesions. PMID- 19643266 TI - Induction of parotitis by fine-needle aspiration in parotid Warthin's tumor. AB - OBJECTIVES: To estimate parotitis caused by fine-needle aspiration (FNA) in parotid Warthin tumor. STUDY DESIGN: Case series with chart review. SETTING: Hospital records were reviewed for 104 parotid tumors (103 patients) including 35 Warthin tumors, which underwent FNA within our department. RESULTS: Three patients with four Warthin tumors among them noticed parotid pain, swelling, and abscess formation as a consequence of acute parotitis after FNA. Examinations of the materials obtained from tumor puncture or drainage before the start of antibiotic therapy showed no bacterial association in any patient. Two of the patients with Warthin tumor underwent parotidectomy, and the surgical specimens indicated histopathological changes with necrosis, abscess, granuloma, and the infiltration of inflammatory cells including Langhans-type multinucleated giant cells. CONCLUSIONS: It is conceivable that Warthin tumor bears the characteristics of inflammation induced by the FNA procedure without any relation to infection. Therefore, it may be better to avoid routine FNA and give priority to diagnostic imagings over FNA in the diagnosis of tumors strongly suspected as Warthin tumor. PMID- 19643267 TI - Deep brain stimulation effects in patients with tinnitus. AB - OBJECTIVE: To report deep brain stimulation (DBS) effects in patients with tinnitus. STUDY DESIGN: Case series with chart review. SETTING: Tertiary medical center. SUBJECTS AND METHODS: Seven patients implanted with DBS systems for movement disorders who also reported having tinnitus were interviewed about their tinnitus conditions. Four were available for testing in a specialized tinnitus clinic with their DBS systems turned off or on. Testing included matching of self rated and psychoacoustically measured tinnitus loudness to measure the impact of DBS on tinnitus. RESULTS: Three of the seven patients reported reduced tinnitus loudness when DBS was turned on. Of the four patients tested in the clinic, results indicated that DBS of the ventralis intermedius nucleus of the thalamus caused decreases in tinnitus loudness in two patients with relatively prolonged residual inhibition. CONCLUSION: These results suggest that DBS of nonauditory thalamus structures may provide tinnitus relief for some patients. PMID- 19643268 TI - Inverted follicular keratosis of the nasal vestibule. PMID- 19643269 TI - Child abuse presenting as oral cavity bruising. PMID- 19643270 TI - Tracheal polyps. PMID- 19643271 TI - Intratympanic injection of autologous blood for traumatic perilymphatic fistulas. PMID- 19643272 TI - Radiotherapy for the treatment of longstanding head and neck hemangioma. PMID- 19643273 TI - Papillary squamous cell carcinoma of the tongue. PMID- 19643274 TI - Isolated intrathyroidal neurofibroma. PMID- 19643275 TI - Does olfactory function improve after endoscopic sinus surgery? PMID- 19643277 TI - Potential hazards of the harmonic scalpel. PMID- 19643278 TI - Multilevel surgery in patients with rapid eye movement-related obstructive sleep apnea. PMID- 19643280 TI - Collaborative approach in assessing community readiness for a pandemic event. PMID- 19643281 TI - Methicillin-resistant Staphylococcus aureus: an assessment of environmental contamination in a burn center. PMID- 19643282 TI - Environmental sampling for Clostridium difficile: swabs or sponges? PMID- 19643283 TI - ID tags-does the ID stand for identification or infectious diseases risk? PMID- 19643284 TI - Mortality associated with Pandrug-resistant Acinetobacter baumannii infections in Thailand. PMID- 19643285 TI - Hepatitis B-related policies: Inconsistent patient safety in Indonesian hospitals. PMID- 19643288 TI - Percutaneous pinning of distal radius fractures: an anatomic study demonstrating the proximity of K-wires to structures at risk. AB - PURPOSE: Closed reduction and percutaneous pinning is a reliable technique for treating 2- and 3-part distal radius fractures. There are currently no data that demonstrate the proximity of at-risk nerves and tendons during percutaneous placement of 5 commonly used K-wires. Whereas the previous literature notes the risk of superficial radial nerve injury with K-wire insertion into the radial styloid, the current study provides specific distances, not only to the superficial radial nerve (SRN) but also to the tendons of the first through fifth extensor compartments during K-wire insertion. METHODS: K-wires (1.5 mm or 0.059 in) were placed percutaneously into the distal radius of 15 cadaver specimens, simulating fixation of a distal radius fracture. After dissection, the distance from the K-wires to the extensor tendons and branches of the SRN were measured and tabulated. RESULTS: The volar radial styloid K-wire was an average distance of 1.47 mm +/- 1.7 from the closest branch of the SRN. One penetrated a branch of the SRN. The dorsal radial styloid K-wire was an average distance of 0.35 mm +/- 0.64 from the closest branch of the SRN. No tendons in the first compartment were found penetrated by or touching the K-wires. The transverse radial K-wire was an average distance of 1.07 mm +/- 1.57 from the branches or trunk of the SRN. One K wire was found piercing the volar branch of the SRN, and 1 K-wire was found piercing the abductor pollicis longus. The dorsal rim K-wire was an average of 2.94 mm +/- 2.11 from the ulnar aspect of the extensor pollicis longus and an average of 1.44 mm +/- 1.65 from the radial aspect of the extensor digitorum communis. The dorsoulnar K-wire was an average distance of 1.88 mm +/- 1.6 ulnar or radial to the extensor digiti quinti proprius and penetrated it in three specimens. CONCLUSIONS: The volar radial styloid, transverse radial, and dorsoulnar K-wires all penetrated either tendons or nerves. It is therefore prudent to make a small incision to identify and protect the underlying structures prior to placement of K-wires used for the fixation of distal radius fractures. Also, care must be taken not to place the dorsal K-wires more than 5 mm ulnar to Lister's tubercle to avoid extensor digitorum communis injury. PMID- 19643287 TI - Using evidence to minimize the cost of trigger finger care. AB - PURPOSE: Critics of U.S. health care cite both underuse and overuse of resources. With more than one third of Americans paying for medical care out of pocket, optimizing the cost-benefit ratio of care is a high priority. Clinical trials have established the success of the different treatment options for patients who present with trigger finger. The economic impact of these differing strategies has not been established. The aim of this study was to perform a cost minimization analysis to identify the least costly strategy for effective treatment of trigger finger using existing evidence in the literature. METHODS: Five strategies for the treatment of trigger finger were identified: (1) a steroid injection followed by surgical release for failure or recurrence, (2) a steroid injection followed by a second injection for failures or recurrence, followed by definitive surgery if needed, (3) 3 steroid injections before definitive surgery if needed, (4) surgical release, and (5) percutaneous release with definitive open surgery if needed. To reflect the costs, we used 2 sources of data: our institution's billing charges to private payers and our institution's reimbursements from Medicare. A literature review identified median success rates of the different treatment strategies. We conducted a series of analyses to evaluate the effect of varying individual costs and success rates. RESULTS: The second strategy is the least costly treatment of those considered in this study. The most costly treatment, surgical release, costs between 248% and 340% more than the second strategy. For surgical or percutaneous release to cost less than the second strategy, the surgical billing charge would need to be lower than $742 for private payers or less than $305 of Medicare reimbursement. CONCLUSIONS: Trigger finger is a common problem with many acceptable treatment algorithms. Management of trigger finger with 2 steroid injections before surgery is the least costly treatment strategy. TYPE OF STUDY/LEVEL OF EVIDENCE: Decision Analysis II. PMID- 19643289 TI - Long-term follow-up of basal joint resection arthroplasty of the thumb with transfer of the abductor pollicis brevis origin to the flexor carpi radialis tendon. AB - PURPOSE: To investigate the long-term functional and clinical outcomes of a tendon transfer during basal joint interposition arthroplasty for osteoarthritis of the basal joint of the thumb, in which the origin of the abductor pollicis brevis (APB) and opponens pollicis is transferred to the flexor carpi radialis tendon, in order to increase the abduction moment arm of the thumb and provide dynamic stabilization of the base of the first metacarpal. METHODS: We observed 22 patients, who received basal joint interposition arthroplasty with APB and opponens pollicis tendon transfer, over an average of 9 years (range, 3-20 years). Subjective outcome measures included patient satisfaction scores, visual analog scale scores for pain, and Disabilities of the Arm, Shoulder and Hand (DASH) scores. Clinical evaluations included thumb range of motion, grip strength, and pinch strength. RESULTS: At an average follow-up of 9 years, 95% of patients (21 out of 22) subjectively scored the procedure as good or excellent and reported improvement in activities of daily living. Mean visual analog scale pain score was 4.4 at rest and 7.8 with activity (out of 100), and mean DASH score was 13.3 (out of 100). Average grip strength of the operated hand was equal to that of the contralateral hand, and lateral and tip pinch strengths were 79% and 93%, respectively, of the contralateral hand. No intraoperative or early postoperative complications were reported, although 1 patient whose procedure was performed as treatment for failed silastic arthroplasty reported metacarpal instability at 9-year follow-up (DASH score of 22). CONCLUSIONS: Basal joint arthroplasty with APB and opponens pollicis tendon transfers provides excellent long-term results for carpometacarpal thumb osteoarthritis. The procedure is safe, with a low complication rate. Its success has long-term durability as measured by patient satisfaction, functional outcome measures, range of motion, and strength. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 19643290 TI - Comparison of the native ulnar head and a partial ulnar head resurfacing implant. AB - PURPOSE: To assess the match in size and shape between the native ulnar head and a partial ulnar head implant in cadaver specimens. METHODS: Ten fresh-frozen cadaver arms (6 male, 4 female, age range 79-91 years) with no history of previous distal radioulnar joint surgery were used. Radiographic measurements before and after implantation were used to compare ulnar head articular height, width, offset, and ulnar variance. Head diameter was measured using photographs of the resected ulnar heads. RESULTS: The partial ulnar head implant consistently reproduced the natural anatomic size and shape for all variables except ulnar head height and ulnar variance. Head height was greater with the implant, but the additional height extended proximally into the distal radioulnar joint synovial recess, which is unlikely to have adverse affects. Ulnar variance match was technique dependent, with a tendency to place the implant in more neutral variance when positive variance was present before surgery. CONCLUSIONS: Our study demonstrated that a partial ulnar head implant, which replaces the articular surfaces, can closely re-create the ulnar head anatomy. By virtue of restoring the anatomy without an extensive dissection, the clinical results should be expected to at least match the functional results of total head replacement, reduce the rehabilitation, and possibly reduce the risk of joint instability. PMID- 19643291 TI - Use of a magnesium-based bone adhesive for flexor tendon-to-bone healing. AB - PURPOSE: Our previous studies in a canine animal model demonstrated that the flexor tendon-to-bone insertion site has a poor capacity to heal. Magnesium-based adhesives have the potential to improve tendon-to-bone healing. Therefore, we hypothesized that magnesium-based bone adhesive (MBA) will improve the tendon-to bone biomechanical properties initially and in the early period after repair. METHODS: Flexor digitorum profundus tendons were injured and repaired into bone tunnels in the distal phalanges of dogs. The bone tunnels were either filled with MBA before completing the repair or left empty (control [CTL]). Histologic appearance, tensile properties, range of motion, and bone density were examined at time zero and 21 days after the repair. RESULTS: There was no histologic evidence of acute inflammation. There appeared to be more mast cells in the MBA group than in the CTL group. Chronic inflammatory infiltrate and fibrosis was slightly higher in the MBA group compared with the CTL group. Tensile properties at time zero were significantly higher in the MBA group compared with the CTL group. However, tensile properties were significantly lower in the MBA group compared with the CTL group at 21 days. Range of motion and bone density were significantly lower in the MBA and CTL groups compared with normal (ie, uninjured) at 21 days; no differences were seen when comparing MBA with CTL. CONCLUSIONS: We found that the initial biomechanical properties of flexor tendon to-bone repairs can be improved with MBA. However, MBA use in vivo led to a decrease in the biomechanical properties of the repair. There was no effect of MBA on bone density or range of motion in the early period after repair. Our histologic analysis suggests that the poor healing in the MBA group may have been due to an allergic response or to increased chronic inflammation resulting from the foreign material. PMID- 19643292 TI - Comparison of loop-tendon versus end-weave methods for tendon transfer or grafting in rabbits. AB - PURPOSE: The loop-tendon method for the stabilization of tendon transfers or grafts has been demonstrated previously to have greater initial tensile strength than that of the end-weave method. To our knowledge, a comparison of the mechanical strengths of these methods over the early postoperative period has not been made. The purpose of this study was to compare the mechanical strengths of loop-tendon and end-weave methods of repair during the early postoperative period in rabbit hind limb tendons. METHODS: In bilateral hind limbs of 30 New Zealand white rabbits of an average weight of 3.5 kg, a distally cut gastrocnemius Achilles' tendon and a proximally cut flexor digitorum superficialis tendon were connected to each other by using the loop-tendon method with 5 stitches in one limb and a 1-pass end-weave method in the contralateral limb. Postoperatively, all rabbits were immobilized by a short-leg cylinder cast. Six rabbits were killed at each of the following time points: immediately after surgery (baseline) and at 1, 2, 3, and 4 weeks postoperatively. Repaired tendons were harvested and were loaded to failure in a tensile load-testing machine to record the ultimate strength and to calculate the absorbed energy. RESULTS: Ultimate tensile loads were significantly higher in the loop-tendon method group than in the end-weave group from baseline to 3 weeks postoperatively, but there was no difference at 4 weeks postoperatively. During the postoperative period, the ultimate tensile load and absorbed energy decreased over the first 2 weeks postoperatively and then increased to reach baseline strengths at 3 weeks postoperatively in both groups. CONCLUSIONS: The loop-tendon method provided greater strength than that of the end-weave method during the early postoperative period in rabbit tendons. The loop-tendon method may provide greater surgical repair strength during the early postoperative rehabilitation period than the end-weave method. PMID- 19643293 TI - Effect of A2 pulley release on repaired tendon gliding resistance and rupture in a chicken model. AB - PURPOSE: Release of part of the A2 pulley has been suggested to improve function after zone II primary flexor tendon repairs. The purpose of this study was to measure the effect of A2 pulley release compared with pulley preservation on repaired tendon gliding resistance and rupture in the early postoperative period in a chicken model. METHODS: We divided 104 long toes from 52 Leghorn chickens into 2 experimental groups. In group 1, the flexor digitorum profundus tendons were cut completely and repaired surgically with either release or preservation of the A2 pulley. The tendon laceration was positioned so that the repair had to glide through the pulley with toe flexion. The toes were subjected to simulated active flexion at the end of the 2nd and 4th postsurgical weeks. The rupture rates of the tendons were recorded. In group 2, the volar two thirds of the tendons were cut and repaired, also in the region of the A2 pulley, with the pulley released or preserved. The force resisting tendon motion and the work of digital flexion with simulated active digital flexion were tested 3, 5, 7, and 14 days after surgery. RESULTS: At the end of the 2nd and 4th weeks, the tendon repairs showed significantly higher rates of rupture in the presence of an intact A2 pulley compared with those with the pulley released. Tendon gliding resistance was significantly increased with preservation of the pulley on postsurgical days 3, 5, 7, and 14; these toes required a greater number of motion cycles to reach steady levels of resistance and showed significantly higher steady resistance after digital motion. CONCLUSIONS: Release of the A2 pulley decreases the rate of repair rupture and the resistance to tendon gliding when the site of tendon repair has to glide through the pulley in the early postsurgical period. The findings of this study support partial release of the A2 pulley to favor successful tendon repair. PMID- 19643294 TI - Arthroscopic treatment of lateral epicondylitis. AB - Lateral epicondylitis refractory to conservative care can be effectively treated by arthroscopic release of the extensor carpi radialis brevis origin. Advantages to the technique include the ability to address other intra-articular sources of pain (capsular tears, radiocapitellar plica, etc.), a potentially faster return to work and sports, and a smaller incision. This article provides step-by-step descriptions and illustrations of the surgical technique. PMID- 19643295 TI - Fracture-dislocation about the finger joints. AB - Fracture-dislocations in the small joints of the fingers are challenging injuries. The surgeon must choose an appropriate treatment based on fracture pattern, joint stability, and injury chronicity. Fracture-dislocations of the proximal interphalangeal joint are notoriously unforgiving, with potential long term sequelae of residual pain and stiffness. Similar injuries in the distal interphalangeal joint are more tolerant of fracture displacement and even joint subluxation. Dorsal dislocations of the metacarpophalangeal joint may be associated with shearing fractures of the metacarpal head but are most notable for the volar plate interposition that may block closed reduction. PMID- 19643296 TI - Soft tissue reconstruction of the hand. AB - There are a number of insults that can compromise the soft tissue envelope of the hand. Soft tissue reconstruction seeks to restore both the aesthetic appearance and the function of the hand. The purpose of this review is to describe recent advances in hand soft tissue reconstruction. Skin grafts and skin substitutes both are useful reconstructive options for certain defects. Digital coverage continues to be subject to refinements that lead to better reconstructions. Flaps based on donor sites from the dorsal metacarpal artery system are finding continually expanding uses in hand reconstruction. Traditional notions of forearm based donor tissue are being challenged, leading to better hand reconstructions with less donor morbidity. Finally, improvements in free tissue transfer enable the expansion of reconstructive possibilities available for hand coverage. PMID- 19643298 TI - Long-term outcomes of first metacarpal extension osteotomy in the treatment of carpometacarpal osteoarthritis. PMID- 19643299 TI - Proximal row carpectomy: role of a radiocarpal interposition lateral meniscal allograft. PMID- 19643301 TI - Foreign-body reaction to the Artelon CMC joint spacer. PMID- 19643303 TI - Models for tendon biomechanical investigations. PMID- 19643306 TI - Development of an intraoperative left atrial thrombus? PMID- 19643305 TI - Potential influence of one-handedness on politics and philosophy of the 20th century. PMID- 19643307 TI - Heart failure in women: a need for prospective data. AB - Heart failure affects 5 million Americans, and nearly 50% of these are women. Sex differences have been noted regarding the underlying etiology, pathophysiology, and prognosis. Women are less likely to have coronary artery disease and more likely than men to have hypertension and valvular disease as the underlying etiology. They often present at an older age with better systolic function than men. For both sexes, there is significant morbidity, but age-adjusted data reveal that women have a better survival. Despite these known sex differences, medical management recommendations are the same for women and men, because prospective sex-specific clinical trials have not been performed. However, our review raises some concerns that women might respond differently to therapy. PMID- 19643308 TI - Professional accountability in health system reform. AB - The momentum for health system reform continues to gain support and cooperation from many groups who were opposed to reform in the past. The uninsured and underinsured numbers have increased with the rising cost of health care and the worsening economy. Designing a health care delivery system that delivers quality patient-centered care will require the direct involvement of patients and medical professionals. The American College of Cardiology is recognized for its commitment to education and quality and a commitment to quality metrics that facilitate best practice. The American College of Cardiology needs to continue its leadership role to ensure that health care reform meets the expectations of our patients and members. PMID- 19643309 TI - Children and clinical studies: the National Heart, Lung, and Blood Institute's new multimedia resource for pediatric research. PMID- 19643311 TI - Moving beyond angiotensin II to also target aldosterone? PMID- 19643310 TI - Effect of spironolactone on left ventricular mass and aortic stiffness in early stage chronic kidney disease: a randomized controlled trial. AB - OBJECTIVES: We sought to determine whether the addition of spironolactone to angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) improves left ventricular mass and arterial stiffness in early-stage chronic kidney disease (CKD). BACKGROUND: Chronic kidney disease is associated with a high risk of cardiovascular disease and a high prevalence of left ventricular hypertrophy and arterial stiffness that confer an adverse prognosis. It is believed that these abnormalities are in part a result of activation of the renin-angiotensin-aldosterone system. METHODS: After an active run-in phase with spironolactone 25 mg once daily, 112 patients with stage 2 and 3 CKD with good blood pressure control (mean daytime ambulatory blood pressure <130/85 mm Hg) on established treatment with ACE inhibitors or ARBs were randomized to continue spironolactone or to receive a matching placebo. Left ventricular mass (cardiac magnetic resonance) and arterial stiffness (pulse wave velocity/analysis, aortic distensibility) were measured before run in and after 40 weeks of treatment. RESULTS: Compared with placebo, the use of spironolactone resulted in significant improvements in left ventricular mass (-14 +/- 13 g vs. +3 +/- 11 g, p < 0.01), pulse wave velocity (-0.8 +/- 1.0 m/s vs. -0.1 +/- 0.9 m/s, p < 0.01), augmentation index (-5.2 +/- 6.1% vs. -1.4 +/- 5.9%, p < 0.05), and aortic distensibility (0.69 +/- 0.86 x 10(-3) mm Hg vs. 0.04 +/- 1.04 x 10(-3) mm Hg, p < 0.01). CONCLUSIONS: The use of spironolactone reduces left ventricular mass and improves arterial stiffness in early-stage CKD. These effects suggest that aldosterone exerts adverse cardiovascular effects in CKD and that spironolactone is worthy of further study as a treatment that could reduce adverse cardiovascular events. (Is Spironolactone Safe and Effective in the Treatment of Cardiovascular Disease in Mild Chronic Renal Failure; NCT00291720). PMID- 19643312 TI - Predictors of cardiac rehabilitation referral in coronary artery disease patients: findings from the American Heart Association's Get With The Guidelines Program. AB - OBJECTIVES: Our purpose was to determine factors independently associated with cardiac rehabilitation referral, which are currently not well described at a national level. BACKGROUND: Substantial numbers of eligible patients are not referred to cardiac rehabilitation at hospital discharge despite proven reductions in mortality and national guideline recommendations. METHODS: We used data from the American Heart Association's Get With The Guidelines program, analyzing 72,817 patients discharged alive after a myocardial infarction, percutaneous coronary intervention, or coronary artery bypass graft surgery between January 2000 and September 2007 from 156 hospitals. We identified factors associated with cardiac rehabilitation referral at discharge and performed multivariable logistic regression, adjusted for clustering, to identify which factors were independently associated with cardiac rehabilitation referral. RESULTS: Mean age was 64.1 +/- 13.0 years, 68% were men, 79% were white, and 30% had diabetes, 66% hypertension, and 52% dyslipidemia; mean body mass index was 29.1 +/- 6.3 kg/m(2), and mean ejection fraction 49.0 +/- 13.6%. All patients were admitted for coronary artery disease (CAD), with 71% admitted for myocardial infarction. Overall, only 40,974 (56%) were referred to cardiac rehabilitation at discharge, ranging from 53% for myocardial infarction to 58% for percutaneous coronary intervention and to 74% for coronary artery bypass graft patients. Older age, non-ST-segment elevation myocardial infarction, and the presence of most comorbidities were associated with decreased odds of cardiac rehabilitation referral. CONCLUSIONS: Despite strong evidence for benefit, only 56% of eligible CAD patients discharged from these hospitals were referred to cardiac rehabilitation. Increased physician awareness about the benefits of cardiac rehabilitation and initiatives to overcome barriers to referral are critical to improve the quality of care of patients with CAD. PMID- 19643314 TI - Eliminating triggers of ventricular fibrillation: the past, present, and future. PMID- 19643313 TI - Long-term follow-up of idiopathic ventricular fibrillation ablation: a multicenter study. AB - OBJECTIVES: This multicenter study sought to evaluate the long-term follow-up of patients ablated for idiopathic ventricular fibrillation (VF). BACKGROUND: Catheter ablation of idiopathic VF that targets ventricular premature beat (VPB) triggers has been shown to prevent VF recurrences on short-term follow-up. METHODS: From January 2000, 38 consecutive patients from 6 different centers underwent ablation of primary idiopathic VF initiated by short coupled VPB. All patients had experienced at least 1 documented VF, with 87% having experienced > or =2 VF episodes in the preceding year. Catheter ablation was guided by activation mapping of VPBs or pace mapping during sinus rhythm. RESULTS: There were 38 patients (21 men) age 42 +/- 13 years, refractory to a median of 2 antiarrhythmic drugs. Triggering VPBs originated from the right (n = 16), the left (n = 14), or both (n = 3) Purkinje systems and from the myocardium (n = 5). During a median post-procedural follow-up of 63 months, 7 (18%) of 38 patients experienced VF recurrence at a median of 4 months. Five of these 7 patients underwent repeat ablation without VF recurrence. Survival free of VF was predicted only by transient bundle-branch block in the originating ventricle during the electrophysiological study (p < 0.0001). The number of significant events (confirmed VF or aborted sudden death) was reduced from 4 (interquartile range 3 to 9) before to 0 (interquartile range 0 to 4) after ablation (p = 0.01). CONCLUSIONS: Ablation for idiopathic VF that targets short coupled VPB triggers is associated with a long-term freedom from VF recurrence. PMID- 19643315 TI - Risk of ventricular arrhythmia after implantable defibrillator treatment in anxious type D patients. AB - OBJECTIVES: We sought to examine the combination of adverse psychological factors (anxiety, depression, and distressed or Type D personality) as a predictor of ventricular arrhythmias in patients with implantable cardioverter-defibrillators (ICDs). BACKGROUND: Little is known about the role of psychological factors and their clustering in the occurrence of life-threatening arrhythmias. METHODS: In this prospective study, 391 patients with an ICD (81% men, age 62.3 +/- 10.4 years) completed anxiety, depression, and Type D personality scales at the time of implantation. The end point was occurrence of ventricular arrhythmia, defined as appropriate ICD therapies, in the first year after implantation. RESULTS: Ventricular arrhythmias occurred in 19% (n = 75) of patients. Increased symptoms of depression (p = 0.81) or anxiety (p = 0.31) did not predict arrhythmias. However, anxious patients with a Type D personality had a significantly increased rate of ventricular arrhythmias (21 of 71; 29.6%) as compared with other ICD patients (54 of 320; 16.9%; hazard ratio [HR]: 1.89; 95% confidence interval [CI]: 1.14 to 3.13; p = 0.013). When controlled for the effects of sex, age, ischemic etiology, left ventricular dysfunction, prolonged QRS duration, and medication, anxious Type D patients (HR: 1.72; 95% CI: 1.03 to 2.89; p = 0.039) and secondary prevention patients (HR: 1.91; 95% CI: 1.14 to 3.20; p = 0.014) were at increased risk of ventricular arrhythmias. CONCLUSIONS: Personality modulated the effect of emotional distress; anxiety predicted a 70% increase in risk of arrhythmia in Type D patients but not in other patients. Anxious Type D patients may be identified and offered additional behavioral support after ICD implantation. PMID- 19643316 TI - Achieving an exercise workload of > or = 10 metabolic equivalents predicts a very low risk of inducible ischemia: does myocardial perfusion imaging have a role? AB - OBJECTIVES: We sought to identify prospectively the prevalence of significant ischemia (> or =10% of the left ventricle [LV]) on exercise single-photon emission computed tomography (SPECT) imaging relative to workload achieved in consecutive patients referred for myocardial perfusion imaging (MPI). BACKGROUND: High exercise capacity is a strong predictor of a good prognosis, and the role of MPI in patients achieving high workloads is questionable. METHODS: Prospective analysis was performed on 1,056 consecutive patients who underwent quantitative exercise gated (99m)Tc-SPECT MPI, of whom 974 attained > or =85% of their maximum age-predicted heart rate. These patients were further divided on the basis of attained exercise workload (<7, 7 to 9, or > or =10 metabolic equivalents [METs]) and were compared for exercise test and imaging outcomes, particularly the prevalence of > or =10% LV ischemia. Individuals reaching > or =10 METs but <85% maximum age-predicted heart rate were also assessed. RESULTS: Of these 974 subjects, 473 (48.6%) achieved > or =10 METs. This subgroup had a very low prevalence of significant ischemia (2 of 473, 0.4%). Those attaining <7 METs had an 18-fold higher prevalence (7.1%, p < 0.001). Of the 430 patients reaching > or =10 METs without exercise ST-segment depression, none had > or =10% LV ischemia. In contrast, the prevalence of > or =10% LV ischemia was highest in the patients achieving <10 METs with ST-segment depression (14 of 70, 19.4%). CONCLUSIONS: In this referral cohort of patients with an intermediate-to-high clinical risk of coronary artery disease, achieving > or =10 METs with no ischemic ST-segment depression was associated with a 0% prevalence of significant ischemia. Elimination of MPI in such patients, who represented 31% (430 of 1,396) of all patients undergoing exercise SPECT in this laboratory, could provide substantial cost-savings. PMID- 19643317 TI - Customized exercise testing. PMID- 19643318 TI - Magnetic resonance imaging at 1.5-T in patients with implantable cardioverter defibrillators. AB - OBJECTIVES: Our aim was to establish and evaluate a strategy for safe performance of magnetic resonance imaging (MRI) at 1.5-T in patients with implantable cardioverter-defibrillators (ICDs). BACKGROUND: Expanding indications for ICD placement and MRI becoming the imaging modality of choice for many indications has created a growing demand for MRI in ICD patients, which is still considered an absolute contraindication. METHODS: Non-pacemaker-dependent ICD patients with a clinical need for MRI were included in the study. To minimize radiofrequency related lead heating, the specific absorption rate was limited to 2 W/kg. ICDs were reprogrammed pre-MRI to avoid competitive pacing and potential pro arrhythmia: 1) the lower rate limit was programmed as low as reasonably achievable; and 2) arrhythmia detection was programmed on, but therapy delivery was programmed off. Patients were monitored using electrocardiography and pulse oximetry. All ICDs were interrogated before and after the MRI examination and after 3 months, including measurement of pacing capture threshold, lead impedance, battery voltage, and serum troponin I. RESULTS: Eighteen ICD patients underwent a total of 18 MRI examinations at 1.5-T; all examinations were completed safely. All ICDs could be interrogated and reprogrammed normally post MRI. No significant changes of pacing capture threshold, lead impedance, and serum troponin I were observed. Battery voltage decreased significantly from pre- to post-MRI. In 2 MRI examinations, oversensing of radiofrequency noise as ventricular fibrillation occurred. However, no attempt at therapy delivery was made. CONCLUSIONS: MRI of non-pacemaker-dependent ICD patients can be performed with an acceptable risk/benefit ratio under controlled conditions by taking both MRI- and pacemaker-related precautions. (Implantable Cardioverter Defibrillators and Magnetic Resonance Imaging of the Heart at 1.5-Tesla; NCT00356239). PMID- 19643319 TI - Magnetic resonance imaging in patients with implantable cardioverter defibrillators and pacemakers. PMID- 19643320 TI - Efficacy of atorvastatin reload in patients on chronic statin therapy undergoing percutaneous coronary intervention: results of the ARMYDA-RECAPTURE (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) Randomized Trial. AB - OBJECTIVES: This study was designed to investigate whether an acute atorvastatin reload before percutaneous coronary intervention (PCI) protects patients receiving chronic statin therapy from periprocedural myocardial damage. BACKGROUND: Previous ARMYDA (Atorvastatin for Reduction of Myocardial Damage During Angioplasty) studies demonstrated that short-term pre-treatment with atorvastatin reduces myocardial infarction during PCI in statin-naive patients with both stable angina and acute coronary syndromes. METHODS: A total of 383 patients (age 66 +/- 10 years, 305 men) with stable angina (53%) or non-ST segment elevation acute coronary syndromes (47%) and chronic statin therapy (55% atorvastatin) undergoing PCI were randomized to atorvastatin reload (80 mg 12 h before intervention, with a further 40-mg pre-procedural dose [n = 192]) or placebo (n = 191). All patients received long-term atorvastatin treatment thereafter (40 mg/day). The primary end point was 30-day incidence of major adverse cardiac events (cardiac death, myocardial infarction, or unplanned revascularization). RESULTS: The primary end point occurred in 3.7% of patients treated with atorvastatin reload and in 9.4% in the placebo arm (p = 0.037); this difference was mostly driven by reduction in periprocedural myocardial infarction. There was lower incidence of post-procedural creatine kinase myocardial band and troponin-I elevation greater than the upper limit of normal in the atorvastatin arm (13% vs. 24%, p = 0.017, and 37% vs. 49%, p = 0.021, respectively). Multivariable analysis identified atorvastatin reload as a predictor of decreased risk of 30-day incidence of major adverse cardiac events (odds ratio: 0.50, 95% confidence interval: 0.20 to 0.80; p = 0.039), mainly in patients with acute coronary syndromes (82% relative risk reduction; p = 0.027). CONCLUSIONS: The ARMYDA-RECAPTURE trial suggests that reloading with high-dose atorvastatin improves the clinical outcome of patients on chronic statin therapy undergoing PCI. These findings may support a strategy of routine reload with high dose atorvastatin early before intervention even in the background of chronic therapy. PMID- 19643321 TI - Recapturing the magic: revisiting the pleiotropic effects of statins in percutaneous coronary revascularization. PMID- 19643322 TI - Large hiatal hernia mimicking left atrial mass: a multimodality diagnosis. PMID- 19643323 TI - President's Page: looking beyond the politics of health care reform. PMID- 19643324 TI - Impact of ventricular assist device support on post-transplant mortality searching for reasons. PMID- 19643326 TI - Don't throw the baby out with the bath water. PMID- 19643328 TI - Clinical significance of iodine-123 metaiodobenzylguanidine cardiac imaging. PMID- 19643330 TI - Sports injuries of the elbow and hand. Preface. PMID- 19643331 TI - The emerging role of elbow arthroscopy in chronic use injuries and fracture care. AB - Arthroscopy is emerging as an invaluable tool for diagnosing and treating elbow pathology. In addition to the advantages of less scarring, decreased risk of infection, less postoperative pain, and a more thorough visualization of the elbow joint, arthroscopy is particularly well suited to the treatment of athletes trying to minimize rehabilitation and inactivity. Indications for elbow arthroscopy now extend well beyond diagnosis and loose body removal, and include the treatment of impingement, arthritis, contractures, fragment stabilization for osteochondritis dessicans, and treatment of certain fractures. This article reviews the basic principles and techniques of elbow arthroscopy and their application to common sports-related conditions, such as valgus overload syndrome, medial collateral ligament insufficiency, and the various causes of lateral elbow pain. Newer applications of elbow arthroscopy in fracture care are addressed as well. PMID- 19643332 TI - Arthroscopic and open radial ulnohumeral ligament reconstruction for posterolateral rotatory instability of the elbow. AB - Arthroscopic repair and/or plication of the radial ulnohumeral ligament (RUHL) complex can be as successful as open repair. The diagnosis of posterolateral rotatory instability (PLRI), made by a combination of positive clinical findings and radiologic evidence, can be confirmed by arthroscopic examination. The authors describe four clinical tests for PLRI. Magnetic resonance arthrography is recommended to assist in the preoperative evaluation. In surgical cases, the means to arthroscopically confirm instability are explained. Finally, the authors describe a repair and a ligament plication technique that can be performed by either arthroscopic or open technique with a high rate of success. Arthroscopic repair/plication of the RUHL is thought to effectively stabilize an elbow with PLRI, producing a high degree of patient satisfaction. PMID- 19643333 TI - Open and arthroscopic management of lateral epicondylitis in the athlete. AB - Lateral epicondylitis is the most common condition affecting the adult elbow. It occurs in middleaged individuals and is self-limiting in most cases. Based on clinical, histologic, and imaging data, the tendinous origin of the extensor carpi radialis brevis is the most likely site of pathology. When conservative measures fail, surgical management may be indicated. This can be accomplished by traditional open methods or by arthroscopic release. This article reviews the relevant anatomy of the common extensor tendon origin at the elbow and provides guidelines for surgical management of recalcitrant epicondylitis. Special emphasis is placed on arthroscopic techniques, which, when required, may allow for a more rapid return of the athlete to sport. PMID- 19643335 TI - Biceps tendon injuries in athletes. AB - Although rare, athletes involved in competitive strength training and contact sports may sustain distal tendon biceps injuries. Treatment of complete distal biceps tendon ruptures in athletes is primarily surgical. Early repair, through either one-incision or two-incision techniques with anatomic reinsertion of the ruptured tendon to the bicipital tuberosity, is highly recommended. In this article the etiology and pathophysiology of distal biceps tendon ruptures, current diagnostic modalities, and surgical indications are discussed. Also, treatment options, surgical techniques, outcomes, and potential complications are reviewed. PMID- 19643334 TI - Medial collateral ligament reconstruction in the baseball Pitcher's elbow. AB - Pitchers are prone to elbow injuries because of high and repetitive valgus stresses on the elbow. The anterior bundle of the medial ulnar collateral ligament (MCL) of the elbow is the primary restraint and is often attenuated with time, leading to functional incompetence and ultimate failure. Pitchers with a history of medial elbow pain, reduced velocity, and loss of command may have an MCL injury in evolution. Physical examination and imaging can confirm the diagnosis. Treatment begins with rest and activity modification. All medial elbow pain is not MCL injury. Surgery is considered only for talented athletes who wish to return to competitive play and may include elite scholastic and other collegiates and professionals. The technique for MCL reconstruction was first described in 1986. Many variations have been offered since then, which can result in predictable outcomes, allowing many to return to the same level of competitive play. PMID- 19643336 TI - Arthroscopic management of scaphoid fractures in athletes. AB - Fractures of the scaphoid are a common athletic injury. In this article the indications and treatment strategy for arthroscopic management of scaphoid fractures and nonunions in athletes are reviewed. Various arthroscopic assisted and percutaneous techniques for the fixation of fractures of the scaphoid are discussed, including the volar and dorsal percutaneous approaches, and arthroscopic reduction by the Geissler technique. In general, these techniques include a small amount of wrist arthroscopy and a significant amount of fluoroscopy. PMID- 19643337 TI - Carpal fractures in athletes excluding the scaphoid. AB - A wide range of hand and wrist injuries occur in today's recreational and elite athletes and account for 3% to 9% of all sports injuries. The onus is on the physician to discriminate between injuries that can be managed with an early return to sport, and those injuries that place the athlete at risk of further injury if they are not managed aggressively from the outset. The physician and the athlete must understand the balance between safe, early return to sport, and prompt surgical treatment that prevents late disability. PMID- 19643338 TI - Repair of arthroscopic triangular fibrocartilage complex tears in athletes. AB - Triangular fibrocartilage complex (TFCC) injuries are a common source of wrist pain in athletes. These injuries constitute a unique orthopedic challenge because of the particular physical demands on these patients. A specialized management approach is often necessary, due to the short recovery time available and the need for high demand performances afterward. Arthroscopic repair of TFCC is becoming the treatment of choice in this group of patients. PMID- 19643339 TI - Management of carpal instability in athletes. AB - Hand and wrist injuries are common in most athletic events and sports. Carpal fractures and ligamentous injuries are common in athletes and require physicians, trainers, and therapists who treat and diagnosis these injuries to have an understanding of the carpal bone anatomy and vascularity along with the potential for progression to instability. Research is still needed to further investigate the optimal treatments of all carpal injuries in athletes along with designing new means to prevent these injuries. PMID- 19643340 TI - Operative fixation of metacarpal and phalangeal fractures in athletes. AB - Metacarpal and phalangeal fractures are common athletic injuries that can significantly affect the athlete's career when they occur during the season and affect the athlete's training when they occur in the off season. This situation is particularly relevant if there are complications or if fixation is not stable enough to permit early range of motion and rehabilitation. This article discusses percutaneous and open reduction techniques of hand fractures as these injuries pertain to athletes. The goal is stable fixation to allow early return to competition and rehabilitation. PMID- 19643342 TI - Acute ulnar collateral ligament injury in the athlete. AB - The functional thumb is a necessity for successful athletic participation. It not only allows the athlete to manipulate athletic equipment but also allows the precise manipulation of objects in the athlete's hand. Injury to the thumb often negates power grip and finesse of the athletic hand. Injuries can range from fractures, to dislocations, to ligamentous injuries. The relatively unconstrained thumb metacarpophalangeal joint is particularly vulnerable to injury from an abduction moment to its distal segment. Such injuries occur from direct contact and with falls on equipment such as racquet handles and ski poles. The stability of the athlete's metacarpophalangeal joint must be restored to allow for a productive return to sport. PMID- 19643341 TI - Management of proximal interphalangeal joint dislocations in athletes. AB - Proximal interphalangeal joint dislocations are common athletic injuries. In dislocations and fracture dislocations, the most important treatment principle is congruent joint reduction and maintenance of stability. This article reviews the relevant anatomy, injury characteristics, and treatment options for proximal interphalangeal joint dislocations and fracture dislocations. Treatment methods discussed include closed reduction, percutaneous fixation, and open reduction. PMID- 19643344 TI - The first Clinics issue on cerebral palsy. PMID- 19643343 TI - Bracing and rehabilitation for wrist and hand injuries in collegiate athletes. AB - Athletic injuries of the hand and wrist are common. The key to management of these injuries is prevention. Certain sports require athletes to participate in positions that pose a higher risk of injury to the fingers and wrists. Once healing of the injured digit and wrist has occurred, rehabilitation of the injury is important. This requires close communication between the therapist and the strength and conditioning coach to allow strengthening exercises but limit traction to the involved injury in order to limit the risk of reinjury. Finally, once the injury has been rehabilitated, protective playing casts and splints are useful to allow the athlete to return early to competition and to decrease the risk of reinjury. PMID- 19643345 TI - Managing the issues facing individuals with CP across the lifespan. PMID- 19643346 TI - Cerebral palsy: classification and epidemiology. AB - This article reviews the historical background, classification, and etiology of cerebral palsy (CP), the most common motor disability of childhood. The various methods employed to measure the prevalence of CP in the population are examined. Causes of CP are numerous, and the etiology multi-factorial. Risk factors are categorized by the timing of their proposed occurrence: prenatal, perinatal, and postnatal. The leading prenatal and perinatal risk factors for CP are birth weight and gestational age. Other risk factors include neonatal encephalopathy, multiple pregnancy, infection and inflammation, and a variety of genetic factors. PMID- 19643347 TI - Common medical comorbidities associated with cerebral palsy. AB - The medical issues associated with the diagnosis of cerebral palsy (CP) can have significant interplay with the neuromuscular issues that most physiatrists manage in the clinical setting. Identification and appropriate management of these common comorbidities by the primary care and subspecialist physicians can have significant impact on the quality of life of the patient and family. Some of these issues are prevalent across all gross motor function classification system (GMFCS) levels of severity, whereas others more commonly complicate the care of those children with the more severe GMFCS levels IV and V. Performance of a complete review of systems to address the potentially complex medical comorbidities and subsequent application of appropriate screening tools can assist in achieving optimal outcomes in children with CP and their families. PMID- 19643350 TI - The adult with cerebral palsy: a provider-consumer perspective. AB - Advances in medical and surgical care over the past 20 years have resulted in children who formerly would have died at birth or in infancy now surviving into adulthood, many with significant, permanent physical disabilities, including those due to cerebral palsy (CP). Increased awareness of these problems is needed by adult health care providers, who will be providing direct care to these individuals, and also by pediatric providers, who may be able to anticipate and prevent some of the long-term problems. This article reviews the common medical surgical problems and their management in adults with CP. In addition the life experience of a 44 year-old with CP is described from a personal perspective. PMID- 19643349 TI - Bone density in cerebral palsy. AB - This article discusses the problem of osteoporosis in cerebral palsy. Osteoporosis remains a major health problem worldwide. Cerebral palsy is the most prevalent childhood condition associated with osteoporosis. Bone density is significantly decreased. Children with cerebral palsy often sustain painful fractures with minimal trauma that impair their function and quality of life. This article addresses the anatomy and structure of bone and bone metabolism, the clinical assessment of bone mass, the causes of osteoporosis and its evaluation and treatment in children with cerebral palsy. PMID- 19643351 TI - Establishing access to technology: an evaluation and intervention model to increase the participation of children with cerebral palsy. AB - Children with a diagnosis of cerebral palsy often have significant physical limitations that prevent exploration and full participation in the environment. Assistive technology systems can provide opportunities for children with physical limitations to interact with their world, enabling play, communication, and daily living skills. Efficient access to and control of the technology is critical for successful use; however, establishing consistent access is often difficult because of the nature of the movement patterns exhibited by children with cerebral palsy. This article describes a 3-phase model of evaluation and intervention developed and used by Assistive Technology Services at the Aaron W. Perlman Center, Cincinnati Children's Hospital Medical Center, to establish successful access to technology systems in children with cerebral palsy. PMID- 19643352 TI - Access to employment and economic independence in cerebral palsy. AB - The employment statistics for people with disabilities are dismal and particularly low for those with cerebral palsy. As practitioners working with young people who have moderate to severe cognitive and physical challenges, including those with cerebral palsy, the authors assert that there are best practices that make a difference. There are states and programs showing successful outcomes. Those who create partnerships among education, businesses, and rehabilitation agencies are seeing direct positive results in employment outcomes for people with disabilities, as well as cultural and perceptional changes in businesses and people who have hiring capability. This article reviews the relevant literature; conclusions are drawn and recommendations made to improve the employment outcomes for youth with cerebral palsy in their transition to adult life. PMID- 19643348 TI - New clinical and research trends in lower extremity management for ambulatory children with cerebral palsy. AB - Cerebral palsy (CP) is the most prevalent physical disability in childhood and includes a group of disorders with varying manifestations. This article focuses on current and future intervention strategies for improving mobility and participation during the lifespan for ambulatory children with CP. The provision and integration of physical therapy and medical and orthopedic surgery management focused primarily on the lower extremities are discussed here. Some of the newer trends are more intense and task-related exercise strategies, greater precision in tone identification and management, and a shift towards musculoskeletal surgery that focuses more on promoting dynamic bony alignment and less on releasing or lengthening tendons. Advances in basic and clinical science and technology development are changing existing paradigms and offering renewed hope for improved functioning for children with CP who face a lifelong disability with unique challenges at each stage in life. PMID- 19643353 TI - Clinical applications of outcome tools in ambulatory children with cerebral palsy. AB - This article provides an overview of outcome tools commonly used to assess ambulatory children with cerebral palsy, research findings from a recent large multi-center study, and ways to integrate the research findings into clinical practice. The information presented in this article and in the referenced articles provides information on: outcome tools' discriminatory ability and responsiveness; readily available comparison data on 7 commonly used outcome tools that can be used at the point of care; prediction equations for the Parent report Pediatric Outcomes Data Collection Instrument (PODCI) by age and Gross Motor Function Classification System (GMFCS) level; and minimum clinically important difference thresholds by GMFCS level. This information can help clinicians select the best outcome tools to discriminate among severity levels and avoid ceiling effects. The scores provided allow direct comparisons between a specific patient and a matched cohort, assisting clinicians in the creation of comprehensive and individualized evaluation and management plans. Use of appropriate outcome tools to assess children with cerebral palsy can lead to best practices and reduced costs in the clinical setting. PMID- 19643354 TI - Understanding function and other outcomes in cerebral palsy. AB - Describing the status of children with cerebral palsy (CP) and quantifying change in their status are 2 central challenges to research and clinical management of CP. The science of assessing and reporting status is outcome measurement, and it is rapidly developing in the arena of CP. Because of the large number of domains to measure, the variability of CP manifestations, and a limited number of "gold standard" evaluations, creating an accurate, comprehensive, responsive, and broadly applicable measurement strategy is a serious endeavor. A range of outcome measures are available to address CP issues across the spectrum of disability. The use of these measures, and others yet to be developed, provides researchers and clinicians the best means of understanding CP and the effects of treatments. PMID- 19643355 TI - Parent-professional partnership. AB - Rehabilitation management of children with cerebral palsy (CP) brings together parents and doctors. The primary goal of the contact is to improve the individual child's potential and to improve the child's functional outcomes. Frequently, parents are interested in not just their own child, but the population of children with cerebral palsy. Physicians can provide information for both purposes. Successful parent-professional relationships are rewarding and powerful. Combining the passion of the parent and the expertise of the physician can enhance collaboration for advocacy efforts that improve outcomes for children with cerebral palsy. An increasingly important component in the parent-medical collaboration is the identification of networks of local and national support for families of children with cerebral palsy. Fortunately, parents and organizations focused on children with cerebral palsy are seeing the necessity for collaboration to build community awareness, implement education programs, and spearhead pediatric cerebral palsy advocacy on a nationwide basis. PMID- 19643356 TI - The rationale for an acute heart failure syndromes clinical trials network. AB - BACKGROUND: Clinical trials involving novel therapies treating acute heart failure syndromes (AHFS) have shown limited success with regard to both efficacy and safety. As a direct result, outcomes have changed little over time and AHFS remains a disease process associated with largely no change in hospitalization rates (80%), hospital length of stay (median 4.5 days), and in-hospital (4-7%) and 60-day mortality (10%). Despite extensive emergency department (ED) involvement during the initial phase of AHFS management, clinical trials have enrolled patients after the ED phase of management, up to 48 hours after initial therapy, long after many patients have experienced significant beneficial effects of standard therapy. As standard therapy has provided symptomatic improvement in up to 70% of patients in these trials, it is not surprising that investigational agents started after 24 to 48 hours of standard therapy have shown limited clinical efficacy when compared with standard therapy. METHODS AND RESULTS: The ability to screen, enroll, and randomize in the emergency setting is fundamental. The unique environment, the ethical complexities of enrollment in emergency-based research, and the need for rapid and standardized study-compliant care represent key challenges to active recruitment in AHFS studies. Specifically, the ability to identify and enroll a large cohort of AHFS patients early (<6 hours) in their presentation has been cited as the primary barrier to the appropriate design of clinical trials that includes this early window. CONCLUSIONS: In response, we have created a network of dedicated academic physicians with experience in clinical trials and acute management of heart failure who together can surmount this barrier and provide a framework for conducting early trials in AHFS. PMID- 19643357 TI - Changes in intrathoracic impedance are associated with subsequent risk of hospitalizations for acute decompensated heart failure: clinical utility of implanted device monitoring without a patient alert. AB - BACKGROUND: Acute decreases in intrathoracic impedance monitoring have been shown to precede heart failure hospitalization in a limited population of heart failure patients. We evaluated the relationship between changes in intrathoracic impedance with hospitalizations associated with acute decompensated heart failure (ADHF) in patients with cardiac resynchronization therapy plus defibrillator (CRT D) devices. METHODS AND RESULTS: The study enrolled 326 heart failure patients who had received CRT-D with impedance-monitoring capabilities (InSync Sentry, Medtronic). The date and duration of ADHF hospitalizations were retrospectively identified before device interrogation to obtain device diagnostic information. During 333 +/- 96 days of device monitoring, 228 patients experienced 540 intrathoracic impedance fluid index threshold crossings events (TCE) at the nominal threshold value (60 Omega. days). During the initial 4-month evaluation period, 17 subjects experienced 22 ADHF hospitalizations. In the subsequent monitoring period (206 +/- 95 days), 18 patients experienced 24 hospitalizations. The occurrence of TCEs during the monitoring period was independently correlated with the subsequent rate of ADHF hospitalization such that each TCE event during the risk stratification period was associated with a 35% increased risk for ADHF hospitalization in the remaining study period (P = .001). Poisson regression indicated that the subgroup of patients with an annual average rate of more than 3 threshold crossings per year during the monitoring period were significantly more likely to be hospitalized for ADHF than those patients with no TCE during the monitoring period (0.76 [0.20-1.325] vs. 0.14 [0.05-0.23] hospitalizations/subject/y [95%CI]; P = .02). Likewise, Kaplan-Meier analysis revealed that subsets of patients with more than 3 TCEs per year or with more than 30 days per year above threshold during the risk stratification period had significantly higher rates of ADHF hospitalization during the post risk stratification period than subjects with no TCE events, respectively. CONCLUSIONS: In this multicenter retrospective cohort study, serial decreases in intrathoracic impedance sufficient to generate a fluid index threshold crossing as well as the net duration that the index remained above threshold during a 4 month monitoring period were associated with subsequent risk of ADHF hospitalization. PMID- 19643358 TI - Ventilatory expired gas at constant-rate low-intensity exercise predicts adverse events and is related to neurohormonal markers in patients with heart failure. AB - BACKGROUND: Ventilatory efficiency (VE/VCO(2) ratio) and the partial pressure of end-tidal carbon dioxide (P(ET)CO(2)), obtained during moderate to high levels of physical exertion demonstrate prognostic value in heart failure (HF). The present investigation assesses the clinical utility of these variables during low intensity exercise. METHODS AND RESULTS: One hundred and thirty subjects diagnosed with HF underwent a 2-minute, constant-rate treadmill session at 2 miles per hour. Both the VE/VCO(2) ratio and P(ET)CO(2) were recorded during exercise (30-second average) and their change (Delta) from rest. B-type and atrial natriuretic peptide (BNP and ANP) were also determined. Only P(ET)CO(2) and DeltaP(ET)CO(2) emerged from the multivariate Cox regression. Receiver operating characteristic curve analysis revealed the prognostic classification schemes were significant with thresholds of < or >or=34 mm Hg (hazard ratio: 4.2, 95% CI: 2.2-8.0, P < .001) and < or >or=1 mm Hg (hazard ratio: 3.5, 95% CI: 1.9 6.6, P < .001) being optimal for P(ET)CO(2) and DeltaP(ET)CO(2), respectively. Moreover, subjects with a P(ET)CO(2)>or=34 mm Hg had a significantly lower BNP (214.1 +/- 431.9 vs. 1110.5 +/- 1854.0 pg/mL, P=.005) and ANP (108.2 +/- 103.6 vs. 246.2 +/- 200.4 pg/mL, P < .001). CONCLUSIONS: The results of this pilot study indicate ventilatory expired gas analysis during a short bout of low intensity exercise may provide insight into prognosis and cardiac stability. PMID- 19643359 TI - Preclinical systolic and diastolic dysfunction assessed by tissue Doppler imaging is associated with elevated plasma pro-B-type natriuretic peptide concentrations. AB - BACKGROUND: Heart failure is a major public health problem. To improve its grave prognosis, early identification of cardiac dysfunction is mandatory. Conventional echocardiography is not suitable for this. Tissue Doppler imaging (TDI), however, could be so. METHODS AND RESULTS: Within a large community-based population-study (n = 1012), cardiac function was evaluated by conventional echocardiography (left ventricular hypertrophy, dilatation, systolic, and severe diastolic dysfunction), TDI, and plasma proBNP. Averages of peak systolic (s'), early diastolic (e'), and late diastolic (a') velocities from 6 mitral annular sites were used. TDI was furthermore quantified by a combined index (eas-index) of diastolic and systolic performance: e'/(a' x s'). Compared with controls, persons with elevated plasma proBNP concentrations (n = 100) displayed lower systolic and diastolic performance by TDI, in terms of lower s' (P = 0.017) and a' (P < .001), and higher e'/a' (P = .002) and eas-index (P < .001). This pattern remained significant after multivariable adjustment for age, sex, body mass index, heart rate, estimated glomerular filtration rate, hypertension, diabetes, ischemic heart disease, and conventional echocardiography. Furthermore, TDI provided incremental information over conventional echocardiography in predicting elevated plasma proBNP concentrations. CONCLUSIONS: Preclinical systolic and diastolic dysfunction by TDI is associated with elevated plasma proBNP levels, even when conventional echocardiography is normal. PMID- 19643360 TI - Anabolics and cardiomyopathy in a bodybuilder: case report and literature review. AB - BACKGROUND: Athletes use androgenic-anabolic steroids to increase strength and muscle mass. Several case reports suggest that it may lead to dilated cardiomyopathy. METHODS AND RESULTS: We report a case of a 41-year-old bodybuilder with severe systolic dysfunction and Class IV heart failure despite maximal medical therapy. He used anabolic steroids and insulin growth factor, and did not have any other risk factors for cardiomyopathy. We briefly review the literature and summarize other reported cases with similar scenarios. In most of them cardiomyopathy was at least partially reversible after discontinuation of anabolics. CONCLUSIONS: Abuse of anabolic steroids may be an uncommon cause of cardiomyopathy in young and otherwise healthy individuals. PMID- 19643361 TI - Are there any significant differences between females and males in the management of heart failure? Gender aspects of an elderly population with symptoms associated with heart failure. AB - BACKGROUND: An increasing interest has been shown in potential gender differences in treating patients with heart failure (HF), a serious condition for the individual. To evaluate whether there are any differences in the prevalence of HF, cardiac function, biomarkers, and the treatment of HF with respect to gender. METHODS AND RESULTS: All persons ages 70 to 80 in a rural municipality were invited to participate in the project; 876 persons accepted. Three cardiologists evaluated the patients including a new history, clinical examination, electrocardiogram, chest x-ray, blood samples, and Doppler echocardiography to assess both systolic and diastolic function. The patients were followed during a mean period of 8 years. CONCLUSION: Females had hypertension more frequently and included fewer smokers than their male counterparts. A female preponderance was seen in those with preserved systolic function, whereas males predominated among those with systolic dysfunction. During the follow-up period, 20% of the males and 14% of the females died of cardiovascular diseases. The results did not show any inferior treatment of females with HF, but it clearly was more difficult to correctly classify female patients presenting with symptoms of HF. PMID- 19643363 TI - Relation between red cell distribution width with echocardiographic parameters in patients with acute heart failure. AB - BACKGROUND: Red cell distribution width (RDW) has recently been discovered to be a novel prognostic marker in patients with heart failure. However, the relation between RDW and echocardiographic parameters in acute heart failure (AHF) has not been studied. METHODS AND RESULTS: We analyzed laboratory findings including RDW, N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiographic parameters in 100 patients with AHF. The mean RDW was 14.2 +/- 2.0% and median NT proBNP was 5183 pg/mL. The mean left ventricular ejection fraction was 33.1 +/- 14.5% and early mitral inflow velocity to early diastolic mitral annular velocity (E/E'), was 21.2 +/- 9.4. When the RDW was considered in tertile categories, the highest tertile group (> 14.5%) had higher E/E' (P < .001) and higher NT-proBNP (P = .02) than the lowest tertile group (< 13.2%). In multiple linear regression analysis, RDW was independently correlated with E/E' even after adjustment of other risk factors (beta-coefficient 0.431, P = .001). The optimal cutoff value of RDW for predicting E/E' > 15, suggesting elevated left ventricular filling pressure (LVFP) was 13.45% (area under the curve 0.633, P < .05). An additive power of RDW with NT-proBNP for predicting E/E' > 15 was found in logistic regression analysis (P = .038). CONCLUSIONS: We found a novel relation between higher levels of RDW and elevated E/E' in patients with AHF. This novel finding raises the possibility that a simple marker, RDW may be associated with elevated LVFP in patients with AHF. PMID- 19643362 TI - Heart failure self-care in developed and developing countries. AB - BACKGROUND: Heart failure (HF) self-care is poor in developed countries like the United States, but little is known about self-care in developing countries. METHODS AND RESULTS: A total of 2082 adults from 2 developed (United States and Australia) and 2 developing countries (Thailand and Mexico) were studied in a descriptive, comparative study. Self-care was measured using the Self-Care of HF Index, which provided scores on self-care maintenance, management, and confidence. Data were analyzed using regression analysis after demographic (age, gender, education), clinical (functional status, experience with the diagnosis, comorbid conditions), and setting of enrollment (hospital or clinic) differences were controlled. When adequate self-care was defined as a standardized score >or=70%, self-care was inadequate in most scales in most groups. Self-care maintenance was highest in the Australian sample and lowest in the Thai sample (P < .001). Self-care management was highest in the US sample and lowest in the Thai sample (P < .001). Self-care confidence was highest in the Mexican sample and lowest in the Thai sample (P < .001). Determinants differed for the three types of self-care (eg, experience with HF was associated only with self-care maintenance). CONCLUSION: Interventions aimed at improving self-care are greatly needed in both the developed and the developing countries studied. PMID- 19643364 TI - Acute left ventricular unloading in dogs with chronic heart failure: continuous aortic flow augmentation versus intra-aortic balloon pumping. AB - BACKGROUND: Continuous aortic flow augmentation (CAFA) therapy with the Cancion System (Orqis Medical, Inc) was shown to effectively unload the left ventricle in dogs with chronic heart failure (HF). This study compared the extent of acute left ventricular (LV) unloading elicited by CAFA to that elicited by intra-aortic balloon counterpulsation (IABP) in normotensive dogs with coronary microembolization-induced HF. METHODS AND RESULTS: Seven HF dogs were studied with both CAFA and IABP in random order and 1 week apart. In both instances, active therapy was maintained for 4 hours. The Cancion system was positioned using a dual femoral approach configuration with a constant pump flow of 250 mL/min. In all dogs and with both devices, LV end-diastolic pressure (EDP), LV end-systolic volume (ESV), and LV ejection fraction (EF) were measured at baseline and at 2 and 4 hours after instituting CAFA or IABP. Plasma samples obtained at the end of 4 hours of therapy were used to measure a host of circulating biomarkers that included neurohormones, cytokines, and A-type and B type natriuretic peptides. IABP had no significant effects on LVEDP, LVESV, and LVEF. In contrast, CAFA significantly decreased LVEDP and LVESV and increased LVEF. Compared with IABP, CAFA was accompanied by significant improvements in circulating levels of neurohormones, cytokines, and natriuretic peptides. CONCLUSIONS: The results indicate that CAFA is more effective than IABP in achieving acute global LV unloading in dogs with chronic HF not complicated by ongoing myocardial ischemia or cardiogenic shock. PMID- 19643366 TI - Left ventricle radio-frequency ablation in the rat: a new model of heart failure due to myocardial infarction homogeneous in size and low in mortality. AB - BACKGROUND: The purpose of the current study was to create a model of myocardial infarction (MI) that is homogeneous in size with a low immediate (24 hours) mortality. METHODS AND RESULTS: Male and female rats (n = 256) underwent left ventricle (LV) ablation (Ab) by a radiofrequency current (1000 kHz; 12 watts for 12 seconds) to promote a MI. A transmural MI occurred in all rats. Post-Ab complex arrhythmias were frequent (atrioventricular block, ventricular tachycardia, and fibrillation), which rapidly and spontaneously reverted to sinus rhythm. Among 66 male rats, immediate mortality occurred in 7.5%. Small MI size dispersion was characterized by smaller variability following Ab (x +/- SD: 45 +/ 8%) when compared with coronary occlusion (Oc; 40 +/- 19%). The histopathologic evaluations identified lesions similar to those which occurred following Oc, with scarring complete at 4 weeks. The hemodynamic and Doppler echocardiograms showed comparable increases in LV dimension, end-diastolic pressure, and pulmonary water content 1 and 4 weeks post-MI. Papillary muscle mechanics 6 weeks post-MI had matched inotropic and lusitropic dysfunction. CONCLUSIONS: LV Ab gave rise to a MI within a narrow size limit and with a low immediate mortality. LV Ab resulted in histopathologic evolution, ventricular dilation, and dysfunction, impairment in myocardial mechanics, and congestive outcome that reproduced a MI from Oc. PMID- 19643367 TI - Decreased immune responses to influenza vaccination in patients with heart failure. PMID- 19643369 TI - Atorvastatin modulates Th1/Th2 response in patients with chronic heart failure. PMID- 19643365 TI - Cardiac cell-specific apoptotic and cytokine responses to reovirus infection: determinants of myocarditic phenotype. AB - BACKGROUND: The pathophysiologic mechanisms underlying viral myocarditis are not well defined. As a result, effective treatments do not exist and viral myocarditis remains a potentially lethal infection of the heart. METHODS AND RESULTS: We used cultured rat cardiac myocytes and fibroblasts to investigate apoptosis and cytokine production in response to infection by myocarditic vs. non myocarditic strains of reovirus. Myocarditic reovirus strain 8B and non myocarditic strain DB188 replicate comparably in each cardiac cell type. However, strain 8B and related myocarditic reoviruses preferentially increase apoptosis of myocytes relative to fibroblasts, whereas DB188 and nonmyocarditic strains preferentially increase fibroblast apoptosis. Infection of cardiac fibroblasts with the nonmyocarditic strain DB188 elicits substantial increases in a panel of cytokines compared to fibroblasts infected with strain 8B or mock-infected controls. Analysis of culture supernatants using cytometric bead arrays revealed that DB188 enhanced release of interleukin (IL)-1beta, IL-4, IL-6, IL-10, IL 12(p70), GRO-KC, tumor necrosis factor-alpha, and MCP-1 relative to 8B or mock infected controls (all P < .05). CONCLUSION: We hypothesize that differential cytokine production and cell-specific apoptosis are important determinants of myocarditic potential of reoviral strains. Therapies that target the beneficial effects of cytokines in limiting cytopathic damage may offer an effective and novel treatment approach to viral myocarditis. PMID- 19643370 TI - Anaerobes. PMID- 19643371 TI - Post-traumatic carotid-jugular arterio-venous fistula. PMID- 19643372 TI - Thoracic aortic aneurysm in the presence of mediastinal and retroperitoneal fibrosis. AB - Inflammatory aneurysms of thoracic aorta are rare. Of all the aneurysms, only 5 10% are inflammatory in nature and are almost exclusively confined to the infrarenal segment of the aorta. We hereby present a patient with a large inflammatory aneurysm involving the thoracic aorta in association with mediastinal fibrosis and idiopathic retroperitoneal fibrosis. PMID- 19643373 TI - Point: why choose pulsed-dose-rate brachytherapy for treating gynecologic cancers? PMID- 19643374 TI - Counterpoint: the dose rate argument--Does size matter after all? PMID- 19643375 TI - Rebuttal to Drs. Stewart, Devlin, and Mutyala. PMID- 19643376 TI - Rebuttal to Drs. Davidson, Hendry, and West: once burned, twice shy? PMID- 19643377 TI - Relationships between hospitals and radiologists. PMID- 19643378 TI - Demonstrating the value of imaging to patients' health. PMID- 19643379 TI - On the logistics of interpretive radiology reporting: moving beyond procrustes. PMID- 19643380 TI - Comparative effectiveness research. PMID- 19643381 TI - Objective quality metrics and personal dashboards for quality improvement. PMID- 19643382 TI - ACR Appropriateness Criteria on developmental dysplasia of the hip--child. AB - Developmental dysplasia of the hip (DDH) affects 1.5 of every 1,000 caucasian Americans and less frequently affects African Americans. Developmental dysplasia of the hip comprises a spectrum of abnormalities, ranging from laxity of the joint and mild subluxation to fixed dislocation. Early diagnosis of DDH usually leads to low-risk treatment with a harness. Late diagnosis of DDH in children may lead to increased surgical intervention and complications. Late diagnosis of DDH in adults can result in debilitating end-stage degenerative hip joint disease. Screening decreases the incidence of late diagnosis of DDH. Clinical evaluation for DDH should be performed periodically at each well-baby visit until the age of 12 months. There is no consensus on imaging screening for DDH. Consideration for screening with ultrasound is balanced between the benefits of early detection of DDH and the increased treatment and cost factors. In addition, randomized trials evaluating primary ultrasound screening did not find significant decrease in late diagnosis of DDH. In the United States, hip ultrasound is selectively performed in infants with risk factors, such as family history of DDH, breech presentation, and inconclusive findings on physical examination. Ultrasound for DDH should be performed after 2 weeks of age because laxity is common after birth and often resolves itself. A pelvic radiograph can optimally be performed after the age of 4 months, when most infants will have ossification centers of the femoral heads. PMID- 19643383 TI - Quantifying radiation safety and quality in medical imaging, part 1: creating the infrastructure. AB - An integral part of cost-benefit analysis within medicine is the comparative assessment of the clinical gains introduced by a service or application compared with the patient costs, which can be measured in economic or clinical terms. When analyzing medical imaging, a number of factors must be included, the most important of which include issues pertaining to patient safety, image quality, and clinical outcomes. Although ionizing radiation has long been recognized as a potential carcinogen capable of introducing harm to patients, the long-term derived benefits have been accepted because of the diagnostic and therapeutic benefits derived from its use. With the increased utilization of high-dose ionizing radiation examinations (such as multidetector computed tomography), it is essential that the medical community create data-driven methodologies to quantify risk in objective terms, develop community-wide radiation standards and "best practice" guidelines (evidence-based medicine), develop new technologies and applications to proactively minimize radiation dose while maintaining quality, and create accountability measures for all pertinent stakeholders. PMID- 19643384 TI - Enhancing patient safety: standardization of CT contrast media practices. AB - Large health care systems with varied hospital cultures, environments, and practices are continually challenged to provide safer and higher quality patient care. The authors describe their experience implementing uniform procedures for computed tomographic contrast media administration and the impact that standardization of these practices had on patient safety at a large integrated health care system. PMID- 19643385 TI - Measuring the quality-of-life effects of diagnostic and screening tests. AB - Health-related quality of life (HRQL) is a central concept for understanding the outcomes of medical care. When used in cost-effectiveness analysis, HRQL is typically measured for conditions persisting over long time frames (years), and quality-adjusted life year (QALY) values are generated. Consequently, years are the basic unit of time for cost-effectiveness analysis results: dollars spent per QALY gained. However, shorter term components of health care may also affect HRQL, and there is increased interest in measuring and accounting for these events. In radiology, the short-term HRQL effects of screening and diagnostic testing may affect a test's cost-effectiveness, even though they may only last for days. The unique challenge in radiology HRQL assessment is to realistically tap into the testing and screening experience while remaining consistent with QALY theory. The authors review HRQL assessment and highlight methods developed to specifically address the short-term effects of radiologic screening and testing. PMID- 19643386 TI - Safe use of imaging contrast agents in children. AB - No imaging contrast agent is completely safe. There are opportunities for improving the safe use of contrast agents in children through a better understanding of many small issues related to contrast toxicity. Many of these opportunities are presented and discussed. PMID- 19643387 TI - High-fidelity medical simulation as an assessment tool for radiology residents' acute contrast reaction management skills. AB - PURPOSE: The aims of this study were to use medical simulation as an assessment tool for the evaluation of radiology residents' compliance with contrast reaction treatment protocols and to gauge their perceptions of the simulation experience. METHODS: A prospective, observational study of postgraduate year 2 and 3 radiology residents' management of simulated life-threatening contrast reactions was designed. After standard didactic teaching on departmental contrast reaction protocols, residents participated individually in high-fidelity medical simulations of acute contrast reactions. Residents' performance of predetermined critical actions was recorded. Presimulation and postsimulation multiple-choice testing evaluated residents' knowledge of departmental protocols. Each resident completed 5-point, Likert-type surveys assessing comfort level while managing contrast reactions and perceptions of the simulation experience. RESULTS: Residents performed a mean of 13 of 20 critical actions (range, 10-16). The average presimulation multiple-choice testing score was 56%, whereas the average postsimulation score was 92% (P = .0003). Subjects' average ratings of comfort level in managing in-hospital contrast reactions before and after study intervention were 3.47 and 4.07, respectively (P = .03). Average ratings for comfort level in the outpatient setting were 3.08 before and 3.69 after the study (P = .69). All residents strongly agreed that the simulation was a valuable educational experience, while 85% strongly agreed that it improved their skills in managing acute contrast reactions. CONCLUSION: Standard didactic instruction may provide insufficient training and reinforcement of acute contrast reaction management skills. Medical simulation may provide a valuable means of assessing residents' skills and comfort levels in managing severe contrast reactions. PMID- 19643388 TI - New rules for mobile diagnostic test providers. PMID- 19643389 TI - Artifacts in cardiac computed tomographic images. PMID- 19643390 TI - Board examination without representation: residents and the ABR. PMID- 19643391 TI - Byrl R. Kirklin. PMID- 19643393 TI - Incidentalomas on CT colonography: do not make a mountain out of a molehill. PMID- 19643394 TI - Working conditions at recycling centres in Sweden--physical and psychosocial work environment. AB - The number of jobs at recycling centres are increasing, at the same time as there are indications of work environment problems. The aim of this paper was to investigate physical and psychosocial working conditions for employees at recycling centres in Sweden, to describe how they were perceived, to compare differences between subgroups, and further to identify proposals for improvement. Employees at 42 recycling centres (n=122) responded a postal questionnaire. Of these 32 employees from 16 recycling centres were interviewed, as also their employer (n=16). The work at recycling centres was reported to be a meaningful service job comprising many social interactions with users, but also substantial physical strain. There was a high frequency of injuries and minor injuries. Several risks were identified. There is a need for several preventive actions, e.g. better planning when building recycling centres, including better machines and equipment and more training, especially in handling hazardous waste. PMID- 19643396 TI - Facile synthesis of N-glycosyl amides using a N-glycosyl-2,4 dinitrobenzenesulfonamide and thioacids. AB - N-Glucosyl-2,4-dinitrobenzenesulfonamide was prepared from N-acetyl-d-glucosamine and 2,4-dinitrobenzenesulfonyl chloride. Amidation of several thioacids using the N-glucosylsulfonamide donor proceeded smoothly to give the desired N glucosylamides in good to high yields. The amidation reactions were carried out at room temperature, under mild conditions, and were completed in a very short time. PMID- 19643397 TI - [The Hirsch's h-index: a new tool for measuring scientific production]. PMID- 19643395 TI - Balancing fidelity and adaptation in the dissemination of empirically-supported treatments: The promise of transdiagnostic interventions. AB - Assessing treatment fidelity is a core methodological consideration in the study of treatment outcome; it influences both the degree to which changes can be attributed to the intervention and the ability to replicate and disseminate the intervention. Efforts to increase access to evidence-based psychological treatments are receiving unprecedented support; but pressures exist to adapt treatments to service settings, running the risk of compromising fidelity. However, little evidence is available to inform the necessary conditions for the transportation of interventions to service provision settings, and the degree to which fidelity is even evaluated or emphasized in dissemination and implementation programs varies dramatically. Moreover, adaptation is associated with several benefits for dissemination efforts and may address relevant barriers to adoption. A particularly promising strategy for maximizing the benefits of both fidelity and adaptation is the use of transdiagnostic interventions. Such treatments allow for greater flexibility of the pacing and content of treatment, while still providing structure to facilitate testing and replication. Preliminary evidence supports the efficacy of this strategy, which may be particularly conducive to dissemination into service provision settings. At this time, further research is needed to evaluate the relationships among fidelity, adaptation, and outcome, and to determine the potential for transdiagnostic treatments to facilitate dissemination. PMID- 19643398 TI - A spreadsheet application for processing long-term EEG recordings. AB - This study develops a Windows application for processing huge tabular text files. The tool has been especially designed for handling EEG files. As a consequence, tables with more than 65,536 rows and 256 columns, which is a limitation found in Microsoft's Excel, can be loaded, visualized and processed with no more restrictions than the ones imposed by the memory of the operating system. Beyond tabular visualization, additional tools are available for chart customization and spreadsheet like cell processing commands. Additionally, commands are included for signal processing, cluster analysis and computationally taxing matrix algebra operations. PMID- 19643399 TI - A computational method for the semi-automated quantitative analysis of tympanic membrane perforations and tympanosclerosis. AB - Tympanic membrane pathological findings such as perforations and tympanosclerotic plaques (along with conductive hearing loss and purulent drainage) are the most typical trademarks of either active or burned-out chronic otitis media. These findings are normally evaluated by an expert using visual subjective analysis. In this work, we present a computational semi-automated method to quantify these pathologies. We also present a validation study of the method using a subset of 39 cases randomly extracted from a set of more than 2000 cases (perforations and tympanosclerosis) of the Hospital de Clinicas de Porto Alegre. The validation was performed using Ground Truth images, generated by experts, and has shown promising results. PMID- 19643401 TI - Etiology of recurrent pregnancy loss in women over the age of 35 years. AB - OBJECTIVE: To determine the rate of embryonic chromosomal abnormalities, thrombophilias, and uterine anomalies in women over the age of 35 years with recurrent pregnancy loss (RPL). DESIGN: Retrospective cohort study. SETTING: Academic reproductive endocrinology and infertility clinic. PATIENT(S): Women>or=35 years old with >or=3 first trimester miscarriages. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Age, number of prior losses, cytogenetic testing of the products of conception (POC), uterine cavity evaluation, parental karyotype, TSH, and antiphospholipd antibody (APA) and thrombophilia testing. Aneuploidy in the POC in women with RPL was compared with sporadic miscarriages (or=35 years. RESULT(S): Among 43 RPL patients, there were 50 miscarriages in which cytogenetic analysis was performed. In the RPL group, the incidence of chromosomal abnormalities in the POC was 78% (39 out of 50) compared with a 70% incidence (98 out of 140) in the sporadic losses. Thrombophilia results in the RPL patients were normal in 38 patients, four patients had APA syndrome, and one had protein C deficiency. Forty out of 43 had normal uterine cavities. Both TSH and parental karyotypes were normal in all of the patients tested. When the evaluation of RPL included karyotype of the POC, only 18% remained without explanation. However, without fetal cytogenetics, 80% of miscarriages would have been unexplained. CONCLUSION(S): In older patients with RPL, fetal chromosomal abnormalities are responsible for the majority of miscarriages. Other causes were present in only 20% of cases. PMID- 19643400 TI - Risk to consumers from mercury in bluefish (Pomatomus saltatrix) from New Jersey: Size, season and geographical effects. AB - Relatively little attention has been devoted to the risks from mercury in saltwater fish, that were caught by recreational fisherfolk. Although the US Food and Drug Administration has issued advisories based on mercury for four saltwater species or groups of fish, there are few data on how mercury levels vary by size, season, or location. This paper examines total mercury levels in muscle of bluefish (Pomatomus saltatrix) collected from coastal New Jersey, mainly by recreational fishermen. Of primary interest was whether there were differences in mercury levels as a function of location, weight and length of the fish, and season, and in what risk mercury posed to the food chain, including people. Selenium was also measured because of its reported protective effects against mercury. Mercury levels averaged 0.35+/-0.02 (mean and standard error)ppm, and selenium levels averaged 0.37+/-0.01ppm (N=206). In this study, 41% of the fish had mercury levels above 0.3ppm, 20% had levels above 0.5ppm, and 4% had levels above 1ppm. Size was highly correlated with mercury levels, but not with selenium. While selenium levels did not vary at all with season, mercury levels decreased significantly. This relationship was not due to differences in the size of fish, since the fish collected in the summer were the smallest, but had intermediate mercury levels. Mercury levels declined from early June until November, particularly for the smaller-sized fish. While there were significant locational differences in mercury levels (but not selenium), these differences could be a result of size. The levels of mercury in bluefish are not sufficiently high to cause problems for the bluefish themselves, based on known adverse health effects levels, but are high enough to cause potential adverse health effects in sensitive birds and mammals that eat them, and to provide a potential health risk to humans who consume them. Fish larger than 50cm fork length averaged levels above 0.3ppm, suggesting that eating them should be avoided by pregnant women, children, and others who are at risk. PMID- 19643402 TI - Simvastatin inhibits the proliferation and the contractility of human endometriotic stromal cells: a promising agent for the treatment of endometriosis. AB - Simvastatin significantly inhibited the proliferation of endometriotic stromal cells, attenuated the collagen gel contraction mediated by these cells, and suppressed endometriotic stromal cell attachment to collagen fibers. Simvastatin is considered to be a promising agent for the treatment of endometriosis associated fibrosis, which is among the major pathologies caused by endometriosis. PMID- 19643403 TI - Understanding adenomyosis: a case control study. AB - OBJECTIVE: To elucidate the clinical profile of adenomyosis by comparison with uterine leiomyomas. DESIGN: Retrospective case-control study. SETTING: Academic medical center. PATIENT(S): The study comprised 76 women undergoing hysterectomy with adenomyosis and 152 women with uterine leiomyomas but no adenomyosis. INTERVENTION(S): Retrospective medical record review of hospital and ambulatory records. MAIN OUTCOME MEASURE(S): Comparison of women undergoing hysterectomy with a sole pathologic finding of adenomyosis and women with leiomyomas alone. RESULT(S): Adenomyosis was independently associated with younger age (41.1 years vs. 44.3 years), history of depression (57.1% vs. 24.7%), dysmenorrhea (65.7% vs. 42.3%), and pelvic pain (52.9% vs. 21.1%) in a multivariable unconditional logistic regression analysis compared with women with leiomyomas, where women from both groups had gynecologic symptoms. Furthermore, in a second multivariate model where all subjects had uteri weighing>150 g, women with adenomyosis were more likely to have a history of depression (52.6% vs. 22.2%) and endometriosis (26.3% vs. 2.8%) compared with women with leiomyomas. CONCLUSION(S): Women undergoing hysterectomy with a histologic diagnosis of adenomyosis have a distinct symptomatology and medical history compared with women with leiomyomas. Better understanding of this disease is required to improve diagnosis and management. PMID- 19643404 TI - Ectopic ovary autotransplanted over rectosigmoid colon: a case report. AB - OBJECTIVE: To report a case of an alive ectopic ovary over rectosigmoid colon serosa that was removed by laparoscopy. DESIGN: Case report. SETTING: Department of Obstetrics and Gynecology. PATIENT(S): A 30-year-old nulliparous woman. INTERVENTION(S): Ultrasonography, laparoscopy, and pathologic assessment. MAIN OUTCOME MEASURE(S): Alive and functional ectopic ovarian tissue in the cul-de-sac over rectosigmoid colon serosa. RESULT(S): At pathologic assessment, an alive ectopic ovary with focal infarct areas was determined. CONCLUSION(S): The treatment should be excision of the mass. However, in asymptomatic and nulliparous women who have future fertility desire, protecting the ectopic ovary to not decrease the ovarian reserve might be a beneficial option. PMID- 19643405 TI - The molecular signature of endometriosis-associated endometrioid ovarian cancer differs significantly from endometriosis-independent endometrioid ovarian cancer. AB - OBJECTIVE: To determine whether endometriosis-associated endometrioid cancer (EAOC) is a specific entity compared with endometrioid cancer not associated with endometriosis (OC). DESIGN: Case-control study. SETTING: University hospital research laboratory. PATIENT(S): Seven patients with endometriosis-associated ovarian cancer EAOC and five patients each with OC, ovarian endometriosis, and benign ovaries. INTERVENTION(S): Ovarian tissue samples were collected from surgical procedures. MAIN OUTCOME MEASURE(S): We hybridized cRNA samples to the Affymetrix HG-U133A microarray chip. Representative genes were validated by real time polymerase chain reaction. RESULT(S): We identified two main groups of genes: The first group contained the genes SICA2, CCL14, and TDGF1. These genes were equally regulated in endometriosis and EAOC but not in OC and benign ovaries. The second group contained the genes StAR, SPINT1, Keratin 8, FoxM1B, FOLR1, CRABP1, and Claudin 7. They were equally regulated in EAOC and OC but not in ovarian endometriosis and benign ovaries. CONCLUSION(S): That the first group is composed of the cytokines SICA2 and CCL14 and the growth factor TDGF1 indicates that the regulation of the autoimmune system and of inflammatory cytokines may be very important in the etiology of endometriosis and EAOC. That the second group is composed of genes that play a central role in cell-cell interaction, differentiation, and cell proliferation indicates that they may be important in the development of ovarian cancer in women with endometriosis. PMID- 19643406 TI - Teleteaching endoscopy: the feasibility of real-time, uncompressed video transmission by using advanced-network technologies. AB - BACKGROUND: Teleteaching of endoscopy has been limited by the exorbitant cost and time inherent in high-quality digital endoscopy video transmission. The Digital Video Transport System (DVTS) transmitted over advanced networks, such as Internet2 and the Asia-Pacific Advanced Network (APAN), provides a unique infrastructure for sharing uncompressed digital videos of endoscopy. This may allow high-quality, real-time, international training of diagnostic and therapeutic endoscopy techniques at a low cost. OBJECTIVE: To test the proof of concept of long-distance teaching through live, interactive, high-resolution video transmission by using advanced networks and the DVTS. We used teleteaching of image-enhanced endoscopy techniques as a model. DESIGN: Prospective multicenter pilot study. SETTING AND PARTICIPANTS: Trainees, faculty, and staff at 3 international endoscopy units. INTERVENTION: An image-enhanced endoscopy video lecture with advanced-network technologies. MAIN OUTCOME MEASUREMENTS: We compared image-based prelecture and postlecture test scores and secondarily assessed technical feasibility and quality. RESULTS: The DVTS transmitted over advanced networks successfully transmitted uncompressed, high-resolution, digital lectures with endoscopic video (digital video format 720 x 480 pixels). Postsession scores improved. Participants highly rated the technical and informational quality. The majority reported a definite interest in participating in future sessions, with a mean rating (out of 5 [scale 1-5]) of 4.7 +/- 0.5. LIMITATIONS: Pilot study with a limited number of participants and sessions. CONCLUSION: The DVTS transmitted over advanced networks such as Internet2 and APAN can provide the infrastructure for transmission of high-resolution, uncompressed video endoscopy for the purpose of teleteaching endoscopy. PMID- 19643408 TI - Bias in experimental nursing research: Strategies to improve the quality and explanatory power of nursing science. AB - In a guest editorial in this journal, Rahm Hallberg [Rahm Hallberg, I., 2006. Challenges for future nursing research: providing evidence for health-care practice. International Journal of Nursing Studies 43, 923-927] called for research which has greater explanatory power to determine the effectiveness of nursing interventions. In this paper we critique the suggestion made by the evidence-based nursing movement that randomisation per se is the principal route to better quality nursing research. In contrast, we evaluate the new CONSORT criteria for pragmatic RCTs, which assess the quality of strategies to reduce selection, performance, attrition and detection biases, allowing many different types of comparative studies to be covered by application of the checklist. We propose that randomisation alone is a necessary but insufficient strategy and that nursing researchers rise to Rahm Hallberg's challenge by adopting the extended criteria to assist in the critical appraisal, design and reporting of all experimental research in nursing. PMID- 19643407 TI - Pharmacotherapy plus endoscopic intervention is more effective than pharmacotherapy or endoscopy alone in the secondary prevention of esophageal variceal bleeding: a meta-analysis of randomized, controlled trials. AB - BACKGROUND: Previous clinical trials on the treatment of esophageal variceal bleeding yielded mixed results regarding the efficacy of endoscopic procedures compared with pharmacotherapy only. OBJECTIVE: To compare the efficacy of endoscopic procedures with that of pharmacotherapy in the prevention of mortality and rebleeding. DESIGN AND SETTING: A systematic literature review was performed to identify randomized, controlled trials of the efficacy of pharmacotherapy and endoscopic therapy. A meta-analysis was performed by using the Comprehensive MetaAnalysis software package. A 2-sided alpha error <.05 was considered statistically significant (P < .05). PATIENTS: Twenty-five clinical trials with a total of 2159 patients were eligible for meta-analysis. OUTCOME MEASUREMENTS: Relative risk (RR) with 95% confidence interval (CI) was computed for all-cause mortality, mortality from rebleeding, all-cause rebleeding, and rebleeding caused by varices. RESULTS: Pharmacotherapy was as effective as endoscopic procedures in preventing rebleeding (RR 1.067; 95% CI, 0.865-1.316; P = .546), variceal rebleeding (RR 1.143; 95% CI, 0.791-1.651; P = .476), all-cause mortality (RR 0.997; 95% CI, 0.827-1.202, P = .978), and mortality from rebleeding (RR 1.171; 95% CI, 0.816-1.679; P = .39). Pharmacotherapy combined with endoscopic procedures did not reduce all-cause mortality (RR 0.787; 95% CI, 0.587-1.054; P = .108) or mortality caused by rebleeding (RR 0.786; 95% CI, 0.445-1.387; P = .405) compared with endoscopic procedures. However, combination therapy (endoscopic procedure plus pharmacotherapy) significantly reduced the incidence of all rebleeding (RR 0.623; 95% CI, 0.523-0.741; P < .001) and variceal rebleeding (RR 0.601; 95% CI, 0.440-0.820; P < .001). LIMITATIONS: Heterogeneity of patient population and different treatment protocols may have affected our meta-analysis. CONCLUSION: Pharmacotherapy may be as effective as endoscopic therapy in reducing rebleeding rates and all-cause mortality. Pharmacotherapy plus endoscopic intervention is more effective than endoscopic intervention alone. PMID- 19643409 TI - Cascade iatrogenesis: factors leading to the development of adverse events in hospitalized older adults. AB - Older adults are at particular risk for injuries associated with hospitalization and the rate of adverse events increases significantly with age. The purpose of this paper is to review factors associated with the development of adverse events in hospitalized older adults, especially those factors that contribute to cascade iatrogenesis. Cascade iatrogenesis is the serial development of multiple medical complications that can be set in motion by a seemingly innocuous first event [Rothschild, J.M., Bates, D.W., Leape, L.L., 2000. Preventable medical injuries in older patients. Archieves of Internal Medicine 160 (October), 2717-2728]. Research has examined how patient characteristics may lead to cascade iatrogenesis, but existing conceptual models and research have not considered the role of nursing care. Using the outcome postoperative respiratory failure as an example, we expand on existing knowledge about factors associated with older adults' risk for developing this complication by presenting a conceptual model of events that may trigger the initial cascade and the nursing care variables that may prevent or mitigate these risks. We believe that this model will help guide research in this area and enable clinicians to identify systemic failures and develop targeted interventions to prevent their occurrence. PMID- 19643410 TI - [Surgeons can learn from pilots: human factors in surgery]. AB - Human factors (HF) study is mandatory to get air transport pilot licences. In aviation, crew resource management (CRM) and declaration of adverse events (feedback) result in improving of air safety. Air missions and surgical procedures have similarities. Bridging the gap is tempting, despite severe warnings against simplistic adaptation. Putting HF theory into surgical practice: how to? Educational principles derived from CRM improve professional attitudes of a team. We propose to translate concepts of CRM to clinical teams. CRM training applying in surgery could allow the work environment to be restructured to reduce human error. Feedback: in aviation, the Bureau of Flight Safety deals with investigations for air events. Pilots, air traffic controllers can anonymously declare nuisance, resulting in a feedback for the whole air force. Adverse events are analysed. Usually, multilevel problems are found, rather than the only responsibility of the last operator. Understanding the mechanisms of human failure finally improves safety. In surgery, CRM and feedback would probably be helpful. Anyway, it requires time; people have to change their mind. Nevertheless people such as fighter pilots, who were very unwilling at the beginning, now consider HF as a cornerstone for security. But it is difficult to estimate the extent of HF-related morbidity and mortality. We propose as a first step to consider CRM and feedback in surgical procedure. HF deals with the mechanisms of human errors and the ways to improve safety and probably improve the surgical team's efficacy. PMID- 19643411 TI - [Intragastric migration of adjustable gastroplasty bands]. AB - BACKGROUND: The incidence of morbid obesity is increasing in France; adjustable gastric banding has become the most common surgical treatment. PATIENTS: We report seven cases of patients who presented with gastric erosion as a complication of gastric banding; this occurred at a mean interval of 4 years following the initial bariatric procedure. RESULTS: In six cases, repair was performed laparoscopically; one case required conversion to an open laparotomy approach. There was no mortality but morbidity occurred in 57% of cases: pleural effusion (two) and wound abscess (two). CONCLUSION: Gastric erosion and migration of adjustable gastric rings can occur at a long interval after laparoscopic gastric banding. Long-term follow-up is necessary in all such patients. PMID- 19643412 TI - Atherogenic lipoprotein phenotype and LDL size and subclasses in drug-naive patients with early rheumatoid arthritis. AB - OBJECTIVE: Subjects with rheumatoid arthritis (RA) have increased cardiovascular risk and may show atherogenic forms of dyslipidemia. The present study investigated whether patients with early RA, beyond alterations in plasma lipids, also show lower LDL size and altered LDL subclass distribution. DESIGN AND METHODS: We identified 25 subjects with RA (47+/-8 years, body mass index (BMI) 25+/-4kg/m(2)) by the American College of Rheumatology diagnostic criteria, with a disease durations <1 year and no prior treatment against it. In patients and 22 healthy subjects matched for age and BMI (controls) we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis. RESULTS: As compared to controls RA patients had higher plasma triglycerides (1.8+/-0.5 vs. 1.0+/ 0.5mmol/L, p<0.0001) and lower HDL-cholesterol concentrations (1.2+/-0.2 vs. 1.4+/-0.2mmol/L, p=0.0027), while total- and LDL-cholesterol concentrations were similar. LDL particle size was lower in RA patients than controls (264+/-7 vs. 281+/-9A, p<0.0001), due to less LDL-I (31+/-6 vs. 38+/-7%, p=0.0004) and LDL-IIA (14+/-3 vs. 16+/-3%, p=0.0182), and more LDL-IIIB (7+/-1 vs. 5+/-1%), -IVA (11+/ 2 vs. 8+/-2%) and -IVB particles (12+/-2 vs. 9+/-2%,) (p<0.0001 for all). Further, about 1/3 of patients showed the complete "atherogenic-lipoprotein phenotype" (e.g. the concomitant presence of high triglycerides, low HDL cholesterol and elevated small, dense LDL). CONCLUSIONS: Beyond plasma lipids, increased levels of small, dense LDL seems to be common in drug-naive patients with early RA. Yet, whether these findings affect the atherogenic process and the clinical endpoints in these subjects remains to be determined by future prospective studies. PMID- 19643413 TI - Comments about the article titled: Validation of a musculoskeletal model of wheelchair propulsion and its application to minimizing shoulder joint forces, written by S.R. Dubowsky, J. Rasmussen, S.A. Sisto, N.A. Langrana (41(2008) 2981 2988). PMID- 19643414 TI - ACL/MCL transection affects knee ligament insertion distance of healing and intact ligaments during gait in the Ovine model. AB - The objective of this study was to assess the impact of combined transection of the anterior cruciate and medial collateral ligaments on the intact and healing ligaments in the ovine stifle joint. In vivo 3D stifle joint kinematics were measured in eight sheep during treadmill walking (accuracy: 0.4+/-0.4mm, 0.4+/ 0.4 degrees ). Kinematics were measured with the joint intact and at 2, 4, 8, 12, 16 and 20 weeks after either surgical ligament transection (n=5) or sham surgery without transection (n=3). After sacrifice at 20 weeks, the 3D subject-specific bone and ligament geometry were digitized, and the 3D distances between insertions (DBI) of ligaments during the dynamic in vivo motion were calculated. Anterior cruciate ligament/medial collateral ligament (ACL/MCL) transection resulted in changes in the DBI of not only the transected ACL, but also the intact lateral collateral ligament (LCL) and posterior cruciate ligament (PCL), while the DBI of the transected MCL was not significantly changed. Increases in the maximal ACL DBI (2 week: +4.2mm, 20 week: +5.7mm) caused increases in the range of ACL DBI (2 week: 3.6mm, 20 week: +3.8mm) and the ACL apparent strain (2 week: +18.9%, 20 week: +24.0%). Decreases in the minimal PCL DBI (2 week: -3.2mm, 20 week: -4.3mm) resulted in increases in the range of PCL DBI (2 week: +2.7mm, 20 week: +3.2mm). Decreases in the maximal LCL DBI (2 week: -1.0mm, 20 week: 2.0mm) caused decreased LCL apparent strain (2 week: -3.4%, 20 week: -6.9%). Changes in the mechanical environment of these ligaments may play a significant role in the biological changes observed in these ligaments. PMID- 19643415 TI - A nonlinear biphasic model of flow-controlled infusion in brain: fluid transport and tissue deformation analyses. AB - A biphasic nonlinear mathematical model is proposed for the concomitant fluid transport and tissue deformation that occurs during constant flow rate infusions into brain tissue. The model takes into account material and geometrical nonlinearities, a hydraulic conductivity dependent on strain, and nonlinear boundary conditions at the infusion cavity. The biphasic equations were implemented in a custom written code assuming spherical symmetry and using an updated Lagrangian finite element algorithm. Results of the model showed that both, geometric and material nonlinearities play an important role in the physics of infusions, yielding important differences from infinitesimal analyses. Geometrical nonlinearities were mainly due to the significant enlargement of the infusion cavity, while variations of the parameters that describe the degree of nonlinearity of the stress-strain curve yielded significant differences in all distributions. For example, a parameter set showing stiffening under tension yielded maximum values of radial displacement and porosity not localized at the infusion cavity. On the other hand, a parameter set showing softening under tension yielded a slight decrease in the fluid velocity for a three-fold increase in the flow rate, which can be explained by the substantial increase of the infusion cavity, not considered in linear analyses. This study strongly suggests that significant enlargement of the infusion cavity is a real phenomenon during infusions that may produce collateral damage to brain tissue. Our results indicate that more experimental tests have to be undertaken in order to determine material nonlinearities of brain tissue over a range of strains. With better understanding of these nonlinear effects, clinicians may be able to develop protocols that can minimize the damage to surrounding tissue. PMID- 19643416 TI - Fixation compliance in a mouse osteotomy model induces two different processes of bone healing but does not lead to delayed union. AB - Delayed unions are a problematic complication of fracture healing whose pathophysiology is not well understood. Advanced molecular biology methods available with mice would be advantageous for investigation. In humans, decreased fixation rigidity and poor reduction are generally associated with delayed unions. In this study, these two factors were combined to observe their effect on bone healing in mice. Two plates with locking screws, one with 14 the bending stiffness of the other, were used to stabilize a 0.45mm gap osteotomy. muCT, radiographs, 4pt-bending tests and histological analysis demonstrated that the different plate types led to two different healing pathways. The less flexible bridging plate induced only intramembranous ossification whereas the more flexible bridging plate induced a mixture of endochondral and intramembranous ossification. However, the different plates led to a delay in healing of only 3-5 days in the period between 14 and 21 post-operative days. In mice, considerable fixation flexibility is necessary to induce secondary bone healing similar to that which occurs in humans, but this was not sufficient to induce a substantial delay in bone healing as would be expected in humans. PMID- 19643417 TI - The fracture toughness of cancellous bone. AB - The mechanical capacity and integrity of cancellous bone is crucial in osteoporosis, a condition which is set to become more prevalent with increasing lifespan and population sizes. The fracture toughness (FT) of cancellous bone has never been examined before and the conditions associated with the growth of a major crack through the lattice of cancellous bone, a cellular solid, may improve our understanding for structural integrity of this material. The aim of this study is to provide (i) basic data on cancellous bone FT and (ii) the experimental support for the hypothesis of Gibson, L.J., Ashby, M.F. [1997a. Chapter 10: Wood. In: Cellular Solids: Structure and Properties, second ed. Cambridge University Press, pp. 387-428; Gibson, L.J., Ashby, M.F., 1997b. Chapter 11: Cancellous Bone. In: Cellular Solids: Structure and Properties, second ed. Cambridge University Press, pp. 429-52] that the FT of cancellous bone tissue is governed by the density of the tissue to a power function of between one and two. 294 SENB and 121 DC(T) specimen were manufactured from 45 human femoral heads, 37 osteoporotic and 8 osteoarthritic, as well as 19 equine thoracic vertebrae. The samples were manufactured in two groups: the first aligned with the trabecular structure (A( parallel)), the second orientated at 90 degrees to the main trabecular orientation (A( perpendicular)). The samples were tested in either tensile or bending mode to provide values of the stress intensity factor (K). The results which were obtained show a strong and significant link between the density of the cancellous bone tissue and that the critical stress intensity values are governed by the density of the tissue to a power function of between 1 and 2 (K(Q) vs. apparent density: A( perpendicular)=1.58, A( parallel)=1.6). Our results provide some fundamental values for the critical stress intensity factor for cancellous bone and also support the previous hypothesis as set by Gibson, L.J., Ashby, M.F., 1997a. Chapter 10: Wood. In: Cellular Solids: Structure and Properties, second ed. Cambridge University Press, pp. 387-428; Gibson, L.J., Ashby, M.F., (1997b). Chapter 11: Cancellous Bone. In: Cellular Solids: Structure and Properties, second ed. Cambridge University Press, pp. 429-52. PMID- 19643418 TI - In vivo measurement of shoulder joint loads during activities of daily living. AB - Until recently the contact loads acting in the glenohumeral joint have been calculated using musculoskeletal models or measured in vitro. Now, contact forces and moments are measured in vivo using telemeterized shoulder implants. Mean total contact forces from four patients during eight activities of daily living are reported here. Lifting a coffee pot (1.5kg) with straight arm caused an average force of 105.0%BW (%body weight) (range: 90-124.6%BW), while setting down the coffee pot in the same position led to higher forces of 122.9%BW on the average (105.3-153.4%BW). The highest joint contact forces were measured when the straight arm was abducted or elevated by 90 degrees or more, with a weight in the hand. Lifting up 2kg from a board up to head height caused a contact force of 98.3%BW (93-103.6%BW); again, setting it down on the board led to higher forces of 131.5%BW (118.8-144.1%BW). In contrast to previously calculated high loads, the contact force during passive holding of a 10kg weight laterally was only 12.3%BW (9.2-17.9%BW), but when lifting it up to belt height it increased to 91.5%BW (87-95%BW). The moments transferred inside the joint at our patients varied much more than did the forces both inter and intra-individually. Our data suggest that patients with shoulder problems or during the first post-operative weeks after shoulder fractures or joint replacements should avoid certain activities encountered during daily living e.g. lifting or holding a weight with an outstretched arm. Some energy-related optimization criteria used in the literature for analytical musculoskeletal shoulder models must now be reconsidered. PMID- 19643419 TI - 3D analysis from micro-MRI during in situ compression on cancellous bone. AB - A mini-compression jig was built to perform in situ tests on bovine trabecular bone monitored by micro-MRI. The MRI antenna provided an isotropic resolution of 78 microm that allows for a volume correlation method to be used. Three dimensional displacement fields are then evaluated within the bone sample during the compression test. The performances of the correlation method are evaluated and discussed to validate the technique on trabecular bone. By considering correlation residuals and estimates of acquisition noise, the measured results are shown to be trustworthy. By analyzing average strain levels for different interrogation volumes along the loading direction, it is shown that the sample size is less than that of a representative volume element. This study shows the feasibility of the 3D-displacement and strain field analyses from micro-MRI images. Other biological tissues could be considered in future work. PMID- 19643420 TI - Statistical osteoporosis models using composite finite elements: a parameter study. AB - Osteoporosis is a widely spread disease with severe consequences for patients and high costs for health care systems. The disease is characterised by a loss of bone mass which induces a loss of mechanical performance and structural integrity. It was found that transverse trabeculae are thinned and perforated while vertical trabeculae stay intact. For understanding these phenomena and the mechanisms leading to fractures of trabecular bone due to osteoporosis, numerous researchers employ micro-finite element models. To avoid disadvantages in setting up classical finite element models, composite finite elements (CFE) can be used. The aim of the study is to test the potential of CFE. For that, a parameter study on numerical lattice samples with statistically simulated, simplified osteoporosis is performed. These samples are subjected to compression and shear loading. Results show that the biggest drop of compressive stiffness is reached for transverse isotropic structures losing 32% of the trabeculae (minus 89.8% stiffness). The biggest drop in shear stiffness is found for an isotropic structure also losing 32% of the trabeculae (minus 67.3% stiffness). The study indicates that losing trabeculae leads to a worse drop of macroscopic stiffness than thinning of trabeculae. The results further demonstrate the advantages of CFEs for simulating micro-structured samples. PMID- 19643421 TI - The influence of footwear on foot motion during walking and running. AB - There are evidences to suggest that wearing footwear constrains the natural barefoot motion during locomotion. Unlike prior studies that deduced foot motions from shoe sole displacement parameters, the aim of this study was to examine the effect of footwear motion on forefoot to rearfoot relative motion during walking and running. The use of a multi-segment foot model allowed accurate both shoe sole and foot motions (barefoot and shod) to be quantified. Two pairs of identical sandals with different midsole hardness were used. Ten healthy male subjects walked and ran in each of the shod condition. The results showed that for barefoot locomotion there was more eversion of the forefoot and it occurred faster than for shod locomotion. In this later condition, the range of eversion was reduced by 20% and the rate of eversion in late stance by 60% in comparison to the barefoot condition. The sole constrained both the torsional (eversion/inversion) and adduction range of motion of the foot. Interestingly, during the push-off phase of barefoot locomotion the rate and direction of forefoot torsion varied between individuals. However, most subjects displayed a forefoot inversion direction of motion while shod. Therefore, this experiment showed that the shoes not only restricted the natural motion of the barefoot but also appeared to impose a specific foot motion pattern on individuals during the push-off phase. These findings have implications for the matching of footwear design characteristics to individual natural foot function. PMID- 19643422 TI - Ionic liquid-mediated bis[(3-methyldimethoxysilyl)propyl] polypropylene oxide based polar sol-gel coatings for capillary microextraction. AB - Two ionic liquids (IL), namely, 1-methyl-3-octylimidazolium chloride (MOIC) and trihexyltetradecylphosphonium tetrafluoroborate (TTPT) were used to prepare polar and nonpolar sol-gel coatings for capillary microextraction (CME). Bis[(3 methyldimethoxysilyl)propyl] polypropylene oxide (BMPO), containing sol-gel active terminal methoxysilyl groups and polar propylene oxide repeating units, was used to prepare polar sol-gel hybrid organic-inorganic coatings. Hydroxy terminated poly(dimethyl-co-diphenylsiloxane) was used as the sol-gel active organic component for nonpolar sol-gel hybrid coatings. Compared to a sol-gel BMPO coating prepared without IL, the sol-gel BMPO coatings prepared with the use of both of these ILs provided more efficient extraction as is evidenced by more pronounced GC peak areas. The MOIC-mediated sol-gel BMPO coating provided larger GC peak areas compared to the TTPT-mediated sol-gel BMPO coating. Scanning electron microscopy results suggested that MOIC provided a more porous morphology of the sol-gel BMPO extraction media compared to that prepared with TTPT. Thus, individual ILs can affect the porosity of sol-gel materials to different degrees. Overall, the sol-gel BMPO coating prepared with the ILs could extract nonpolar to polar analytes directly from aqueous samples. Detection limits were on the order of nanograms per liter (1.9-330.5 ng/L) depending on the analyte class. Furthermore, the MOIC-mediated sol-gel BMPO coating demonstrated high thermal stability (330 degrees C), solvent resistance, and fast extraction equilibrium (10-15 min) for polar and moderately polar analytes. PMID- 19643423 TI - Analysis of pesticide residues by fast gas chromatography in combination with negative chemical ionization mass spectrometry. AB - A combination of fast GC with narrow-bore column and bench top quadrupole mass spectrometer (MS) detector in negative chemical ionization (NCI) mode (with methane as reagent gas) is set up and utilized for the ultratrace analysis of 25 selected pesticides. The observed pesticides, belonging to the endocrine disrupting chemicals (EDCs), were from different chemical classes. A comparative study with electron impact (EI) ionization was also carried out (both techniques in selected ion monitoring (SIM) mode). The programmed temperature vaporizer (PTV) injector in solvent vent mode and narrow-bore column (15mx0.15mm I.D.x0.15microm film of 5% diphenyl 95% dimethylsiloxane stationary phase) were used for effective and fast separation. Heptachlor (HPT) as internal standard (I.S.) was applied for the comparison of results obtained from absolute and normalized peak areas. Non-fatty food matrices were investigated. Fruit (apple - matrix-matched standards; orange, strawberry, plum - real samples) and vegetable (lettuce - real sample) extracts were prepared by a quick and effective QuEChERS sample preparation technique. Very good results were obtained for the characterization of fast GC-NCI-MS method analysing EDCs pesticides. Analyte response was linear from 0.01 to 150microgkg(-1) with the R(2) values in the range from 0.9936 to 1.0000 (calculated from absolute peak areas) and from 0.9956 to 1.0000 (calculated from peak areas normalized to HPT). Instrument limits of detection (LODs) and quantification (LOQs) were found at pgmL(-1) level and for the majority of analytes were up to three orders of magnitude lower for NCI compared to EI mode. In both ionization modes, repeatability of measurements expressed as relative standard deviation (RSDs) was less than 10% which is in very good agreement with the criterion of European Union. PMID- 19643424 TI - Determination of linear aliphatic aldehydes in heavy metal containing waters by high-performance liquid chromatography using 2,4-dinitrophenylhydrazine derivatization. AB - A simple and sensitive method is described for the determination of picomolar amounts of C(1)-C(9) linear aliphatic aldehydes in waters containing heavy metal ions. In this method, aldehydes were first derivatized with 2,4 dinitrophenylhydrazine (DNPH) at optimized pH 1.8 for 30 min and analyzed by HPLC with UV detector at 365 nm. Factors affecting the derivatization reaction of aldehydes and DNPH were investigated. Cupric ion, an example of heavy metals, is a common oxidative reagent, which may oxidize DNPH and greatly interfere with the determination of aldehydes. EDTA was used to effectively mask the interferences by heavy metal ions. The method detection limits for direct injection of derivatized most aldehydes except formaldehyde were of the order of 7-28 nM. The detection limit can be further lowered by using off-line C(18) adsorption cartridge enrichment. The recoveries of C(1)-C(9) aldehydes were 93-115% with a relative standard deviation of 3.6-8.1% at the 0.1 microM level for aldehydes. The HPLC-DNPH method has been applied for determining aldehyde photoproducts from Cu(II)-amino acid complex systems. PMID- 19643426 TI - Determination of biogenic amines in wines by pre-column derivatization and high performance liquid chromatography coupled to mass spectrometry. AB - A new HPLC method for determining biogenic amines in wines is developed. This method is based on pre-column amine derivatization, further separation of derivatives and on-line hyphenation of HPLC to atmospheric pressure chemical ionization mass spectrometry (APCI-MS). Biogenic amines have been derivatized with 1,2-naphthoquinone-4-sulfonate at 65 degrees C and pH 9.2 for 5 min. The separation of derivatives has been accomplished in a C(18) analytical column using an elution gradient based on increasing the percentage of methanol. Derivatives have been ionized in positive mode and detected by selected ion monitoring. The operating conditions of the APCI-MS system (voltages, temperatures and gases) have been thoroughly optimized to obtain the maximum sensitivity for all analytes. In the selected conditions, APCI-MS spectra display little fragmentation and good signal-to-noise ratio. Depending on the amine characteristics, the main spectral peaks are due to mono- and di-derivative products. Figures of merit of the method have been established under the selected conditions using red wine samples. Recoveries ranging from 94% to 106% have been obtained which prove excellent accuracy of the method in the determination of histamine, putrescine, cadaverine, tryptamine, phenylethylamine, tyramine and serotonin in red wines. The proposed method has been applied to the analysis of commercial wines from different Spanish regions. PMID- 19643425 TI - Effect of increasing concentration of ammonium acetate as an additive in supercritical fluid chromatography using CO2-methanol mobile phase. AB - The effects of increasing concentrations of ammonium acetate additive in supercritical fluid chromatography were studied on silica, 2-ethyl-pyridine and endcapped 2-ethyl-pyridine stationary phases. The study involved the addition of increasing concentrations of the ammonium acetate either in the mobile phase modifier (methanol) or in the sample solvent. The effects of ammonium acetate on retention and peak shape of the analytes were evaluated. Compounds that exhibited satisfactory chromatographic behaviour in the absence of the additive were virtually unaffected by its presence in the mobile phase or sample solvent. Nevertheless, compounds that exhibited late elution and strongly tailing peak shapes when pure methanol was used showed dramatically improved chromatographic behaviour in the presence of the additive. Shorter retention was observed not only when the modifier was introduced in the mobile phase but also when it was in the sample solvent. PMID- 19643427 TI - Preparation and characterization of zirconium-based magnetic sorbent for arsenate removal. AB - In this study, a zirconium-based magnetic sorbent is developed by a coprecipitation technology. The characterization of the sorbent and its adsorption behavior are systematically investigated. It is shown that the sorbent has a small mean diameter of 543.7 nm, a specific surface area of 151 m(2)/g, and a pH(zpc) of 7. The sorbent has a rough surface and many pores developed on the surface. It has a molecular formula of ZrO(OH)(2) x 1.6 Fe(3)O(4) x 2.5 H(2)O, which was determined by the thermal gravimetric analysis, the elemental analysis, and the digestion experiments. The sorption equilibrium can be reached within 25 h. Better adsorption can be obtained at lower pH, and the optimal initial pH is from 2.6 to 3.3. The maximum adsorption capacity of 45.6 mg-As/g is achieved, which is much higher than many reported sorbents. FTIR spectra analysis indicates that -OH groups play an important role in the uptake. Some of the arsenate are reduced to arsenite after its adsorption onto the magnetic sorbent; the divalent iron in the sorbent may provide electrons for the reduction. A conceptual model for the adsorption of arsenate by the magnetic sorbent is proposed to illustrate the mechanism. PMID- 19643428 TI - Acid-base properties of the alumina surface: influence of the titration procedures on the microcalorimetric results. AB - The enthalpy changes associated with the protonation and deprotonation of an alumina surface have been determined on the basis of microcalorimetry experiments and acid-base potentiometric titrations at 25 degrees C. It has been shown that the results may vary significantly according to the experimental procedure. In order to do so, the potentiometric and microcalorimetric titrations have been carried out first from an acidic pH to basic pH and second from a pH near the pH(zpc) of alumina to acidic or basic pH. It has been demonstrated that the pK(a) values deduced from the potentiometric titrations are the same whatever the experimental protocol whereas the only way to obtain meaningful enthalpies of proton exchange is to carry out microcalorimetric titrations by starting around the point of zero charge. PMID- 19643429 TI - Adsorption and inactivation behavior of horseradish peroxidase on cellulosic fiber surfaces. AB - The physical immobilization behavior of horseradish peroxidase (HRP) on cellulosic fiber surfaces was characterized using adsorption and inactivation isotherms measured by the depletion method followed by fitting of Langmuir's and Freundlich's models to the experimental data. The adsorption and inactivation behavior of simpler and relatively non-porous high and low crystalline cellulosic substrates (microcrystalline cellulose and regenerated cellulose) as well as more complex and porous cellulosic pulp fibers (bleached kraft softwood fibers) were investigated. The effect of the sorbent surface energy on HRP adsorption was demonstrated by increasing the hydrophobicity of the cellulosic fibers using an internal sizing agent. The influence of the fiber surface charge density on HRP adsorption was studied via modification of the cellulosic fibers using TEMPO (2,2,6,6-tetramethyl-1-piperidiniloxy radical)-mediated oxidation methods. Results showed that hydrophobic interactions had a much larger effect on HRP adsorption than electrostatic interactions. More hydrophobic fiber surfaces (lower polar surface energy) result in larger enzyme-fiber binding affinity constants and higher binding heterogeneity. It was also found that oxidation of the cellulosic fiber substrate reduces enzyme adsorption affinity but significantly increases the loading capacity per unit weight of the surface. PMID- 19643430 TI - The use of main concept analysis to measure discourse production in Cantonese speaking persons with aphasia: a preliminary report. AB - Discourse produced by speakers with aphasia contains rich and valuable information for researchers to understand the manifestation of aphasia as well as for clinicians to plan specific treatment components for their clients. Various approaches to investigate aphasic discourse have been proposed in the English literature. However, this is not the case in Chinese. As a result, clinical evaluations of aphasic discourse have not been a common practice. This problem is further compounded by the lack of validated stimuli that are culturally appropriate for language elicitation. The purpose of this study was twofold: (a) to develop and validate four sequential pictorial stimuli for elicitation of language samples in Cantonese speakers with aphasia, and (b) to investigate the use of a main concept measurement, a clinically oriented quantitative system, to analyze the elicited language samples. Twenty speakers with aphasia and ten normal speakers were invited to participate in this study. The aphasic group produced significantly less key information than the normal group. More importantly, a strong relationship was also found between aphasia severity and production of main concepts. While the results of the inter-rater and intra-rater reliability suggested the scoring system to be reliable, the test-retest results yielded strong and significant correlations across two testing sessions one to three weeks apart. LEARNING OUTCOMES: Readers will demonstrate better understanding of (1) the development and validation of newly devised sequential pictorial stimuli to elicit oral language production, and (2) the use of a main concept measurement to quantify aphasic connected speech in Cantonese Chinese. PMID- 19643431 TI - Immunohistochemical characterization of canine prostatic intraepithelial neoplasia. AB - The development of prostate cancer is believed to be a multistep process, progressing sequentially from normal epithelium, to prostatic intraepithelial neoplasia (PIN) and, finally, to invasive neoplasia. Malignant stem cells within the basal cell layer of the prostatic epithelium are believed to play an important role in the failure of androgen-ablation therapy that occurs in the most advanced form of prostate cancer. The aim of the present study was to immunohistochemically characterize the lesions of canine PIN. Prostatic tissue from five dogs with PIN was compared with normal prostate tissue from nine further dogs. There was an increase in the number of basal epithelial cells in lesions consistent with PIN as defined by expression of the nuclear protein p63. These lesions had elevated expression of proliferating cell nuclear antigen (PCNA) and heterogeneous labelling for the nuclear androgen receptor (AR). These findings suggest that the basal cells present in PIN may play a role in canine prostate carcinogenesis and that the proliferation of these cells occurs despite the heterogeneous expression of the AR. PMID- 19643432 TI - The prognostic value of the Tpeak-Tend interval in patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. AB - INTRODUCTION: The Tpeak-Tend interval (TpTe) has been linked to increased arrhythmic risk. TpTe was investigated before and after primary percutaneous coronary intervention (pPCI) in patients with ST-segment elevation myocardial infarction (STEMI). METHOD: Patients with first-time STEMI treated with pPCI were included (n = 101; mean age 62 years; range 39-89 years; 74% men). Digital electrocardiograms were taken pre- and post-PCI, respectively. Tpeak-Tend interval was measured in leads with limited ST-segment deviation. The primary end point was all-cause mortality during 22 +/- 7 months (mean +/- SD) of follow-up. RESULTS: Pre- and post-PCI TpTe were 104 milliseconds [98-109 milliseconds] and 106 milliseconds [99-112 milliseconds], respectively (mean [95% confidence interval], P = .59). A prolonged pre-PCI TpTe was associated with increased mortality (hazard ratio, 10.5 [1.7-20.4] for a cutoff value of 100 milliseconds). Uncorrected QT and heart rate-corrected QT intervals (Fridericia-corrected QT) were prolonged after PCI (QT: 401 vs 410 milliseconds, P = .022, and Fridericia corrected QT: 430 vs 448 milliseconds, P < .0001). CONCLUSION: In patients with STEMI undergoing pPCI, pre-PCI TpTe predicted subsequent all-cause mortality, and the QT interval was increased after the procedure. PMID- 19643433 TI - The electrocardiogram in left ventricular hypertrophy: past and future. AB - The electrocardiographic diagnosis of left ventricular hypertrophy (LVH) has been centered on improving the diagnostic sensitivity and specificity of the method, using criteria whose precise relationship to increased left ventricular mass are not established. Although the electrocardiogram (ECG) has been displaced to a secondary role in the prediction of left ventricular mass, ECG/LVH has been shown to be a strong predictor of morbidity and early mortality. There are strong clues that each of the parameters in ECG/LVH is related to cardiac contractility and ejection. It is suggested that research be redirected to an exploration of these relationships and predicted that this will lead to both a better understanding of this venerable tool and an improvement in its usefulness to the clinician and patient. PMID- 19643435 TI - Duration of indomethacin treatment of the preterm patent ductus arteriosus as directed by echocardiography. AB - OBJECTIVE: To determine whether the duration of indomethacin administration could be shortened in infants with good early constrictive response of patent ductus arteriosus (PDA). STUDY DESIGN: Infants born at< 30 weeks' gestational age were assessed with echocardiography in the first 12 hours of life and treated with indomethacin (0.1 mg/kg) if the PDA was >2 mm in diameter. Randomization occurred before the second dose to either standard treatment (2 more doses of indomethacin at 0.1 mg/kg irrespective of echocardiographic findings) or to echocardiographically directed duration of indomethacin treatment (ECHO; further doses only if the PDA was>1.6 mm). Serial echocardiography was performed to day 28 of age. The primary outcome was failure of PDA closure. RESULTS: The infants were randomized to either the ECHO arm (n=34) or the standard treatment arm (n=40). No differences between the arms were seen in terms of failure of PDA closure, PDA reopening, need for further doses of indomethacin, or need for surgical ligation. More doses of indomethacin were given in the standard treatment arm (median, 3 doses [range, 1 to 12] vs 1 dose [range, 1 to 15]; P < .0001). CONCLUSION: Echocardiographically directed duration of indomethacin treatment is effective in achieving PDA closure and offers the potential for dose minimization. PMID- 19643437 TI - Variation in inpatient therapy and diagnostic evaluation of children with Henoch Schonlein purpura. AB - OBJECTIVE: To describe variation regarding inpatient therapy and evaluation of children with Henoch Schonlein purpura (HSP) admitted to children's hospitals across the United States. STUDY DESIGN: We conducted a retrospective cohort study of children discharged with a diagnosis of HSP between 2000 and 2007 by use of inpatient administrative data from 36 children's hospitals. We examined variation among hospitals in the use of medications, diagnostic tests, and intensive care services with multivariate mixed effects logistic regression models. RESULTS: During the initial HSP hospitalization (n = 1988), corticosteroids were the most common medication (56% of cases), followed by opioids (36%), nonsteroidal antiinflammatory drugs (35%), and antihypertensive drugs (11%). After adjustment for patient characteristics, hospitals varied significantly in their use of corticosteroids, opioids, and nonsteroidal antiinflammatory drugs; the use of diagnostic abdominal imaging, endoscopy, laboratory testing, and renal biopsy; and the use of intensive care services. By contrast, hospitals did not differ significantly regarding administration of antihypertensive drugs or performance of skin biopsy. CONCLUSIONS: The significant variation identified may contribute to varying HSP clinical outcomes between hospitals, warrants further investigation, and represents a potentially important opportunity to improve quality of care. PMID- 19643436 TI - Utility of early insulin response and proinsulin to assess insulin resistance. AB - OBJECTIVE: To determine whether obesity and premature adrenarche are additive events increasing the risk of insulin resistance and beta-cell failure, using early insulin response (EIR) or the insulinogenic index and proinsulin (PI) as markers. STUDY DESIGN: This was a prospective case-control study conducted at a tertiary care academic medical center involving 81 prepubertal, predominantly Hispanic children (34 males, 47 females), classified as lean controls (4 males, 6 females; mean age, 6.5 +/- 1.2 years; mean body mass index [BMI] z-score, 0.08 +/ 0.6), obese controls (20 males, 10 females; mean age, 7.2 +/- 1.5 years; mean BMI z-score, 2.5 +/- 0.5), lean premature adrenarche (3 males, 11 females; mean age, 7.1 +/- 1.2 years; mean BMI z-score, 0.09 +/- 0.6), and obese premature adrenarche (7 males, 20 females; mean age, 7.3 +/- 1.0; mean BMI z-score, 2.2 +/- 0.4). Fasting glucose (G(0)), insulin (I(0)), PI(0), androgen levels, insulin like growth factor 1, insulin-like growth factor binding protein 1, and lipid levels were obtained. An oral glucose tolerance test was performed. EIR was calculated as (I(30) - I(0))/(G(30) - G(0)). Between-group differences were assessed by 2-way analysis of variance, with interactions and associations explored with correlation/regression. RESULTS: EIR was greater in the obese subjects with and without premature adrenarche. Combined analysis of the independent variables obesity and premature adrenarche showed that the obese premature adrenarche group had the highest EIR. The obese subjects with premature adrenarche had greater fasting PI levels than their lean counterparts. The differences in fasting PI/I ratio among the groups were not statistically significant. CONCLUSIONS: Using EIR and PI as markers to assess the risk of insulin resistance and impaired insulin secretion indicates that obese children with premature adrenarche may be at greater risk for the development of prediabetes and type 2 diabetes mellitus compared with their lean counterparts. PMID- 19643434 TI - Glycemic control in youth with diabetes: the SEARCH for diabetes in Youth Study. AB - OBJECTIVE: To assess correlates of glycemic control in a diverse population of children and youth with diabetes. STUDY DESIGN: This was a cross-sectional analysis of data from a 6-center US study of diabetes in youth, including 3947 individuals with type 1 diabetes (T1D) and 552 with type 2 diabetes (T2D), using hemoglobin A(1c) (HbA(1c)) levels to assess glycemic control. RESULTS: HbA(1c) levels reflecting poor glycemic control (HbA(1c) >or= 9.5%) were found in 17% of youth with T1D and in 27% of those with T2D. African-American, American Indian, Hispanic, and Asian/Pacific Islander youth with T1D were significantly more likely to have higher HbA(1c) levels compared with non-Hispanic white youth (with respective rates for poor glycemic control of 36%, 52%, 27%, and 26% vs 12%). Similarly poor control in these 4 racial/ethnic groups was found in youth with T2D. Longer duration of diabetes was significantly associated with poorer glycemic control in youth with T1D and T2D. CONCLUSIONS: The high percentage of US youth with HbA(1c) levels above the target value and with poor glycemic control indicates an urgent need for effective treatment strategies to improve metabolic status in youth with diabetes. PMID- 19643438 TI - Associations between physical activity, fitness, and academic achievement. AB - OBJECTIVES: To explore the associations between objectively assessed intensity levels of physical activity and academic achievement and test whether cardiovascular fitness mediates the association between physical activity and academic achievement. STUDY DESIGN: Cross-sectional data were gathered in Swedish 9th-grade students (n = 232; mean age = 16 years; 52% girls). School grades, pubertal phase, skinfold thickness, cardiovascular fitness, and physical activity were measured objectively. Mother's education, family structure, and parental monitoring were self-reported. Data were analyzed with linear regression analyses. RESULTS: After controlling for confounding factors, academic achievement was associated with vigorous physical activity in girls (beta = .30, P < .01; explained variance of the model 26%), which remained after inclusion of fitness (beta = .23, P < .05; explained variance 29%). The association was not mediated by fitness. In boys, academic achievement was associated with pubertal phase (beta = .25, P < .05). After inclusion of fitness, it was only associated with fitness (beta = .25, P < .05; explained variance of the model 30%). CONCLUSION: In girls, academic achievement was associated with vigorous physical activity and not mediated by fitness, whereas in boys only fitness was associated with academic achievement. Further studies are necessary to investigate the potential longitudinal effect of vigorous physical activity on academic achievement, the role of fitness herein and the implications of these findings for schools. PMID- 19643439 TI - Metabolic abnormalities and cardiovascular risk factors in children with myositis. AB - OBJECTIVE: To characterize the metabolic abnormalities and risk factors for future cardiovascular disease in children with myositis. STUDY DESIGN: Seventeen patients with severe juvenile myositis, primarily referred because of refractory disease, were examined with standardized disease activity and damage measures. Body mass index, fasting insulin and lipid levels, 2-hour oral glucose tolerance test results, and cytokine levels were obtained. RESULTS: Most patients (71%) had blood pressures >75th percentile; 23.5% of patients had hypertension; and body mass index was >85th percentile in 47%. Metabolic abnormalities were also frequent: 41.2% had an elevated fasting insulin level, 47.1% had hypertriglyceridemia, and 25% met criteria for the metabolic syndrome. Although insulin resistance was common (on the basis of homeostasis model assessment and glucose-to-insulin ratio), insulin secretion appeared to be unaffected. Thigh muscle damage assessed with magnetic resonance imaging significantly correlated with fasting insulin level, glucose level, and glucose-to-insulin ratio. Glucose indices also correlated with the proinflammatory cytokines interleukin (IL)-2 and IL-12 and inversely with anti-inflammatory cytokines IL-1RA and IL-10. CONCLUSIONS: In this referral cohort of children with severe juvenile myositis, metabolic abnormalities and predictors of cardiovascular disease were common, suggesting an increased risk of future cardiovascular disease. Indicators of insulin resistance correlated with muscle damage on magnetic resonance imaging and proinflammatory cytokines and inversely with anti-inflammatory cytokines. PMID- 19643441 TI - Adolescent preventive health care: what do parents want? AB - OBJECTIVE: To understand parental opinions about which topics should be discussed during adolescent preventive health visits and how best to incorporate adolescent confidentiality into these visits. STUDY DESIGN: Cross-sectional, web-based survey of a national sample of 1025 parents of adolescents. RESULTS: Response rate was 71%. From a list of 18 possible topics, the 3 most frequently selected as being "very important for the doctor to discuss during adolescent well child examinations" were "diet/nutrition" (75%), "exercise/sports" (67%), and "physical changes of puberty" (60%). There was variability in topic popularity by parents' race/ethnicity and gender and by adolescents' age, health status, and gender. Most parents (66%) believed it was "very/somewhat" important for adolescents to have private time with the doctor during these visits, yet a substantial proportion of parents (46%) preferred that the doctor disclose to them the confidential information obtained during these private encounters. CONCLUSIONS: Parents find numerous topics important for discussion during well adolescent health care visits suggesting that parents might value a broad range of preventive care services for adolescents. However, some parents appear conflicted about incorporating adolescent confidentiality into prevention-focused visits. PMID- 19643440 TI - Effects of treatment with oxandrolone for 4 years on the frequency of severe arithmetic learning disability in girls with Turner syndrome. AB - OBJECTIVES: To study androgen treatment effects on arithmetic performance in girls with Turner syndrome. STUDY DESIGN: Forty-four girls, ages 10 to 14 years at baseline, completed 4 years of treatment with oxandrolone (Ox) or placebo (Pl). All received growth hormone and estrogen replacement therapy. We assessed the number of girls with severe learning disability (LD, standard score 0.99) and differed significantly under failure conditions (420 N): 2 Hz=8292 microstrain/s; (500 N): 30 Hz=80,840 microstrain/s. Measured and FEA-calculated strains were similar. Fracture surfaces were indistinguishable (2 Hz versus 30 Hz). SIGNIFICANCE: Fatigue failure was significantly more likely at 2 Hz than 30 Hz whereas base material and loading magnitude seemed to have only minor influence. Absolute strain was identical at these frequencies suggesting strain rate sensitivity for this commercially pure titanium implant. Both the Weibull and SEM analyses support an identical failure mechanism with damage accumulation more severe at lower frequencies, an interpretation consistent with strain rate sensitivity. PMID- 19643471 TI - Clinical fracture of cross-linked UHMWPE acetabular liners. AB - Highly cross-linked ultrahigh molecular weight polyethylene (UHMWPE) is increasingly used as a bearing material in total hip replacements. Cross-linking of UHMWPE has been shown to increase wear resistance but decrease its fracture resistance. We analyzed the clinical fracture failure of four cross-linked UHMWPE total hip replacement components of four different designs via microscopic observation of the fracture surfaces, and found that in all cases fractures initiated at stress concentrations in an unsupported region of the component (termed the elevated rim). Finite element analyses (FEA) of each individual implant design were then conducted. Results from this analysis demonstrated that the predicted magnitude and orientation of maximum principal stress due to mechanical loading of the elevated rim was sufficient to propagate initiated fatigue cracks in each case. FEA also predicted that cracks may arrest after some amount of growth due to a steep stress gradient near the initiation site. Further, while anatomical positioning of the implant and material properties affect the risk of fracture, we examined whether these failures are strongly related to the notched elevated rim design feature that is common to the four failed cases presented here. We believe that cross-linked UHMWPE remains an excellent bearing material for total hip replacements but that designs employing this material should mitigate stress concentrations or other design features that increase the risk of fracture. PMID- 19643470 TI - Natural background and anthropogenic inputs of polycyclic aromatic hydrocarbons (PAH) in sediments of South-Western Barents Sea. AB - Polycyclic aromatic hydrocarbons (PAH) were measured in sediment cores from 13 locations in South-Western Barents Sea as part of a detailed study of the Norwegian seabed under the MAREANO program. The generally low PAH levels found, an average around 200 ng g(-1) dry weight for sum PAH, indicate low inputs of petroleum hydrocarbons to the marine environment in the area. Differences in PAH composition and various PAH ratios indicate a natural, mostly petrogenic origin of PAH in sediments from the open sea locations, while the fjord locations show higher pyrogenic PAH contents with an increase towards upper sediment layers, indicating low inputs from human activities. Petrogenic PAH levels increase in deeper sediments at open sea locations, also when normalised to total organic carbon (TOC) contents, suggesting natural leakages of oil-related hydrocarbons in the area. PMID- 19643472 TI - Amphiphilic multi-arm-block copolymer conjugated with doxorubicin via pH sensitive hydrazone bond for tumor-targeted drug delivery. AB - Folate-conjugated unimolecular micelles based on amphiphilic hyperbranched block copolymer, Boltorn H40-poly(l-aspartate-doxorubicin)-b-poly(ethylene glycol)/FA conjugated poly(ethylene glycol) (H40-P(LA-DOX)-b-PEG-OH/FA), were synthesized as a carrier for tumor-targeted drug delivery. The anticancer drug DOX was covalently conjugated onto the hydrophobic segments of the amphiphilic block copolymer arms by pH-sensitive hydrazone linkage. The size of the unimolecular micelles was determined as approximately 17-36 and 10-20 nm by dynamic light scattering (DLS) and transmission electron microscopy (TEM), respectively. The release profiles of the DOX from the H40-P(LA-DOX)-b-PEG-OH/FA micelles showed a strong dependence on the environmental pH values. The DOX release rate increased in the acidic medium due to the acid-cleavable hydrazone linkage between the DOX and micelles. Cellular uptake of the H40-P(LA-DOX)-b-PEG-OH/FA micelles was found to be higher than that of the H40-P(LA-DOX)-b-PEG-OH micelles because of the folate-receptor-mediated endocytosis, thereby providing higher cytotoxicity against the 4T1 mouse mammary carcinoma cell line. Degradation studies showed that the H40-P(LA-DOX)-b-PEG-OH/FA copolymer hydrolytically degraded into polymer fragments within six weeks. These results suggest that H40-P(LA-DOX)-b-PEG-OH/FA micelles could be a promising nanocarrier with excellent in vivo stability for targeting the drugs to cancer cells and releasing the drug molecules inside the cells by sensing the acidic environment of the endosomal compartments. PMID- 19643469 TI - H1N1 2009 influenza virus infection during pregnancy in the USA. AB - BACKGROUND: Pandemic H1N1 2009 influenza virus has been identified as the cause of a widespread outbreak of febrile respiratory infection in the USA and worldwide. We summarised cases of infection with pandemic H1N1 virus in pregnant women identified in the USA during the first month of the present outbreak, and deaths associated with this virus during the first 2 months of the outbreak. METHODS: After initial reports of infection in pregnant women, the US Centers for Disease Control and Prevention (CDC) began systematically collecting additional information about cases and deaths in pregnant women in the USA with pandemic H1N1 virus infection as part of enhanced surveillance. A confirmed case was defined as an acute respiratory illness with laboratory-confirmed pandemic H1N1 virus infection by real-time reverse-transcriptase PCR or viral culture; a probable case was defined as a person with an acute febrile respiratory illness who was positive for influenza A, but negative for H1 and H3. We used population estimates derived from the 2007 census data to calculate rates of admission to hospital and illness. FINDINGS: From April 15 to May 18, 2009, 34 confirmed or probable cases of pandemic H1N1 in pregnant women were reported to CDC from 13 states. 11 (32%) women were admitted to hospital. The estimated rate of admission for pandemic H1N1 influenza virus infection in pregnant women during the first month of the outbreak was higher than it was in the general population (0.32 per 100 000 pregnant women, 95% CI 0.13-0.52 vs 0.076 per 100 000 population at risk, 95% CI 0.07-0.09). Between April 15 and June 16, 2009, six deaths in pregnant women were reported to the CDC; all were in women who had developed pneumonia and subsequent acute respiratory distress syndrome requiring mechanical ventilation. INTERPRETATION: Pregnant women might be at increased risk for complications from pandemic H1N1 virus infection. These data lend support to the present recommendation to promptly treat pregnant women with H1N1 influenza virus infection with anti-influenza drugs. FUNDING: US CDC. PMID- 19643473 TI - Skeletal muscle cell proliferation and differentiation on polypyrrole substrates doped with extracellular matrix components. AB - Conducting polymers have been developed as substrates for in vitro studies with a range of cell types including electrically-excitable cells such as nerve and smooth muscle. The goal of this study was to optimise and characterise a range of polypyrrole materials to act as substrates for electrical stimulation of differentiating skeletal myoblasts. Although all of the polymer materials provided suitable substrates for myoblast adhesion and proliferation, significant differences became apparent under the low-serum conditions used for differentiation of primary myoblasts. The significance of the work lies in the design and control of polymer materials to facilitate different stages of skeletal muscle cell proliferation and/or differentiation, opening up opportunities for engineering of this tissue. This paper therefore constitutes not just a biocompatibility assessment but a comprehensive study of how synthesis conditions affect the final outcome in terms of cell response. PMID- 19643474 TI - Targeted delivery and controlled release of doxorubicin to cancer cells using modified single wall carbon nanotubes. AB - A targeted drug delivery system that is triggered by changes in pH based on single wall carbon nanotubes (SWCNTs), derivatized with carboxylate groups and coated with a polysaccharide material, can be loaded with the anticancer drug doxorubicin (DOX). The drug binds at physiological pH (pH 7.4) and is only released at a lower pH, for example, lysosomal pH and the pH characteristic of certain tumor environments. By manipulating the surface potentials of the modified nanotubes through modification of the polysaccharide coating, both the loading efficiency and release rate of the associated DOX can be controlled. Folic acid (FA), a targeting agent for many tumors, can be additionally tethered to the SWCNTs to selectively deliver DOX into the lysosomes of HeLa cells with much higher efficiency than free DOX. The DOX released from the modified nanotubes has been shown to damage nuclear DNA and inhibit the cell proliferation. PMID- 19643475 TI - Apoptosis and S phase of the cell cycle in BeWo trophoblastic and HeLa cells are differentially modulated by Toxoplasma gondii strain types. AB - Transplacental transmission of Toxoplasma gondii causes congenital toxoplasmosis, one of the most severe forms of infection. The ability of the parasite to survive intracellularly largely depends on the blocking of different proapoptotic signaling cascades of the host cells. During pregnancy, however, alterations in the incidence of apoptosis are associated with abnormal placental morphology and function. The aim of this study was to evaluate the incidence of apoptosis and cell proliferation in trophoblastic (BeWo cell line) and uterine cervical (HeLa cell line) cells infected with a highly virulent RH strain or a moderately virulent ME49 strain of T. gondii. BeWo and HeLa cells were infected with RH or ME49 tachyzoites (2:1 and 5:1; parasite:cell) or medium alone (control). After 2 h, 6 h and 12 h of incubation, cells were fixed in 10% formalin and analyzed by immunohistochemistry to determine the apoptosis (expression of cytokeratin 18 neo epitope--clone M30) and cell in S phase (expression of proliferating cell nuclear antigen--PCNA) indices. RH strain-infected BeWo and HeLa cells showed a lower apoptosis index than non-infected controls, whereas a higher apoptosis index was found in ME49 strain-infected cells compared to controls. In addition, RH infected cells displayed lower apoptosis index than ME49-infected cells, even though active caspase-3 was detected in both cell types infected with either RH or ME49 strains as well in non-infected cells in all analyzed times of infection. Also, the cell S phase indices were higher in ME49 strain-infected BeWo and HeLa cells as compared to non-infected controls and RH strain-infected cells. These results indicate that RH and ME49 strains of T. gondii possess opposing mechanism of interference in apoptosis and cell cycle S phase of both BeWo and HeLa cells and these differences can be associated to evasion strategies of the parasite to survive inside the host cells. PMID- 19643476 TI - JAK2 and MPL gene mutations in V617F-negative myeloproliferative neoplasms. AB - We report three novel mutations in JAK2 exons 12, 19 and 25 in V617F-negative patients with polycythemia vera, essential thrombocythemia and idiopathic myelofibrosis. Scanning of JAK2 exons 12-25 and MPL exon 10 revealed the presence of JAK2 alterations in six and MPL W515L/K mutations in five of 34 patients with myeloproliferative disorders. Our results confirm that routine JAK2 analysis should include exon 12 mutations in polycythemia vera patients. MPL gene mutations seem to be associated with thrombocytosis, regardless of the type of myeloproliferative neoplasm. PMID- 19643477 TI - mTOR inhibitor RAD001 (Everolimus) enhances the effects of imatinib in chronic myeloid leukemia by raising the nuclear expression of c-ABL protein. AB - Constitutive tyrosine kinase (TK) activity of p210 BCR-ABL fusion protein of chronic myeloid leukemia (CML) usurps physiological functions of normal p145 c ABL protein. Accordingly, its inhibition by imatinib mesylate (IM) lets p145 c ABL translocate into the nuclear compartment, which drives cell growth arrest and apoptotic death. Here we show that IM and the mammalian target of rapamycin (mTOR) inhibitor RAD001 (Everolimus) have additive effects on BCR-ABL-expressing cells. Those effects are at least partly conditional upon the enhanced nuclear accumulation of p145 c-ABL through events encompassing post-translational modifications of p145 c-ABL (Thr(735) phosphorylation) precluding its nuclear export and of 14-3-3 sigma (Ser(186) phosphorylation by c-Jun N-terminal kinase [JNK]) promoting p145 c-ABL nuclear re-import. PMID- 19643478 TI - Supreme court of Canada's "Beautiful Mind" case. AB - The Supreme Court of Canada's (SCC) first case involving capacity and the refusal of involuntary psychiatric treatment involved a self described "professor" who had been referred to as "Canada's Beautiful Mind". He had been found not criminally responsible on account of mental disorder for uttering death threats. While considered incapable of making a treatment decision by psychiatrists and a review board, three levels of court, including the SCC, found him to be capable. "Professor" Starson therefore continued to refuse treatment for his psychosis and spent over seven years detained because he refused the treatment required to become well enough to be released. This refusal of treatment is permitted under Ontario law, although it is not permitted in some other Canadian provinces, and in many other countries. This article describes Starson's situation, Ontario's law with respect to consent to treatment and relevant Canadian constitutional and criminal law. It provides an analysis of the Consent and Capacity Board decision and the court appeals. Implications from Starson's case are analyzed in relation to what happened to Starson, human rights and comparative law pertaining to involuntary patients' refusal of treatment, especially their relevance to the Canadian Charter of Rights and Freedoms, and laws in some other countries. Many Canadian and foreign jurisdictions where laws apparently accord with human rights codes do not allow a person to refuse the treatment required to restore their liberty. We conclude that a law that allows a person with a mental illness to be incarcerated indefinitely in a "hospital" because needed psychiatric treatment cannot, by law, be provided is not justifiable in a caring democratic jurisdiction. PMID- 19643479 TI - Small interfering RNA-directed targeting of Toll-like receptor 4 inhibits human prostate cancer cell invasion, survival, and tumorigenicity. AB - A major cause of tumor treatment failure is cancer cell metastasis. Toll-like receptor 4 (TLR4)-mediated signaling has been implicated in tumor cell invasion, survival, and metastasis in a variety of cancers. In this study, we investigated the biological roles of TLR4 in prostate metastatic cell invasion and survival, and the potential of gene silencing of TLR4 using small interfering RNA (siRNA) for treatment of cancer. In cultured human prostate cancer cell lines, TLR4 were higher PC3 and DU145 as compared with the poorly metastatic LNCaP indicating that up-regulation of TLR4 was positively correlated with metastasis of tumor cell. In the highly metastatic cancer cell PC3, gene silencing of TLR4 using siRNA significantly inhibited TLR4 mRNA expression and protein level. Knockdown of TLR4 in PC3 cells resulted in a dramatic reduction of tumor cell migration and invasion as indicated by a Matrigel invasion assay. Furthermore, TLR4 siRNA suppressed cell viability and ultimately caused the induction of apoptotic cell death. The effects were associated with abrogating TLR4-mediated signaling to downstream target molecules such as myeloid differentiation factor 88 (MyD88), adaptor-inducing IFN-beta (TRIF), and interferon regulatory factor-1 (IRF-1). In a mouse prostate cancer model, administration with the plasmid construct expressing siRNA for TLR4 obviously inhibited established tumor growth and survival. These studies revealed evidence of a multifaceted signaling network operating downstream of TLR4-mediated tumor cell invasion, proliferation, and survival. Thus, RNA interference-directed targeting of TLR4 may raise the potential of its application for cancer therapy. PMID- 19643480 TI - A surgical strategy for the correction of Fraser syndrome cryptophthalmos. AB - PURPOSE: To describe a systematic approach for managing the structural adnexal anomalies encountered in Fraser syndrome, a multisystem, autosomal recessive condition associated with cryptophthalmos. DESIGN: Retrospective, noncomparative, interventional case series. PARTICIPANTS: All patients with Fraser syndrome related cryptophthalmos managed at a Moorfields Eye Hospital during a 23-year period between 1984 and 2007. METHODS: All patients' clinical records were reviewed. The age of the patient at presentation, sex, ethnic origin, parental consanguinity, associated systemic features, length of follow-up, and surgical interventions were recorded. MAIN OUTCOME MEASURES: The sequence of surgical procedures performed for the different morphologic cryptophthalmos subtypes, postoperative visual acuity, and corneal survival. RESULTS: The study includes 13 eyes of 7 patients. Cryptophthalmos was complete in 3 eyes and abortive in 10 eyes; no cases of incomplete cryptophthalmos were encountered in this series. The aim of surgical intervention in the latter was to optimize visual potential. Surgical steps included dissection of corneal adhesions from keratinized cornea, mucous membrane graft, Mustarde eyelid switch flap with subsequent division, and further lower lid augmentation as required (n = 10). For complete cryptophthalmos, surgery was recommended if cosmetic improvement was sought and enough tissue remained after any repair of abortive cryptophthalmos in the fellow eye. Surgery in these cases involved the creation of fornices, with subsequent upper and lower lid reconstruction with local skin/muscle flaps (n = 1). Postoperative acuities ranged from perception of light to 20/200. Good outcomes in terms of corneal health were achieved in 6 of the 10 eyes operated on for incomplete cryptophthalmos. CONCLUSIONS: Although Fraser syndrome is rare, the periocular surgical management of these complex cases may be planned using a systematic approach as described in this study, which is the largest such series to date. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 19643481 TI - Diplopia and fluoroquinolones. AB - PURPOSE: To report a possible association between fluoroquinolones and diplopia. DESIGN: Database study. PARTICIPANTS: A total of 171 subjects were studied. METHODS: Spontaneous reports from the National Registry of Drug-Induced Ocular Side Effects, World Health Organization, and Food and Drug Administration were collected on fluoroquinolones and diplopia. MAIN OUTCOME MEASURES: Data garnered from the spontaneous reports include the type of fluoroquinolone, age, gender, adverse drug reaction (ADR), dosage, duration of therapy until onset of ADR, concomitant drugs, other systemic disease, and dechallenge and rechallenge data. RESULTS: A total of 171 case reports of diplopia associated with fluoroquinolones were reported, including 76 men, 91 women, and 4 case reports in which the gender was not specified. The median age was 51.6 years. Dosage varied between the different fluoroquinolone drugs, with the median dosage within the range recommended in the package insert for each different fluoroquinolone. Median time from beginning of therapy to appearance of the ADR was 9.6 days (range 1 day to 5 months). Seventeen subjects also had concomitant tendinitis, 49 patients were 60 years or older, 1 patient had renal cysts, and 4 patients were taking systemic anti-inflammatory steroids. There were 53 positive dechallenge and 5 positive rechallenge case reports. CONCLUSIONS: According to World Health Organization criteria, the relationship between fluoroquinolone therapy and diplopia is "possible." This causality assessment is based on the time relationship of drug administration and ADR development, the multiple positive dechallenge and rechallenge reports, and the plausible mechanism by which diplopia could occur: possible tendinitis of the extraocular muscles. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 19643482 TI - Refractive and corneal aberrometric changes after intracorneal ring implantation in corneas with pellucid marginal degeneration. AB - PURPOSE: To evaluate refractive, visual, and aberrometric changes in corneas with pellucid marginal degeneration (PMD) implanted with intracorneal ring segments (ICRS) during a 6-month follow-up. DESIGN: Retrospective, consecutive case series. PARTICIPANTS: We included 21 consecutive eyes of 15 patients ranging in age from 21 to 73 years old and with a diagnosis of PMD. This diagnosis was made on the basis of slit-lamp (inferior corneal thinning), corneal topography ("butterfly" pattern), and refractive findings (significant against-the-rule astigmatism with best spectacle-corrected visual acuity loss). METHODS: A multicenter, retrospective analysis of patients undergoing ICRS implantation for the management of PMD in 4 ophthalmologic centers was performed. Surgery was indicated in all cases because of reduced best spectacle-corrected visual acuity (BSCVA) and/or contact lens intolerance or dissatisfaction. Mechanical corneal tunnelization was performed in 7 eyes and femtosecond laser-assisted tunnelization in 14 eyes. Intacs were implanted in only 3 eyes whereas KeraRings in 18 eyes. Refractive and corneal aberrometric changes were analyzed during a 6 month follow-up. MAIN OUTCOMES MEASURES: Uncorrected corrected visual acuity (UCVA) and BSCVA, refraction, keratometry, and root mean square (RMS) for different kinds of corneal aberrations. RESULTS: The UCVA did not improve at 6 months after surgery (P = 0.11). The BSCVA increased from a mean preoperative value of 0.54 to a mean postoperative value of 0.75 (P = 0.06). At 6 months, 44.44% of eyes gained > or =2 lines of BSCVA. Sphere (P = 0.02), cylinder (P<0.01), and spherical equivalent (P<0.01) were reduced significantly after surgery (P< or =0.02). Mean keratometry decreased significantly from 44.95 diopters (D) preoperatively to 43.19 D at 6 months postoperatively (P<0.01). The RMS values for astigmatism, higher order residual, and coma-like aberrations were significantly reduced with surgery (P = 0.03). In addition, significant negative correlations of preoperative RMS astigmatism (r = -0.90) and primary spherical aberration (r = -0.86) with postoperative BSCVA were also found. Segment ring explantation was performed in a total of 4 eyes owing to poor visual outcome. CONCLUSIONS: Implantation of an ICRS is an effective option for the treatment of 2nd-order and higher aberrations in corneas with PMD. Preoperative corneal astigmatism and spherical aberration seem to be limiting factors for a good visual outcome. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this manuscript. PMID- 19643483 TI - Efficacy and safety of besifloxacin ophthalmic suspension 0.6% compared with moxifloxacin ophthalmic solution 0.5% for treating bacterial conjunctivitis. AB - OBJECTIVE: To compare the clinical and antimicrobial efficacy of besifloxacin ophthalmic suspension 0.6% with that of moxifloxacin ophthalmic solution 0.5% for the treatment of bacterial conjunctivitis. DESIGN: Multicenter, randomized, double-masked, parallel-group, active-controlled, noninferiority study. PARTICIPANTS: Patients 1 year of age or older with clinical manifestations of bacterial conjunctivitis. METHODS: Eligible patients were randomized to either besifloxacin suspension or moxifloxacin solution, instilled in the infected eye(s) 3 times daily for 5 days, and participated in study visits on days 1, 5 (+/-1 day), and 8 (+1 day). Assessments included clinical evaluation of signs and symptoms, visual acuity, biomicroscopy, and culture of the infected eye(s) at each visit, as well as direct ophthalmoscopy on days 1 and 8. MAIN OUTCOME MEASURES: The primary efficacy end points were clinical resolution and microbial eradication of baseline bacterial infection on day 5 in patients with culture confirmed bacterial conjunctivitis. Secondary end points included clinical resolution and microbial eradication on day 8, individual clinical outcomes, microbial and clinical outcomes by bacterial species, and safety. RESULTS: A total of 1161 patients (533 with culture-confirmed bacterial conjunctivitis) were randomized. Based on the 95% confidence interval (CI) of the difference, besifloxacin was noninferior to moxifloxacin for clinical resolution on day 5 (58.3% vs. 59.4%, respectively; 95% CI, -9.48 to 7.29) and day 8 (84.5% vs. 84.0%, respectively, 95% CI, -5.6% to 6.75%) and for microbial eradication on day 5 (93.3% vs. 91.1%, respectively, 95% CI, -2.44 to 6.74) and day 8 (87.3% vs. 84.7%; 95% CI, -3.32 to 8.53). There was no statistically significant difference between the 2 treatment groups for either efficacy end points on days 5 or 8 (P>0.05). Besifloxacin and moxifloxacin were well tolerated. The cumulative frequency of ocular adverse events was similar between treatments (12% and 14% with besifloxacin and moxifloxacin, respectively). However, eye irritation occurred more often in moxifloxacin-treated eyes (0.3% for besifloxacin vs. 1.4% for moxifloxacin; P = 0.0201). CONCLUSIONS: Besifloxacin ophthalmic suspension was non inferior to moxifloxacin ophthalmic suspension and provided similar safety and efficacy (clinical and microbiological) outcomes when used for the treatment of bacterial conjunctivitis. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 19643484 TI - Evaluation of injection frequency and visual acuity outcomes for ranibizumab monotherapy in exudative age-related macular degeneration. AB - OBJECTIVE: To evaluate the visual outcomes for intravitreal ranibizumab administered on an as-needed basis for exudative age-related macular degeneration (AMD) and to investigate the relationship between injection frequency and visual outcome in this setting. DESIGN: Retrospective, interventional case series. PARTICIPANTS: A total of 131 eyes with treatment-naive, exudative AMD undergoing ranibizumab monotherapy. METHODS: Intravitreal ranibizumab was administered on an as-needed basis guided by clinical examination and optical coherence tomography (OCT). The OCT scans were evaluated by the treating physicians for the presence of intraretinal fluid, subretinal fluid, intraretinal cysts, or increasing pigment epithelial detachment size. Clinical data including visual acuity (VA), choroidal neovascularization lesion morphology, and treatment course were collected retrospectively for analysis. MAIN OUTCOME MEASURES: Mean change in best-corrected Snellen VA. RESULTS: The mean age was 81.3 years, mean follow-up was 12+/-4.3 months (minimum 6 months, median 12 months), and mean number of injections was 5.2+/-2.8. Mean baseline Snellen VA for the entire population was 20/110 and significantly improved at 6 months (20/80; P = 0.0002) and at last follow-up (20/90; P = 0.0066). At 6 months, 31% of eyes had gained at least 3 lines of VA and 90.5% had avoided loss of 3 lines. On average, it took 3.0 injections and 3.5 months to achieve a "dry" or "flat" macula on OCT after initiating treatment. Resolution of intra- and subretinal fluid on OCT did not correlate with the degree of vision improvement. Eyes receiving more frequent injections (defined as <2 months mean inter-injection interval) gained more vision (+2.3 lines at 6 months) than eyes receiving injections less frequently (+0.46 lines at 6 months; P = 0.012). At 6 months, 3.1% of those in the more frequent injection group lost >3 lines of vision compared with 15.9% in the >2 months interval group (P = 0.011). CONCLUSIONS: In a population receiving as needed injections of ranibizumab for exudative AMD, visual improvement was related to the frequency of injections received but not to the resolution of fluid by OCT. Treatment with ranibizumab on a strictly as-needed basis may result in undertreatment and significantly less visual gain. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 19643485 TI - Intracorneal ring segment implantation in corneas with post-laser in situ keratomileusis keratectasia. AB - PURPOSE: To evaluate the refractive and aberrometric changes in corneas with post LASIK keratectasia implanted with intracorneal ring segments (ICRS) during a 2 year follow-up. DESIGN: Retrospective, consecutive case series. PARTICIPANTS: Thirty-four eyes of 25 patients (age range, 20-59 years) with post-LASIK ectasia were included. Ectasia was diagnosed by slit-lamp appearance of corneal thinning, unstable topographic steepening, progressive corneal thinning on ultrasonic pachymetry, decreased visual acuity, and unstable refraction. METHODS: Intracorneal ring segment implantation was performed in all cases by 2 surgeons from 2 different ophthalmologic centers with the aim of correcting the spherocylindrical error and improving the visual quality. Corneal tunnels were created by means of mechanical dissection in 20 eyes and femtosecond laser technology in 14 eyes. Intacs (Addition Technology, Inc, Fremont, CA) were inserted in 24 eyes, and KeraRings (Mediphacos, Belo Horizonte, Brazil) in 10 eyes. In all cases a follow-up of 12 months was completed, with a total of 15 eyes examined 24 months after surgery. MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BSCVA), refraction, keratometry, and corneal aberrations. RESULTS: Uncorrected visual acuity did not improve after surgery (P = 0.17). Best spectacle-corrected visual acuity increased significantly at 6 months (P = 0.02). Some 38.89% of eyes gained 2 or more lines of BSCVA at 6 months, and this percentage increased to 60% at 24 months. There was a nonsignificant reduction of sphere at 6 months (P = 0.28). Manifest cylinder was reduced significantly during the postoperative follow-up (P = 0.05, preoperative to 6 months; P = 0.04, 6-12 months). The cornea was on average flatter at 6 months (P<0.01), with a posterior nonsignificant regression of the achieved flattening (P = 0.73). In regard to corneal aberrations, a statistically significant reduction was found in coma-like root mean square (RMS) (P = 0.03) after surgery. Segment ring explantation was performed in 6 eyes, and ring reposition was performed in 2 eyes. The apical curvature gradient was significantly higher in the group of explanted eyes (P = 0.03). CONCLUSIONS: Intracorneal ring segment implantation is a useful option for the treatment of coma-like aberrations and astigmatism in post-LASIK corneal ectasia. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 19643486 TI - Wavefront-guided photorefractive keratectomy in eyes with prior radial keratotomy: a multicenter study. AB - PURPOSE: To investigate the outcomes of wavefront-guided photorefractive keratectomy (WG PRK) using prophylactic mitomycin C (MMC) in eyes that had previously undergone radial keratotomy (RK). DESIGN: Retrospective, observational, consecutive case series. PARTICIPANTS: Thirty-two eyes of 27 patients with previous RK that underwent WG PRK with MMC. METHODS: The records were reviewed of consecutive RK patients whose eyes underwent WG PRK with MMC in 4 centers with postoperative follow-up of 6 months or longer (range, 6-21 months). Eyes were divided into myopic WG PRK and hyperopic WG PRK groups based on their preoperative spherical equivalent (SE). Preoperative best spectacle corrected visual acuity (BSCVA) was compared with postoperative uncorrected visual acuity (UCVA) and BSCVA to ascertain efficacy and safety. Change in SE and attempted versus achieved SE were evaluated. Incidences of haze and other complications were recorded. MAIN OUTCOME MEASURES: Uncorrected visual acuity, BSCVA, SE, corneal haze, and other complications. RESULTS: In the myopic WG PRK group (n = 9), UCVA improved by 3 lines on average (P = 0.015) with UCVA of > or =20/20 in 56% and > or =20/40 in 100% of eyes; 55% were within 0.5 diopter (D), and 100% were within 1 D of attempted refraction. In the hyperopic WG PRK group (n = 23), UCVA improved for 3 lines on average (P<0.001), with UCVA of > or =20/20 in 48% and > or =20/40 in 100% of eyes; 57% were within 0.5 D and 74% were within 1 D of attempted refraction. One eye lost 2 lines of BSCVA as a result of the development of mild to moderate haze, but recovered in 4 months. No eyes lost more than 2 lines of BSCVA. Six eyes (19%; 6/32) experienced the development of haze in the postoperative course, with mild to moderate haze in 1 eye and trace haze in the other 5 eyes. No other complications were noted. CONCLUSIONS: Wavefront-guided PRK with MMC in eyes with prior RK improved the UCVA significantly and was safe over the short follow-up of this series. Although haze occurred, no eye suffered persistent visual loss of 2 or more lines. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 19643487 TI - GS-101 antisense oligonucleotide eye drops inhibit corneal neovascularization: interim results of a randomized phase II trial. AB - PURPOSE: Pathologic corneal neovascularization not only reduces corneal transparency and visual acuity, but also is one of the most significant preoperative and postoperative risk factors for graft rejection after corneal transplantation. The aim of this study was to test tolerability and efficacy of gene signal (GS)-101 eye drops, an antisense oligonucleotide against insulin receptor substrate-1, versus placebo on inhibition of progressive corneal neovascularization. DESIGN: Randomized, double-blind, multicenter, phase II clinical study. PARTICIPANTS AND CONTROLS: Interim analysis on 40 patients with progressive corneal neovascularization resulting from various underlying diseases being nonresponsive to conventional therapy. INTERVENTIONS: Four groups of 10 patients were treated for 3 months in this dose-finding study comparing 3 doses of GS-101 (eye drops twice daily; 43, 86, and 172 microg/day total) with placebo (10 patients per group). MAIN OUTCOME MEASURES: The primary end point was the area covered by pathologic corneal blood vessels, which was measured morphometrically on digitized slit-lamp pictures using image analysis techniques. RESULTS: GS-101 eye drops were well tolerated. All serious and 95% of all other adverse events were categorized by the investigators as unrelated. In 3 patients, there was a potentially related side effect of ocular surface discomfort. At a dose of 86 microg/day (43 microg/drop), GS-101 eye drops produced a significant inhibition and regression of corneal neovascularization (-2.04+/-1.57% of total corneal area; P = 0.0047), whereas the low dose tended to stabilize it (0.07+/ 2.94%; P = 0.2088) compared with placebo (0.89+/-2.15%), where corneal neovascularization progressed in all patients. There was no apparent benefit to the higher dose (1.60+/-7.63%). CONCLUSIONS: The interim results of this phase II study suggest that GS-101 eye drops at an optimal dose of 86 microg/day are an effective and noninvasive approach specifically to inhibit and regress active corneal angiogenesis, a major risk factor for corneal graft transplantation and graft rejection. Safety concerns were not detected. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 19643488 TI - Spectral domain optical coherence tomography imaging of geographic atrophy margins. AB - OBJECTIVE: To test in vivo whether spectral domain optical coherence tomography (SD-OCT) provides adequate resolution for reproducible measurement of photoreceptor (PR) layer at the margins of geographic atrophy (GA), and if it delineates the relationship between PR layer and retinal pigment epithelium at the margins of GA. DESIGN: Prospective consecutive case series. PARTICIPANTS: Patients with GA secondary to nonneovascular age-related macular degeneration (AMD) identified during routine follow-up at Duke Eye Center between January 3, 2006, and June 3, 2007, and who consented to participate in this study. METHODS: We used SD-OCT to image eyes. Multiple B-scans from each eye were saved and independently graded by 2 graders and the following locations were marked: (1) site where PR thickness began to decline below its baseline, (2) site where PR layer disappeared, and (3) site of the GA margin. These data were processed to calculate the locations of PR losses relative to GA margins and were categorized as (A) bridging across GA margins, (B) entirely within GA margins, or (C) entirely outside GA margins. MAIN OUTCOME MEASURES: Location of PR loss (bridging across GA margins, entirely within GA margins, or entirely outside GA margins) was calculated. Distances from the GA margin were measured for beginning and ending of PR loss. Interobserver agreement was determined for categories of PR loss as well as locations of PR loss relative to the GA margin. RESULTS: We analyzed 500 unique scans. The PR loss occurred most frequently bridging across the GA margin (65% scans), second most frequently entirely inside the GA margin (29% scans), and least frequently entirely outside the GA margin (6% scans). Loss of PR started an average of 61 microm (standard deviation [SD] +/- 235) outside the GA margin, ended an average of 311+/-273 microm inside the GA margin, and spanned an average of 372+/-179 microm. CONCLUSIONS: Relative to GA margins in non-neovascular AMD with GA, SD-OCT provides adequate resolution for quantifying PR loss. It may also serve as a means of tracking disease progression in future interventional trials. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 19643490 TI - Outcomes of surgical bleb revision for complications of trabeculectomy. AB - OBJECTIVE: To describe the results of revision surgery for complications of trabeculectomy in a case series from an academic glaucoma service. DESIGN: Retrospective case series. PARTICIPANTS: A total of 177 eyes of 167 adult patients who underwent revision of trabeculectomy at the Wilmer Eye Institute between 1994 and 2007. METHODS: Three indications for surgery were identified: hypotony without leak, bleb leak, and bleb dysesthesia. Revision was deemed successful when all of the following were true: the primary indication was eliminated, further intraocular pressure (IOP)-lowering surgery was not required, no major complication occurred, and a new bleb-related problem did not develop. Patients with less than 3 months of follow-up were excluded unless failure occurred earlier. Surgical procedures included variations on excision of thin or leaking conjunctiva with advancement. MAIN OUTCOME MEASURES: Change in IOP, change in visual acuity, need for further IOP-lowering surgery, and complications after bleb revision. RESULTS: Subjects' mean age was 67+/-14 years, 54% were female, and mean follow-up was 2.8+/-2.7 years, with a mean interval from trabeculectomy to revision of 3.5+/-3.7 years. Overall success rate was 63% (112/177), which was slightly higher for leak repair (65%; 64/98) and hypotony (63%; 32/51) than for dysesthesia (57%; 16/28) indications. By Kaplan-Meier analysis, overall cumulative success rates at 1, 2, 5, and 10 years after bleb revision were 80%, 75%, 50%, and 41%, respectively. IOP and visual acuity improved significantly in both hypotony and leak groups (P values ranging from 0.004 to <0.0001). Additional IOP-lowering surgery was required in 9%. In multivariate regression analysis adjusting for age, gender, and number of prior surgeries, patients with glaucoma other than primary open-angle glaucoma were twice as likely to have failed bleb revision. CONCLUSIONS: Surgical bleb revision often provides successful resolution of bleb-related complications. Most patients maintain IOP control without need for further IOP-lowering surgery. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 19643489 TI - Acute Vogt-Koyanagi-Harada disease in enhanced spectral-domain optical coherence tomography. AB - OBJECTIVE: To demonstrate unique membranous structures seen on enhanced spectral domain optical coherence tomography (SD-OCT) images of eyes with acute Vogt Koyanagi-Harada (VKH) disease. DESIGN: Retrospective, observational case series. PARTICIPANTS: Twenty eyes of 10 consecutive patients diagnosed with acute VKH disease. METHODS: We reviewed fundus photographs, conventional OCT images, fluorescein angiograms (FA), and enhanced SD-OCT images, including serial sections through the macula, obtained at the initial visit and periodically after steroid treatment until complete resolution of serous retinal detachment. MAIN OUTCOME MEASURES: Findings on enhanced SD-OCT imaging and FA in eyes with VKH disease. RESULTS: All 20 eyes had multifocal serous retinal detachment in the posterior fundus that appeared as multilobular dye pooling on late-phase FA. In 17 of the 20 eyes (85%), some areas of dye pooling corresponded to cystoid spaces on enhanced SD-OCT images and in 14 of the 20 (70%) eyes, there were areas of dye pooling and cystoid spaces in the fovea. The floors of the cystoid spaces consisted of a membranous structure of uniform thickness (mean thickness in the fovea of 14 eyes, 62.5+/-3.3 microm). The membranous structure, on SD-OCT, seemed to include a highly reflective line, which was continuous with the line representing the junction of the photoreceptor inner and outer segments (IS/OS) in attached areas of the retina. Intraretinal split was seen to overlie the abnormal IS/OS line in the vicinity of cystoid spaces involving the fovea in 9 of the 20 eyes (45%). During the course of steroid therapy, the membranous structure changed to a granular structure. CONCLUSIONS: The membranous structure that can be seen in eyes with acute VKH disease seems to represent a portion of the outer segment layer that has become separated from the inner segment layer by cystoid spaces. We hypothesize that the membranous form of the outer segment is bound with the action of inflammatory products, such as fibrin, and this membranous structure changes to a granular structure as steroid therapy "dissolves" the fibrin holding the outer segments together. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article. PMID- 19643491 TI - Functional visual loss in idiopathic intracranial hypertension. AB - OBJECTIVE: To identify and describe patients with idiopathic intracranial hypertension (IIH) with concurrent functional visual loss (FVL). DESIGN: Observational, retrospective case series. PARTICIPANTS: Seventeen patients with IIH and FVL. METHODS: Clinical features were collected retrospectively. Data from 281 cases of IIH were analyzed for concurrence of FVL. MAIN OUTCOME MEASURES: Occurrence of FVL diagnosed at presentation or on subsequent follow-up. RESULTS: Seventeen patients had FVL and IIH. Of the 17 patients with FVL and IIH, 11 (65%) had FVL on presentation, with the remaining 6 patients developing FVL after initial presentation. Two patients in this cohort had documented recurrence of their IIH. There were several common patterns of FVL. All 17 patients had functional visual fields, with 82% having tubular fields and 71% exhibiting nonphysiologic constriction on perimetry testing. Seventy-six percent of patients had nerve/field mismatch showing no atrophic disc changes. Eighty-eight percent of patients had significant psychiatric, psychosocial, or other medical comorbidities. The majority of patients were managed surgically at some point in their clinical history, with 53% having nerve decompression, shunt, or both. Three patients had optic nerve sheath fenestrations after the diagnosis of FVL. CONCLUSIONS: Results suggest a high prevalence of FVL in IIH with a potential association with psychiatric illness and psychosocial stressors requiring careful consideration before surgical intervention. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 19643492 TI - Descemet's stripping endothelial keratoplasty: safety and outcomes: a report by the American Academy of Ophthalmology. AB - OBJECTIVE: To review the published literature on safety and outcomes of Descemet's stripping endothelial keratoplasty (DSEK) for the surgical treatment of endothelial diseases of the cornea. DESIGN: Peer-reviewed literature searches were conducted in PubMed and the Cochrane Library with the most recent search in February 2009. The searches yielded 2118 citations in English-language journals. The abstracts of these articles were reviewed and 131 articles were selected for possible clinical relevance, of which 34 were determined to be relevant to the assessment objectives. RESULTS: The most common complications from DSEK among reviewed reports included posterior graft dislocations (mean, 14%; range, 0% 82%), followed by endothelial graft rejection (mean, 10%; range, 0%-45%), primary graft failure (mean, 5%; range, 0%-29%), and iatrogenic glaucoma (mean, 3%; range, 0%-15%). Average endothelial cell loss as measured by specular microscopy ranged from 25% to 54%, with an average cell loss of 37% at 6 months, and from 24% to 61%, with an average cell loss of 42% at 12 months. The average best corrected Snellen visual acuity (mean, 9 months; range, 3-21 months) ranged from 20/34 to 20/66. A review of postoperative refractive results found induced hyperopia ranging from 0.7 to 1.5 diopters (D; mean, 1.1 D), with minimal induced astigmatism ranging from -0.4 to 0.6 D and a mean refractive shift of 0.11 D. A review of graft survival found that clear grafts at 1 year ranged from 55% to 100% (mean, 94%). CONCLUSIONS: The evidence reviewed is supportive of DSEK being a safe and effective treatment for endothelial diseases of the cornea. In terms of surgical risks, complication rates, graft survival (clarity), visual acuity, and endothelial cell loss, DSEK appears similar to penetrating keratoplasty (PK). It seems to be superior to PK in terms of earlier visual recovery, refractive stability, postoperative refractive outcomes, wound and suture-related complications, and intraoperative and late suprachoroidal hemorrhage risk. The most common complications of DSEK do not appear to be detrimental to the ultimate vision recovery in most cases. Long-term endothelial cell survival and the risk of late endothelial rejection are beyond the scope of this assessment. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 19643493 TI - Subfoveal deposits secondary to idiopathic epiretinal membranes. AB - PURPOSE: To describe the subfoveal deposits secondary to idiopathic epiretinal membranes (ERMs) and to assess their effect on the preoperative and postoperative course. DESIGN: Retrospective, observational case series. PARTICIPANTS: One hundred patients operated on consecutively for idiopathic ERMs in a single center. METHODS: The files of 100 consecutive patients operated on for idiopathic ERMs were reviewed by 2 independent investigators. Fellow eyes were used as matched controls. Patients with an ERM in the contralateral eye were excluded, as well as those with no available fundus photographs or optical coherence tomography (OCT) scans. In all, 87 eyes were included in the study. MAIN OUTCOME MEASURES: Comparison of subfoveal deposit frequency in eyes with an ERM and their fellow eyes, as shown by Stratus OCT scans and fundus photographs, and preoperative and postoperative best-corrected visual acuity (VA) in eyes with an ERM. RESULTS: A subfoveal deposit was found on both preoperative fundus photographs and OCT scans in 15 eyes with an ERM (17.2%) versus 5 (5.7%) in control fellow eyes (P = 0.0303). The group of patients with a subfoveal deposit was 5.3 years older, on average, than the group without (P = 0.0206). Time of onset of ERMs and macular thickness were not different between the 2 groups (P = 0.5663 and P = 0.7488, respectively). There was no significant difference regarding gender ratio or mean preoperative and postoperative VA (P = 0.9498 and P = 0.9902, respectively). CONCLUSIONS: In this series, subfoveal deposits seemed to be associated with the presence of ERMs. Interestingly, they did not preclude good postoperative VA. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 19643494 TI - Correlation between metamorphopsia and epiretinal membrane optical coherence tomography findings. AB - PURPOSE: To examine the retinal morphologic features of metamorphopsia caused by epiretinal membrane (ERM) and to determine whether spectral-domain optical coherence tomography (SD-OCT) correlated with metamorphopsia. DESIGN: Retrospective case series. PARTICIPANTS: This study included 19 eyes of 19 patients with ERM diagnosed by clinical ophthalmic findings and SD-OCT. METHODS: The 19 eyes were classified into 3 groups based on Amsler chart results: no metamorphopsia (n = 4), local metamorphopsia (n = 8), and broad metamorphopsia (n = 7). The thickness of the 3 inner retinal layers: inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL), on 5 horizontal SD OCT cross-sections (1 line through the fovea, 2 regularly spaced lines superior to the fovea, and 2 regularly spaced lines inferior to the fovea) were measured using the electronic calipers of the SD-OCT system. MAIN OUTCOME MEASURES: Correlation between INL, OPL, and ONL thickness with metamorphopsia and visual acuity. RESULTS: Metamorphopsia was detected in the same position as edematous areas of the INL with a thickness >50 mum. The maximum INL thickness was relatively significantly different between the subjects with no metamorphopsia and those with local or broad metamorphopsia (vs local, P = 0.06; vs broad, P = 0.04). Visual acuity significantly correlated with both maximum INL thickness (A = -0.681; P = 0.001) and maximum ONL thickness (A = -0.708; P<0.001) in metamorphopsia. CONCLUSIONS: Metamorphopsia induced by ERM may be related to the edematous areas of the INL detected with SD-OCT. The classification of ERM based on INL thickness is a potentially useful indication for surgery. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article. PMID- 19643495 TI - A Phase IIIb study to evaluate the safety of ranibizumab in subjects with neovascular age-related macular degeneration. AB - OBJECTIVE: To evaluate the safety and efficacy of intravitreal ranibizumab in a large population of subjects with neovascular age-related macular degeneration (AMD). DESIGN: Twelve-month randomized (cohort 1) or open-label (cohort 2) multicenter clinical trial. PARTICIPANTS: A total of 4300 subjects with angiographically determined subfoveal choroidal neovascularization (CNV) secondary to AMD. METHODS: Cohort 1 subjects were randomized 1:1 to receive 0.3 mg (n = 1169) or 0.5 mg (n = 1209) intravitreal ranibizumab for 3 monthly loading doses. Dose groups were stratified by AMD treatment history (treatment-naive vs. previously treated). Cohort 1 subjects were retreated on the basis of optical coherence tomography (OCT) or visual acuity (VA) criteria. Cohort 2 subjects (n = 1922) received an initial intravitreal dose of 0.5 mg ranibizumab and were retreated at physician discretion. Safety was evaluated at all visits. MAIN OUTCOME MEASURES: Safety outcomes included the incidence of ocular and nonocular adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes included changes in best-corrected VA over time. RESULTS: Some 81.7% of cohort 1 subjects and 49.9% of cohort 2 subjects completed the 12-month study. The average total number of ranibizumab injections was 4.9 for cohort 1 and 3.6 for cohort 2. The incidence of vascular and nonvascular deaths during the 12-month study was 0.9% and 0.7% in the cohort 1 0.3 mg group, 0.8% and 1.5% in the cohort 1 0.5 mg group, and 0.7% and 0.9% in cohort 2, respectively. The incidence of death due to unknown cause was 0.1% in both cohort 1 dose groups and cohort 2. The number of vascular deaths and deaths due to unknown cause did not differ across cohorts or dose groups. Stroke rates were 0.7%, 1.2%, and 0.6% in the 0.3 mg and 0.5 mg groups and cohort 2, respectively. At month 12, cohort 1 treatment-naive subjects had gained an average of 0.5 (0.3 mg) and 2.3 (0.5 mg) VA letters and previously treated subjects had gained 1.7 (0.3 mg) and 2.3 (0.5 mg) VA letters. CONCLUSIONS: Intravitreal ranibizumab was safe and well tolerated in a large population of subjects with neovascular AMD. Ranibizumab had a beneficial effect on VA. Future investigations will seek to establish optimal dosing regimens for persons with neovascular AMD. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 19643497 TI - Effect of intraocular lens asphericity on quality of vision after cataract removal: an intraindividual comparison. AB - PURPOSE: To determine the effect of intraocular lens (IOL) asphericity on quality of vision after cataract removal. DESIGN: Intraindividual, prospective, randomized clinical trial. PARTICIPANTS: Twenty-six cataract patients received 2, one-piece, blue-light-filtering hydrophobic acrylic IOLs each. METHODS: One eye was implanted with a spherical (SN60AT, Alcon) and the contralateral eye with an aspheric (SN60WF, Alcon) IOL with -0.2 mum spherical aberration (SA). All trial specific measurements (corneal topography, wavefront sensing, high-contrast visual acuity [HCVA], contrast sensitivity [CS]) were performed 6 months after surgery. A paired Student t-test or Wilcoxon test was used to check intergroup differences. MAIN OUTCOME MEASURES: Absolute values and intraindividual differences (Delta(i)) of corneal and ocular higher order aberrations and best corrected visual Strehl ratio based on the optical transfer function (BCVSOTF) values for virtual pupil diameters of 3, 4, 5, and 6 mm were computed. Photopic and mesopic HCVA, photopic, and high-mesopic CS as well as high-mesopic disability glare (DG) were measured using the Frankfurt-Freiburg Contrast and Acuity Test System. RESULTS: No intergroup difference of demographic data, pupillometry, and corneal aberrations were observed. Coma and trefoil root mean square and SA were significantly lower in the aspheric group resulting in higher BCVSOTF, mesopic HCVA, and photopic and high mesopic CS. All Delta(i) values with exception of photopic HCVA and DG indicated significantly better performance of the aspheric IOL. CONCLUSIONS: An aspheric IOL with -0.2 microm SA provide higher quality of vision than spherical IOL in terms of retinal image quality, mesopic HCVA and CS. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosures may be found after the references. PMID- 19643496 TI - Effects of intraocular ranibizumab and bevacizumab in transgenic mice expressing human vascular endothelial growth factor. AB - OBJECTIVE: This study compared the effects of intraocular injections of ranibizumab (RBZ) and bevacizumab (BVZ) in transgenic mouse models in which human vascular endothelial growth factor (VEGF) causes subretinal neovascularization (NV) or exudative retinal detachment. DESIGN: Randomized trials in animal models. PARTICIPANTS: Transgenic mice in which the rhodopsin promoter drives expression of human VEGF in photoreceptors (rho/VEGF mice) and double transgenic mice with doxycycline-inducible expression of human VEGF in photoreceptors (Tet/opsin/VEGF mice). METHODS: Rho/VEGF mice received intraocular injections of RBZ, BVZ, or vehicle, and after various time periods the area of subretinal NV was measured. Tet/opsin/VEGF mice were given an intraocular injection of RBZ, BVZ, or vehicle, and after 5 days of doxycycline treatment the presence or absence of retinal detachment was determined. MAIN OUTCOME MEASURES: Area of subretinal NV per retina in rho/VEGF mice and the occurrence of retinal detachment in Tet/opsin/VEGF mice. RESULTS: In rho/VEGF mice, intraocular injections of RBZ or BVZ strongly suppressed subretinal NV, but the duration of effect was greater for BVZ. Three injections of 10 microg of BVZ over the course of 2 weeks not only suppressed subretinal NV in the injected eye but also caused significant suppression in the fellow eye, indicating a systemic effect. In doxycycline treated Tet/opsin/VEGF mice, intraocular injection of 10 microg of BVZ significantly reduced the incidence of exudative retinal detachment compared with injection of 10 microg of RBZ. Injection of 25 microg of BVZ reduced the incidence of retinal detachment in both eyes. CONCLUSIONS: Intraocular injections of RBZ and BVZ had similar efficacy in rho/VEGF mice, but the duration of effect was greater for BVZ. In Tet/opsin/VEGF mice, in which expression levels of human VEGF are very high and the phenotype is severe, BVZ showed greater efficacy than RBZ. In both models, higher doses or repeated injections of BVZ, but not RBZ, resulted in a systemic effect. These data suggest that BVZ is not inferior to RBZ for treatment of subretinal NV in mice and is superior in a severe model. The systemic effects of BVZ after intraocular injection deserve further study and consideration of their potential consequences. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 19643498 TI - Refractive and aberrometric outcomes of intracorneal ring segments for keratoconus: mechanical versus femtosecond-assisted procedures. AB - OBJECTIVE: To compare visual, refractive, and corneal aberrometric outcomes in keratoconic eyes implanted with intracorneal ring segments (ICRS) implantation using either a mechanical or a femtosecond laser-assisted procedure. DESIGN: Retrospective, consecutive case series. PARTICIPANTS: A total of 146 consecutive eyes of 106 patients with the diagnosis of keratoconus (68 unilateral and 39 bilateral) were included. Two groups were created according to the surgical technique used for corneal tunnelization: Mechanical group (mechanical tunnelization, 63 eyes) and Femtosecond group (femtosecond laser-assisted tunnelization, 83 eyes). Intracorneal ring segments implantation was indicated because of the existence of reduced best spectacle-corrected visual acuity (BSCVA) or contact lens intolerance. METHODS: Intracorneal ring segments implantations were performed by 6 surgeons following the same protocol except for the incision location. A total of 55 eyes were implanted with Intacs (Addition Technology, Inc, Fremont, CA) and 8 eyes were implanted with KeraRings (Mediphacos, Belo Horizonte, Brazil) in the Mechanical group, and 25 eyes were implanted with Intacs and 58 eyes were implanted with KeraRings in the Femtosecond group. Mean follow-up was 10.66+/-8.20 months, ranging from 1 month to 24 months. MAIN OUTCOME MEASURES: Uncorrected visual acuity (UCVA), BSCVA, refraction, keratometry, and root mean square (RMS) for different kinds of corneal aberrations. RESULTS: By reporting only for statistically significant changes, UCVA improved in both groups at 6 months (P< or =0.02) and BSCVA improved in the Femtosecond group (P<0.01). The refraction improved in both groups at 6 months (P< or =0.02). The cornea on average was flatter in both groups at 6 months (P<0.01). Root mean square astigmatism was reduced in the Femtosecond group (P = 0.03), but there was an increase in some higher-order aberrations (P = 0.03). Significant differences were found between the 2 groups for eyes implanted with Intacs for primary spherical aberration, coma, and other higher-order aberrations, favoring the Femtosecond group (P< or =0.01). A significant negative correlation was found between the preoperative corneal aberrations and the postoperative BSCVA in the Mechanical group (r>0.63, P< or =0.04). CONCLUSIONS: Intracorneal ring segments implantation using both mechanical and femtosecond laser-assisted procedures provide similar visual and refractive outcomes. A more limited aberrometric correction is observed for eyes with mechanical implantation. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article. PMID- 19643499 TI - Visual acuity and intraocular pressure after Descemet's stripping endothelial keratoplasty in eyes with and without preexisting glaucoma. AB - PURPOSE: (1) To characterize the pattern of intraocular pressure (IOP) changes after Descemet's stripping endothelial keratoplasty (DSEK) in patients without preexisting glaucoma and in those with preexisting glaucoma, with and without prior glaucoma surgery. (2) To compare vision and IOP outcomes among the 3 groups. DESIGN: A retrospective chart review. PARTICIPANTS: A total of 805 DSEK cases performed in 641 patients by a single surgeon from December 2003 to August 2007 were available in the database. Only the first-treated eye of each patient with at least 1-year follow-up was included. Four hundred cases qualified: 315 eyes had no glaucoma (C); 64 eyes had glaucoma with no previous glaucoma surgery (G); and 21 eyes had prior glaucoma surgery (GS). Eyes with preexisting retinal problems were included in the analysis. METHODS: Data analysis included calculation of incidence of postoperative IOP elevation. The study criteria for postoperative IOP elevation were IOP > or =24 mmHg or IOP increase > or =10 mmHg from baseline. Kruskal-Wallis test was used to compare visual acuity (VA) and IOP among the 3 groups preoperatively and at 1-, 3-, 6-, and 12-month postoperative visits. MAIN OUTCOME MEASURES: Visual acuity (Snellen) and IOP (millimeters of mercury). RESULTS: The incidence of postoperative IOP elevation by the study criteria was 35%, 45%, and 43% for groups C, G, and GS, respectively. Elevated IOP was medically managed by initiating or increasing glaucoma medications or reducing steroids in 27%, 44%, and 38% of the patients in groups C, G, and GS, respectively. A subsequent glaucoma procedure was performed in 0.3%, 5%, and 19% of patients in groups C, G, and GS, respectively. Only the control group had statistically significant IOP elevation at 12 months (median increase of 2 mmHg) when compared with baseline (P<0.0001). All 3 groups had statistically significant improvement in vision at 12 months when compared with baseline (12 month median VA = 20/40 for C and G; and 20/50 for GS, P<0.0001). CONCLUSIONS: All groups had a substantial incidence of IOP elevation after DSEK. Close monitoring of IOP is warranted. In this cohort, preexisting glaucoma did not seem to have a negative effect on VA after DSEK. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 19643500 TI - Pentacam assessment of posterior lamellar grafts to explain hyperopization after Descemet's stripping automated endothelial keratoplasty. AB - PURPOSE: To evaluate changes in posterior corneal curvature as a possible cause of the hyperopic refractive shift observed after Descemet's stripping automated endothelial keratoplasty (DSAEK). DESIGN: Prospective, noncomparative, interventional case series. PARTICIPANTS: Thirty-four eyes of 29 patients with Fuchs' endothelial dystrophy or pseudophakic bullous keratopathy. METHODS: A standard DSAEK procedure was performed in 34 eyes using the pull-through technique for graft delivery. When cataract was present (n = 7), phacoemulsification with posterior chamber intraocular lens implantation was combined. Each eye underwent Pentacam (Oculus, Wetzlar, Germany) evaluation 1, 3, and 12 months after surgery. Corneal graft thickness was calculated on Scheimpflug scans at 9 locations (1 central, 4 peripheral, and 4 mid peripheral). The mean radius of posterior corneal curvature (Rm) was recorded. At each postoperative examination time, manifest refraction was determined and compared with pre-DSAEK values in simple procedures or with intended postoperative refraction, if cataract surgery had been performed. MAIN OUTCOME MEASURES: Manifest refraction, Rm, and corneal graft thickness at 1, 3, and 12 months after surgery. RESULTS: The mean+/-standard deviation posterior corneal curvature was 6.5+/-0.56 mm before surgery and varied from 5.52+/-0.39 mm 1 month after surgery to 5.83+/-0.37 mm at 3 months after surgery and 5.92+/-0.35 mm at 12 months after surgery. The grafts were significantly thicker in the periphery and mid periphery than in the center at all examination times. Thickening diminished significantly over time at all locations. The average reduction of corneal thickness was higher at the edges (91.5 microm) than in the mid periphery (38.3 microm) or in the center (24.2 microm). The average postoperative spherical equivalent+/-standard deviation changed from -0.31+/-2.35 diopters (D) before surgery to 1.03+/-2.21 D 1 month after surgery, 0.61+/-2.07 D 3 months after surgery, and +0.31+/-2.03 D 12 months after surgery. CONCLUSIONS: The difference in thickness between center and periphery of the DSAEK graft induces a change in posterior corneal curvature, resulting in a hyperopic shift that decreases with time and is negligible for spectacle correction. However, when performing a triple procedure, intraocular lens selection should take into account the refractive change induced by DSAEK. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references. PMID- 19643501 TI - British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children. AB - SUMMARY AND KEY RECOMMENDATIONS: The aim of these guidelines is to describe a practical but evidence-based approach to the diagnosis and treatment of central nervous system tuberculosis in children and adults. We have presented guidance on tuberculous meningitis (TBM), intra-cerebral tuberculoma without meningitis, and tuberculosis affecting the spinal cord. Our key recommendations are as follows: 1. TBM is a medical emergency. Treatment delay is strongly associated with death and empirical anti-tuberculosis therapy should be started promptly in all patients in whom the diagnosis of TBM is suspected. Do not wait for microbiological or molecular diagnostic confirmation. 2. The diagnosis of TBM is best made with lumbar puncture and examination of the cerebrospinal fluid (CSF). Suspect TBM if there is a CSF leucocytosis (predominantly lymphocytes), the CSF protein is raised, and the CSF:plasma glucose is <50%. The diagnostic yield of CSF microscopy and culture for Mycobacterium tuberculosis increases with the volume of CSF submitted; repeat the lumbar puncture if the diagnosis remains uncertain. 3. Imaging is essential for the diagnosis of cerebral tuberculoma and tuberculosis involving the spinal cord, although the radiological appearances do not confirm the diagnosis. A tissue diagnosis (by histopathology and mycobacterial culture) should be attempted whenever possible, either by biopsy of the lesion itself, or through diagnostic sampling from extra-neural sites of disease e.g. lung, gastric fluid, lymph nodes, liver, bone marrow. 4. Treatment for all forms of CNS tuberculosis should consist of 4 drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) for 2 months followed by 2 drugs (isoniazid, rifampicin) for at least 10 months. Adjunctive corticosteroids (either dexamethasone or prednisolone) should be given to all patients with TBM, regardless of disease severity. 5. Children with CNS tuberculosis should ideally be managed by a paediatrician with familiarity and expertise in paediatric tuberculosis or otherwise with input from a paediatric infectious diseases unit. The Children's HIV Association of UK and Ireland (CHIVA) provide further guidance on the management of HIV-infected children (www.chiva.org.uk). 6. All patients with suspected or proven tuberculosis should be offered testing for HIV infection. The principles of CNS tuberculosis diagnosis and treatment are the same for HIV infected and uninfected individuals, although HIV infection broadens the differential diagnosis and anti-retroviral treatment complicates management. Tuberculosis in HIV infected patients should be managed either within specialist units by physicians with expertise in both HIV and tuberculosis, or in a combined approach between HIV and tuberculosis experts. The co-administration of anti retroviral and anti-tuberculosis drugs should follow guidance issued by the British HIV association (www.bhiva.org). PMID- 19643503 TI - Fisher syndrome and Bickerstaff brainstem encephalitis (Fisher-Bickerstaff syndrome). AB - Since identification of the autoantibodies in Fisher syndrome, remarkable progress has been made in our understanding of that syndrome and related conditions. Because of the similarities in the clinical presentations of it and Bickerstaff brainstem encephalitis, opinions differ as to whether the two are distinct or related syndromes and whether the lesions responsible for ophthalmoplegia, ataxia and areflexia are in the peripheral or central nervous system. The finding that both conditions have autoantibodies in common suggested that the autoimmune mechanism is the same in both and they are not distinct conditions. Common autoantibodies, antecedent infections, and neuroimaging and neurophysiological results from a large study offer conclusive evidence that these conditions form a continuous spectrum with variable central and peripheral nervous system involvement. A new eponymic terminology "Fisher-Bickerstaff syndrome" may be helpful for nosology. A considerable number of patients with Bickerstaff brainstem encephalitis have associated Guillain-Barre syndrome, indicative that these two disorders are closely related on a continuous spectrum. That finding is further evidence of continuity between Bickerstaff brainstem encephalitis and Fisher syndrome, a variant of Guillain-Barre syndrome. PMID- 19643502 TI - Individual differences in changes in infants' interest in social signals in relation to developmental index. AB - Detection of social signals, such as biological motion and social causality, is of basic importance in early infancy. There have also been some accounts that infants' visual preference or reaction to social signals change during development because of their changing understanding of such signals, and the detective abilities of primary social signals are related to later social development. In this study, we attempted to find different developmental patterns in individuals in terms of their visual preference for biological motion and socially causal movements at 4, 9, and 18 months and 4 and 9 months, respectively, using a cluster analysis. It was found that for both types of social signals, the infants who demonstrated an increased interest in social stimuli at 9 months scored higher on the developmental index than those who showed a decrease, suggesting a difference in the quality of understanding of social signals at 9 months. PMID- 19643504 TI - Kaposiform hemangioendothelioma (with Kasabach Merritt syndrome) of the head and neck: case report and review of the literature. AB - An infant initially diagnosed with a parotid hemangioma presented with stridor and thrombocytopenia. Diagnosis of Kaposiform hemangioendothelioma was confirmed with biopsy. The child succumbed to multi-system organ failure related to consumptive coagulopathy despite aggressive medical management. Kaposiform hemangioendothelioma is a rare head and neck tumor that may be mistaken for a hemangioma on preliminary diagnosis, which may lead to increased morbidity and mortality especially in the setting of Kasabach-Merritt phenomenon. A platelet count may provide an early and important clue to the possibility of coagulopathy; prompting physicians to look for a diagnosis other than a simple hemangioma. PMID- 19643505 TI - Recurrent acute otitis media and gastroesophageal reflux disease in children. is there an association? AB - OBJECTIVE: To investigate whether there is a relationship between gastroesophageal reflux disease (GERD) and recurrent acute otitis media (RAOM) in infants and children. Possible risk factors are also explored. MATERIAL AND METHODS: 221 consecutive children who had symptoms and signs associated with GERD and had undergone a prolonged ambulatory 24-h esophageal pH-monitoring. Thirty four children were excluded from the study due to age, neurological deficits, congenital abnormalities, immunodeficiency syndromes or other chronic systemic disorders. The remaining 187 children (96 boys and 91 girls), aged between 40 days and 33 months (mean age of 18.3 months) were assigned into three groups according to their Reflux Index (RI%). Group A: 49 children (26.2%) without GERD (control group); Group B: 78 children (41.7%) with low to moderate RI; and Group C: 60 children (32.1%) with severe GERD. Parental interviews and personal medical files of the National Health System were used for data collection. However, episodes of acute otitis media were taken into account only if they were diagnosed by a physician. The follow-up period ranged from 6 to 8 years in order to cover the peaks of otitis media incidence in childhood. RESULTS: The results revealed that 6 children from Group A (12.24%), 11 from Group B (14.1%) and 19 from Group C (31.67%) presented episodes of RAOM. The difference was statistically significant (p=0.01). Furthermore, in children who received anti reflux treatment, the incidence of RAOM substantially decreased and eventually became approximate to that of the control Group A (12.32%). Logistic regression revealed that the strongest risk factor for recurrent otitis media was severe GERD (odds ratio, 4), then attendance at day-care centres (odds ratio, 3), followed by allergies (odds ratio, 2.7). CONCLUSIONS: Severe GERD could be implicated in the multifactorial etiology of RAOM in infants and children. PMID- 19643506 TI - Functional versatility of transcription factors in the nervous system: the SRF paradigm. AB - Individual transcription factors in the brain frequently display broad functional versatility, thereby controlling multiple cellular outputs. In accordance, neuron restricted mutagenesis of the murine Srf gene, encoding the transcription factor serum response factor (SRF), revealed numerous SRF functions in the nervous system. First, SRF controls immediate early gene (IEG) activation associated with perception of synaptic activity, learning and memory. Second, processes linked to actin cytoskeletal dynamics are mediated by SRF, such as developmental neuronal migration, outgrowth and pathfinding of neurites, as well as synaptic targeting. Therefore, SRF seems to be instrumental in converting synaptic activity into plasticity-associated structural changes in neuronal connectivities. This highlights the decisive role of SRF in integrating cytoskeletal actin dynamics and nuclear gene expression. Finally, we relate SRF to the multi-functional transcription factor CREB and point out overlapping, distinct and concerted functions of these two transcriptional regulators in the brain. PMID- 19643507 TI - Effect of delay on measurement of blood glucose levels in young subjects with type 1 diabetes. AB - We investigated the effect of a 3-h time-lag between blood sampling and glucose measurement in type 1 diabetes. Blood glucose decreased by 0.47 mmol/L despite samples being collected in fluoride tubes and placed on ice. The extent of reduction differs among subjects, prevailing blood glucose and time-of-day of sample withdrawal. PMID- 19643509 TI - Governance in non-for-profit hospitals: effects of board members' remuneration and expertise on CEO compensation. AB - Although hospitals vary in terms of their governance structures, little research has focused on the effectiveness of these governance mechanisms through the study of executive contracting. Using a sample of 80 non-for-profit private hospitals in the Netherlands, I investigate whether differences in governance structures of hospitals are informative for explaining the variations in chief executive pay. After controlling for important economic determinants of CEO compensation in hospitals (i.e., type and size of the hospital, CEO type and job complexity, market conditions and performance attributes), the results suggest that CEOs on average earn more (1) when the hospital's supervisory board members receive more remuneration (a higher absolute as well as an excessive remuneration) and (2) when supervisory board members have a lower level of expertise. The findings suggest that supervisory boards are more effective in controlling agency problems (i.e., aligning CEO pay to economic conditions) when their members have more expertise, but at the same time that the monitoring function is hampered when supervisory board members receive a large (excessive) remuneration. PMID- 19643508 TI - Outcomes of patients with hepatitis C undergoing simultaneous liver-kidney transplantation. AB - BACKGROUND/AIMS: The number of simultaneous liver-kidney transplants (SLK) has increased since the MELD era. Data on short- and long-term outcomes of hepatitis C virus positive (HCV+) SLK compared to HCV+ liver transplant alone (LTA) recipients are limited. METHODS: A case-control study comparing outcomes of HCV+SLK versus transplant year-matched HCV+ LTA (1:1) was performed. RESULTS: 38/142 (26.7%) SLK recipients were HCV+. LTA controls had lower MELD (17.4+/-8.6) at transplant than SLK (34.5+/-6.6) (p=0.001). There were increased early post transplant infection episodes in SLK (56.3%) versus LTA (21.6%) (p=0.001) and a trend towards increased early mortality in the SLK group (p=0.08). However, there was no difference in long-term patient and graft survival, time to HCV recurrence, % >or=stage 2 fibrosis, renal function, and graft function between the groups. Ten SLK recipients were treated for HCV recurrence with pegylated interferon+ribavirin: two had sustained virologic response, five stopped due to side effects, and three had no response. None had liver or kidney rejection on treatment. CONCLUSION: Our data represent the largest analysis of HCV+ SLK outcomes to date. We demonstrate increased early complications in SLK versus LTA recipients, likely due to being more critically ill at transplant (higher MELD) and complications unrelated to HCV within the first year. However, long-term outcomes, i.e. HCV recurrence, graft/renal dysfunction, are similar to LTA. In addition, while data are limited, treatment of HCV recurrence with interferon appeared safe in our SLK recipients. PMID- 19643510 TI - Ubiquitous aspartic proteinase as an actor in the stress response in buckwheat. AB - The aspartic protease (FeAP9) gene from buckwheat resembles the exon-intron structure characteristic for typical aspartic proteinases, including the presence of the leader intron in the 5'-UTR. RT PCR experiments and gel protein blot analysis indicated that FeAP9 was present in all analyzed organs: developing seeds, seedlings, flowers, leaves, roots and stems. Using Real-time PCR, we found that FeAP9 expression is upregulated in buckwheat leaves under the influence of different abiotic stresses, including dark, drought and UV-B light, as well as wounding and salicylic acid. PMID- 19643511 TI - Use of a battery-operated needle driver for intraosseous access by novice users: skill acquisition with cadavers. AB - STUDY OBJECTIVES: We determine skill acquisition and performance by using a battery-operated, intraosseous needle driver in cadavers. METHODS: This was a prospective study of the EZ-IO, a battery-operated intraosseous needle driver (Vidacare Corp). Operators received a 5-minute presentation (with 1 insertion demonstration) and then performed 3 tibial insertions on a cadaver. Insertion time was measured from skin placement until stylet removal. Another participant recorded the time and determination of "success." Success required stable bone position and infusion of fluid without extravasation. After testing, operators completed a questionnaire including ease of use (1 to 5; 1=very difficult, 5=very easy), speed versus central line (faster, same, slower), ease of use versus a central line (easier, same, harder), and willingness to use the device in future cardiac arrest situations (yes, maybe, no). RESULTS: Operators included 42 emergency medicine attending physicians, 13 other physicians, 31 emergency medicine residents, and 13 nonphysicians (emergency medical services, etc). None had previous experience with the EZ-IO, and 80 of 99 (80.8%) had never placed an intraosseous needle. Two hundred eighty-nine of 297 insertions (97.3%) were successful. Success rates for the first, second, and third insertion were 96.9%, 94.9%, and 100%, respectively. Median insertion time was 6 seconds (range 3 to 25 seconds), with interquartile range 5 to 8 seconds. The mean ease of use rating was 4.8 (95% confidence interval 4.70 to 4.90). All operators subjectively rated the device faster and easier than a central line; 98 of 99 (99%) expressed willingness to use the device in a cardiac arrest. CONCLUSION: The EZ-IO requires minimal training, is easy to use, and is fast. Skill acquisition is rapid, with a high success rate on the initial insertion after a brief training session and a single demonstration. PMID- 19643512 TI - Mapping the ribonucleolytic active site of bovine seminal ribonuclease. The binding of pyrimidinyl phosphonucleotide inhibitors. AB - Bovine seminal ribonuclease (BS-RNase) is a 27kDa homodimeric enzyme and a member of the pancreatic RNase A superfamily. It is the only RNase with a quaternary structure and it is a mixture of two dimeric forms. In the most abundant form the active site is formed by the swapping of the N-terminal segments. BS-RNase is a potent antitumor agent with severe side effects such as aspermatogenicity, and immunosuppression. As a first step towards the design of potent inhibitors of this enzyme we mapped its active site through the study of the binding of uridine 2'-phosphate (U2'p), uridine 3'-phosphate (U3'p), uridine 5'-diphosphate (UDP), cytidine 3'-phosphate (C3'p), and cytidine 5-phosphate (C5'p), by kinetics, and X ray crystallography. These phosphonucleotides are potent inhibitors with C3'p being the most potent with a K(i) value of 22 microM. Absorption, distribution, metabolism, and excretion pharmacokinetic property predictions reveal U2'p, U3'p, and C5'p as the most promising with respect to oral bioavailability. In vivo studies on the aspermatogenic effect have shown that C3'p and C5'p inhibit significantly this biological action of BS-RNase. PMID- 19643514 TI - Challenging the current strategy of radiological protection of the environment: arguments for an ecosystem approach. AB - The system of radiological protection of the environment that is currently under development is one contribution to the general need to adequately protect the environment against stress. Dominated by operational goals, it emphasizes conceptual and methodological approaches that are readily accessible today: reference organisms supported by individual-based traditional ecotoxicological data. Whilst there are immediate advantages to this approach (pragmatism, consistency with other approaches in use for man and biota), there are also clear limitations, especially in a longer run perspective, that need to be acknowledged and further considered. One can mention a few: uncertainties generated by the need for various extrapolations (from lower to higher levels of biological organisation, ...), various features missed such as potential ecological impact through impairment of ecosystem processes, trans-generational impacts as mediated through genomic instability, indirect effects mediated through trophic interactions or disruption of ecological balances,... Such limitations have already been faced in other fields of environmental protection against other stressors, pushing a number of environment professionals to assign stronger emphasis on more systemic approaches. This review discusses the advantages and limitations of the current approach designed for the radiological protection of non-human biota in the broader context of environment protection as a whole, with especial reference to upcoming trends and evolutions. This leads in particular to advocating the need to boost scientific and methodological approaches featuring the ecosystem concept as a mean to access a unified goal of protection: preserving life sustainability through protection of ecosystem structure and functioning. PMID- 19643513 TI - Novel naphthalimide derivatives as potential apoptosis-inducing agents: design, synthesis and biological evaluation. AB - A series of novel naphthalimide derivatives with flexible alkyl/aryl moieties were designed and synthesized. Their antitumor activities were evaluated against HeLa, A549, P388, HL-60, MCF-7, HCT-8 and A375 cancer cell lines in vitro. The preliminary results showed that most of the derivatives had comparable antitumor activities over Amonafide with the IC(50) values of 10(-6) to 10(-5)M. More importantly, flow cytometric analysis indicated that the derivatives could effectively induce G(2)/M arrest and progress to apoptosis in HL-60 cell line after double staining with annexin V-FITC and propidium iodide. The present work provided a novel class of naphthalimide-based derivatives with potent apoptosis inducing and antitumor activities for further optimization. PMID- 19643515 TI - Waste disposal and the recommendations of the International Commission on Radiological Protection - challenges for radioecology and environmental radiation protection. AB - The 2007 Recommendations of the International Commission on Radiological Protection (ICRP) represent a change from a process-based to an exposure-based approach, where exposure situations are categorised as planned, emergency, and existing exposure situations. Although the new Recommendations contain further changes based on, inter alia, scientific developments since the publication of the 1990 Recommendations, they overall represent more continuity than change - a notable exception being the direct consideration of environmental protection. The implications of the new Recommendations for radioactive waste management are fairly marginal, as earlier recommendations in this area are still considered valid. This communication provides a brief overview of the current ICRP system for radiological protection as applied to radioactive waste management, as well as an outlook including the possibility of using the developing ICRP system for management of environmental effects as an 'alternative way of reasoning' when building the safety case for a specific waste disposal concept. PMID- 19643516 TI - An update on the Journal's progress. PMID- 19643517 TI - Wear behaviour in total ankle replacement: a comparison between an in vitro simulation and retrieved prostheses. AB - BACKGROUND: To minimise wear of the meniscal component in total ankle replacement, a three-component artificial joint has recently been developed. This new prosthesis has convex spherical tibial and anticlastic talar metal components with non-anatomic but ligament-compatible shapes in the sagittal plane, and a fully conforming ultra-high-molecular-weight-polyethylene meniscal component inserted in between. The in vitro wear of meniscal components can be assessed using a four-station joint simulator. The study was aimed at comparing wear patterns obtained in vitro with those observed in implant retrievals with the same design. METHODS: The wear tests were run in a joint wear simulator at a frequency of 1.1 Hz for two million cycles. Three bearings within corresponding metal components were subjected to flexion/extension (range 0-58 degrees), anterior-posterior translation (0-5.2 mm), internal-external rotation (-1.9 degrees to +5.7 degrees), and a maximum axial load of 2.6 KN. These conditions were taken from the most recent findings in ankle joint mechanics. Three prostheses of the same type were harvested from patients due to replacement failures not associated with the device, 24, 24 and 9 months, respectively, after implantation. The in vitro worn components and the three retrievals were analysed by using a scanning electron microscope, a Coordinate Measuring Machine, and micro-Raman spectroscopy. FINDINGS: Visual and microscopic observations, analyses, and Raman crystallinity-based measurements showed similarity between the patterns generated experimentally in the wear simulator and those seen in retrievals with similar wear life. INTERPRETATION: A joint wear simulator like the one used in this study, once configured properly, appears to be suitable to assess wear rates also in total ankle prostheses. PMID- 19643518 TI - Effect of various forearm axially rotated postures on elbow load and elbow flexion angle in one-armed arrest of a forward fall. AB - BACKGROUND: Falling onto the outstretched hand is a major cause of upper extremity injury. The overall objectives of this study were to develop an experimental model for elbow load during a simulated fall onto one-armed arrest using three different forearm axially rotated postures as alternative fall arrest strategies. Additionally, the relationship between the elbow flexion angle and different axially rotated postures were also investigated. METHODS: Fifteen healthy young male Taiwanese graduate students with an average age of 23 years were studied. Subjects performed a one-armed arrest of a 5 cm fall onto a force plate. Each subject fell onto the force plate with his forearm 45 degrees axial externally rotated (ER), non-rotated (NR), and 45 degrees axial internally rotated (IR) postures. Kinematics and kinetics of the upper extremity were calculated and analyzed by using laboratory-developed motion analysis procedures. FINDINGS: The valgus-varus shear forces in the ER group were 1.4 times greater than the NR group, and 2.7 times greater than the IR group. The elbow joint remained at almost full extension in the ER (3.9 degrees) group, while elbow flexion angle was observed in the NR (24.6 degrees) and IR (40.3 degrees) groups. INTERPRETATION: A fall onto the outstretched hand with an externally rotated forearm should be avoided in order to reduce excessive valgus-varus shear force on the elbow joint. Knowledge of elbow kinematics and kinetics during a forward fall with various forearm axially rotated posture may be helpful in preventing injuries. PMID- 19643519 TI - Emerging therapies for patients with advanced chronic lymphocytic leukaemia. AB - Chronic lymphocytic leukaemia is a common lymphoid malignancy with a variable clinical course. While some patients never require treatment or can be managed effectively with palliative chemotherapy, others experience early disease progression and death. The development of new prognostic markers has helped in the identification of patients with high risk disease, even among those diagnosed at early stage. Recent prospective trials have established chemo-immunotherapy combinations as the new standard of care for CLL patients requiring therapy. Unfortunately, patients whose tumour cells have certain genomic aberrations, such as a chromosome 17 deletion, have a disease that is frequently refractory to conventional therapy and should have their treatment tailored accordingly. Younger patients with high risk disease should be referred for allogeneic haematopoietic cell transplantation if they have an appropriate donor. For the remaining high risk patients, a number of new compounds are emerging, which could lead to further improvement in their outcome. PMID- 19643520 TI - Association of blood pressure increases during hemodialysis with 2-year mortality in incident hemodialysis patients: a secondary analysis of the Dialysis Morbidity and Mortality Wave 2 Study. AB - BACKGROUND: Intradialytic increases in blood pressure (BP) can complicate the management of hypertension in hemodialysis (HD) patients. However, the long-term consequences are uncertain. Thus, we sought to determine whether BP increases during HD were associated with greater 2-year mortality in incident HD patients. STUDY DESIGN: Secondary analysis of a prospective dialysis cohort. SETTING & PARTICIPANTS: Incident HD patients in the Dialysis Morbidity and Mortality Wave 2 Study. PREDICTORS: Changes in systolic BP (SBP) during HD (ie, postdialysis SBP - predialysis SBP), averaged from 3 HD sessions before enrollment. OUTCOME: Time to 2-year all-cause mortality. MEASUREMENTS: Cox regression was used to model hazard ratios for mortality associated with changes in SBP during HD while adjusting for demographics, comorbid conditions, interdialytic weight gain, laboratory variables, and antihypertensive agents. RESULTS: Of 1,748 patients, 12.2% showed greater than 10-mm Hg increases in SBP during HD. In adjusted analyses, every 10-mm Hg increase in SBP during HD was associated independently with a 6% increased hazard of death (hazard ratio, 1.06; 95% confidence interval, 1.01 to 1.11). When also adjusted for diastolic BP and postdialysis SBP, the adjusted hazard of death associated with increasing SBP during HD remained significant (hazard ratio, 1.12; 95% confidence interval, 1.05 to 1.21 per 10-mm Hg increase in SBP during HD). However, in analyses adjusted for predialysis SBP, there was a significant interaction between change in SBP and predialysis SBP. In analyses stratified by predialysis SBP, trends for increased mortality associated with increasing SBP during dialysis were present in patients with predialysis SBP less than 160 mm Hg. However, this relationship was significant only in patients with predialysis SBP less than 120 mm Hg. LIMITATIONS: Secondary analysis with a limited number of baseline BP measurements and limited information about dialysis prescription. CONCLUSIONS: Increasing SBP by more than 10 mm Hg during HD occurs in approximately 10% of incident patients, and although increasing SBP during HD was associated with decreased 2-year survival, these findings were limited to patients with predialysis SBP less than 120 mm Hg. PMID- 19643521 TI - An uncommon cause of membranous glomerulonephritis. PMID- 19643523 TI - Caries experience in primary molars and its impact on the variability in permanent tooth emergence sequences. AB - OBJECTIVES: A history of caries in the primary molars is associated with an advanced emergence of their permanent successors. Hence, caries in the primary molars may have an impact on the emergence order of the permanent teeth. The aim of the present study was to fully investigate the variability in permanent tooth emergence, taking into account the (caries) status of the primary molars. METHODS: For this purpose data available from the Signal Tandmobiel project were used. In this prospective longitudinal survey data were collected from a representative sample of 4468 children, examined yearly by trained dentist examiners. Bayesian statistical analyses taking into account the interval censored character of the data were performed. RESULTS: 56% of all examined primary molars were sound; between 2.5 and 7.2% of the first and second primary molars were extracted due to caries. When both primary molars were sound, the most prevalent emergence order was '4-3-5-7' (first premolar-canine-second premolar-second molar) in the maxilla and '3-4-5-7' in the mandible. When both maxillary primary molars were affected by caries (i.e., decayed, filled or extracted due to caries), the sequence '4-5-3-7' was the most prevalent whereas sequences '3-4-5-7' and '4-3-5-7' were less prevalent. When both mandibular primary molars were affected by caries, the prevalence of sequences '4-3-5-7', '4 3-7-5' and '4-5-3-7' increased whereas the prevalence of sequences '3-4-5-7' and '3-4-7-5' decreased. CONCLUSIONS: A history of caries in the primary molars is associated with an altered emergence order of canines, premolars and second molars. PMID- 19643522 TI - Urban built environments and trajectories of mobility disability: findings from a national sample of community-dwelling American adults (1986-2001). AB - As people age, they become more dependent on their local communities, especially when they are no longer able to drive. Uneven or discontinuous sidewalks, heavy traffic, and inaccessible public transportation, are just some of the built environment characteristics that can create barriers for outdoor mobility in later adulthood. A small body of literature has been investigating the role of the built environment on disability, but has been limited to cross-sectional analyses. The purpose of this paper is to further advance this area of research by examining the role of the built environment on long-term trajectories of mobility disability in a national sample of American adults (age 45+) followed over a 15-year period. Using multilevel logistic growth curve models with nationally representative data from the Americans' Changing Lives Study (1986 2001), we find that trajectories of mobility disability are steeper in older age groups. Women and those with lower education had a higher odds of mobility disability over time. The presence of just one chronic health condition doubled the odds of mobility disability at each of the four study waves. Among older adults (age 75+), living in neighborhoods characterized by more motorized travel was associated with an odds ratio for mobility disability that was 1.5 times higher in any given year than for older adults living in environments that were more pedestrian friendly. These results suggest that the built environment can exacerbate mobility difficulties for older adults. When considering ways to minimize disability as the population ages, simple changes in the built environment may be easier to implement than efforts to change risk factors at the individual level. PMID- 19643525 TI - Can vaginal pH be measured from the wet mount slide? AB - OBJECTIVES: To assess the accuracy of vaginal pH measurement on wet mount microscopy slides compared with direct measurements on fresh vaginal fluid. We also tested whether differences in accuracy were dependent on the sampling devices used or on the diagnosis of the vaginal infections. STUDY DESIGN: Using a cotton swab, cytobrush or wooden spatula a vaginal fluid specimen was collected from 84 consecutive women attending a vulvo-vaginitis clinic. A pH strip (pH range 4-7, Merck) was brought in contact with the vaginal fluid on the sampling device and on the glass slide after adding one droplet of saline and performing microscopy by two different people unaware of the microscopy results of the clinical exam. Values were compared by Fisher exact and Student's t-tests. RESULTS: pH measurement from microscopy slides after the addition of saline causes systematic increases of pH leading to false positive readings. This is true for all types of disturbance of the flora and infections studied, and was seen in the abnormal as well as in the normal or intermediate pH range. CONCLUSION: Vaginal pH should be measured by bringing the pH strip in direct contact with fresh vaginal fluid without first adding saline. PMID- 19643526 TI - Efficiency of perchlorate consumption in road flares, propellants and explosives. AB - When an explosive detonates or a propellant or flare burns, consumption of the energetic filler should be complete but rarely is, especially in the presence of large amounts of non-combustible materials. Herein we examine three types of perchlorate-containing devices to estimate their potential as sources of contamination in their normal mode of functioning. Road flares, rocket propellants and ammonium nitrate (AN) emulsion explosives are potentially significant anthropogenic sources of perchlorate contamination. This laboratory evaluated perchlorate residue from burning of flares and propellants as well as detonations of ammonium nitrate emulsion explosives. Residual perchlorate in commercial products ranged from 0.094mg perchlorate per gram material (flares) to 0.012mg perchlorate per gram material (AN emulsion explosives). The rocket propellant formulations, prepared in this laboratory, generated 0.014mg of perchlorate residue per gram of material. PMID- 19643527 TI - Cultural shift towards sustainability in the construction industry of Hong Kong. AB - Sustainable development is forward-looking; it is a continuous mission for future developments of human society. A genuinely sustainable society is one that initiates developments in sustainable ways. The development of a genuinely sustainable society is supported by its citizens who think and act according to a recognized code of conduct - the sustainable culture. Similar to other forms of culture, sustainable culture of a society is not static, but changes over time. The changes found in a sustainable culture are reflections of the status of sustainability in a society and these changes should be measured from time to time. The resulting measurement gives very important information for decision makers, in the government and in the private sector, to examine the magnitude of changes that have taken place in a given period of time. The results will also enable them to review and adjust policies in order to better accommodate changes according to the trends of society. This paper provides a method - the T-model, to investigate and measure the extent of change of sustainable culture through two extensive surveys among participants of the construction industry of Hong Kong. The change in sustainable culture is reflected by the change in attitude and practice among construction participants, this can be found in their performance in project development, design and construction operations. The data of these changes are collected and converted to numerical scores. The T-model synthesized these scores and revealed the change of sustainable culture within the specific study time frame. PMID- 19643528 TI - Monitoring the volume and lateral spread of disposed sediments by acoustic methods, Oslo Harbor, Norway. AB - Acoustic equipment, including interferometric sonar and parametric sub-bottom profiler, have been used to determine the volume and lateral spread of dredged sediments disposed in the natural submarine depression in the Bekkelag Basin, inner Oslofjord since the beginning of the Oslo Harbor remediation project in 2006. This natural depression is used as a subaqueous confined disposal facility (CDF). Calculation of the volume of disposed sediments in the CDF is based on elevation change, derived from two high-resolution bathymetric datasets obtained in 2004, i.e. before the onset of the remediation project, and in April 2008. Seismic profiles across the CDF have been used to estimate the settlement of the original seabed, caused by loading-induced dewatering and compaction of the seabed sediments under the disposed masses. Detailed bathymetry and backscatter data demonstrate the lateral spread of disposed sediments within a well-confined area covering ca. 195,000m(2). The sea bottom within this area is distinctly softer than the surrounding seabed as shown by very low acoustic backscatter amplitude, signifying a very loose surface character of the disposed sediments. The thickness of the disposed sediments reaches 6m the deepest part of the original depression. The volume calculation of the disposed sediments in the CDF, based solely on bathymetry data, gives a value of ca. 310,000-320,000m(3). Settlement of the original seabed as a result of loading has been estimated to be 30cm at 5m thickness of the disposed sediments. Under the condition that the settlement rate is linearly correlated to the thickness of disposed sediments, the settlement corrected volume of disposed sediments is ca. 330,000-340,000m(3). Presented results demonstrate high accuracy and good reproducibility of acoustic seafloor data, and indicate a great potential of such methods as monitoring tools in environmental projects that involve dredging and subaqueous disposal. PMID- 19643529 TI - Instantaneous frequency-based ultrasonic temperature estimation during focused ultrasound thermal therapy. AB - Focused ultrasound thermal therapy relies on temperature monitoring for treatment guidance and assurance of targeting and dose control. One potential approach is to monitor temperature change through ultrasonic-backscattered signal processing. The current approach involves the detection of echo time-shifts based on cross correlation processing from segmented radiofrequency (RF) data. In this study, we propose a novel ultrasonic temperature-measurement approach that detects changes in instantaneous frequency along the imaging beam direction. Focused ultrasound was used as the heating source, and the 1-D beamformed RF signals provided from an ultrasound imager were used to verify the proposed algorithm for temperature change estimation. For comparison, a conventional cross-correlation technique was also evaluated. Heating experiments testing tissue-mimicking phantoms and ex vivo porcine muscles were conducted. The results showed that temperature can be well estimated by the proposed algorithm in the temperature range, where the relationship of sound speed versus temperature is linear. Compared with the cross correlation-based algorithm, the proposed new algorithm yields a six-fold increase in computational efficiency, along with comparable contrast-detection ability and precision. This new algorithm may serve as an alternative method for implementing temperature estimation into a clinical ultrasound imager for thermal therapy guidance. PMID- 19643530 TI - Butein induces G(2)/M phase arrest and apoptosis in human hepatoma cancer cells through ROS generation. AB - We investigated the molecular effects of 3,4,2',4'-tetrahydroxychalcone (butein) treatment in two human hepatoma cancer cell lines-HepG2 and Hep3B. Butein treatment inhibited cancer cell growth by inducing G(2)/M phase arrest and apoptosis. Butein-induced G(2)/M phase arrest was associated with increased ATM, Chk1, and Chk2 phosphorylations and reduced cdc25C levels. Additionally, butein treatment enhanced inactivated phospho-Cdc2 levels, reduced Cdc2 kinase activity, and generated reactive oxygen species (ROS) that was accompanied by JNK activation. The extent of butein-induced G(2)/M phase arrest significantly decreased following pretreatment with N-acetyl-l-cysteine or glutathione and following JNK phosphorylation reduction by SP600125. Both N-acetyl-l-cysteine and glutathione also decreased butein-mediated apoptosis. Taken together, these results imply a critical role of ROS and JNK in the anticancer effects of butein. PMID- 19643533 TI - The Health Risk assessment of Pb and Cr leached from fly ash monolith landfill. AB - As of 2004, nearly two hundred thousand tons of fly ash monoliths are created each year in Taiwan to confine heavy metals for reducing the leaching quantity by precipitation. However, due to abnormal monolith fracture, poorly liner quality or exceeding usage over designed landfill capacity, serious groundwater pollution of the landfills has been reported. This research focuses on Pb and Cr leaching from monolithic landfill to assess the risk of groundwater pollution in the vicinity. The methodology combines water budget simulations using HELP model with fate and risk simulations using MMSOILS model for 5 kinds of landfill structures and 2 types of leaching models, and calculates the risk distribution over 400 grids in the down gradient direction of groundwater. The results demonstrated that the worst liner quality will cause the largest risk and the most significant exposure pathway is groundwater intake, which accounted for 98% of the total risk. Comparing Pb and Cr concentrations in the groundwater with the drinking water standards, only 14.25% of the total grids are found to be under 0.05 mg/L of Pb, and over 96.5% of the total grids are in the safety range of Cr. It indicates that Pb leaching from fly ash monolithic landfills may cause serious health risks. Without consideration of the parameters uncertainty, the cancer and noncancer risk of Pb with the sanitary landfill method was 4.23E-07 and 0.63, respectively, both under acceptable levels. However, by considering the parameters uncertainty, the non-carcinogenic risk of Pb became 1.43, exceeding the acceptable level. Only under the sealed landfill method was the hazard quotient below 1. It is important to use at least the sealed landfill for fly ash monoliths containing lead to effectively reduce health risks. PMID- 19643532 TI - Virotherapy against malignant glioma stem cells. AB - Glioblastoma multiforme, the most common primary intracranial malignancy, is associated with very poor outcome despite advances in surgical techniques and chemo- and radiation therapy. Many novel treatment modalities are being investigated with varying amount of success. Evolution of cancer stem cell hypothesis provides a new venue for developmental therapeutics. In this review, we highlight the literature regarding the existence of glioma stem cells and their characteristics. We also discuss the potential for virotherapy, a novel therapeutic approach utilizing conditionally replicative viruses, to directly target this population of self-renewing cancer stem cells. PMID- 19643535 TI - Chemically modified activated carbon with 1-acylthiosemicarbazide for selective solid-phase extraction and preconcentration of trace Cu(II), Hg(II) and Pb(II) from water samples. AB - A new sorbent 1-acylthiosemicarbazide-modified activated carbon (AC-ATSC) was prepared as a solid-phase extractant and applied for removing of trace Cu(II), Hg(II) and Pb(II) prior to their determination by inductively coupled plasma optical emission spectrometry (ICP-OES). The separation/preconcentration conditions of analytes were investigated, including effects of pH, the shaking time, the sample flow rate and volume, the elution condition and the interfering ions. At pH 3, the maximum static adsorption capacity of Cu(II), Hg(II) and Pb(II) onto the AC-ATSC were 78.20, 67.80 and 48.56 mg g(-1), respectively. The adsorbed metal ions were quantitatively eluted by 3.0 mL of 2% CS(NH2)2 and 2.0 mol L(-1) HCl solution. Common coexisting ions did not interfere with the separation. According to the definition of IUPAC, the detection limits (3sigma) of this method for Cu(II), Hg(II) and Pb(II) were 0.20, 0.12 and 0.45 ng mL(-1), respectively. The relative standard deviation under optimum conditions is less than 4.0% (n=8). The prepared sorbent was applied for the preconcentration of trace Cu(II), Hg(II) and Pb(II) in certified and water samples with satisfactory results. PMID- 19643534 TI - Use of grape stalk, a waste of the viticulture industry, to obtain activated carbon. AB - Grape stalk is an organic waste produced in great amounts in the industrialization processes of grape. This work presents the results of studies carried out to use this waste as raw material to prepare activated carbon through the physical and chemical route. The physicochemical characterization of this material suggests the presence of unusually high levels of ashes. Metal content was determined and high levels of potassium, sodium, iron, calcium and magnesium in carbonized and raw grape stalk were exhibited. This characteristic made difficult physical activation at high temperatures. A leaching step was included before the activation with steam, and adsorbents with surface areas between 700 and 900 m(2)/g were obtained. Physical activation was also performed at lower temperatures using carbonized grape stalk without leaching, leading to the development of some grade of porosity, with an area of 412 m(2)/g. These results would indicate the catalytic effect of the minerals present in this raw material. Chemical activation using phosphoric acid as activating agent seemed to be a very efficient method as final products with BET areas between 1000 and 1500 m(2)/g were obtained. PMID- 19643531 TI - Focal adhesion kinase: a prominent determinant in breast cancer initiation, progression and metastasis. AB - Focal adhesion kinase (FAK) is an intracellular non-receptor tyrosine kinase. In addition to its role as a major mediator of signal transduction by integrins, FAK also participates in signaling by a wide range of extracellular stimuli including growth factors, G-protein-coupled receptor agonists, cytokines, and other inflammatory mediators. The link between FAK and breast cancers is strongly suggested by a number of reports showing that FAK gene is amplified and overexpressed in a large fraction of breast cancer specimens. In addition, increased FAK expression and activity frequently correlate with metastatic disease and poor prognosis. Since its discovery in early 1990s, numerous studies have shown a role for FAK in the regulation of cell spreading, adhesion, migration, survival, proliferation, differentiation, and angiogenesis. Many of these studies in cultured cells provided strong evidence to connect FAK expression/activation to the promotion of cancer. Recently, a prominent role of FAK in promoting mammary tumorigenesis, progression and metastasis has been unveiled by different animal models of human breast cancer, including xenograft models in immunodeficient rodents and spontaneous tumor models in transgenic mice that have specific deletion of FAK in the mammary epithelial cells during embryonic or postnatal development. These in vivo studies established FAK as a prominent determinant in mammary cancer initiation, progression and metastasis. Furthermore, a novel function of FAK in maintaining mammary cancer stem/progenitor cells in vivo has been recently reported, which may provide a novel cellular mechanism of FAK in promoting breast cancer initiation and progression. The wealth of knowledge accumulated over almost two decades of research on FAK should help to design potentially novel therapies for breast cancer. PMID- 19643536 TI - An investigation on magnetic susceptibility of hazardous saline-alkaline soils from the contaminated Hai River Basin, China. AB - Magnetic susceptibility can provide rich environmental information, especially for hazardous heavy metals and saline-alkaline in the contaminated soils. Magnetic susceptibility in four vertical profiles from saline-alkaline soils in lower Hai River basin was investigated. Soil sites were extended from alluvial fan to coastal plain areas. They are aligned along a latitudinal strip. Magnetic parameters including low/high frequency susceptibility, frequency-dependent susceptibility was measured. Moreover, some standard pedological parameters such as pH value and organic matter content were also determined. The results showed that low frequency magnetic susceptibility values is very high at the surface and decreases with the profile to a low value. In all profiles from alluvial fan frequency-dependent susceptibility greater than 3% may suggest the presence of relatively more super-paramagnetic particles. Magnetic susceptibility showed obvious vertical distribution in alluvial fan higher than coastal plain. No significant correlations between organic matter, pH and low frequency magnetic susceptibility were found, while there is a negative correlation between organic matter and frequency-dependent susceptibility. A positive correlation between pH and frequency-dependent susceptibility was found in the study areas. PMID- 19643537 TI - Application of natural and modified hectorite clays as adsorbents to removal of Cr(VI) from aqueous solution--thermodynamic and equilibrium study. AB - A hectorite (H) clay sample has been modified with 2-mercaptobenzimidazole (MBI) using homogeneous and heterogeneous routes. Both modification methodologies resulted in similar products, named H(HOM) and H(HET), respectively. These materials were characterized by CO(2) gas adsorption, elemental analysis, nuclear magnetic nuclei of carbon-13 and silicon-29. The effect of two variables (contact time and metal concentration) has been studied using batch technique at room temperature and pH 2.0. After achieving the best conditions for Cr(VI) adsorption, isotherms of this adsorbate on using the chosen adsorbents were obtained, which were fitted to non-linear Sips isotherm model. The maximum number of moles adsorbed was determined to be 11.63, 12.85 and 14.01 mmol g(-1) for H, H(HOM) and H(HET), respectively, reflecting the maximum adsorption order of H(HET)>H(HOM)>H. The energetic effects (Delta(int)H degrees , Delta(int)G degrees and Delta(int)S degrees ) caused by chromium ion adsorption were determined through calorimetric titrations. PMID- 19643539 TI - The effect of pH on anaerobic fermentation of primary sludge at room temperature. AB - The effect of pH in the range of 3.0-11.0 on anaerobic fermentation of primary sludge (PS) was investigated at room temperature. The experimental results showed that the concentrations of soluble chemical oxygen demands (SCOD), soluble protein and carbohydrate and short-chain fatty acids (SCFAs) under alkaline conditions were significantly higher than those under other pHs. At fermentation time of 5 days, the average SCFAs concentration increased from 968 to 3511mg COD/L with the increase of pH from 3.0 to 10.0. However, further increasing pH to 11.0 resulted in the decrease of SCFAs. At pH 10.0, acetic, propionic and iso valeric acids were the three main products, and the volatile suspended solids (VSS) reduction reached 38%. It was also observed that at any pH value investigated, there were obvious ammonia and phosphorus releases during fermentation. According to this study it is obvious that alkaline pH benefited the soluble organic carbon production from PS. PMID- 19643538 TI - Lead-selective poly(vinyl chloride) electrodes based on some synthesized benzo substituted macrocyclic diamides. AB - A series of recently synthesized benzo- and pyridine-substituted macrocyclic diamides were studied to characterize their abilities as lead ion carriers in PVC membrane electrodes. The electrode based on 3,15,21-triaza-4,5;13,14-dibenzo 6,9,12-trioxabicycloheneicosa-1,17,19-triene-2,16-dione exhibits a Nernstian response for Pb2+ ions over a wide concentration range (1.3 x 10(-2) to 3.6 x 10( 6) mol L(-1)) with a limit of detection of 2.0 x 10(-6) mol L(-1) (0.4 ppm). The response time of the sensor is approximately 16 s, and the membrane can be used for more than two months without observing any deviation. The electrode revealed comparatively good selectivities with respect to many cations including alkali earth, transition and heavy metal ions. The proposed sensor could be used in pH range of 3.7-6.5. It was used as an indicator electrode in potentiometric titration of chromate ions with a lead ion solution. PMID- 19643540 TI - Ozonation of trifluralin particles: an experimental investigation with a vacuum ultraviolet photoionization aerosol time-of-flight mass spectrometer. AB - The ozonation of trifluralin coated on azelaic acid particles is investigated with a vacuum ultraviolet photoionization aerosol time-of-flight mass spectrometer. The suspended trifluralin particles with the mean diameter of 270nm react with approximately 100ppm ozone in an aerosol reaction chamber under ambient pressure and room temperature (1atm, 298K). The time-of-flight mass spectra of the trifluralin particles and the solid state ozonides are obtained. The assignments of the mass spectra reveal that the major primary ozonides of trifluralin particles are 2,6-dinitro-N-propyl-N-propanoyl-4-(trifluoromethyl) benzamine and 2,6-dinitro-N-(propan-2(and 3)-ol)-N-propyl-4-(trifluoromethyl) benzamine. The major secondary ozonides of trifluralin 2-ethyl-7-nitro-5 (trifluoromethyl) benzimidazole-3-oxide, 2,6-dinitro-N-propyl-4-(trifluoromethyl) benzenamine and 2,6-dinitro-N-(formyl)-N-propyl-4-(trifluoromethyl) benzamine are observed. The primary ozonides are directly resulted from the oxidation of N propyl groups. The pathways of the primary ozonation are proposed in the paper. PMID- 19643541 TI - Qualitative lead extraction from recycled lead-acid batteries slag. AB - The pyrometallurgic process that the exhausted batteries are submitted for the recovery of metallic lead generates great amount of a by-product called slag. The slag is composed mainly of iron ( approximately 60%) and lead ( approximately 6%), and this residue cannot be disposed in conventional landfill due to the high lead content. This work presents a new methodology for the extraction of lead from slag, based on the complexing effect of EDTA, a chelating ligand that has the ability to solubilize several heavy metals. As the iron (Fe(2+)/Fe(3+)) have a formation's constant with EDTA higher than the lead and is present in high concentrations in the samples, the fluoride ion (F(-)) was employed to mask the iron ions. The tests were carried out in a qualitative way, confirming the lead extraction by the formation of a yellow precipitate of lead iodide. PMID- 19643542 TI - Nonideal behavior during complete dissolution of organic immiscible liquid: 1. Natural porous media. AB - Experiments were conducted to investigate the complete dissolution of organic immiscible liquid residing within natural porous media. Organic-liquid dissolution was investigated by conducting experiments with homogeneously packed columns containing a residual saturation of organic liquid (trichloroethene). The porous media used comprised different textures (ranges of particle-size distributions) and organic-carbon contents. The dissolution behavior that was observed for the soil and aquifer sediment systems deviated from the behavior typically observed for systems composed of ideal sands. Specifically, multi-step elution curves were observed, with multiple extended periods of relatively constant contaminant flux. This behavior was more pronounced for the two media with larger particle-size distributions. Conversely, this type of dissolution behavior was not observed for the control system, which consisted of a well sorted sand. It is hypothesized that the pore-scale configuration of the organic liquid and of the flow field is more complex for the poorly sorted media, and that this greater complexity constrains dissolution dynamics, leading to the observed nonideal behavior. PMID- 19643543 TI - Pain, perceived injustice and the persistence of post-traumatic stress symptoms during the course of rehabilitation for whiplash injuries. AB - The present study assessed the role of pain and pain-related psychological variables in the persistence of post-traumatic stress symptoms following whiplash injury. Individuals (N=112) with whiplash injuries who had been admitted to a standardized multidisciplinary rehabilitation program were asked to complete measures of pain, post-traumatic stress symptoms, physical function and pain related psychological variables at three different points during their treatment program. The findings are consistent with previous research showing that indicators of injury severity such as pain, reduced function and disability, and scores on pain-related psychological were associated with more severe post traumatic stress symptoms in individuals with whiplash injuries. Contrary to expectations, indicators of pain severity did not contribute to the persistence of post-traumatic stress symptoms. Univariate analyses revealed that self reported disability, pain catastrophizing and perceived injustice were significant determinants of the persistence of post-traumatic stress symptoms. In multivariate analyses, only perceived injustice emerged as a unique predictor of the persistence of post-traumatic stress symptoms. The results suggest that early adequate management of pain symptoms and disability consequent to whiplash injury might reduce the severity of post-traumatic stress symptoms. The development of effective intervention techniques for targeting perceptions of injustice might be important for promoting recovery of post-traumatic stress symptoms consequent to whiplash injury. PMID- 19643544 TI - Psychodynamic interpersonal therapy and improvement in interpersonal difficulties in people with severe irritable bowel syndrome. AB - The aim of the present study was to assess the relationship between change in interpersonal difficulties with change in chronic pain, health status and psychological state in 257 irritable bowel syndrome (IBS) patients in a randomized control trial comparing psychotherapy, antidepressant and usual care. We assessed at three time points interpersonal problems (IIP-32), abdominal pain and bowel symptoms, psychological distress (SCL-90), and health status (SF-36). Analysis included repeated measures (ANOVA) to assess change over time and multiple regressions to identify whether change in IIP was associated with outcome after controlling for psychological status. The main findings were: (1) difficulties with social inhibition and dependency were associated with longer disease duration; (2) change in mean IIP-32 over 15 months was significantly correlated with changes in pain, but these relationships were mediated by change in psychological distress; (3) change in IIP-32 was an independent predictor of improved health status at 15 months only in the psychotherapy group. These results indicate that improvement in interpersonal problems in IBS patients appear to be primarily associated with reduced psychological distress but, in addition, the association with improved health status following psychotherapy suggests that specific help with interpersonal problems may play a role in improving health status of patients with chronic painful IBS. PMID- 19643545 TI - The ecology of the Trypanosoma cruzi transmission cycle: Dispersion of zymodeme 3 (Z3) in wild hosts from Brazilian biomes. AB - Two main genotypes in Trypanosoma cruzi subpopulations can be distinguished by PCR amplification of sequences from the mini-exon gene non-transcribed spacer, respectively, T. cruzi I (TCI) and T. cruzi II (TCII). This technique is also capable of distinguishing a third assemblage of subpopulations that do not fit in these genotypes and that remain known as zymodeme Z3 (Z3). The distribution pattern as well as the mammalian host range of this latter T. cruzi sublineage still remains unclear. Thus, the intention of our study was to increase the information regarding these aspects. The mini-exon analysis of T. cruzi isolates obtained from sylvatic animals in the Amazon Forest, Atlantic Rainforest, Caatinga and Pantanal showed that prevalence of the Z3 subpopulation in nature was low (15 out of 225 isolates, corresponding to 7%). A higher prevalence of Z3 was observed in the Caatinga (15%) and the Pantanal (12%). Infection by Z3 was observed in mammalian hosts included in Carnivora, Chiroptera, Didelphimorphia, Rodentia and Xernathra. The T. cruzi Z3 subpopulation was observed also in mixed infections (33%) with TCI (n=2) and TCII (n=3). These results demonstrate that T. cruzi Z3 displays a wider distribution and host range than formerly understood as it has been demonstrated to be able infect species included in five orders of mammalian host species dispersed through all forest strata of the four Brazilian biomes evaluated. PMID- 19643546 TI - Non-smoking youths' "perceived" addiction to tobacco is associated with their susceptibility to future smoking. AB - Smoking initiation places adolescents at risk for adult onset diseases, including heart disease, respiratory illness, and cancer. Adolescents that smoke have levels of 'perceived' tobacco addiction that are associated with several measures of nicotine dependence. Nonsmoking adolescents also report feeling addicted to tobacco even with minimal or no prior tobacco use, suggesting some vulnerability to tobacco use. The purpose of this study was to examine the association between perceived tobacco addiction and smoking susceptibility among adolescents with very minimal tobacco use. A cross-sectional analysis was conducted of data obtained from 5155 nonsmokers who completed the British Columbia Youth Survey of Smoking and Health II, a school-based survey conducted during 2004. Measures included demographics, tobacco use (ever puffed a cigarette), substance use (marijuana and alcohol), exposure to family members' smoking in the home, peers' tobacco use, depressive symptoms, perceived physical and mental addiction to tobacco, and smoking susceptibility. The adolescents who were most susceptible to smoking were female, younger and in a lower school grade; had ever puffed a cigarette, had used alcohol or marijuana; had family members or peers who smoked; had higher depression scores, and higher perceived physical and mental addiction to tobacco. In multivariate logistic regression analysis, perceived mental addiction but not perceived physical addiction to tobacco was significantly associated with smoking susceptibility. Understanding factors associated with smoking initiation, and ways to identify "at- risk" adolescents can enhance early intervention and prevention programs. Perceived mental addiction to tobacco appears to be an important indicator of smoking susceptibility. PMID- 19643547 TI - "Blinding" of AMP-dependent kinase by methylglyoxal: a mechanism that allows perpetuation of hepatic insulin resistance? AB - AMP-dependent kinase (AMPK) is a regulatory carrefour and a key target for therapeutics. The role of AMPK in regulating cellular energy status (by sensing low energy using [AMP] as its signal) and activating catabolic pathways while inhibiting anabolic routes, places this enzyme at a central control point in maintaining energy homeostasis. The exquisite allosteric sensing of AMP is done by a domain with three arginine residues, which make it very vulnerable to glycation, especially by the alpha-dicarbonyl methylglyoxal (MG). MG accumulates in hyperglycemia, insulin resistance, diabetes and when there is excess flux of reactive oxygen species coming from the mitochondria. We hypothesize that excess MG in the above-mentioned conditions blocks the sensing of AMP by AMPK, thereby favoring gluconeogenesis (thus hepatic glucose output and hyperglycemia) and lipogenesis (hepatic steatosis and high VLDL), hallmarks of insulin resistance and diabetes. Our hypothesis may explain, for instance, the perpetuation of hepatic insulin resistance, as well as part of the action of metformin, which is a potent anti-glycation agent. Future targets for type 2 diabetes treatments will likely be those that can effect beneficial changes in the activity of AMPK, and our theory predicts that anti-glycation agents may become part of that armamentarium. PMID- 19643548 TI - Screening for essential fatty acid deficiency in at risk infants. AB - Essential fatty acids are critical during the initial years of infancy and are necessary for brain development, visual maturity, and cardiovascular health. Essential fatty acid deficiency (EFAD) develops where there is inadequate status of omega-3 or omega-6 fatty acids. This paper raises the idea and question of whether screening for EFAD in at risk infants is beneficial and assesses the efficacy of introducing this as a preventative clinical measure. The introduction of the screening program is analysed against the criteria outlined by the UK National Screening Committee. Screening to detect EFAD in at risk infants satisfies many of the criteria proposed by the UK screening committee, including condition assessed, accepted screening tests, and screening program fundamentals. While a range of benefits are reported in the treatment of fatty acid deficiencies, several areas require further investigation prior to establishment. Hence, a trial screening program is proposed to more fully analyse the cost benefits. PMID- 19643549 TI - "Open data" and Hardy's example of seminal correspondence 101 years ago: publication practices revisited. PMID- 19643550 TI - The Salted Food Addiction Hypothesis may explain overeating and the obesity epidemic. AB - One plausible explanation for the controversy that surrounds the causes and clinical management of obesity is the notion that overeating and obesity may only be a couple of "symptoms" associated with a yet to be discovered medical disorder. OBJECTIVES: To introduce the Salted Food Addition Hypothesis. This theory proposes that salted food acts in the brain like an opiate agonist, producing a hedonic reward which has been perceived as being only peripherally "flavorful", "tasty" or "delicious". The Salted Food Addition Hypothesis also proposes that opiate receptor withdrawal has been perceived as "preference," "urges," "craving" or "hunger" for salted food. METHODS: The Salted Food Addiction Hypothesis is made manifest by individually presenting a basic review of its primary coexisting components; the Neurological Component and the Psychosocial Component. We also designed a prospective study in order to test our hypothesis that opiate dependent subjects increase their consumption of salted food during opiate withdrawal. RESULTS: The neuropsychiatric evidence integrated here suggests that salted food acts like an, albeit mild, opiate agonist which drives overeating and weight gain. The opiate dependent group studied (N=27) developed a 6.6% increase in weight during opiate withdrawal. CONCLUSIONS: Salted Food may be an addictive substance that stimulates opiate and dopamine receptors in the brain's reward and pleasure center more than it is "tasty", while salted food preference, urge, craving and hunger may be manifestations of opiate withdrawal. Salted food and opiate withdrawal stimulate appetite, increases calorie consumption, augments the incidence of overeating, overweight, obesity and related illnesses. Obesity and related illnesses may be symptoms of Salted Food Addiction. PMID- 19643552 TI - [What are we going to do with our trainees?]. PMID- 19643551 TI - Topographical assessment of symptom resolution following open carpal tunnel release. AB - PURPOSE: Patients with carpal tunnel syndrome commonly present with paresthesias and pain extending into the small finger and proximal to the hand. This study was conducted to assess the ability of carpal tunnel release to relieve symptoms outside of the median nerve distribution. METHODS: We enrolled 34 consecutive surgical patients (40 wrists) diagnosed exclusively with carpal tunnel syndrome based on the history, physical examination, and electrodiagnostic studies. Preoperative symptoms were categorized as pain, numbness, tingling, or "burning and electrical shocks." The presence or absence of each symptom type was recorded in 5 topographical areas (zone I, palmar thumb/index/long; zone II, small finger; zone III, volar forearm; zone IV, volar arm; and zone V, dorsal hand/forearm/arm). Patients were contacted at 4 to 6 weeks postoperatively to assess resolution of each symptom type by topographic zone. RESULTS: Preoperatively, the cohort reported symptoms in all zones: zone I, 120 reports; zone II, 47 reports; zone III, 33 reports; zone IV, 7 reports; and zone V, 23 reports. Numbness (n = 40) and tingling (n = 38) were the most common symptoms, followed by pain (n = 29) and "burning/shocks" (n = 16). Postoperatively, the total number of reports within the 5 zones decreased from 230 to 20. The probability that surgery would eliminate patient symptoms was 88% (104 of 120) in zone I, 96% (45 of 47) in zone II, 97% (32 of 33) in zone III, 86% (6 of 7) in zone 4, and 100% (23 of 23) in zone V. Across zones, the overall probability of symptom resolution was as follows: pain > 80%, numbness/tingling > 85%, and "burning/shocks" > 90%. CONCLUSIONS: Symptoms experienced outside of the median nerve distribution had a high likelihood of resolution after carpal tunnel release. Over 85% of symptoms in each of the anatomic zones studied resolved. Feelings of burning or shock-like sensations were most reliably relieved at early follow-up. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV. PMID- 19643553 TI - [Gestational prolapse: an exceptional case]. PMID- 19643554 TI - Prevalence of Salmonella associated with chick mortality at hatching and their susceptibility to antimicrobial agents. AB - The prevalence of Salmonella associated mortality at hatching was investigated in three hatcheries in Jos, central Nigeria. Their susceptibility to antimicrobial agents was also evaluated. S. Kentucky and S. Hadar were isolated. While half of the isolates were from internal organs, 26.7% came from meconial swabs of dead-in shell embryos, 17.8% from intestinal samples and 4.4% from egg shells. S. Hadar is known to colonise only the gut and is classified as non-invasive, but in this study 82% were obtained from internal organs which suggests that infections with this serotype may also cause invasive disease. Antimicrobial susceptibility tests showed a high prevalence of antimicrobial resistance in the study area with complete resistance to gentamycin, enrofloxacin, nalidixic acid, tetracycline and streptomycin and substantial resistance to triple sulphur and ciprofloxacin. Six multiple resistance profiles were recorded with a high level of multiple resistance to quinolones. Quinolone resistance has implications for veterinary and human therapy as their misuse in poultry could lead to the emergence of resistant animal and zoonotic pathogens. PMID- 19643555 TI - Evaluation of ceftiofur and cefquinome for phenotypic detection of methicillin resistance in Staphylococcus aureus using disk diffusion testing and MIC determinations. AB - Methicillin-resistant Staphylococcus aureus (MRSA) have emerged in animals. Testing 98 mecA negative and 71 mecA positive S. aureus we compared the usefulness of ceftiofur and cefquinome to cefoxitin, for detection of MRSA and found that these cephalosporins are not as efficient as cefoxitin. PMID- 19643556 TI - A model to predict motor performance in preterm infants at 5 years. AB - BACKGROUND: Approximately 60% of preterm infants who are assessed at 5 years for motor performance in a standardized multidisciplinary follow-up program are found to have normal results, indicating that, for these children, routine motor assessment at this age is unnecessary. AIM: To improve the efficiency of our follow-up practice for motor assessment by developing a model to predict motor performance of preterm infants at 5 years with a maximal sensitivity (>or=90%). STUDY DESIGN: Longitudinal design. SUBJECTS: We included preterm infants (n=371) with a gestational age of 5.0 cm (p=.031) and for multiple tumors (p=.032), but not for tumors 5 cm or multiple tumors. PMID- 19643562 TI - [Tobacco-associated lesions of the oral cavity and motivation for smoking cessation: a study of 121 cases]. AB - Tobacco use produces many changes to the oral cavity including non-malignant, precancerous, and malignant lesions. Most of these oral lesions and changes can be detected by a simple visual inspection of the oral cavity. METHODS: We evaluated the motivation for smoking cessation of patients with oral lesions. RESULTS: Visual inspection of the oral cavity in 121 patients made 58 % of them motivated to smoking cessation. DISCUSSION: Inspection of oral cavity showing lesions caused by tobacco is a good way to initiate tobacco cessation. PMID- 19643563 TI - Early return to function after hip resurfacing: is it better than contemporary total hip arthroplasty? AB - Our hypothesis was that return of function for young patients undergoing resurfacing total hip arthroplasty (THA) with metal-on-metal bearings or contemporary THA with ceramic bearings would be comparable. Results from 337 unilateral hip resurfacing patients were compared with results from 266 unilateral ceramic-on-ceramic THA patients. Early differences in Harris Hip Scores were observed, but all differences faded by 24 months. Hip resurfacing seems to be a viable alternative to THA for well-selected patients. However, the public perception of improved functional capabilities was not demonstrated in this patient population. Resurfacing patients may be more impaired (slightly higher pain scores/lower function scores) than their THA counterparts in the early postoperative period, but these differences disappear by 24 months when both groups report Harris Hip Scores in the excellent range. PMID- 19643564 TI - Fifteen-year to twenty-year results of cementless Harris-Galante porous femoral and Harris-Galante porous I and II acetabular components. AB - This study examined long-term survivorship of primary total hip arthroplasty (THA) using cementless Harris-Galante porous femoral and Harris-Galante porous I or II acetabular components. Of 113 hips (101 patients) studied, 60 hips (53 patients) were available for follow-up at a mean of 17.2 years after surgery. A total of 10 hips had documented revision, and 2 hips had failed radiographically. The average Harris hip score was 82. Radiographically, 12 hips demonstrated eccentric wear, 8 had osteolysis, and 1 had a broken tine. The overall survival rate was 87.7%; the mean volumetric wear rate was 74.96 mm(3); and the mean polyethylene linear penetration rate was 0.153 mm/y, similar to that of well cemented THA in other series. This long-term outcome for an early-generation cementless THA is promising and provides a standard by which to judge the newer generation of cementless implants. PMID- 19643565 TI - Postoperative mortality and factors related to mortality after bipolar hemiarthroplasty in patients with femoral neck fractures. AB - The purpose of this study was to determine the mortality rate and factors related to mortality in elderly patients with acute and monotraumatic femoral neck fractures. This study included 241 patients with femoral neck fractures after bipolar hemiarthroplasty. We analyzed the mortality rate and the relationship between postoperative mortality and risk factors, such as age, sex, body mass index, the time to surgery, and the Society of Anesthesiologists' score. The postoperative mortality rate 1 and 3 years after surgery was 11.2% and 19.5%, respectively. There proved to be a relationship between postoperative mortality and age, the time to surgery, and the Society of Anesthesiologists score. We recommend that surgery should not be delayed, and caution should be exercised for the high-risk group patients. PMID- 19643566 TI - An in vivo study of the effect of distal femoral resection on passive knee extension. AB - A previous study showed that 1 mm of distal femoral resection restored knee extension 4.5 degrees . We determined the relationship with a more accurate measurement technique. Twenty-six subjects treated with total knee arthroplasty were studied. Digital photographs of the extended knee with and without 1.5 and 3.0 mm thick augments placed between the femoral component and distal femur were analyzed, and knee extension was measured. One millimeter of distal femoral resection restored 1.8 degrees of extension that is less correction than the previous study reported. Because an attempt to correct a 10 degrees extension deficit by resecting the distal femur could require 5 mm or more of bone removal that moves the joint line too proximal, we recommend exploring other techniques before resecting the femur. PMID- 19643567 TI - Isolated acetabular revision hip arthroplasty with the use of uncemented cup. AB - We evaluated the clinical and radiological results of isolated acetabular revision hip arthroplasty. Forty-three hips underwent isolated acetabular revision with uncemented cup and were followed up for an average of 76 months. The monoblock femoral stems were used in 20 hips and modular femoral stems in 23 hips. The average Harris Hip Score improved to 87 at last follow-up from 57 preoperatively. All femoral stems maintained stable fixation with bone ingrowth and no subsidence at last follow-up. Five hips with the monoblock stem underwent rerevision due to loosening of cup with osteolysis. The isolated acetabular revision is encouraging, but in reflection of the results of the monoblock head, the visual inspection of the femoral head is not enough for evaluation of its surface status. PMID- 19643568 TI - Biomechanical consequences of patellar component medialization in total knee arthroplasty. AB - The optimal amount of patellar component medialization in knee arthroplasty is unknown. We measured the impact, on patellofemoral kinematics and contact force distribution, of 0.0-, 2.5-, and 5.0-mm patellar component medialization in 7 cadaveric specimens implanted with knee arthroplasty components. The knees were flexed dynamically in a weight-bearing rig. Medialization led to lateral shift of the patellar bone, slight medial shift of the patellar component in the femoral groove, lateral tilt of the patella, reduced patellofemoral contact force in later flexion, and lateral shift of the center of pressure in early flexion. Effects on shift and tilt were proportional to the amount of medialization. As a result of this investigation, we recommend medializing the patellar component slightly-on the order of 2.5 mm. PMID- 19643570 TI - Selective visual working memory in fear of spiders: the role of automaticity and material-specificity. AB - Following cognitive models of anxiety, biases occur if threat processing is automatic versus strategic. Therefore, most of these models predict attentional bias, but not explicit memory bias. We suggest dividing memory into the highly automatic working memory (WM) component versus long-term memory when investigating bias in anxiety. WM for threat has rarely been investigated although its main function is stimulus monitoring, particularly important in anxiety. We investigated WM for spiders in spider fearfuls (SFs) versus non anxious controls (NACs). In Experiment 1 (23 SFs/24 NACs), we replicated an earlier WM study, reducing strategic processing options. This led to stronger group differences and, thus, clearer WM threat biases. There were no group differences in Experiment 2 (18 SFs/19 NACs), using snakes instead of spiders to test whether WM biases are material-specific. This article supports cognitive models of anxiety in that biases are more likely to occur when reducing strategic processing. However, it contradicts the assumption that explicit memory biases are not characteristic of anxiety. PMID- 19643569 TI - Do parental psychopathology and unfavorable family environment predict the persistence of social phobia? AB - Parental psychopathology and unfavorable family environment are established risk factors for onset of offspring social phobia (SP), but their associations with the further course, e.g., persistence of the disorder, remain understudied. A community cohort of 1395 adolescents and their parents was followed-up over almost 10 years using the DIA-X/M-CIDI. Parental diagnostic interviews were supplemented by family history data. Parental rearing was retrospectively assessed by the Questionnaire of Recalled Parental Rearing Behavior in offspring, and family functioning by the Family Assessment Device in parents. Persistence measures (proportion of years affected since onset) were derived from diagnostic interviews, using age of onset, age of recency, and course information. Lack of emotional warmth and dysfunctional family functioning characteristics were associated with higher SP persistence, particularly in interaction with parental psychopathology. Predictors for SP persistence differ from those predicting SP onset. Unfavorable family environment alone and in interaction with parental disorders predict higher SP persistence. PMID- 19643571 TI - An examination of the MASC Social Anxiety Scale in a non-referred sample of adolescents. AB - Social phobia is prevalent during adolescence and is associated with negative outcomes. Two self-report instruments are empirically validated to specifically assess social phobia symptomatology in youth: the Social Phobia and Anxiety Inventory for Children and the Social Anxiety Scale for Adolescents. The Multidimensional Anxiety Scale for Children is a broad-band measure of anxiety containing a scale assessing the social phobia construct. The present study investigated the MASC Social Anxiety Scale in relation to other well-established measures of social phobia and depression in a non-referred sample of adolescents. Results support the convergent validity of the MASC Social Anxiety Scale and provide some support for its discriminant validity, suggesting its utility in the initial assessment of social phobia. Receiver Operating Characteristics (ROCs) calculated the sensitivity and specificity of the MASC Social Anxiety Scale. Binary logistic regression analyses determined the predictive utility of the MASC Social Anxiety Scale. Implications for assessment are discussed. PMID- 19643572 TI - The short- and long-term effect of duloxetine on painful physical symptoms in patients with generalized anxiety disorder: results from three clinical trials. AB - Generalized anxiety disorder (GAD) is associated with painful physical symptoms (PPS). These post hoc analyses of previous trial data assessed PPS and their response to duloxetine treatment in GAD patients. Studies 1 and 2 (n=840) were 9- to 10-week efficacy trials; study 3 (n=887) was a relapse prevention trial comprising a 26-week open-label treatment phase and a 26-week double-blind, placebo-controlled treatment continuation phase. Mean baseline visual analog scale scores (VAS, 0-100; n=1727) ranged from 26 to 37 for overall pain, headache, back pain, shoulder pain, interference with daily activities, and time in pain while awake. In studies 1 and 2, improvement on all VAS scores was greater in duloxetine-treated than in placebo-treated patients (p4 cmN0 or N+ received RT (36Gy+2 week gap+23.4Gy) with either MMC/CDDP or MMC/5-FU (MMC 10mg/m(2) d1 of each sequence; 5-FU 200mg/m(2)/day c.i.v. daily; CDDP 25mg/m(2) weekly). Forty patients/arm were needed to exclude a RECIST objective response rate (ORR), 8 weeks after treatment, of <75% (Fleming 1, alpha=10%, beta=10%). RESULTS: The ORR was 79.5% (31/39) (lower bound confidence interval [CI]: 68.8%) with MMC/5-FU versus 91.9% (34/ 37) (lower bound CI: 82.8%) with MMC/CDDP. In the MMC/5-FU group, two patients (5.1%) discontinued treatment due to toxicity versus 11 (29.7%) in the MMC/CDDP group. Nine grade 3 haematological events occurred with MMC/CDDP versus none with 5-FU/MMC. The rate of other toxicities did not differ. There was no toxic death. Thirty-one patients in the MMC/5-FU arm (79.5%) and 18 in the MMC/CDDP arm (48.6%) were fully compliant with the protocol treatment (p=0.005). CONCLUSIONS: Radio-chemotherapy with MMC/CDDP seems promising as only MMC/CDDP demonstrated enough activity (RECIST ORR >75%) to be tested further in phase III trials; MMC/5-FU did not. MMC/CDDP also had an overall acceptable toxicity profile. PMID- 19643600 TI - The histone deacetylase inhibitor suberoylanilide hydroxamic acid sensitises human hepatocellular carcinoma cells to TRAIL-induced apoptosis by TRAIL-DISC activation. AB - This paper shows that the histone deacetylase inhibitor SAHA sensitised at sub toxic doses human hepatocellular carcinoma cells (HepG2, Hep3B and SK-Hep1) to TRAIL-induced apoptosis, while it was ineffective in primary human hepatocytes (PHHs). In particular in HCC cells SAHA increased the expression of death receptor 5 (DR5) and caused a decrement of c-Flip. These two modifications provoked in the presence of TRAIL the rapid production of TRAIL-DISC and the activation of caspase-8. Consequently SAHA/TRAIL combination induced many apoptotic events, such as a cleavage of Bid into tBid, dissipation of mitochondrial membrane potential, activation of caspase-3 with the consequent cleavage of both NF-kB and Akt. The decrease in NF-kB level seemed to be responsible for the reduction in the content of IAP family antiapoptotic proteins while the decrease in Akt level caused a reduction in phospho-Bad. These events led to the activation of caspase-9, which contributed to the strong apoptotic activity of TRAIL. Sensitisation of human hepatocellular carcinoma cells to TRAIL induced apoptosis by SAHA may suggest new strategies for the treatment of liver tumours. PMID- 19643601 TI - Glutathione S-transferase P1 Ile105Val polymorphism and colorectal cancer risk: a meta-analysis and HuGE review. AB - Colorectal cancer is the third most common form of cancer and the fourth most frequent cause of cancer deaths worldwide. Its development is influenced by both environmental and genetic factors. The glutathione S-transferase P1 gene (GSTP1) is a particularly attractive candidate for colorectal cancer susceptibility because it codes the enzyme involved in the metabolism of environmental carcinogens such as polycyclic aromatic hydrocarbons (PAHs). However, epidemiologic findings have been inconsistent. To investigate a putative association of GSTP1 Ile105Val polymorphism with the risk of colorectal cancer, we performed a meta-analysis and HuGE review of 16 published case-control studies (involving a total of 4386 colorectal cancer patients and 7127 controls). We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, the comparison of Val versus Ile allele showed no differential susceptibility to colorectal cancer (OR=0.98, 95% CI: 0.92-1.04). A protective effect was found in recessive, with an OR of 0.86 (95% CI: 0.76-0.98). Whereas no significant association was observed in either dominant or codominant model. In stratified subgroup analysis, no effect of Val allele was seen in subjects of Caucasian and Asian descent, and in healthy and hospital controls. In conclusion, the meta-analysis suggests that the GSTP1 Ile105Val polymorphism is unlikely to increase considerably the risk of sporadic colorectal cancer, and it should be confirmed in further studies. PMID- 19643602 TI - High consistency enzymatic hydrolysis of hardwood substrates. AB - The feasibility of using a laboratory peg mixer to carry out high consistency enzymatic hydrolysis of lignocellulosic substrates was investigated. Two hardwood substrates, unbleached hardwood pulp (UBHW) and organosolv pretreated poplar (OPP), were used in this study. Hydrolysis of UBHW and OPP at 20% substrate consistency led to a high glucose concentration in the final hydrolysate. For example, a 48 h enzymatic hydrolysis of OPP resulted in a hydrolysate with 158 g/L of glucose. This is the highest glucose concentration ever obtained from enzymatic hydrolysis of lignocellulosic substrates. Fermentation of UBHW and OPP hydrolysates with high glucose content led to high ethanol concentrations, 50.4 and 63.1 g/L, respectively after fermentation. Our results demonstrate that using common pulping equipment to carry out high consistency hydrolysis can overcome the rheological problems and greatly increase the sugar and ethanol concentrations after the hydrolysis and fermentation. PMID- 19643604 TI - Copper and cadmium sorption onto kraft and organosolv lignins. AB - The relative metal sorption ability of kraft and organosolv lignins was examined as a function of solution chemistry (pH, ionic strength (I), sorbate-to-sorbent ratio) and reaction time. The surface charge characteristics and functional group composition of these lignins, especially kraft lignin, are favorable for metal sorption. Sorption of Cu and Cd increased with increasing pH and decreasing I. Description of sorption isotherms required the more complex Sips equation, as compared to the simpler Langmuir and Freundlich formulations, indicative of the presence of binding sites with varying affinities on these lignin biosorbents. Sorption capacity varied in the following order: softwood organosolv lignin75%. CPB-specific information was collected online. Blood samples were collected for analysis of haemoglobin, lactate, amylase, creatinine and C-reactive protein: pre-CPB, at weaning from CPB and on day 1 postoperatively. RESULTS: Randomisation formed two uniform groups. Choice of static or dynamic blood-flow control during CPB had no significant effects on organ function as judged by lactate, amylase or creatinine levels. On increasing oxygen demand, oxygen balance was maintained by increasing venous oxygen extraction rates in the static flow mode and by increasing the pump flow rate in the dynamic group. CONCLUSIONS: Independent of the blood-flow control mode, oxygen balance remained preserved. However, the dynamic mode provided higher oxygen delivery, which may increase margins of safety and protection of organ function. PMID- 19643621 TI - Exercise capacity of a contemporary cohort of children with hypoplastic left heart syndrome after staged palliation. AB - OBJECTIVE: Outcome of staged palliation for hypoplastic left heart syndrome has improved over the past decades. However, only little is known about the exercise capacity of children with palliated hypoplastic left heart syndrome where a systemic right ventricle supports the systemic circulation. The aim of the study was to assess exercise capacity in a contemporary cohort of children with hypoplastic left heart syndrome palliated in a single centre according to a uniform surgical strategy. METHODS: Standardised cardiopulmonary exercise testing on a treadmill was performed in 46 consecutive hypoplastic left heart patients (median age: 6.0 (4.1-11.4) years). All but one patient reached the anaerobic threshold. Exercise data were compared to normal values obtained with a similar exercise protocol in a large cohort of paediatric volunteers. RESULTS: Oxygen uptake at anaerobic threshold (26.9+/-6.0 ml kg(-1)min(-1); 74.5+/-18.2% of predicted) and maximal oxygen uptake (31.0+/-6.8 ml kg(-1)min(-1); 60.8+/-15.0% of predicted) were significantly reduced compared with controls (P<0.0001 for both). The limitation in exercise capacity was due to an impaired rise in heart rate (158+/-23 bpm; 79.7+/-11.5% of predicted; P<0.0001) and oxygen pulse (4.5+/ 1.6 ml per beat; 85.5+/-22.0% of predicted; P<0.0001). Furthermore, respiration during exercise was inefficient with an elevated respiratory rate and reduced maximal tidal volume and minute ventilation at maximal exercise. CONCLUSIONS: The exercise capacity of children with hypoplastic left heart syndrome is markedly reduced. Limitations in heart rate increase and stroke volume augmentation are the major contributors to this. An abnormal ventilatory response to exercise also adds to their limitation in exercise tolerance. However, the degree of physical disability does not justify discouraging these patients from school and leisure sports. PMID- 19643623 TI - Delayed dislocation of a transapically implanted aortic bioprosthesis. AB - Trans-apical aortic bioprosthesis implantation is currently evaluated as an alternative technique in high-risk patients. We report the case of a delayed upward displacement of a prosthesis after this procedure. It is hypothesised that the asymmetric calcification of the native valve and the presence of a mitral prosthesis caused the dislocation. PMID- 19643622 TI - Off-pump total left anterior descending area re-vascularisation using left internal thoracic artery auto Y graft; angiographic early and 3-year follow-up results. AB - BACKGROUND: We evaluated the efficacy of a well-prepared left internal thoracic artery (LITA) auto Y graft for simultaneous left anterior descending artery (LAD) and diagonal artery (DA) re-vascularisation in selected patients for the reduction of the number of required grafts and improved graft patency, while limiting technical problems. METHODS: Twenty well-controlled diabetic patients, mean age 62.8+/-8.3, 17 males and three females, underwent isolated elective off pump coronary artery bypass grafting using the LITA auto Y graft from July 2003 to August 2004. RESULTS: In-hospital data and angiographic results at 6 months after the surgery showed that there was no early mortality, early graft failure and major morbidity except for two cases of superficial wound infection. The 3 year follow-up results including angiographic findings (mean of 37+/-3.3-month follow-up) demonstrated that all patients are alive and have excellent graft patency in both the LAD and DA. Only two cases required right coronary artery (RCA) stenting during the follow-up period. Compared with our previous routine LITA composite Y graft technique, it is assumed that LITA auto Y graft technique may reduce the number of mobilised conduits or avoided sequential anastomosis. CONCLUSIONS: This small study showed that our technique is technically feasible and may be safely performed to the selective patients. The LITA auto Y graft might be an additional surgical option, in terms of not only preserving the other grafts and maintaining patency in the LAD area bypass, but also preventing the need for sequential anastomoses. PMID- 19643625 TI - Fulminant prosthetic valve endocarditis caused by Listeria monocytogenes. PMID- 19643626 TI - Why Fontan procedure fails in the long term. PMID- 19643627 TI - Impact of chest tube clearance on postoperative morbidity after thoracotomy: results of a prospective, randomised trial. AB - OBJECTIVE: In many centres of thoracic surgery, milking of chest tubes is performed to prevent them from blocking. The usefulness of chest tube clearance is discussed controversially. Therefore, we investigated the impact of postoperative chest tube milking on postoperative outcome in a prospective, randomised trial. METHODS: Within a period of 11 months, 145 patients undergoing pulmonary resection through thoracotomy were included in the study. Two chest tubes each (silicone drainage, Redax, Mirandola, Italy) were placed in all patients (ventral tube 21Ch and dorsal tube 24Ch). Milking was applied to both chest tubes for 1 min every 2h within the first 48 h postoperatively and continuous suction of -20 cm H(2)O was maintained for 48 h. Duration of chest tube drainage, quantity and quality of effusion or air leakage, co-morbidity, length of hospital stay and 30-day postoperative morbidity and mortality were analysed. Furthermore, outcome was measured by assessment of chest radiographs at the time of discharge from hospital. RESULTS: Randomisation resulted in milking of chest tubes of 73 patients and in observation of chest tubes without any manipulation in 72 patients. Twenty-one patients had to be excluded from further analysis due to violation from the study protocol (n=9), necessity of replacement of a chest tubes (n=9) and re-operation for bleeding (n=3). The 30-day mortality rate was 1.4% in each group and the 30-day morbidity was 49.3% in the milking group and 52.8% in the observation group. Milking of chest tubes was not associated with a lower postoperative mortality or morbidity (p=0.99 and p=0.67, respectively; chi-square test). We observed a significant increase of postoperative pleural effusion drainage in the milking group 48 h after surgery (p=0.004; unpaired t-test). No correlation was seen between milking of chest tubes and the duration of chest tube drainage, quality of effusion, air leakage or length of hospitalisation. CONCLUSIONS: We showed for the first time that postoperative chest tube milking is associated with a significant increase of pleural fluid drainage. Postoperative morbidity and mortality was not improved and therefore chest tube milking cannot be recommended as a routine postoperative procedure. PMID- 19643628 TI - Involvement of E-cadherin cleavage in reperfusion injury. AB - OBJECTIVE: E-cadherin is a major cell-to-cell adhesion molecule, of which the ectodomain is cleaved from epithelial cells to yield a soluble form after the pathological alteration of the alveolar epithelium. We investigated the excretion level of soluble E-cadherin in a rat lung isotransplant model, and demonstrated the involvement of this molecule in the pathogenesis of reperfusion injury after lung transplantation. METHODS: Inbred male Lewis rats were used as both donor and recipient animals, and they were subjected to left lung isotransplantation. After 6 h of ischaemia, the left lung was transplanted into a recipient rat and reperfused for 4 h. The animals were injected intravenously with (125)I-labelled albumin at 3 h after the onset of reperfusion as a marker of pulmonary albumin leakage. We assessed pulmonary alveolar septal damage quantitatively based on the (125)I-albumin concentration ratio of bronchoalveolar lavage fluid (BALF) to plasma. Soluble E-cadherin fragments were detected in BALF on Western blot analysis using affinity-purified antibodies specific to rat E-cadherin synthetic peptides. RESULTS: The BALF supernatant-to-plasma ratio of the graft lung was significantly increased compared to that of the control group. Western blot analysis showed a marked release of soluble E-cadherin into BALF, and its increase in BALF was associated with alveolar septal damage. CONCLUSIONS: These results suggest that one potential mechanism of lung reperfusion injury involves the cleavage of E-cadherin. PMID- 19643629 TI - Gene therapies for pulmonary hypertension-from experimental trials to bedside aspects. AB - Accompanying the continuously deepening understanding of the mechanism of pulmonary hypertension that many genes are found to be aetiologically involved in its development, burgeoning literature manifest that gene therapies aimed at correcting these genetic defects have the ability to restore deficient pulmonary gene expression, over-express biologically active gene products, reverse established disease and regenerate pulmonary vasculature, and may constitute a promising therapeutic strategy for pulmonary hypertension. Therefore, to provide new information to basic scientists and clinical investigators, we present a review that attempts a clear description of the therapeutic potential of gene therapy in the treatment of pulmonary hypertension. PMID- 19643630 TI - Anomalous partial pulmonary venous drainage. PMID- 19643631 TI - Retinal phosphenes and discrete dark noises in rods: a new biophysical framework. AB - Spontaneous rhodopsin activation produces discrete noises indistinguishable from single-photon responses. However, there is a serious discrepancy between the apparent energy barrier of thermal events compared with that of the photon-driven process. Current estimates of the activation energies of discrete dark noises in vertebrate rod and cone pigments are approximately 40-50 cal/mol for activation by photon and approximately 20-25 kcal/mol for activation by heat. To reconcile this discrepancy, it was assumed that thermal activation and photon activation of rhodopsin follow different molecular mechanisms. The most convincing hypothesis for a separate low-energy thermal pathway is that the discrete dark noises of rods arise in a small subpopulation of rhodopsins, where the Schiff base linking the chromophore to the protein part has been deprotonated. According to Narici et al.' experiments (2009, Radiation Measurements), phosphene perception in space travel is due to the ionizing radiation-induced free radicals that generate chemiluminescent photons from lipid peroxidation. These photons are absorbed by the photoreceptors chromophores, which modify the rhodopsin molecules (bleaching) and start the photo-transduction cascade resulting in the perception of phosphenes. Here, we point out that not only retinal phosphenes but also the discrete dark noise of rods can be due to the natural redox related (free radical) bioluminescent photons in the retina. In other words, under regulated conditions, lipid peroxidation is a natural process in cells and also in retinal membranes. Since the natural lipid peroxidation is one of the main sources of bioluminescent photons and the photoreceptors have the highest oxygen demand and polyunsaturated fatty acid (PUFA) concentration, there is a continuous, low level bioluminescent photon emission in the retina without any external photonic stimulation. During photopic or scotopic vision, evanescent bioluminescent photon emission is negligible. In contrast, in dark-adapted retinal cells this evanescent bioluminescent photon emission is not negligible. Therefore, our hypothesis is that the discrete dark noise of rods can be due to these bioluminescent photons. PMID- 19643632 TI - Screening of polycyclic polyprenylated acylphloroglucinols from Garcinia species using precursor ion discovery (PID) scan and ultra performance liquid chromatography electrospray ionization Q-TOF tandem mass spectrometry. AB - A strategy was newly developed to rapidly screen polycyclic polyprenylated acyl phloroglucinols (PPAPs) from the plant matrices of nine Garcinia species using ultra-performance liquid chromatography (UPLC) coupled with comprehensive mass spectrometric approaches including precursor ion discovery (PID) and tandem mass (MS/MS) scans. The PPAPs share the same diagnostic product ion at m/z 177.02 in positive MS/MS scan, which may be increased as the base peak by ramping the cone voltage from 45 to 100 V. With this ramping cone voltage PID scan, it is feasible to selectively screen the PPAPs from 29 samples of nine Garcinia species. This approach has proven to be a powerful, highly selective, and sensitive tool for rapid screening and detection of nontargeted components in natural products before the purification and structural elucidation process. PMID- 19643634 TI - Evaluation of transcatheter arterial embolization with gelatin sponge particles, microcoils, and n-butyl cyanoacrylate for acute arterial bleeding in a coagulopathic condition. AB - PURPOSE: To evaluate the outcome of transcatheter arterial embolization with gelatin sponge particles, microcoils, and N-butyl cyanoacrylate (NBCA) for acute arterial hemorrhage in the setting of coagulopathy. MATERIALS AND METHODS: Coagulopathy is defined by a platelet count less than 5 x 10(4)/microL and/or International Normalized Ratio (INR) greater than 1.5. Forty-six patients (31 male patients; mean age, 62 years) with acute arterial hemorrhage in a coagulopathic condition were treated by transcatheter arterial embolization with gelatin sponge particle, microcoils, and NBCA. RESULTS: Because of failure of hemostasis or recurrent hemorrhage, 10 patients who underwent gelatin sponge particle embolization also received transcatheter arterial embolization with microcoils or NBCA embolization and two patients who underwent microcoil embolization also received transcatheter arterial embolization with NBCA. The gelatin sponge particle group consisted of 27 hemorrhagic arteries in 25 patients, the microcoil group had 20 in 20 patients, and the NBCA group had 16 in 13 patients. The mean platelet count and mean INR value were 5.8 x 10(4)/microL +/- 3.5 and 1.81 +/- 0.50, respectively. The primary hemostatic rate, recurrent hemorrhage rate, and mean treatment time for the gelatin sponge particle, microcoil, and NBCA groups were 67%, 23%, and 25 minutes +/- 10; 80%, 0%, and 37 min +/- 19; and 100%, 0%, and 9 min +/- 4, respectively. Primary and secondary hemostasis were achieved in 50 (80%) and 60 (95%) of the 63 hemorrhagic arteries, respectively. Three hemorrhagic arteries in which transcatheter arterial embolization failed were treated with surgical repair. CONCLUSIONS: Although transcatheter arterial embolization with microcoils took a greater amount of time, transcatheter arterial embolization with NBCA or microcoils was more effective and feasible than that with gelatin sponge particle in terms of hemostasis and prevention of recurrent hemorrhage in a coagulopathic condition. PMID- 19643633 TI - Collision induced unfolding of protein ions in the gas phase studied by ion mobility-mass spectrometry: the effect of ligand binding on conformational stability. AB - Ion mobility spectrometry, with subsequent mass spectrometric detection, has been employed to study the stability of compact protein conformations of FK-binding protein, hen egg-white lysozyme, and horse heart myoglobin in the presence and absence of bound ligands. Protein ions, generated by electrospray ionization from ammonium acetate buffer, were activated by collision with argon gas to induce unfolding of their compact structures. The collisional cross sections (Omega) of folded and unfolded conformations were measured in the T-Wave mobility cell of a Waters Synapt HDMS (Waters, Altrincham, UK) employing a calibration against literature values for a range of protein standards. In the absence of activation, collisional cross section measurements were found to be consistent with those predicted for folded protein structures. Under conditions of defined collisional activation energies partially unfolded conformations were produced. The degree of unfolding and dissociation induced by these defined collision energies are related to the stability of noncovalent intra- and intermolecular interactions within protein complexes. These findings highlight the additional conformational stability of protein ions in the gas phase resulting from ligand binding. PMID- 19643635 TI - Diffusion-weighted imaging characteristics of primary central nervous system germinoma with histopathologic correlation: a retrospective study. AB - RATIONALE AND OBJECTIVES: The aim of this study was to quantify, using diffusion weighted magnetic resonance imaging, the microscopic rate of water diffusion in pure germinoma and to determine whether or not the apparent diffusion coefficient (ADC) values correlated with the different histologic components. MATERIALS AND METHODS: A retrospective analysis of echoplanar diffusion-weighted magnetic resonance images was conducted on 10 patients with 11 germinoma lesions. All images were obtained using 1.5-T magnets with a b value of 1000 s/mm(2). Regions of interest were drawn separately within the solid and the cystic or necrotic components of each germinoma, as well as within the normal gray and white matter of the respective cases, to calculate ADCs. The diffusion characteristics of the germinomas were assessed using mean and normalized ADC values. Histologic samples from all cases were blindly reviewed and then correlated with the ADC values. RESULTS: Data are expressed as mean +/- standard error. Evaluation of the solid components revealed that 36% of germinomas (4 of 11) had predominantly restricted diffusion (ADC(solid), 694.71x10(-6)+/-74.54x10(-6) s/mm(2); ADC ratio, 0.84+/ 0.07) compared to normal brain. The majority (55% [6 of 11]) had normal diffusion (ADC(solid), 947.64x10(-6)+/-54.38x10(-6) s/mm(2); ADC ratio, 1.14+/-0.10). Only 9% (1 of 11) had increased diffusion (ADC(solid), 1172.30x10(-6)+/-48.52x10(-6) s/mm(2); ADC ratio, 1.67+/-0.16). The cystic and necrotic components had a mean ADC ratio of 2.55+/-0.25. There was no significant correlation between the histologic components and the ADC values of germinomas. CONCLUSIONS: The vast majority of germinomas demonstrated predominantly restricted (36%) or normal (55%) diffusion. The histologic components were not correlated with the ADC values. PMID- 19643636 TI - CT-guided biopsies of pancreatic lesions: impact of contrast application prior to versus following needle placement. AB - RATIONALE AND OBJECTIVES: Pancreatic lesions are frequently detected in pancreatic phase only, which may lead to false negative findings in CT-guided biopsies. We evaluated the accuracy and complication rate of CT guided biopsies of pancreatic lesions with i.v.-contrast application following needle placement in comparison to biopsy after contrast enhanced CT. MATERIALS AND METHODS: In 30 patients planning and needle placement was performed on the basis of a native planning CT and prior diagnostic CT or MRT. After needle placement contrast enhanced CT was performed to confirm needle course and adjusted if necessary (group 1). In 30 additional patients biopsy was planned based on contrast enhanced CT and needle was placed in the lesion. Control scans confirmed correct needle position (group 2). An 18G coaxial system was used for both groups. Statistical analysis was performed with Student's t and Fisher's exact test for comparison of lesion size, location as well as accuracy and complication rates. RESULTS: Mean lesion size was significantly smaller in group 1 (31 mm vs. 39 mm; p = 0.02). Diagnostic accuracy and sensitivity for malignancy in group 1 was 93% and 92% versus 80% and 77% in group 2. Complications related to the procedure, i.e. haematoma (n = 5, group 1/n = 2, group 2) and pain (n = 0, group 1/n = 2, group 2) did not statistically differ. CONCLUSION: CT-guided biopsy of pancreatic lesions with i.v.-contrast application following needle placement is a reliable method and provides superior accuracy compared to biopsies performed after contrast enhanced planning CT. PMID- 19643637 TI - Venous thrombosis and congenital absence of inferior vena cava in a patient with menorrhagia and pelvic pain. AB - BACKGROUND: Agenesis of the inferior vena cava (IVC) is an uncommon congenital vascular malformation. We report a case in a teenage female recently started on oral contraception. CASE: Because of menorrhagia, the patient had begun an oral contraceptive pill (OCP) 1(1/2) months prior to presentation. She initially presented with pelvic and lower back pain, and imaging showed a pelvic deep venous thrombosis (DVT) and an interrupted IVC. Anticoagulation was started, the OCP was discontinued, and a discussion occurred regarding the treatment options for her menorrhagia following her recent diagnosis. SUMMARY AND CONCLUSION: The case presented shows the rare occurrence of the congenital absence of an IVC with pelvic thrombosis in a young female with a history of menorrhagia and new onset of pelvic pain. The evaluation of this case report leads to a comprehensive review in the treatment choice for menorrhagia with the preceding history of a thrombotic event. PMID- 19643638 TI - Changes in genital anatomy and microbiology in girls between age 6 and age 12 years: a longitudinal study. AB - STUDY OBJECTIVE: To study changes in genital anatomy and occurrence of human papillomavirus and Gardnerella vaginalis in girls resulting from growth and development. DESIGN: At age 11-12 years, an invitation was sent to 180 girls to attend a follow-up examination. All girls had previously participated in a study exploring anogenital anatomy and microbiology in children selected for non-abuse at age 5 and 6. The genital area was examined with a colposcope and microbiological samples for Gardnerella vaginalis (GV) and human papillomavirus (HPV) were collected. GV was identified by conventional criteria and HPV by a PCR method. RESULTS: Thirty-one girls were examined twice, at mean age 5.7 and 12.0 years. At first examination all were pre-pubertal. At second examination 21 girls were B2/P2 or above. Significantly more girls had developed a structure called a fossa groove. A thick and redundant hymen with a tendency of folding outward was more common at the second examination. Two girls had GV and one girl had HPV-16 identified. Another girl was classified to have a deep notch and a probable transection in her hymen, and this girl reported a painful insertion of a tampon. All girls denied sexual activity. CONCLUSION: The main genital finding in girls entering puberty is the hymen becoming thick and redundant with a tendency of folding out. In the study findings associated with sexual activity were discovered in two girls, and the possibility of alternative explanations is discussed. PMID- 19643639 TI - Vitamin D insufficiency is prevalent among pregnant African American adolescents. AB - STUDY OBJECTIVE: Recent attention has focused on vitamin D insufficiency but few data exist on vitamin D status among pregnant minority youth. DESIGN: A screening study was undertaken in adolescents having prenatal blood samples drawn for other routine tests obtained during the second trimester (18+/-1.8 week gestation, n=44) or third trimester of pregnancy (28.4+/-2.1 week gestation, n=36). Serum 25 hydroxyvitamin D (25(OH)D) was measured and significant determinants of vitamin D insufficiency in this cohort were identified. SETTING: Urban prenatal clinic. PARTICIPANTS: Eighty pregnant African American adolescents (< or = 18 y of age). MAIN OUTCOME MEASURE(S): Vitamin D status, STDs, hemoglobin, season, birth weight RESULTS: Serum 25(OH)D in this group averaged 21.6+/-8 ng/mL (age 16.5+/-1.1 y, n=80), and did not significantly differ between the second (20.95+/-8.2 ng/mL, n=44) and third trimester cohorts (22.5+/-7.9 ng/mL, n=36). Vitamin D insufficiency (< 20 ng/mL) was evident in 46.25% and vitamin D deficiency (<15 ng/mL) was evident in 21.25% of those studied. Significant predictors of suboptimal vitamin D status included sampling during the winter months (P=0.004), lower hemoglobin concentration (P=0.019), and higher second trimester leptin levels (P=0.018). Inverse associations between 25(OH)D and bacterial vaginosis were evident when controlled for season of sampling (P=0.02, n=80). CONCLUSIONS: Vitamin D insufficiency was prevalent among urban pregnant minority adolescents. Further studies are needed to address the impact of this finding on maternal and neonatal calcium homeostasis and bone health. PMID- 19643640 TI - Comparison of clinical evaluation of genitourinary symptoms in female adolescents among primary care versus emergency department physicians. AB - OBJECTIVE: To compare clinical approaches to assessment and treatment of female adolescents with genitourinary symptoms among primary care and emergency department (ED) physicians. DESIGN: A chart review was performed of the evaluation and treatment of 472 patients presenting between July 1, 2005, and June 30, 2006. SETTING: Suburban and tertiary care EDs and primary care settings. PARTICIPANTS: Female patients age 13-21 years with genitourinary symptoms. INTERVENTIONS: None. OUTCOME MEASURES: Physician assessment of sexual history, performance of pelvic exam and sexually transmitted infection (STI) tests, empiric treatment of suspected STIs. RESULTS: Patients seen in primary care settings were more likely to be asked about sexual history, including contraceptive use, than patients in the ED (P<0.001). After adjustment for age and race, there was no statistically significant difference between the ED and primary care sites in performance of pelvic exams or gonorrhea and chlamydia tests. However, there was a higher likelihood that older adolescents would undergo pelvic exams (P=0.001), and STI testing (P=0.002) than younger patients. There was no significant difference in empiric treatment of patients with positive STI tests between ED and primary care sites or across the age spectrum. CONCLUSIONS: ED physicians should obtain sexual histories on patients with genitourinary symptoms. Both primary care and ED clinicians should consistently test for STIs in sexually active patients who have genitourinary symptoms. Physicians in both settings should have a low threshold for testing and empirically treating adolescents with symptoms or physical exam findings consistent with STIs. PMID- 19643641 TI - Vaginal stones in a 5-year-old girl: a novel approach of removal. AB - BACKGROUND: Primary vaginal stones in children are extremely rare and removal can be difficult. We describe a procedure for safe extraction of vaginal stones. CASE: A 5-year-old, wheelchair-bound girl was referred to the urologic department with recurrent febrile urinary tract infection. Diagnostics of the kidneys showed no abnormalities. The bladder appeared to contain two stones. On urethro cystoscopy no stones were seen. Vaginoscopy identified vaginal stones. After 4 weeks of estrogen treatment, a second procedure via vaginal introduction of a nephroscope in combination with an ultrasonic device, effectively disintegrated the stones. SUMMARY AND CONCLUSION: We recommend the use of a nephroscope in visualizing the vagina and cervix and facilitating instrumentation in prepubertal girls. PMID- 19643642 TI - Hypoplastic uterus and clitoris enlargement in Swyer syndrome. AB - BACKGROUND: Swyer syndrome is associated with absent testicular differentiation in a 46XY phenotypic female. CASE: A 17-year-old female presented with primary amenorrhea and 46XY karyotype. Breast and pubic hair development were Tanner 2, and clitoral enlargement was noted. Magnetic resonance imaging revealed a hypoplastic uterus and 2 "normal ovaries." Serum follicle-stimulating hormone and luteinizing hormone were elevated. Testosterone and androstenedione were in the female range. Dehydroepiandrosterone sulfate was slightly elevated. Laparoscopic bilateral gonadectomy was performed. Pathology reports showed bilateral microscopic benign hilar cell tumors. SUMMARY AND CONCLUSION: The diagnosis was a real puzzle for the clinicians because of the association of clitoral hypertrophy without hirsutism, female internal genitalia, and a 46XY karyotype. Clitoral enlargement can be explained by transient androgen secretion by the hilar cells found in the resected gonads. PMID- 19643643 TI - Recurrent bilateral serous cystadenomas in a premenarchal girl: a case report and literature review. AB - BACKGROUND: Ovarian serous cystadenomas are rare in children. No case of recurrence after surgical resection in a premenarchal girl has been published. CASE: An 8-year-old presented with abdominal pain and ultrasound showed bilateral ovarian cystic masses with normal clinical and laboratory exam. Cystectomies were performed revealing serous cystadenomas. Ten months later, her pain returned and ultrasound showed new cysts. Persistence of cysts and symptoms required repeat surgery with the same pathology. SUMMARY AND CONCLUSION: Premenarchal girls with ovarian cystic masses require surgical intervention in cases of persistent symptoms, uncertain diagnosis, or concern for ovarian torsion. With reassuring imaging and tumor markers, conservation of the ovary can be achieved with cystectomy alone. Ultrasound follow-up is recommended after surgical resection until bimanual exam can be performed. PMID- 19643644 TI - Urinary tract infection as a single presenting sign of multiple vaginal foreign bodies: case report and review of the literature. AB - BACKGROUND: Vaginal foreign bodies in children usually present with foul-smelling discharge and/or vaginal bleeding. Rarely, these basic clinical diagnostic signs are not present. CASE: We report on a 5(1/2)-year-old girl with recurrent lower urinary tract infection as the sole presentation of multiple vaginal foreign bodies. Ultrasound of the lower urinary tract was inconclusive, and cystography indicated for recurrent urinary tract infections was declined by the patient in an outpatient setting. Cystography under general anesthesia raised the suspicion of foreign vaginal objects, and the definitive diagnosis was made by vaginoscopy. The relevant literature covering this subject is reviewed. CONCLUSION: High level of suspicion and strict basic diagnostic protocol are the most important steps for a timely diagnosis of this condition. PMID- 19643645 TI - Mullerian adenosarcoma of the uterine cervix in an adolescent girl. AB - BACKGROUND: Cervical adenosarcoma is a rare gynecological tumor which is prone to recur locally. A case of cervical adenosarcoma in a 14-year-old girl treated in order to preserve fertility. CASE: A 14-year-old girl presented with a pedunculated mass protruding from the vagina. Simple excision was performed. Histological evaluation revealed adenosarcoma. Her clinical course has been uneventful for fifteen months. SUMMARY AND CONCLUSION: Adenosarcoma is a low malignant potential tumor of the female genital tract. A simple excision may be an option for young women who need to preserve their fertility. It is mandatory to monitor regularly the cervical base of the lesion for the purpose of the high potential of the local recurrence. PMID- 19643646 TI - Evaluation of an HIV/STD sexual risk-reduction intervention for pregnant African American adolescents attending a prenatal clinic in an urban public hospital: preliminary evidence of efficacy. AB - STUDY OBJECTIVE: To evaluate an intervention to reduce HIV/STD-associated behaviors and enhance psychosocial mediators for pregnant African-American adolescents. DESIGN: A randomized controlled trial. Participants completed baseline and follow-up assessments. SETTING: An urban public hospital in the Southeastern U.S. PARTICIPANTS: Pregnant African-American adolescents (N=170), 14 20 years of age, attending a prenatal clinic. INTERVENTION: Intervention participants received two 4-hr group sessions enhancing self-concept and self worth, HIV/STD prevention skills, and safer sex practices. Participants in the comparison condition received a 2-hr session on healthy nutrition. MAIN OUTCOME MEASURES: Consistent condom use. RESULTS: Intervention participants reported greater condom use at last intercourse (adjusted odds ratio=3.9, P=0.05) and consistent condom use (AOR=7.9, P=0.05), higher sexual communication frequency, enhanced ethnic pride, higher self-efficacy to refuse risky sex, and were less likely to fear abandonment as a result of negotiating safer sex. CONCLUSIONS: Interventions for pregnant African-American adolescents can enhance condom use and psychosocial mediators. PMID- 19643647 TI - Discussions of vaginal douching with family members. AB - PURPOSE: This study examined women's personal douching history and the information they were given by others. METHODS: Participants in the study (N=199; mean age=28.92) completed a 48-question survey on douching practices and attitudes. RESULTS: Fifty-seven percent of participants had douched and 39% currently douche. The majority of women reported douching after menstruation, before or after sex, or as needed. Reasons for douching included maintaining cleanliness, feeling good and fresh, eliminating vaginal odor, and removing menstrual blood. Most women (69%) had at least one discussion about douching, with 49% having a discussion with their mother and 22% with a health care provider (HCP). Of the women who currently do not douche, 47% stopped after a HCP instructed them to quit; whereas, 100% of women whose HCP encouraged douching went on to douche. Furthermore, 66% of women planned to discuss douching with a younger girl, with 57% encouraging or being neutral and 43% discouraging it. Women who have previously douched were more likely to discuss and encourage douching than women who had never douched. Also, women who have received a discussion about douching or were encouraged to douche were more likely to douche than women who had not received a discussion or were discouraged. CONCLUSIONS: Results from this study suggest that younger generations may be taught about or encouraged to douche by their mothers. By giving women accurate information and discouraging douching, women may be less likely to douche or encourage douching in their daughters. PMID- 19643648 TI - Gynecologic issues of adolescents with Down syndrome, autism, and cerebral palsy. AB - STUDY OBJECTIVE: The gynecologic issues of adolescents with disabilities are understudied. The purpose of this study was to identify and compare the presenting complaints, treatments, and follow-up of adolescent girls with Down syndrome (DS), autism, and cerebral palsy (CP) presenting to a specialized gynecologic clinic for women with developmental disabilities. SETTING: Outpatient gynecology clinic. PARTICIPANTS: Forty four adolescents (<21 y); 13 with DS, 14 with autism, and 17 with CP who presented to the clinic from 1999 to 2006. INTERVENTIONS: None. MAIN OUTCOME MEASURES: A retrospective review of the electronic medical records to collect data on age at presentation to clinic, ethnicity, menstrual history, chief complaint, treatment, and follow-up. RESULTS: Mean age at presentation to clinic was 15+/-3.5 years, and age of menarche was 12.5+/-2 years; age at menarche did not significantly differ between groups. The most frequent complaints were irregular bleeding (n=10) and mood/behavioral changes (n=6). Girls with autism were significantly (chi(2)=8.89, P=.012) more likely to present with behavioral issues than the other 2 groups. Initial management for the behavior issues in the autism group included nonsteroidal anti inflammatory drugs (NSAID), oral contraceptives, and education. CONCLUSION: The most common gynecologic complaints of adolescent girls with DS, autism, and CP centered on menstruation and mood disorders. Patients with autism were more likely to present with behavioral issues related to the onset of periods. PMID- 19643649 TI - EPIC- and CHANCE-HSQC: two 15N-photo-CIDNP-enhanced pulse sequences for the sensitive detection of solvent-exposed tryptophan. AB - Photochemically induced dynamic nuclear polarization (photo-CIDNP) of nuclei other than (1)H offers a tremendous potential for sensitivity enhancement in liquid state NMR under mild, physiologically relevant conditions. Photo-CIDNP enhancements of (15)N magnetization are much larger than those typically observed for (1)H. However, the low gyromagnetic ratio of (15)N prevents a full fruition of the potential signal-to-noise gains attainable via (15)N photo-CIDNP. Here, we propose two novel pulse sequences, EPIC- and CHANCE-HSQC, tailored to overcome the above limitation. EPIC-HSQC exploits the strong (1)H polarization and its subsequent transfer to non-equilibrium N(z) magnetization prior to (15)N photo CIDNP laser irradiation. CHANCE-HSQC synergistically combines (1)H and (15)N photo-CIDNP. The above pulse sequences, tested on tryptophan (Trp) and the Trp containing protein apoHmpH, were found to display up to 2-fold higher sensitivity than the reference NPE-SE-HSQC pulse train (based on simple (15)N photo-CIDNP followed by N-H polarization transfer), and up to a ca. 3-fold increase in sensitivity over the corresponding dark pulse schemes (lacking laser irradiation). The observed effects are consistent with the predictions from a theoretical model of photo-CIDNP and prove the potential of (15)N and (1)H photo CIDNP in liquid state heteronuclear correlation NMR. PMID- 19643650 TI - [Quantification of the volumetric benefit of image-guided radiotherapy (IGRT) in prostate cancer: margins and presence probability map]. AB - PURPOSE: To quantify the prostate and seminal vesicles (SV) anatomic variations in order to choose appropriate margins including intrapelvic anatomic variations. To quantify volumetric benefit of image-guided radiotherapy (IGRT). PATIENTS AND METHODS: Twenty patients, receiving a total dose of 70 Gy in the prostate, had a planning CT scan and eight weekly CT scans during treatment. Prostate and SV were manually contoured. Each weekly CT scan was registered to the planning CT scan according to three modalities: radiopaque skin marks, pelvis bone or prostate. For each patient, prostate and SV displacements were quantified. 3D maps of prostate and SV presence probability were established. Volumes including minimal presence probabilities were compared between the three modalities of registration. RESULTS: For the prostate intrapelvic displacements, systematic and random variations and maximal displacements for the entire population were: 5mm, 2.7 mm and 16.5mm in anteroposterior axis; 2.7 mm, 2.4mm and 11.4mm in superoinferior axis and 0.5mm, 0.8mm and 3.3mm laterally. Margins according to van Herk recipe (to cover the prostate for 90% of the patients with the 95% isodose) were: 8mm, 8.3mm and 1.9 mm, respectively. The 100% prostate presence probability volumes correspond to 37%, 50% and 61% according to the registration modality. For the SV, these volumes correspond to 8%, 14% and 18% of the SV volume. CONCLUSIONS: Without IGRT, 5mm prostate posterior margins are insufficient and should be at least 8mm, to account for intrapelvic anatomic variations. Prostate registration almost doubles the 100% presence probability volume compared to skin registration. Deformation of SV will require either to increase dramatically margins (simple) or new planning (not realistic). PMID- 19643651 TI - Intravenous immune globulins to treat eosinophilic fasciitis: a case report. PMID- 19643652 TI - A fetal autopsy case of body stalk anomaly. AB - Body stalk anomaly (BSA) is a sporadic polymalformative syndrome incompatible with extrauterine life. In utero detection of BSA by two-dimensional and three dimensional ultrasonography and magnetic resonance imaging has been well documented. We herein describe a case of body stalk anomaly diagnosed at autopsy. The fetus had a large anterior midline abdominal wall defect with eventration of the visceral organs into the amnio-peritoneal sac and a completely absent umbilical cord. The associated anomalies included club foot, absent diaphragm, genitourinary, and gastrointestinal defects. The observed congenital anomalies supported the theory of embryonic dysgenesis as the etiologic factor. One of the major objectives in the performance of fetal autopsy is to be able to detect abnormalities that can have implications in future pregnancies. Despite the negligible familial recurrence rate of the broad spectrum of anomalies associated with this abdominal wall defect, the present case of fetal autopsy indeed delights to serve the living. PMID- 19643653 TI - Exploratory study of a non-invasive method based on acoustic emission for assessing the dynamic integrity of knee joints. AB - The paper presents the development of a new measurement system based on acoustic emission (AE) for assessing the dynamic integrity of knee joints, and the evaluation of its efficacy, through an exploratory study using healthy and osteoarthritic knees. For the former, the paper describes the system implemented to acquire joint angle-based AE and the protocol developed to obtain repeatable results. For the latter, the paper reports significant differences between healthy and osteoarthritic knees using statistical analysis of AE occurrence and distribution of AE features in different movement phases. Osteoarthritic knees are found to produce 6-10 times more acoustic emissions than healthy knees, with amplitudes which can be 20 dB higher, and durations which can be 10 times longer. These findings lead to a visual representation method of AE feature profiles based on multidimensional density of AE hits per repeated movement and the use of principal component analysis for objective assessment of the clinical status of knee joints. PMID- 19643654 TI - Finite element analysis of the middle ear transfer functions and related pathologies. AB - With developments in software and micro-measurement technology, a three dimensional middle ear finite element (FE) model can now be more easily constructed to study sound transfer function. Many FE models of the middle ear have been constructed to date, and each has its own particular advantages and disadvantages. In this article, we review the latest developments and technologies in the field of the FE models of the middle ear, and the use of FE in the study of middle ear pathology. Proposals are made for future developments in the field of finite element analysis of middle ear transfer function. PMID- 19643655 TI - Outdoor environmental assessment of attention promoting settings for preschool children. AB - The restorative potential of green outdoor environments for children in preschool settings was investigated by measuring the attention of children playing in settings with different environmental features. Eleven preschools with outdoor environments typical for the Stockholm area were assessed using the outdoor play environment categories (OPEC) and the fraction of visible sky from play structures (sky view factor), and 198 children, aged 4.5-6.5 years, were rated by the staff for inattentive, hyperactive and impulsive behaviors with the ECADDES tool. Children playing in large and integrated outdoor areas containing large areas of trees, shrubbery and a hilly terrain showed less often behaviors of inattention (p<.05). The choice of tool for assessment of attention is discussed in relation to outdoor stay and play characteristics in Swedish preschool settings. The results indicate that the restorative potential of green outdoor environments applies also to preschool children and that environmental assessment tools as OPEC can be useful when to locate and develop health-promoting land adjacent to preschools. PMID- 19643656 TI - An investigation into the potential hypoalgesic effects of different amplitudes of PA mobilisations on the lumbar spine as measured by pressure pain thresholds (PPT). AB - Mobilisation of the spine is a common technique used in clinical practice. Studies have shown that mobilisation to the spine can decrease pain. The optimum treatment dose for achieving this has not so far been investigated. Previous studies that demonstrate the pain relieving effects of mobilisations have used large amplitude of oscillations. The importance of amplitude on pain relief has not been established. The current study aims to: a) Investigate the importance of amplitude as part of the treatment dose. b) To explore the extent of any pain reliving effects seen following mobilisations. The study employed a randomised, single blind, within-subjects repeated measure design. Thirty asymptomatic subjects participated. The subjects completed three experimental conditions on three separate occasions. The conditions were: large amplitude of oscillations (forces between 50 and 200N), small amplitude of oscillations (150N-200N) and quasi-static (maintained at 200N). Each condition involved a 3x1minute central PA mobilisation at a frequency of 1.5Hz on the lumbar spine. Pressure pain thresholds (PPT) were measured immediately before and after each intervention at 4 different sites. The sites were chosen to determine the extent of the hypoalgesic response. Results demonstrated a significant increase in PPT following lumbar mobilisations (p=0.013) at all measured sites. However, no significant difference was found between amplitude conditions (p=0.864). This study suggests that in asymptomatic subjects a systemic hypoalgesic response is caused by lumbar mobilisation regardless of amplitude. PMID- 19643657 TI - Ultrasonographically detected changes in Achilles tendons and self reported symptoms in elite gymnasts compared with controls--an observational study. AB - There are no published data on the prevalence of Achilles tendinopathy in gymnasts. 40 elite gymnasts and 41 controls of mean (SD) age 16.3 (2.1) years had bilateral AT thickness (at 3 points along the tendon in longitudinal and transverse views) and abnormality measured using ultrasound (US). Data on a history of AT symptoms were gathered using a questionnaire. Among female gymnasts there were 17.5% of Achilles tendons (ATs) with current symptoms, compared with none of the controls (chi(2)=6.2, p<0.05). Similarly, among male gymnasts 12.5% of ATs were currently symptomatic, compared with none of the controls (chi(2)=6.62, p<0.01). US scanning showed gymnasts had significantly (p<0.001 to p<0.05) thicker ATs for 5 out of 6 measures, and had more irregular longitudinal AT thickness (p<0.05). 32.5% of female gymnast ATs had US abnormalities, compared with 6.2% of female control ATs (chi(2)=7.43, p<0.01). Similarly, 35% of male gymnast ATs had US abnormalities, compared with 4% of male control ATs (chi(2)=7.43, p=0<01). There was no relationship between AT symptoms and US detected abnormalities in the gymnasts. Achilles tendinopathy is a common problem in gymnasts. The poor correlation between signs and symptoms suggests pathology is not always symptomatic. PMID- 19643658 TI - The influence of different sitting postures on head/neck posture and muscle activity. AB - To date the influence that specific sitting posture has on the head/neck posture and cervico-thoracic muscle activity has been insufficiently investigated. Therefore the aim of this study was to investigate whether three different thoraco-lumbar sitting postures affect head/neck posture and cervico-thoracic muscle activity. Twenty (10 men, 10 women) asymptomatic subjects were placed in 3 standardized thoraco-lumbar sitting postures (lumbo-pelvic, thoracic upright and slump) to investigate their influence on cervico-thoracic muscle activity and head/neck posture. There were significant differences in lumbar and thoracic curvatures in the 3 different sitting postures (P<0.002). Slump sitting was associated with greater head/neck flexion, anterior translation of the head (P<0.001) and increased muscle activity of cervical erector spinae (CES) compared to thoracic and lumbo-pelvic sitting (P=0.001). Thoracic upright sitting showed increased muscle activity of thoracic erector spinae (TES) compared to slump and lumbo-pelvic postures (P=0.015). Upper trapezius (UT) demonstrated no significant difference in muscle activation in the 3 sitting postures (P<0.991). This study demonstrates that different sitting postures affect head/neck posture and cervico thoracic muscle activity. It highlights the potential importance of thoraco lumbar spine postural adjustment when training head/neck posture. PMID- 19643659 TI - A common role of insula in feelings, empathy and uncertainty. AB - Although accumulating evidence highlights a crucial role of the insular cortex in feelings, empathy and processing uncertainty in the context of decision making, neuroscientific models of affective learning and decision making have mostly focused on structures such as the amygdala and the striatum. Here, we propose a unifying model in which insula cortex supports different levels of representation of current and predictive states allowing for error-based learning of both feeling states and uncertainty. This information is then integrated in a general subjective feeling state which is modulated by individual preferences such as risk aversion and contextual appraisal. Such mechanisms could facilitate affective learning and regulation of body homeostasis, and could also guide decision making in complex and uncertain environments. PMID- 19643660 TI - Determination of the formation constant for the inclusion complex between Lanthanide ions and Dansyl chloride derivative by fluorescence spectroscopy: theoretical and experimental investigation. AB - In this paper, a sensitive, easy, efficient, and suitable method for the calculation of K(f) values of complexation between one derivative of Dansyl chloride [5-(dimethylamino) naphthalene-1-sulfonyl 4-phenylsemicarbazide] (DMNP) and Lanthanide(III) (Ln) ions is proposed, using both spectrofluorometric and spectrophotometric methods. Determination of K(f) showed that DMNP was mostly selective towards the erbium (III) ion. The validity of the method was also confirmed calculating the Stern-Volmer fluorescence quenching constants (K(sv)) that resulted in the same consequence, obtained by calculating the K(f) of complexation values. In addition, the UV-vis spectroscopy was applied for the determination of K(f) only for the Ln ions that had interactions with DMNP. Finally, the DFT studies were done on Er(3+) and the DMNP complex for distinguishing the active sites and estimating the pair wise interaction energy. It can be concluded that this derivative of Dansyl chloride with inherent high fluorescence intensity is a suitable reagent for the selective determination of the Er(3+) ion which can be used in constructing selective Er(3+) sensors. PMID- 19643661 TI - Cellular phone and Internet-based individual intervention on blood pressure and obesity in obese patients with hypertension. AB - PURPOSE: The present study evaluated whether an intervention using a short message service (SMS) by cellular phone and Internet would improve blood pressure, weight control, and serum lipids of obese patients with hypertension during 8 weeks. METHODS: This is a quasi-experimental design with pre- and follow up tests. Participants were recruited from the family medicine outpatient department of tertiary care hospital located in an urban city of South Korea. Twenty-eight patients were assigned to an intervention group and 21 to a control group. The goal of intervention was to bring blood pressure, body weight, and serum lipids levels close to normal ranges. Patients in the intervention group were requested to record their blood pressure and body weight in a weekly web based diary through the Internet or by cellular phones. The researchers sent optimal recommendations as an intervention to each patient, by both cellular phone and Internet weekly. The intervention was applied for 8 weeks. RESULTS: Systolic (SBP) and diastolic blood pressures (DBP) significantly decreased by 9.1 and 7.2 mmHg respectively at 8 weeks from the baseline in the intervention group (p<0.05). However, after 8 weeks from the baseline both SBP and DBP in the control group had not changed significantly. Yet, There were significant mean decreases in body weight and waist circumference by 1.6 kg (p<0.05) and 2.8 cm (p<0.05) in the intervention group, respectively. In the control group increases in body weight and waist circumference (p<0.05) mean changes were also significant. High density lipoprotein cholesterol (HDL-C) significantly increased, with a mean change of 3.7 mg/dl at 8 weeks from baseline in the intervention group (p<0.05). The mean change of HDL-C in the control group was, however, not significant. CONCLUSION: During 8 weeks using this web-based intervention by way of cellular phone and Internet SMS improved blood pressure, body weight, waist circumference, and HDL-C in patients with obese hypertension. PMID- 19643663 TI - Inter-hemispheric functional coupling of eyes-closed resting EEG rhythms in adolescents with Down syndrome. AB - OBJECTIVE: We tested the hypothesis that inter-hemispheric directional functional coupling of eyes-closed resting EEG rhythms is abnormal in adolescents with Down syndrome (DS). METHODS: Eyes-closed resting EEG data were recorded in 38 DS adolescents (18.7 years +/-0.67 SE, IQ=49+/-1.9 SE) and in 17 matched normal control subjects (NYoung=19.1 years +/-0.39 SE). The EEG data were recorded from 8 electrodes (Fp1, Fp2, C3, C4, T3, T4, O1, O2) referenced to vertex. EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), and beta 2 (20-30 Hz). Power of EEG rhythms was evaluated by FFT for control purposes, whereas inter-hemispheric directional EEG functional coupling was computed by directed transfer function (DTF). RESULTS: As expected, alpha, beta, and gamma power was widely higher in NYoung than DS subjects, whereas the opposite was true for delta power. As a novelty, DTF (directionality) values globally prevailed from right to left occipital areas in NYoung subjects and in the opposite direction in DS patients. A control experiment showed that this DTF difference could not be observed in the comparison between DS adults with mild cognitive impairment and normal age matched adults. CONCLUSIONS: These results indicate a peculiar abnormal directional inter-hemispheric interplay in visual occipital areas of DS adolescents. SIGNIFICANCE: Direction of inter-hemispheric EEG functional coupling unveils a new abnormal brain network feature in DS adolescents. PMID- 19643662 TI - Prevalence of influenza A and B antibodies in pregnant women and their offspring. AB - BACKGROUND: Influenza is associated with substantial morbidity and mortality in pregnant women and neonates, but few countries offer annual influenza vaccination with the inactivated vaccine to all women who are, or intend to become, pregnant. OBJECTIVES: To provide seroepidemiological information on influenza A and B antibodies in pregnant women and their offspring in Germany. STUDY DESIGN: Anti influenza antibodies were determined using commercially available enzyme-linked immunosorbent assays (ELISA) on serum obtained from 209 women and their newborns at delivery. RESULTS: The prevalence of antibodies against influenza A virus was 93.8% [89.6-96.6%] in the mothers and 96.7% [93.2-98.6%] in the newborns. The prevalence of antibodies against influenza B virus was 42.1% [35.3-49.1%] in the mothers and 78.5% [72.3-83.8%] in their newborns, which was a significant difference. The antibody concentrations against both influenza A and influenza B viruses were significantly lower in mother than in their newborns. CONCLUSIONS: Because of active placental transport of IgG antibodies, neonates have higher prevalence and/or concentrations of influenza A and B virus-specific antibodies induced by natural infections than their mothers. Considering these serological findings, especially the lower prevalence of maternal antibody against influenza B virus, annual influenza vaccination may improve the protection of pregnant women and their offspring against influenza. PMID- 19643664 TI - Sleep and society. PMID- 19643665 TI - The ubiquitin-editing enzyme A20 (TNFAIP3) is a central regulator of immunopathology. AB - Nuclear factor (NF)-kappaB has an important role in immunity and inappropriate NF kappaB activity has been linked with many autoimmune and inflammatory diseases. Multiple mechanisms normally ensure the proper termination of NF-kappaB activation. In this context, the intracellular ubiquitin-editing protein A20 (also known as Tumor Necrosis Factor Alpha-Induced Protein 3 or TNFAIP3) is a key player in the negative feedback regulation of NF-kappaB signaling in response to multiple stimuli. Moreover, A20 also regulates tumor necrosis factor (TNF) induced apoptosis. Recent genetic studies demonstrate a clear association between several mutations in the human A20 locus and immunopathologies such as Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, psoriasis and type 1 diabetes. These findings further illustrate the importance of A20 in the resolution of inflammation and the prevention of human disease. PMID- 19643667 TI - Infections and autoimmunity--friends or foes? AB - Autoimmunity can be triggered by many environmental factors, among which infectious agents are pivotal. Here, we summarize current knowledge of the relationship between infection and autoimmunity. An autoimmune disease can be induced or triggered by infectious agents, which can also determine its clinical manifestations. Most infectious agents, such as viruses, bacteria and parasites, can induce autoimmunity via different mechanisms. In many cases, it is not a single infection but rather the 'burden of infections' from childhood that is responsible for the induction of autoimmunity. The development of an autoimmune disease after infection tends to occur in genetically susceptible individuals. By contrast, some infections can protect individuals from specific autoimmune diseases (i.e. the hygiene hypothesis). PMID- 19643666 TI - SOCS1 and SOCS3 in the control of CNS immunity. AB - In the decade following their initial discovery, the suppressor of cytokine signaling (SOCS) proteins have been studied for their potential use as immunomodulators in disease. SOCS proteins, especially SOCS1 and SOCS3, are expressed by immune cells and cells of the central nervous system (CNS) and have the potential to impact immune processes within the CNS, including inflammatory cytokine and chemokine production, activation of microglia, macrophages and astrocytes, immune cell infiltration and autoimmunity. We describe CNS-relevant in vitro and in vivo studies that have examined the function of SOCS1 or SOCS3 under various neuroinflammatory or neuropathological conditions, including exposure of CNS cells to inflammatory cytokines or bacterial infection, demyelinating insults, stroke, spinal cord injury, multiple sclerosis and glioblastoma multiforme. PMID- 19643668 TI - The role of environmental factors in primary biliary cirrhosis. AB - The etiology of primary biliary cirrhosis (PBC) is enigmatic, although it is clearly related to a combination of genetic predisposition and environmental stimulation. PBC is a chronic autoimmune cholestatic liver disease that occurs throughout the world with a reported latitudinal gradient in prevalence and incidence. PBC is also characterized by a 60% concordance in monozygotic twins and is considered a model autoimmune disease because of several features common to other conditions and the relatively homogeneous serological and biochemical features. Several risk factors have been suggested to be associated with PBC, including exposure to infectious agents and chemical xenobiotics. This review will attempt to place such factors in perspective. PMID- 19643669 TI - Novel insights into the biological function of mast cell carboxypeptidase A. AB - When mast cells are activated they can respond by releasing their secretory granule compounds, including mast cell-specific proteases of chymase, tryptase and carboxypeptidase A (MC-CPA) type. MC-CPA is a dominant protein component of the mast cell granule and the MC-CPA gene is extremely highly expressed. Despite this, relatively little has been known of its biological function. However, the recent generation of mouse strains lacking MC-CPA has opened up new possibilities for investigations related to this protease. This recent development has revealed a role for MC-CPA in regulating innate immunity responses, including the degradation of harmful substances such as the vasoconstrictive factor endothelin 1 and snake venom toxins. Here, we summarize the current knowledge of MC-CPA. PMID- 19643670 TI - Personality changes in temporal lobe epilepsy. PMID- 19643671 TI - End-of-dose emergent psychopathology in ambulatory patients with epilepsy on stable-dose lamotrigine monotherapy: a case series of six patients. AB - OBJECTIVE: Specific psychological withdrawal symptoms following the cessation of treatment with many drugs that affect the central nervous system, including anxiolytics and antidepressants, have been well documented. Studies have investigated withdrawal symptoms associated with some of the older antiepileptic drugs, but the potential for withdrawal symptoms associated with newer antiepileptic drugs, including lamotrigine, has not yet been investigated. METHODS: Using a retrospective chart review, we identified six patients with epilepsy who reported transient emergent psychological symptoms during stable, chronic lamotrigine monotherapy. RESULTS: These symptoms included anxiety, emotional lability, and irritability. In each case, the symptoms resulted in marked subjective distress and reliably occurred in the 1-2h before the patients were due to take their next dose of medication. CONCLUSIONS: Lamotrigine withdrawal symptoms exist and can occur as an end-of-dose phenomenon, even in patients on stable medication doses. End-of-dose withdrawal from lamotrigine is a clinically significant adverse effect that can hamper successful treatment with this medication. PMID- 19643672 TI - A multicenter, outpatient, open-label study to evaluate the dosing, effectiveness, and safety of topiramate as monotherapy in the treatment of epilepsy in clinical practice. AB - This 24-week, multicenter, open-label trial was designed to evaluate the dosing, effectiveness, and safety of topiramate monotherapy for epilepsy and to identify patient and clinical characteristics predictive of optimally effective stabilized monotherapy doses. Of 406 randomized patients, 244 comprised the evaluable-for efficacy population (12 weeks of treatment and stabilized topiramate dose during final 28 days); 213 were on topiramate monotherapy at the end of the trial. The mean stabilized daily dose of topiramate over the last 28 days of treatment (primary endpoint) was significantly lower for patients reporting one to three seizures (low seizure frequency, n=147) than for those reporting more than three seizures (high seizure frequency, n=66) during a 3-month retrospective baseline period (191 mg vs 239 mg, P=0.003). Patients in the low-seizure-frequency group reached a stable topiramate dose after a median of 36 days, compared with 53 days for patients in the high-seizure-frequency group. Linear and stepwise regression analyses showed baseline seizure frequency and lifetime seizure count to be significant (P<0.05) predictors of the stabilized dosage. Most treatment-emergent adverse events (TEAEs) were mild to moderate; those occurring with cumulative incidence rates >10% in either seizure frequency group were paresthesia, fatigue, anorexia, dizziness, somnolence, headache, and hypoesthesia; 18.2% of patients discontinued topiramate because of a TEAE, 5.1% reported serious TEAEs, and no deaths were reported during the study. PMID- 19643673 TI - Remembrance. In memoriam: Ed Bromfield, M.D., 1951-2009. PMID- 19643674 TI - Transient News Events Test: feasibility in assessment of post-temporal lobectomy remote memory deficits. AB - Although anterograde memory deficits are well documented in patients with epilepsy, the extent to which remote memory deficits occur is less clear. This is due in part to a lack of reliable methods for assessment. The present study examined the feasibility of using the Transient News Events Test (TNET) to assess remote memory in subjects status post anterior temporal lobectomy (ATL) for the treatment of refractory seizures. Results indicated significantly poorer performance of the patient group compared to healthy controls. The decrement in performance within the patient group was evident only for items from more recent time periods. Reasons for an apparent stability of the most remote memories with ATL and implications regarding hippocampal function are reviewed. In conclusion, the TNET provides a feasible method for assessment of remote memory function in patients with epilepsy, with decrements in performance noted in comparison to a healthy control group in this retrospective study. PMID- 19643675 TI - Neurogenic claudication and radiculopathy as delayed presentations of retained spinal bullet. AB - BACKGROUND CONTEXT: Firearm injuries to the spine may cause injury to the neurological structures and/or to the spine, including ligaments and bones. PURPOSE: Patients usually present with symptoms immediately after injury. However, only a few cases have been reported where a patient is neurologically intact after the initial injury but develops deficits several months or years later. Almost all these cases develop delayed neurological deficit because of bullet migration. STUDY DESIGN: Case report. METHODS: A discussion, with a relevant review of the literature, the clinical histories, and radiological findings of two patients who experienced delayed neurological symptoms after gunshot wounds to the spine. RESULTS: One patient presented after 14 years and the other after 5 months from the day of injury. Both cases are unique in that the delayed symptoms appeared because of formation of a reactive mass around the site of bullet impact. Lack of serial imaging studies is a barrier to the exclusion of bullet migration as an alternate cause of delayed symptoms. CONCLUSION: These cases illustrate that retained intraspinal bullets can present with delayed neurological findings secondary to reactive changes around the bullet. PMID- 19643676 TI - Patient-centered health care: are opioids a special case? PMID- 19643677 TI - The prevention of discitis during discography. AB - BACKGROUND CONTEXT: Because of the severe complications, discitis represents the most feared complication stemming from discography. Varying needle techniques have been used to prevent discitis, and evidence for the use of intravenous (IV) and/or intradiscal antibiotics is conflicting and often lacking. Consequently, no consensus has been formed for disc infection prevention during discography. PURPOSE: The objectives of this review are to summarize and integrate all the available basic science, animal, and clinical evidence regarding prevention of infection from discography and to develop areas of future research. STUDY DESIGN: A comprehensive review of the literature dealing with discitis stemming from discography was conducted. METHODS: The MEDLINE and SCOPUS databases were searched focusing on prospective and retrospective studies and published case reports on the prevention of discitis. A meta-analysis could not be completed because of the scarcity of data and published randomized controlled trials. RESULTS: Of the seven articles that specifically focused on the prevention of discitis, no randomized or controlled trials were located. Two prospective, nonrandomized trials, three retrospective case series, and two literature reviews have been published, but no consensus has been formed for the prevention of discitis during discography. Fifteen articles focused on penetration, efficacy, and dosage of antibiotics into intervertebral discs for the prevention of discitis. There are 14 additional articles that report incidences of discitis. CONCLUSIONS: Based on the available clinical evidence, IV or intradiscal antibiotics during discography have not been conclusively shown to decrease the rate of discitis over sterile technique alone. Animal model research supports prophylactic antibiotic use when used before iatrogenic inoculation of intervertebral discs. Both single- and double-needle techniques when used with stylettes are superior to nonstyletted techniques. PMID- 19643678 TI - Subdural hematoma after microdiscectomy: a case report and review of the literature. AB - BACKGROUND CONTEXT: Subdural hematomas (SDHs) have been described as a rare complication from durotomy after lumbar spine surgery. In half of the reported cases, the durotomy was unnoticed intraoperatively. The most common presenting symptom was persistent headache. PURPOSE: To report a case of SDH after routine microdiscectomy and to review the literature. STUDY DESIGN: Case report and review of the literature. METHODS: Retrospective review of patient's history and imaging studies. RESULTS: A 39-year-old female underwent routine microdiscectomy for L5-S1 herniated disc. There were no complications, and no dural tear was noted. Approximately 1 week postoperatively, the patient complained of severe headaches. Imaging revealed a right intracranial chronic SDH and a lumbar pseudomeningocele. Operative exploration of her lumbar wound revealed a dural tear, which was closed primarily. The patient had subsequent resolution of her SDH. CONCLUSIONS: The authors present a case of a routine microdiscectomy complicated by delayed cerebrospinal leak causing a chronic SDH. This report illustrates the need for a comprehensive evaluation of headaches after spine surgery. PMID- 19643679 TI - Single photon emission computerized tomography (SPECT) scan-positive facet joints and other spinal structures in a hospital-wide population with spinal pain. AB - BACKGROUND CONTEXT: The current criterion standard for zygapophyseal (facet) joint pain diagnosis is placebo-controlled triple comparative local anesthetic facet joint or medial branch blocks. Single photon emission computerized tomography (SPECT) scanning is a less invasive modality that has been widely used in patients with spinal pain for the diagnosis of facet joint arthritis. Previous studies have shown that SPECT results correlate well with response to facet joints steroid injections. PURPOSE: To evaluate the prevalence of SPECT scan positive facet joints and other spinal areas in different age groups in a hospital-wide population with spinal pain. STUDY DESIGN: Retrospective study. METHODS: This study included 534 patients who underwent a SPECT scan for spinal pain over 7.5 years in our hospital. All referrals from all doctors for any cervical or lumbar spinal pain were included, and the results were reviewed. RESULTS: A total of 486 patients (91.1%) had at least one positive abnormality on SPECT scan; 81.3% had increased uptake in different structures and regions of the spine. This included 42.8% increased uptake in the facet joint 29.8% in the vertebral bodies/end plates, and 5.9% in sacroiliac joints. The prevalence of increased uptake in the lumbosacral and cervical spine was 44% and 37%, respectively. When patients were divided into five age groups (below 40, 40-49, 50-59, 60-69, and 70 years and older), there was a significantly higher increased prevalence in advancing age groups. CONCLUSIONS: In a hospital-wide population with spinal pain, there is a 42.88% prevalence of increased uptake in the facet joint on SPECT. The incidence increases significantly with advancing age. SPECT can play a role in investigating patients with spinal pain. PMID- 19643680 TI - Electrochemistry of the interaction of furazolidone and bovine serum albumin. AB - The electrochemical behavior of the interaction of furazolidone (Fu) with bovine serum albumin (BSA) was investigated by cyclic voltammetry and differential pulse voltammetry at a glassy carbon electrode. Fu shows an irreversible reduction at 0.34 V in pH 4.0 Britton-Robinson buffer (B-R) buffer-10% DMF solution. After the addition of BSA into the Fu solution, the reductive peak currents decreased without any significant shift of the peak potential and the appearance of new peaks. The electrochemical parameters of the interaction system were calculated in the absence and presence of BSA. This electrochemical method was further applied to the determination of BSA samples and the results were in good agreement with the traditional cellulose acetate electrophoresis. The linear dynamic range was between 10.0 and 80.0 mg l(-1). The detection limit was 7.6 mg l(-1) and the recoveries were obtained from 97.0% to 104.0%. PMID- 19643681 TI - Marine aerobic biofilm as biocathode catalyst. AB - Stainless steel electrodes were immersed in open seawater and polarized for some days at -200 mV vs. Ag/AgCl. The current increase indicated the formation of biofilms that catalysed the electrochemical reduction of oxygen. These wild, electrochemically active (EA) biofilms were scraped, resuspended in seawater and used as the inoculum in closed 0.5L electrochemical reactors. This procedure allowed marine biofilms that are able to catalyse oxygen reduction to be formed in small, closed small vessels for the first time. Potential polarisation during biofilm formation was required to obtain EA biofilms and the roughness of the surface favoured high current values. The low availability of nutrients was shown to be a main limitation. Using an open reactor continuously fed with filtered seawater multiplied the current density by a factor of around 20, up to 60 microA/cm(2), which was higher than the current density provided in open seawater by the initial wild biofilm. These high values were attributed to continuous feeding with the nutrients contained in seawater and to suppression of the indigenous microbial species that compete with EA strains in natural open environments. Pure isolates were extracted from the wild biofilms and checked for EA properties. Of more than thirty different species tested, only Winogradskyella poriferorum and Acinetobacter johsonii gave current densities of respectively 7% and 3% of the current obtained with the wild biofilm used as inoculum. Current densities obtained with pure cultures were lower than those obtained with wild biofilms. It is suspected that synergic effects occur in whole biofilms or/and that wild strains may be more efficient than the cultured isolates. PMID- 19643682 TI - Carbon nanotubes based electrochemical biosensor for detection of formaldehyde released from a cancer cell line treated with formaldehyde-releasing anticancer prodrugs. AB - This paper reports the development of an electrochemical biosensor for the detection of formaldehyde in aqueous solution, based on the coupling of the enzyme formaldehyde dehydrogenase and a carbon nanotubes (CNT)-modified screen printed electrode (SPE). We monitored the amperometric response to formaldehyde released from U251 human glioblastoma cells situated in the biosensor chamber in response to treatment with various anticancer prodrugs of formaldehyde and butyric acid. The current response was higher for prodrugs that release two molecules of formaldehyde (AN-193) than for prodrugs that release only one molecule of formaldehyde (AN-1, AN-7). Homologous prodrugs that release one (AN 88) or two (AN-191) molecules of acetaldehyde, showed no signal. The sensor is rapid, sensitive, selective, inexpensive and disposable, as well as simple to manufacture and operate. PMID- 19643683 TI - New high-performance liquid chromatography method for the determination of (R) warfarin and (S)-warfarin using chiral separation on a glycopeptide-based stationary phase. AB - Warfarin is a well-known anticoagulant agent that occurs in two enantiomers, (R) (+)-warfarin and (S)-(-)-warfarin. A new liquid chromatography method for the determination of both enantiomers was developed, validated and applied in in vitro studies with the aim of evaluating the accumulation of (R)-warfarin and (S) warfarin in the hepatoma HepG2 cell line. OptiMEM cell cultivation medium samples and cellular lysates were purified using Waters Oasis MAX extraction cartridges. The chiral separation of warfarin and the internal standard p-chlorowarfarin enantiomers was performed on an Astec Chirobiotic V2 column at a flow rate of 1.2mL/min. The mobile phase was composed of 31% acetonitrile, 5% of methanol and 64% of ammonium acetate buffer (10mmol/L, pH 4.1). The enantiomers were quantified using a fluorescence detector (lambda(excit)=320nm, lambda(emiss)=415nm). The limit of detection was found to be 0.121micromol/L of (S)-warfarin and 0.109micromol/L of (R)-warfarin. The range of applicability and linearity was estimated from 0.25 to 100micromol/L. The precision ranged from 1.3% to 12.2% of the relative standard deviation, and the accuracy reached acceptable values from 95.5% to 108.4%. The new bioanalytical method confirmed the same accumulation of (R)-warfarin and (S)-warfarin in the hepatoma HepG2 cell line. PMID- 19643684 TI - Etiology of and risk factors for transient and persistent aminotransferase elevation in a population of virus-free blood donors: a multicentre study. AB - AIM: We evaluated the etiology and risk factors for transient and persistently elevated aspartate and/or alanine aminotransferase levels in virus-free blood donors. METHODS: INCLUSION CRITERIA: HBsAg/HBV-DNA and anti-HCV/HCV-RNA negative blood donors with elevated aspartate aminotransferase and/or alanine aminotransferase, observed in 5 blood transfusion centres in Italy from 2004 to 2005. Aspartate aminotransferase/alanine aminotransferase levels were measured at entry and every 2 months during a period of 6 months. RESULTS: 291 individuals were evaluated (144 with persistent and 147 with transient abnormal aminotransferases). High body mass index was the most frequent (75.5%) etiological factor and was more common in the persistent elevated levels group, compared to the transient elevated levels group (82.0% vs 65.3%; p<0.01). Excessive alcohol intake (>2 units/day) was reported in 23.6%, with no differences between the two groups. Instead, recent use of medication or paint exposure were most frequently associated with transient elevated levels than persistent elevated levels (61.6% vs 23.3% for drugs and 13.7% vs 4.3% for paint, p<0.001). Considering the participants with transient elevated levels as controls, the multivariate analysis showed that high body mass index was the only independent predictor of persistent elevated aminotransferase levels (OR=5.3; 95%CI=1.88-13.42 for those with body mass index>29.9). CONCLUSIONS: In virus-free blood donors, excessive body mass index is the most frequent etiological factor of abnormal aminotransferases and it is the sole risk factor associated with persistently elevated aminotransferases. PMID- 19643685 TI - Cyanoacrylate glue injection for acutely bleeding oesophageal varices: Is it ready for prime time? PMID- 19643686 TI - IL-1beta-511 and IL-1RN*2 polymorphisms in inflammatory bowel disease: An Italian population study and meta-analysis of European studies. AB - BACKGROUND: Several studies have tried to find possible associations between genetic polymorphisms and inflammatory bowel disease prevalence and/or phenotype. Our objectives were to test the frequency and phenotypic association of two polymorphisms of the interleukin-1 pathway, IL-1beta-511 and IL-1RN*2, in inflammatory bowel disease patients and controls from an Italian population, and to compare our data with previously published similar studies in Europe. METHODS: We screened 290 inflammatory bowel disease patients (178 ulcerative colitis and 112 Crohn's disease) and 106 controls for IL-1beta-511 and IL-1RN*2 polymorphisms by polymerase chain reaction (PCR)-based methods. The prevalence of the IL-1beta 511 and IL-1RN*2 polymorphisms in European inflammatory bowel disease patients was calculated by a meta-analysis of previously published studies using the Mantel-Haenszel method. RESULTS: No correlation between the IL-1 polymorphisms and inflammatory bowel disease prevalence was found in our study population. Crohn's disease patients with the IL-1beta-511 mutation had a higher rate of complicated disease. A trend for an association between the IL-1RN*2 mutation and a higher risk for inflammatory bowel disease has been found only in studies with Northern European populations. CONCLUSIONS: The IL-1beta-511 mutation can be associated with complex disease behaviour in Italian Crohn's disease patients. The IL-1RN*2 mutation may play a role in Northern European people with inflammatory bowel disease. PMID- 19643687 TI - Prima digestio fit in ore. PMID- 19643688 TI - Positron emission tomography for the detection of colorectal adenomas. AB - BACKGROUND: (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET) has been reported to detect colorectal adenomas. AIMS: This study aimed at evaluating the sensitivity of (18)F-FDG PET with computed tomography image fusion (PET/CT) for detecting colorectal adenomas. METHODS: We retrospectively compared the results of 92 (18)F-FDG PET/CT studies followed by colonoscopy. Colonoscopy and histology were considered as the gold standard. RESULTS: One hundred fifty seven lesions were observed. All the 12 malignancies were identified by (18)F-FDG PET/CT but only 27 out of 119 resected adenomas (sensitivity 22.7%) and none of the hyperplastic polyps were detected. At the univariate and multivariate analyses there was a significant statistical association between adenomas sized more than 10mm, presence of villous component and high-grade dysplasia and the ability of (18)F-FDG PET/CT to detect adenomas. (18)F-FDG PET/CT showed an overall sensitivity of 29.8%, a specificity of 81.1%, a positive predictive value (PPV) of 84.8% and a negative predictive value (NPV) of 24.6% for the neoplastic colorectal lesions globally considered. CONCLUSION: (18)F-FDG PET/CT has a low sensitivity for detecting adenomas. However, because of the specificity and PPV of the technique for neoplastic colorectal lesions, the presence of a focal colorectal FDG uptake justifies the patient undergoing colonoscopy. PMID- 19643689 TI - [Infection-triggered familial or recurrent acute necrotizing encephalopathy]. AB - Acute necrotizing encephalopathy (ANE) presents in children after common viral infections. Most cases of ANE are non-familial and non-recurrent and have been mainly reported in Asian patients, although ANE affects children worldwide. Recently, missense mutations in the gene encoding the nuclear pore protein Ran Binding Protein 2 (RANBP2) have been found in several families with familial or recurrent cases of ANE. We describe a Spanish family with familial and recurrent ANE without mutations in RANBP2. Mutations in RANBP2 are not the sole susceptibility alleles for familial or recurrent ANE. PMID- 19643690 TI - [Protocol for the diagnosis and follow up of patients with cystic fibrosis]. AB - Cystic fibrosis (CF) is the most common severe recessive genetic disease in Caucasians. During the last years, new therapies and aggressive management of the lung disease have contributed significantly to the increased life expectancy in CF patients. A review and update of CF diagnosis and management of lung disease are included. The sweat chloride test (SCT) remains the gold standard for CF diagnosis and should be performed properly. However, in a few patients SCT results may not be conclusive to clarify the CF diagnosis. Patients with CF should be followed up in specialist Units by an expert multidisciplinary expert applying standard clinical protocols and using lung function tests, and microbiological and imaging studies. An overview with the recommendations for treatment of early onset and chronic infections due to Pseudomonas aeruginosa, Staphylococcus aureus and other uncommon pathogens is included. Furthermore, the management of other aspects of CF lung disease and complications is provided, as well as the indications for lung transplantation. This document has been prepared by the members of the CF working group of the Spanish Paediatrics Pulmonary Society to provide an update to the earlier documents published in this Journal in 1999. PMID- 19643691 TI - Management of hepatocellular carcinoma in the age of liver transplantation. AB - Hepatocellular carcinoma is one of the most frequently encountered malignancies worldwide. Its association with cirrhosis increases the difficulty of diagnosis and therapy. Different approaches, ranging from medical treatment to highly complex ablative and surgical therapies, including liver resection and transplantation have significantly improved the outcome of this disease. This article reviews the current diagnostic challenges and the available surveillance and classification protocols. Available therapeutic approaches, indications, contraindications and outcome of liver resection, liver transplantation, living donor liver transplantation, are outlined in detail. Ablative procedures and their role and efficiency as "bridging" methods to liver transplantation are included in the review. PMID- 19643692 TI - Prognostic factors for the recovery of hand function following trapeziectomy with ligamentoplasty stabilisation. AB - INTRODUCTION: Numerous procedures are in use to treat trapeziometacarpal osteoarthritis. Most of these techniques impair hand function. In a series of trapeziectomies stabilized by ligament reconstruction with tendon suspension, we investigated whether eventual parameters influenced hand function and dexterity. HYPOTHESIS: Some parameters influence hand function recovery following trapeziectomy combined to ligamento-tendinous stabilization. MATERIALS AND METHODS: This is a continuous, retrospective, single surgeon series; 60 cases of thumb trapeziometacarpal osteoarthritis were treated with trapeziectomy and ligament reconstruction (40 palmaris longus, and 20 half flexor carpi radialis) with no additional metacarpophalangeal (MCP) joint surgery. Besides assessing classical clinical outcome criteria (pain, mobility, force), we analyzed hand function: this was obtained with a questionnaire about different everyday movements. Five types of grip were included in this analysis: spherical, pinch grasp, key pinch, power grip, and precision pinch. RESULTS: Fifty-one trapeziectomies (85%) were evaluated at an average follow-up of 7.5 years (5 11.5). Ninety-four percent of patients had good results for pain. The average Kapandji score for mobility was 9.6 (6-10) with a mean web angle at 36.5 degrees. Hyperextension of the MCP joint occurred in 36 cases and measured an average of 26 degrees (5 degrees-50 degrees). Compared to the contralateral side average strength was 97% with the Jamar dynamometer and 88% for the key pinch. The rate of satisfaction was 96%. Collapse of trapezial height was constant, and at last follow-up, the trapezial index was 50% of its preoperative initial value. The results relative to hand function assessment were good in 58% of patients. The spherical grip was the most difficult to restore. The analysis of the 42% of patients with average or poor hand function showed five prognostic factors for a poor outcome: young age at surgery, persisting postoperative pain, postoperative hyperextension of the MCP joint, reduced postoperative web angle and trapezial space collapse. LEVEL OF EVIDENCE: Level IV. Therapeutic study. PMID- 19643693 TI - Dual-source computed tomography angiography image quality in patients with fast heart rates. AB - BACKGROUND: Dual-source computed tomography (DSCT) provides diagnostic quality images of the coronary arteries over a wide range of heart rates (HRs). Current dose reduction techniques, including electrocardiographic (ECG) dose modulation and prospective triggering, are optimized for use in patients with relatively slow (<70 beats/min) HRs by limiting radiation dose to the ideal phases of image acquisition. OBJECTIVE: We evaluated coronary vessel image quality (IQ) at different reconstruction phases in patients with fast HRs (>80 beats/min) to assess potential feasibility of prospective triggering techniques on DSCT. METHODS: Patients (n=101) underwent 64-slice DSCT with retrospective ECG-gating without beta-blocker premedication. Image reconstructions were performed at 10% R R wave phase intervals (0%-90%). Patients were grouped by mean HR: group A, <60 beats/min (n=22); group B, 60-80 beats/min (n=57); group C, >80 beats/min (n=22). Coronary artery IQ was assessed by 2 readers in consensus on a 5-point scale. RESULTS: Optimal IQ occurred at 70% phase for all arteries in groups A and B. In group C, optimal IQ occurred at 30% and 40% phases. The 70% phase achieved diagnostic IQ in 97% of group A and 86% of group B. A widened reconstruction window (30%-50%) was necessary for diagnostic IQ in a similar high proportion (84%) of group C. CONCLUSION: Optimal IQ occurs during late-systolic phases for patients with fast HRs (>80 beats/min). Late-systolic phase prospective triggering is potentially feasible in these patients; however, given the widened reconstruction windows required, a higher radiation dose may be required compared with patients with slower HRs (<80 beats/min). PMID- 19643694 TI - Intracoronary thrombus. AB - We present the case of a 62 year old patient admitted with acute chest pain. Coronary CT angiography demonstrated presence of a high grade lesion with pronounced remodeling and the impression of an intracoronary thrombus in the proximal left circumflex coronary artery. Invasive angiography confirmed the presence of a thrombus; thrombus fragments were removed using an extraction device. PMID- 19643695 TI - Efficiency of timing delays and electrode positions in optimization of biventricular pacing: a simulation study. AB - Electrode positions and timing delays influence the efficacy of biventricular pacing (BVP). Accordingly, this study focuses on BVP optimization, using a detailed 3-D electrophysiological model of the human heart, which is adapted to patient-specific anatomy and pathophysiology. The research is effectuated on ten heart models with left bundle branch block and myocardial infarction derived from magnetic resonance and computed tomography data. Cardiac electrical activity is simulated with the ten Tusscher cell model and adaptive cellular automaton at physiological and pathological conduction levels. The optimization methods are based on a comparison between the electrical response of the healthy and diseased heart models, measured in terms of root mean square error (E(RMS)) of the excitation front and the QRS duration error (E(QRS)). Intra- and intermethod associations of the pacing electrodes and timing delays variables were analyzed with statistical methods, i.e., t -test for dependent data, one-way analysis of variance for electrode pairs, and Pearson model for equivalent parameters from the two optimization methods. The results indicate that lateral the left ventricle and the upper or middle septal area are frequently (60% of cases) the optimal positions of the left and right electrodes, respectively. Statistical analysis proves that the two optimization methods are in good agreement. In conclusion, a noninvasive preoperative BVP optimization strategy based on computer simulations can be used to identify the most beneficial patient-specific electrode configuration and timing delays. PMID- 19643696 TI - Compression of multidimensional biomedical signals with spatial and temporal codebook-excited linear prediction. AB - In this paper, we propose a model-based lossy coding technique for biomedical signals in multiple dimensions. The method is based on the codebook-excited linear prediction approach and models signals as filtered noise. The filter models short-term redundancy in time; the shape of the power spectrum of the signal and the residual noise, quantized using an algebraic codebook, is used for reconstruction of the waveforms. In addition to temporal redundancy, redundancy in the coding of the filter and residual noise across spatially related signals is also exploited, yielding better compression performance in terms of SNR for a given bit rate. The proposed coding technique was tested on sets of multichannel electromyography (EMG) and EEG signals as representative examples. For 2-D EMG recordings of 56 signals, the coding technique resulted in SNR greater than 3.4 +/- 1.3 dB with respect to independent coding of the signals in the grid when the compression ratio was 89%. For EEG recordings of 15 signals and the same compression ratio as for EMG, the average gain in SNR was 2.4 +/- 0.1 dB. In conclusion, a method for exploiting both the temporal and spatial redundancy, typical of multidimensional biomedical signals, has been proposed and proved to be superior to previous coding schemes. PMID- 19643698 TI - Toward online data reduction for portable electroencephalography systems in epilepsy. AB - Portable EEG units are key tools in epilepsy diagnosis. Current systems could be made physically smaller and longer lasting by the inclusion of online data reduction methods to reduce the power required for storage or transmission of the EEG data. This paper presents a real-time data reduction algorithm based upon the discontinuous recording of the EEG: noninteresting background sections of EEG are discarded online, with only potentially diagnostically interesting sections being saved. MATLAB simulations of the algorithm on an EEG dataset containing 982 expert marked events in 4 days of data show that 90% of events can be correctly recorded while achieving a 50% data reduction. The described algorithm is formulated to have a direct, low power, hardware implementation and similar data reduction strategies could be employed in a range of body-area-network-type applications. PMID- 19643699 TI - Flight dynamics and control of evasive maneuvers: the fruit fly's takeoff. AB - We have approached the problem of reverse-engineering the flight control mechanism of the fruit fly by studying the dynamics of the responses to a visual stimulus during takeoff. Building upon a prior framework [G. Card and M. Dickinson, J. Exp. Biol., vol. 211, pp. 341-353, 2008], we seek to understand the strategies employed by the animal to stabilize attitude and orientation during these evasive, highly dynamical maneuvers. As a first step, we consider the dynamics from a gray-box perspective: examining lumped forces produced by the insect's legs and wings. The reconstruction of the flight initiation dynamics, based on the unconstrained motion formulation for a rigid body, allows us to assess the fly's responses to a variety of initial conditions induced by its jump. Such assessment permits refinement by using a visual tracking algorithm to extract the kinematic envelope of the wings [E. I. Fontaine, F. Zabala, M. Dickinson, and J. Burdick, "Wing and body motion during flight initiation in Drosophila revealed by automated visual tracking," submitted for publication] in order to estimate lift and drag forces [F. Zabala, M. Dickinson, and R. Murray, "Control and stability of insect flight during highly dynamical maneuvers," submitted for publication], and recording actual leg-joint kinematics and using them to estimate jump forces [F. Zabala, "A bio-inspired model for directionality control of flight initiation," to be published.]. In this paper, we present the details of our approach in a comprehensive manner, including the salient results. PMID- 19643697 TI - A tissue framework for simulating the effects of gastric electrical stimulation and in vivo validation. AB - Gastric pacing is used to modulate normal or abnormal gastric slow-wave activity for therapeutic purposes. New protocols are required that are optimized for motility outcomes and energy efficiency. A computational tissue model was developed, incorporating smooth muscle and interstitial cell of Cajal layers, to enable predictive simulations of slow-wave entrainment efficacy under different pacing frequencies. Concurrent experimental validation was performed via high resolution entrainment mapping in a porcine model (bipolar pacing protocol: 2 mA amplitude; 400 ms pulsewidth; 17-s period; midcorpus). Entrained gastric slow wave activity was found to be anisotropic (circular direction: 8.51 mm x s(-1); longitudinal: 4.58 mm x s(-1)), and the simulation velocities were specified accordingly. Simulated and experimental slow-wave activities demonstrated satisfactory agreement, showing similar propagation patterns and frequencies (3.5 3.6 cycles per minute), and comparable zones of entrainment (ZOEs; 64 cm(2)). The area of ZOE achieved was found to depend on the phase interactions between the native and entrained activities. This model allows the predictions of phase interactions between native and entrained activities, and will be useful for determining optimal frequencies for gastric pacing, including multichannel pacing studies. The model provides a framework for the development of more sophisticated predictive gastric pacing simulations in future. PMID- 19643700 TI - A Bayesian clustering method for tracking neural signals over successive intervals. AB - This paper introduces a new, unsupervised method for sorting and tracking the action potentials of individual neurons in multiunit extracellular recordings. Presuming the data are divided into short, sequential recording intervals, the core of our strategy relies upon an extension of a traditional mixture model approach that incorporates clustering results from the preceding interval in a Bayesian manner, while still allowing for signal nonstationarity and changing numbers of recorded neurons. As a natural byproduct of the sorting method, current and prior signal clusters can be matched over time in order to track persisting neurons. We also develop techniques to use prior data to appropriately seed the clustering algorithm and select the model class. We present results in a principal components space; however, the algorithm may be applied in any feature space where the distribution of a neuron's spikes may be modeled as Gaussian. Applications of this signal classification method to recordings from macaque parietal cortex show that it provides significantly more consistent clustering and tracking results than traditional methods based on expectation-maximization optimization of mixture models. This consistent tracking ability is crucial for intended applications of the method. PMID- 19643701 TI - Sensitivity and spatial resolution of transvenous leads in implantable cardioverter defibrillator. AB - It has been previously documented that the main features and sensing performance of electrograms (EGMs) recorded in implantable cardioverter defibrillators (ICDs) depend on lead configuration. Although this dependence has been ascribed to differences in lead sensitivity and spatial resolution, the quantification of these two properties on ICD has not yet been attempted. In this paper, an operative framework to study the spatial resolution of ICD transvenous leads is presented. We propose to quantify the spatial resolution of ICD transvenous leads based on a new characterization called lead resolution volume (ResV). We analyzed the sensitivity distribution and the ResV of two unipolar (tip-can and coil-can ) and two bipolar (true or tip-ring and integrated or tip-coil) ICD transvenous lead configurations. A detailed 3-D model of the human thorax based on the visible human man dataset was used to compute the lead sensitivity and computer simulations of simple cardiac dynamics were used to quantify the ResV. Differences in the sensitivity distribution throughout the ventricular myocardium (VM) were observed for each lead configuration. In our computer model of the human thorax, the ResV was found to comprise 7%, 35%, 45%, and 70% of the VM for true bipolar, integrated bipolar, tip-can unipolar, and coil-can unipolar ICD leads, respectively. Furthermore, our analysis shows that the spatial resolution depends on both lead sensitivity and cardiac dynamics, and therefore, it can vary for different heart rhythms. PMID- 19643702 TI - Directional PC12 cell migration along plastic nanotracks. AB - The design of materials to promote the development and/or regeneration of neuronal tissue requires the understanding of the mechanisms by which the underlying substrate topography can modulate neuronal cell differentiation and migration. We recently demonstrated that plastic nanogratings (alternating lines of grooves and ridges of submicrometer size) can effectively change the neuronal polarity state, selecting bipolar cells with aligned neurites. Here, we address the effect of nanogratings on the migration properties of differentiating PC12 cells and correlate their behavior with the polarity state induced by the substrate. During neuronal differentiation, cell-substrate interaction is sufficient to induce directional migration along the nanogratings. Control cells contacting flat substrates migrated freely in all directions, while cells differentiating on nanogratings showed slower migration characterized by an angular restriction that confined cell movements. Finally, we show that directional migration on nanogratings is linked to a specific organization of the cell cytoskeleton reflecting the nanograting directionality. PMID- 19643703 TI - In vivo feasibility of real-time monitoring of focused ultrasound surgery (FUS) using harmonic motion imaging (HMI). AB - In this study, the Harmonic Motion Imaging for Focused Ultrasound (HMIFU) technique is applied to monitor changes in mechanical properties of tissues during thermal therapy in a transgenic breast cancer mouse model in vivo. An HMIFU system, composed of a 4.5-MHz focused ultrasound (FUS) and a 3.3-MHz phased array imaging transducer, was mechanically moved to image and ablate the entire tumor. The FUS transducer was driven by an amplitude-modulated (AM) signal at 15 Hz. The acoustic intensity ( I(spta)) was equal to 1050 W/cm(2) at the focus. A digital low-pass filter was used to filter out the spectrum of the FUS beam and its harmonics prior to displacement estimation. The resulting axial displacement was estimated using 1-D cross-correlation on the acquired RF signals. Results from two mice with eight lesions formed in each mouse (16 lesions total) showed that the average peak-to-peak displacement amplitude before and after lesion formation was respectively equal to 17.34 +/- 1.34 microm and 10.98 +/- 1.82 microm ( p << 0.001). Cell death was also confirmed by hematoxylin and eosin histology. HMI displacement can be used to monitor the relative tissue stiffness changes in real time during heating so that the treatment procedure can be performed in a time-efficient manner. The HMIFU system may, therefore, constitute a cost-efficient and reliable alternative for real-time monitoring of thermal ablation. PMID- 19643704 TI - Multiple nuclei tracking using integer programming for quantitative cancer cell cycle analysis. AB - Automated cell segmentation and tracking are critical for quantitative analysis of cell cycle behavior using time-lapse fluorescence microscopy. However, the complex, dynamic cell cycle behavior poses new challenges to the existing image segmentation and tracking methods. This paper presents a fully automated tracking method for quantitative cell cycle analysis. In the proposed tracking method, we introduce a neighboring graph to characterize the spatial distribution of neighboring nuclei, and a novel dissimilarity measure is designed based on the spatial distribution, nuclei morphological appearance, migration, and intensity information. Then, we employ the integer programming and division matching strategy, together with the novel dissimilarity measure, to track cell nuclei. We applied this new tracking method for the tracking of HeLa cancer cells over several cell cycles, and the validation results showed that the high accuracy for segmentation and tracking at 99.5% and 90.0%, respectively. The tracking method has been implemented in the cell-cycle analysis software package, DCELLIQ, which is freely available. PMID- 19643705 TI - Complex-valued multistate associative memory with nonlinear multilevel functions for gray-level image reconstruction. AB - A widely used complex-valued activation function for complex-valued multistate Hopfield networks is revealed to be essentially based on a multilevel step function. By replacing the multilevel step function with other multilevel characteristics, we present two alternative complex-valued activation functions. One is based on a multilevel sigmoid function, while the other on a characteristic of a multistate bifurcating neuron. Numerical experiments show that both modifications to the complex-valued activation function bring about improvements in network performance for a multistate associative memory. The advantage of the proposed networks over the complex-valued Hopfield networks with the multilevel step function is more outstanding when a complex-valued neuron represents a larger number of multivalued states. Further, the performance of the proposed networks in reconstructing noisy 256 gray-level images is demonstrated in comparison with other recent associative memories to clarify their advantages and disadvantages. PMID- 19643706 TI - Multilayer SOM with tree-structured data for efficient document retrieval and plagiarism detection. AB - This paper proposes a new document retrieval (DR) and plagiarism detection (PD) system using multilayer self-organizing map (MLSOM). A document is modeled by a rich tree-structured representation, and a SOM-based system is used as a computationally effective solution. Instead of relying on keywords/lines, the proposed scheme compares a full document as a query for performing retrieval and PD. The tree-structured representation hierarchically includes document features as document, pages, and paragraphs. Thus, it can reflect underlying context that is difficult to acquire from the currently used word-frequency information. We show that the tree-structured data is effective for DR and PD. To handle tree structured representation in an efficient way, we use an MLSOM algorithm, which was previously developed by the authors for the application of image retrieval. In this study, it serves as an effective clustering algorithm. Using the MLSOM, local matching techniques are developed for comparing text documents. Two novel MLSOM-based PD methods are proposed. Detailed simulations are conducted and the experimental results corroborate that the proposed approach is computationally efficient and accurate for DR and PD. PMID- 19643707 TI - A multiagent evolutionary algorithm for combinatorial optimization problems. AB - Based on our previous works, multiagent systems and evolutionary algorithms (EAs) are integrated to form a new algorithm for combinatorial optimization problems (CmOPs), namely, MultiAgent EA for CmOPs (MAEA-CmOPs). In MAEA-CmOPs, all agents live in a latticelike environment, with each agent fixed on a lattice point. To increase energies, all agents compete with their neighbors, and they can also increase their own energies by making use of domain knowledge. Theoretical analyses show that MAEA-CmOPs converge to global optimum solutions. Since deceptive problems are the most difficult CmOPs for EAs, in the experiments, various deceptive problems with strong linkage, weak linkage, and overlapping linkage, and more difficult ones, namely, hierarchical problems with treelike structures, are used to validate the performance of MAEA-CmOPs. The results show that MAEA-CmOP outperforms the other algorithms and has a fast convergence rate. MAEA-CmOP is also used to solve large-scale deceptive and hierarchical problems with thousands of dimensions, and the experimental results show that MAEA-CmOP obtains a good performance and has a low computational cost, which the time complexity increases in a polynomial basis with the problem size. PMID- 19643708 TI - On utilizing association and interaction concepts for enhancing microaggregation in secure statistical databases. AB - This paper presents a possibly pioneering endeavor to tackle the Microaggregation Techniques (MATs) in secure statistical databases by resorting to the principles of associative neural networks (NNs). The prior art has improved the available solutions to the MAT by incorporating proximity information, and this approach is done by recursively reducing the size of the data set by excluding points that are farthest from the centroid and points that are closest to these farthest points. Thus, although the method is extremely effective, arguably, it uses only the proximity information while ignoring the mutual interaction between the records. In this paper, we argue that interrecord relationships can be quantified in terms of the following two entities: 1) their "association" and 2) their "interaction." This case means that records that are not necessarily close to each other may still be "grouped," because their mutual interaction, which is quantified by invoking transitive-closure-like operations on the latter entity, could be significant, as suggested by the theoretically sound principles of NNs. By repeatedly invoking the interrecord associations and interactions, the records are grouped into sizes of cardinality " k," where k is the security parameter in the algorithm. Our experimental results, which are done on artificial data and benchmark real-life data sets, demonstrate that the newly proposed method is superior to the state of the art not only based on the Information Loss (IL) perspective but also when it concerns a criterion that involves a combination of the IL and the Disclosure Risk (DR). PMID- 19643709 TI - New delay-dependent exponential H(infinity) synchronization for uncertain neural networks with mixed time delays. AB - This paper establishes an exponential H(infinity) synchronization method for a class of uncertain master and slave neural networks (MSNNs) with mixed time delays, where the mixed delays comprise different neutral, discrete, and distributed time delays. The polytopic and the norm-bounded uncertainties are separately taken into consideration. An appropriate discretized Lyapunov Krasovskii functional and some free-weighting matrices are utilized to establish some delay-dependent sufficient conditions for designing delayed state-feedback control as a synchronization law in terms of linear matrix inequalities under less restrictive conditions. The controller guarantees the exponential H(infinity) synchronization of the two coupled MSNNs regardless of their initial states. Detailed comparisons with existing results are made, and numerical simulations are carried out to demonstrate the effectiveness of the established synchronization laws. PMID- 19643710 TI - Wireless support to poststroke rehabilitation: MyHeart's neurological rehabilitation concept. AB - Recent studies suggest that the quality of recovery after a stroke can be increased by early and more intensive rehabilitation. Portable unobtrusive devices are promising candidates for the realization of stroke-rehabilitation systems that complement care in the post-acute rehabilitation phase, both in the clinic and at home. The proposed system allows patients to increase the amount of motor exercise they can perform in autonomy, providing them with a real-time feedback based on wearable sensors embedded in the garment's tissue across the upper limb and trunk. A dynamic time warping algorithm allows for the recognition of correct and incorrect motor exercises. After the feedback phase, data are stored in a central location for review and statistics. Workstations can be installed either at home or at the hospital to support patients, independent of their location. The performance of the system on healthy subjects was quantified for seven types of motor exercises for upper limb's rehabilitation. Finally, we present the preliminary results of a pilot clinical study to test the system's acceptability and usability by post-stroke patients, and physicians in a clinical setting. PMID- 19643711 TI - Improved noninvasive intracranial pressure assessment with nonlinear kernel regression. AB - The only established technique for intracranial pressure (ICP) measurement is an invasive procedure requiring surgically penetrating the skull for placing pressure sensors. However, there are many clinical scenarios where a noninvasive assessment of ICP is highly desirable. With an assumption of a linear relationship among arterial blood pressure (ABP), ICP, and flow velocity (FV) of major cerebral arteries, an approach has been previously developed to estimate ICP noninvasively, the core of which is the linear estimation of the coefficients f between ABP and ICP from the coefficients w calculated between ABP and FV. In this paper, motivated by the fact that the relationships among these three signals are so complex that simple linear models may be not adequate to depict the relationship between these two coefficients, i.e., f and w , we investigate the adoption of several nonlinear kernel regression approaches, including kernel spectral regression (KSR) and support vector machine (SVM) to improve the original linear ICP estimation approach. The ICP estimation results on a dataset consisting of 446 entries from 23 patients show that the mean ICP error by the nonlinear approaches can be reduced to below 6.0 mmHg compared to 6.7 mmHg of the original approach. The statistical test also demonstrates that the ICP error by the proposed nonlinear kernel approaches is statistically smaller than that estimated with the original linear model (p < 0.05). The current result confirms the potential of using nonlinear regression to achieve more accurate noninvasive ICP assessment. PMID- 19643712 TI - An accelerometer-based device for sleep apnea screening. AB - This paper presents a body-fixed-sensor-based approach to assess potential sleep apnea patients. A trial involving 15 patients at a sleep unit was undertaken. Vibration sounds were acquired from an accelerometer sensor fixed with a noninvasive mounting on the suprasternal notch of subjects resting in supine position. Respiratory, cardiac, and snoring components were extracted by means of digital signal processing techniques. Mainly, the following biomedical parameters used in new sleep apnea diagnosis strategies were calculated: heart rate, heart rate variability, sympathetic and parasympathetic activity, respiratory rate, snoring rate, pitch associated with snores, and airflow indirect quantification. These parameters were compared to those obtained by means of polysomnography and an accurate microphone. Results demonstrated the feasibility of implementing an accelerometry-based portable device as a simple and cost-effective solution for contributing to the screening of sleep apnea-hypopnea syndrome and other breathing disorders. PMID- 19643713 TI - Fast rigid registration of vascular structures in IVUS sequences. AB - Intravascular ultrasound (IVUS) technology permits visualization of high resolution images of internal vascular structures. IVUS is a unique image-guiding tool to display longitudinal view of the vessels, and estimate the length and size of vascular structures with the goal of accurate diagnosis. Unfortunately, due to pulsatile contraction and expansion of the heart, the captured images are affected by different motion artifacts that make visual inspection difficult. In this paper, we propose an efficient algorithm that aligns vascular structures and strongly reduces the saw-shaped oscillation, simplifying the inspection of longitudinal cuts; it reduces the motion artifacts caused by the displacement of the catheter in the short-axis plane and the catheter rotation due to vessel tortuosity. The algorithm prototype aligns 3.16 frames/s and clearly outperforms state-of-the-art methods with similar computational cost. The speed of the algorithm is crucial since it allows to inspect the corrected sequence during patient intervention. Moreover, we improved an indirect methodology for IVUS rigid registration algorithm evaluation. PMID- 19643714 TI - 3-D retinal curvature estimation. AB - We study 3-D retinal curvature estimation from multiple images that provides the fundamental geometry of the human retina and could be used for 3-D retina visualization and disease diagnosis purposes. An affine camera model is used for 3-D reconstruction due to its simplicity, linearity, and robustness. A major challenge is that a series of optics is involved in the retinal imaging process, including an actual fundus camera, a digital camera, and the optics of the human eye, all of which cause significant nonlinear distortions in retinal images. In this paper, we develop a new constrained optimization method that considers both the geometric shape of the human retina and nonlinear lens distortions. Moreover, we examine a variety of lens distortion models to approximate the optics of the human eye in order to create a smooth spherical surface for curvature estimation. The experimental results on both synthetic data and real retinal images validate the proposed algorithm. PMID- 19643715 TI - Wearable and mobile system to manage remotely heart failure. AB - Cardiovascular diseases (CVDs) account for 45% of all deaths in the western world according to the 2004 World Health Organization statistics report. Heart failure (HF), CVD's primary paradigm, mainly affects people older than 65. The European MyHeart Project's mission is to empower citizens to fight CVD by leading a preventative lifestyle and allowing early diagnosis. This paper presents the iterative design and development of the HF management system, part of MyHeart Project. The system daily measures vital body signals to assess HF. The methodology applied herein has involved stakeholders in an iterative process: concept validation, feasibility, efficiency, patients' experience, and patients' acceptance. The final solution allows patient self-management of their chronic condition. PMID- 19643716 TI - Mutual information preconditioning improves structure learning of Bayesian networks from medical databases. AB - Bayesian networks (BNs) represent one of the most successful tools for medical diagnosis, selection of the optimal treatment, and prediction of the treatment outcome. In this paper, we present an algorithm for BN structure learning, which is a variation of the standard search-and-score approach. The proposed algorithm overcomes the creation of redundant network structures that may include nonsignificant connections between variables. In particular, the algorithm finds what relationships between the variables must be prevented, by exploiting the binarization of a square matrix containing the mutual information (MI) among all pairs of variables. Two different binarization methods are implemented. The first one is based on the maximum relevance minimum redundancy selection strategy. The second one uses a threshold. The MI binary matrix is exploited as a preconditioning step for the subsequent greedy search procedure that optimizes the network score, reducing the number of possible search paths in the greedy search. Our algorithm has been tested on two different medical datasets and compared against the standard search-and-score algorithm as implemented in the DEAL package. PMID- 19643717 TI - Development and impact of radio-frequency identification-based workflow management in health promotion center: using interrupted time-series analysis. AB - Radio-frequency identification (RFID) technology is being used increasingly for its efficiency and safety. The goal of this study is to evaluate the RFID technology within a hospital information system (HIS) for better workflow management in a health promotion center. We developed an RFID (433 mHz) real-time tracking system to monitor patients at the room level. Then we implemented an automatic workflow management by integrating RFID system with HIS. If a patient has finished one examination, the next step is determined automatically by previous number of examined patients and duration in each examination room. We performed interrupted time-series analysis of the mean waiting time for patients in a health promotion center compared with a control group of outpatients in the hospital's radiology department before and after the implementation of an RFID based system. After implementation of the RFID system, the mean waiting time of patients in the health promotion center decreased significantly (from 5.4 to 4.3 min, 20% decrease) compared with the control group (from 3.8 to 3.5 min, 8% decrease). The RFID system integrated with HIS increases workflow efficiency by shortening the mean waiting time during the workflow process and provides valuable real-time data for physicians and staff regarding workflow efficiency. PMID- 19643718 TI - [Neurobiological and pharmacologic aspects of atypical antipsychotic drugs]. AB - Atypical (second generation) antipsychotic drugs have radically changed and revolutionized the pharmacological treatment of schizophrenia and related disorders. The currently approved atypical antipsychotic drugs, which are available, are characterized by relatively weak affinities for D2-type dopamine receptors and relatively high affinities for 5-HT2A serotonin receptors, when compared with typical (conventional) antipsychotic drugs. The strong interaction with 5-HT2A receptors, with a relative sparing of D2-type dopamine receptors, is likely responsible for the optimal effects of atypical antipsychotic drugs on affective and cognitive symptoms in comparison with conventional antipsychotic drugs. In addition to these actions, several atypical antipsychotic drugs are characterized by a "fast dissociation" rate from D2-dopamine receptors. Mediating special signal transduction pathways, their activity on neuronal survival and plasticity might also contribute to their clinical advantage over typical neuroleptic drugs. By modulating chemical neurotransmission and the intracellular signal transduction systems, antipsychotic drugs may influence a variety of functions regulating neuronal resilience and viability and may have their potential for neuroprotection. PMID- 19643719 TI - [Genetic polymorphism in patients with colorectal and with head and neck cancer]. AB - Colorectal cancer is the second most frequent cause of death among malignant diseases. The mortality of head and neck cancer in Hungary increased by 265 percent in the last thirty years. Both malignancies belong to the most current public health problems in Hungary. The influence of two allelic polymorphisms of GSTM1 and GSTT1, and that of p53 gene codon 72 on colon cancer was investigated. In case of head and neck cancer the effects of the Arg194Trp and Arg399Gln polymorphisms of XRCC1 gene were analyzed. Intraoperative removed tissue samples were processed and cancer free human samples were used as matched controls. The formalin fixed samples were deparaffinized and digested with proteinase K. Genotyping was performed by PCR amplification, and in case of head and neck cancer a PCR-RFLP method was applied. No significant difference was found between tumor patients and controls in the investigated polymorphisms. A significant difference in survival was found between the GSTM1 and p53 gene variants in Dukes'B stage colorectal patients. The survival difference among the XRCC1 194 alleles by head and neck patients in clinical stage III proved to be also significant. The complex analysis of this type of genetic variants may be the future way of the personal risk assessment and the real chance for personal therapy. PMID- 19643720 TI - [Normal values of sacroiliac index according to gender and age]. AB - Using quantitative sacroiliac joint scintigraphy for identifying patients with active sacroiliitis the diagnosis is relied on the abnormally high values of sacroiliac (SI) index. However, the normal range of SI index and the threshold for detecting the disease are still under discussion in the literature. AIM: The aim of the study was to determine SI indices in a sample representing normal population for establishing normal values and the optimal threshold for our laboratory. The author investigated the effect of age and gender on SI indices. METHODS: SI indices in 740 nonarthritic control subjects were determined by standard method. Data were analyzed separately for males and females in different age groups (in 10-year intervals). RESULTS: Mean SI index derived for the control groups showed significant negative linear correlation with age and statistically significant differences between genders. The intra-individual difference between left and right SI joint was similar in each groups. CONCLUSIONS: The ranges of normal SI indices are different for males and females and for different age groups. For diagnosing bilateral sacroiliitis, the upper limit of 99% confidence interval is recommended as optimal cut-off value. The data between upper limits of 95% and 99% confidence intervals should be interpreted as uncertain category. The detection of unilateral sacroiliitis is possible even by the increased rate in difference between left and right SI index. The anatomic variability of sacrum should be taken into account during quantitative sacroiliac scintigraphy. PMID- 19643721 TI - [Whooping cough in an urban high school in Hungary. Conclusions of a local pertussis outbreak]. AB - Although incidence of pertussis has been gradually decreased with the introduction of active immunization, total eradication is not possible. This has been shown by national and international data, as well. In the early 2000's, slow increase in incidence of pertussis was observed. AIM: To demonstrate the presence of Bordetella pertussis in the Hungarian population by presenting 17 cases of adolescent pertussis. METHODS: Etiology of pertussis was confirmed by quantification of pertussis-antibodies in blood samples taken from permanently coughing patients in the firstly identified subject's vicinity which latter was explored by retrospective data collection. RESULTS: In the vicinity of the first identified patient epidemiologic research identified another 16 patients all of which were confirmed by serological tests. CONCLUSIONS: If permanent coughing is present, pertussis needs to be ruled out. Immunity against pertussis obtained by vaccination fades by the end of childhood. Bordetella pertussis circulates in the national population. A booster-vaccination against pertussis in the regular vaccination course for the 11-year old children is recommended. Pertussis in adolescents and in adults is mild and atypical, but in case of prolonged coughing it needs to be considered. PMID- 19643722 TI - [Our experience with nephron-sparing surgery in the past nine years]. AB - Surgical therapy is the only curative therapeutic approach for the treatment of renal cell carcinoma. Nephron-sparing surgery for renal cell carcinoma, when performed by proper indication, provides recurrence-free and long-term survival rates similar to those observed after a radical surgical procedure. AIM: In this retrospective study we present our experiences on open nephron-sparing surgery. We describe the rates of different indications of nephron-sparing surgery, the rates of different hystopathological findings, the complications and the long term cancer specific survival rates. METHODS: We reviewed retrospectively the data of 33 patients who had nephron-sparing surgery with T1 tumors between 1999 and 2008 in our department. The last patients' status evaluation was carried out in March 2009. The mean follow up was 4.64 years. RESULTS: 82% of the patients had an elective indication, 3% had relative and 15% had absolute indication for nephron-sparing surgery procedure. The mean tumor greatest dimension was 2.86cm. The hystopathologic review revealed 94% clear cell, 6% papillary renal cell carcinomas in the class of malignant renal tumors. The 1- and 5-year cancer specific survival chance were 93.8%. We had to do nephrectomy because of postoperative bleeding and urinoma in 3 cases. CONCLUSION: Nephron-sparing surgery is an acceptable and safe treatment that provides excellent long-term cancer specific survival rates for T1a renal cell carcinoma patients. PMID- 19643724 TI - [Compression hand injury -- compression therapy]. PMID- 19643723 TI - [The requirements and difficulties of patient movement during medical nursing]. PMID- 19643727 TI - Intrinsic pathway of apoptosis in peripheral blood eosinophils of Churg-Strauss syndrome. AB - OBJECTIVES: Churg-Strauss syndrome (CSS) is a rare necrotizing vasculitis associated with asthma, blood and tissue eosinophilia and granuloma formation. We wondered whether eosinophil accumulation in CSS results from the defect of intrinsic apoptosis pathway in blood eosinophils, leading to their prolonged survival. METHODS: We analysed immunophenotype (flow cytometry), expression of apoptosis-related genes (real-time PCR) and spontaneous apoptosis in blood eosinophils isolated from nine patients in exacerbation (active CSS), seven patients in remission (inactive CSS) and 14 matched healthy subjects. Serum IL-5 levels were also measured. RESULTS: In active CSS, blood eosinophils were characterized by small (<2-fold) decrease in expression of a few genes, primarily proapoptotic (e.g. BCL2L13, CASP2, CARD4) or involved in regulation of NF-kappaB (IKBKB, REL), but they did not differ in the rate of spontaneous apoptosis, when compared with other groups. Only selected genes were positively (BNIPL, PYCARD, CASP8, CRADD, BCAP31), or negatively (IKBKE) correlated with disease activity. In active CSS, eosinophils expressed activation markers (CD69, CD25), especially in subjects with most severe disease and elevated serum IL-5. CONCLUSIONS: High susceptibility of peripheral blood eosinophils to spontaneous apoptosis in vitro, and minor changes in expression of apoptotic-related genes in transcriptome analysis, do not support the hypothesis on intrinsic defect in apoptosis, as the cause of eosinophil accumulation in CSS. PMID- 19643728 TI - Aldo-keto reductase family 1 member B10 promotes cell survival by regulating lipid synthesis and eliminating carbonyls. AB - Aldo-keto reductase family 1 member B10 (AKR1B10) is primarily expressed in the normal human colon and small intestine but overexpressed in liver and lung cancer. Our previous studies have shown that AKR1B10 mediates the ubiquitin dependent degradation of acetyl-CoA carboxylase-alpha. In this study, we demonstrate that AKR1B10 is critical to cell survival. In human colon carcinoma cells (HCT-8) and lung carcinoma cells (NCI-H460), small-interfering RNA-induced AKR1B10 silencing resulted in caspase-3-mediated apoptosis. In these cells, the total and subspecies of cellular lipids, particularly of phospholipids, were decreased by more than 50%, concomitant with 2-3-fold increase in reactive oxygen species, mitochondrial cytochrome c efflux, and caspase-3 cleavage. AKR1B10 silencing also increased the levels of alpha,beta-unsaturated carbonyls, leading to the 2-3-fold increase of cellular lipid peroxides. Supplementing the HCT-8 cells with palmitic acid (80 mum), the end product of fatty acid synthesis, partially rescued the apoptosis induced by AKR1B10 silencing, whereas exposing the HCT-8 cells to epalrestat, an AKR1B10 inhibitor, led to more than 2-fold elevation of the intracellular lipid peroxides, resulting in apoptosis. These data suggest that AKR1B10 affects cell survival through modulating lipid synthesis, mitochondrial function, and oxidative status, as well as carbonyl levels, being an important cell survival protein. PMID- 19643729 TI - Redox mechanisms involved in the selective activation of Nrf2-mediated resistance versus p53-dependent apoptosis in adenocarcinoma cells. AB - We have investigated the role of reactive oxygen species and thiol-oxidizing agents in the induction of cell death and have shown that adenocarcinoma gastric (AGS) cells respond differently to the oxidative challenge according to the signaling pathways activated. In particular, apoptosis in AGS cells is induced via the mitochondrial pathway upon treatment with thiol-oxidizing agents, such as diamide. Apoptosis is associated with persistent oxidative damage, as evidenced by the increase in carbonylated proteins and the expression/activation of DNA damage-sensitive proteins histone H2A.X and DNA-dependent protein kinase. Resistance to hydrogen peroxide is instead associated with Keap1 oxidation and rapid translocation of Nrf2 into the nucleus. Sensitivity to diamide and resistance to hydrogen peroxide are correlated with GSH redox changes, with diamide severely increasing GSSG, and hydrogen peroxide transiently inducing protein-GSH mixed disulfides. We show that p53 is activated in response to diamide treatment by the oxidative induction of the Trx1/p38(MAPK) signaling pathway. Similar results were obtained with another carcinoma cell line, CaCo2, indicating that these findings are not limited to AGS cells. Our data suggest that thiol-oxidizing agents could be exploited as inducers of apoptosis in tumor histotypes resistant to ROS-producing chemotherapeutics. PMID- 19643730 TI - Slc26a9 is inhibited by the R-region of the cystic fibrosis transmembrane conductance regulator via the STAS domain. AB - SLC26 proteins function as anion exchangers, channels, and sensors. Previous cellular studies have shown that Slc26a3 and Slc26a6 interact with the R-region of the cystic fibrosis transmembrane conductance regulator (CFTR), (R)CFTR, via the Slc26-STAS (sulfate transporter anti-sigma) domain, resulting in mutual transport activation. We recently showed that Slc26a9 has both nCl(-)-HCO(3)(-) exchanger and Cl(-) channel function. In this study, we show that the purified STAS domain of Slc26a9 (a9STAS) binds purified (R)CFTR. When Slc26a9 and (R)CFTR fragments are co-expressed in Xenopus oocytes, both Slc26a9-mediated nCl(-) HCO(3)(-) exchange and Cl(-) currents are almost fully inhibited. Deletion of the Slc26a9 STAS domain (a9-DeltaSTAS) virtually eliminated the Cl(-) currents with only a modest affect on nCl(-)-HCO(3)(-) exchange activity. Co-expression of a9 DeltaSTAS and the (R)CFTR fragment did not alter the residual a9-DeltaSTAS function. Replacing the Slc26a9 STAS domain with the Slc26a6 STAS domain (a6-a9 a6) does not change Slc26a9 function and is no longer inhibited by (R)CFTR. These data indicate that the Slc26a9-STAS domain, like other Slc26-STAS domains, binds CFTR in the R-region. However, unlike previously reported data, this binding interaction inhibits Slc26a9 ion transport activity. These results imply that Slc26-STAS domains may all interact with (R)CFTR but that the physiological outcome is specific to differing Slc26 proteins, allowing for dynamic and acute fine tuning of ion transport for various epithelia. PMID- 19643731 TI - Magnitude of a conformational change in the glycine receptor beta1-beta2 loop is correlated with agonist efficacy. AB - The efficacy of agonists at Cys-loop ion channel receptors is determined by the rate they isomerize receptors to a pre-open flip state. Once the flip state is reached, the shut-open reaction is similar for low and high efficacy agonists. The present study sought to identify a conformational change associated with the closed-flip transition in the alpha1-glycine receptor. We employed voltage-clamp fluorometry to compare ligand-binding domain conformational changes induced by the following agonists, listed from highest to lowest affinity and efficacy: glycine > beta-alanine > taurine. Voltage-clamp fluorometry involves labeling introduced cysteines with environmentally sensitive fluorophores and inferring structural rearrangements from ligand-induced fluorescence changes. Agonist affinity and efficacy correlated inversely with maximum fluorescence magnitudes at labeled residues in ligand-binding domain loops D and E, suggesting that large conformational changes in this region preclude efficacious gating. However, agonist affinity and efficacy correlated directly with maximum fluorescence magnitudes from a label attached to A52C in loop 2, near the transmembrane domain interface. Because glycine experiences the largest affinity increase between closed and flip states, we propose that the magnitude of this fluorescence signal is directly proportional to the agonist affinity increase. In contrast, labeled residues in loops C, F, and the pre-M1 domain yielded agonist-independent fluorescence responses. Our results support the conclusion that a closed-flip conformation change, with a magnitude proportional to the agonist affinity increase from closed to flip states, occurs in the microenvironment of Ala-52. PMID- 19643732 TI - A coated vesicle-associated kinase of 104 kDa (CVAK104) induces lysosomal degradation of frizzled 5 (Fzd5). AB - Receptor internalization is recognized as an important mechanism for controlling numerous cell surface receptors. This event contributes not only to regulate signal transduction but also to adjust the amount of cell surface receptors. Frizzleds (Fzds) are seven-pass transmembrane receptor family proteins for Wnt ligands. Recent studies indicated that Fzd5 is internalized in response to Wnt stimulation to activate downstream signaling pathways. After internalization, it appears that Fzd5 is recycled back to the plasma membrane. However, whether internalized Fzd5 is sorted to lysosomes for protein degradation remains unclear. We here report that a coated vesicle-associated kinase of 104 kDa (CVAK104) selectively induces lysosomal degradation of Fzd5. We identify CVAK104 as a novel binding partner of Dishevelled (Dvl), a scaffold protein in the Wnt signaling pathway. Interestingly, we find that CVAK104 also interacts with Fzd5 but not with Fzd1 or Fzd4. CVAK104 selectively induces intracellular accumulation of Fzd5 via the clathrin-mediated pathway, which is suppressed by coexpression of a dominant negative form of Rab5. Fzd5 is subsequently degraded by a lysosomal pathway. Indeed, knockdown of endogenous CVAK104 by RNA interference results in an increase in the amount of Fzd5. In contrast, Wnt treatment induces Fzd5 internalization but does not stimulate its degradation. Overexpression or knockdown of CVAK104 results in a significant suppression or activation of the Wnt/beta-catenin pathway, respectively. These results suggest that CVAK104 regulates the amount of Fzd5 by inducing lysosomal degradation, which probably contributes to the suppression of the Wnt signaling pathway. PMID- 19643733 TI - SLIMMER (FHL1B/KyoT3) interacts with the proapoptotic protein Siva-1 (CD27BP) and delays skeletal myoblast apoptosis. AB - The fhl1 gene encoding four-and-a-half LIM protein-1 (FHL1) and its spliced isoform, SLIMMER, is mutated in reducing body myopathy, X-linked myopathy with postural muscle atrophy, scapuloperoneal myopathy, and rigid spine syndrome. In this study we have identified a novel function for SLIMMER in delaying skeletal muscle apoptosis via an interaction with the proapoptotic protein Siva-1. Siva-1 was identified as a SLIMMER-specific-interacting protein using yeast two-hybrid screening, direct-binding studies, and glutathione S-transferase pulldown analysis of murine skeletal muscle lysates. In C2C12 skeletal myoblasts, SLIMMER and Siva co-localized in the nucleus; however, both proteins exhibited redistribution to the cytoplasm following the differentiation of mononucleated myoblasts to multinucleated myotubes. In sections of mature skeletal muscle from wild type mice, SLIMMER and Siva-1 co-localized at the Z-line. SLIMMER and Siva-1 were also enriched in Pax-7-positive satellite cells, muscle stem cells that facilitate repair and regeneration. Significantly, SLIMMER delayed Siva-1 dependent apoptosis in C2C12 myoblasts. In skeletal muscle sections from the mdx mouse model of Duchenne muscular dystrophy, SLIMMER and Siva-1 co-localized in the nucleus of apoptotic myofibers. Therefore, SLIMMER may protect skeletal muscle from apoptosis. PMID- 19643735 TI - Commentary: Strengths and limitations of the discordant twin-pair design in social epidemiology. Where do we go from here? PMID- 19643734 TI - Nanoparticle-delivered suicide gene therapy effectively reduces ovarian tumor burden in mice. AB - There is currently no effective therapy for patients with advanced ovarian cancer. To address the need for a more effective treatment for this deadly disease, we conducted preclinical tests in ovarian tumor-bearing mice to evaluate the therapeutic efficacy of using a cationic biodegradable poly(beta-amino ester) polymer as a vector for nanoparticulate delivery of DNA encoding a diphtheria toxin suicide protein (DT-A). The promoter sequences of two genes that are highly active in ovarian tumor cells, MSLN and HE4, were used to target DT-A expression to tumor cells. Administration of DT-A nanoparticles directly to s.c. xenograft tumors and to the peritoneal cavity of mice bearing primary and metastatic ovarian tumors resulted in a significant reduction in tumor mass and a prolonged life span compared to control mice. Minimal nonspecific tissue and blood chemistry toxicity was observed following extended treatment with nanoparticles. DT-A nanoparticle therapy suppressed tumor growth more effectively than treatment with clinically relevant doses of cisplatin and paclitaxel. Our findings suggest that i.p. administration of polymeric nanoparticles to deliver DT-A encoding DNA, combined with transcriptional regulation to target gene expression to ovarian tumor cells, holds promise as an effective therapy for advanced-stage ovarian cancer. PMID- 19643737 TI - Editorial: CEACAM1: fine-tuned for fine-tuning. PMID- 19643738 TI - Editorial: Mouse models to study sepsis syndrome in humans. PMID- 19643739 TI - Editorial: Hemopexin: newest member of the anti-inflammatory mediator club. PMID- 19643736 TI - Innate immune control and regulation of influenza virus infections. AB - Adaptive immune responses are critical for the control and clearance of influenza A virus (IAV) infection. However, in recent years, it has become increasingly apparent that innate immune cells, including natural killer cells, alveolar macrophages (aMphi), and dendritic cells (DC) are essential following IAV infection in the direct control of viral replication or in the induction and regulation of virus-specific adaptive immune responses. This review will discuss the role of these innate immune cells following IAV infection, with a particular focus on DC and their ability to induce and regulate the adaptive IAV-specific immune response. PMID- 19643740 TI - Shovel-ready science: Moses applies for a GO grant. PMID- 19643743 TI - Soil moisture and metolachlor volatilization observations over three years. AB - A 3-yr study was conducted to focus on the impact of surface soil water content on metolachlor (2-chloro-N-(2-ethyl-6-methylphenyl)-N-(2-methoxy-1-methylethyl) acetamide) volatilization from a field with different surface soil water regimes created by subsurface water flow paths. Metolachlor vapor fluxes were measured at two locations within the field where local meteorological and soil conditions were relatively constant, except for surface soil water content, which differed significantly. Surface soil water content at the two sites differed in response to the presence of subsurface flow pathways. Detailed soil moisture observations over the duration of the study showed that for the first 2 yr (2004 and 2005), surface soil water contents at the dry location (V1) were nearly half those at the wetter location (V2). Cumulative metolachlor vapor fluxes during 2004 and 2005 at V1 were also about half that at V2. In the third year (2006), early season drought conditions rendered the soil water content at the two locations to be nearly identical, resulting in similar metolachlor volatilization losses. Analysis of infrared soil surface temperatures suggests a correlation between surface soil temperatures and metolachlor volatilization when soils are wet (2004 and 2005) but not when the soils are dry (2006). Field-averaged metolachlor volatilization losses were highly correlated with increasing surface soil water contents (r(2) = 0.995). PMID- 19643744 TI - Performance of a dispersion model to estimate methane loss from cattle in pens. AB - Accurate measurements of enteric methane (CH(4)) emissions from cattle (Bos taurus) are necessary to improve emission coefficients used in national emissions inventories, and to evaluate mitigation strategies. Our study was conducted to evaluate a novel approach that allowed near continuous CH(4) measurement from beef cattle confined in pens. The backward Lagrangian Stochastic (bLS) dispersion technique was used in conjunction with global position system (GPS) information from individual animals, to evaluate CH(4) emissions from pens of cattle. The dispersion technique was compared to estimates of CH(4) production using the SF(6) tracer technique. Sixty growing beef cattle were fed a diet containing 60% barley silage (dry matter basis) supplemented with either barley (Hordeum vulgare L.) grain or corn (Zea mays L.) distillers dried grains. The results show that daily CH(4) emissions were about 7% lower for the dispersion technique than for the tracer technique (185 vs. 199 g CH(4) animal(-1) d(-1)). The precision of the dispersion technique, relative to the SF(6) tracer technique, expressed by the Pearson coefficient was 0.76; the relative accuracy given by the concordance coefficient was 0.69. The bLS dispersion technique was able to detect differences (P < 0.05) due to diet and has the added advantage of measuring the pattern of CH(4) production during the 24-h period, with emissions ranging from 161 to 279 g CH(4) animal(-1) d(-1). Configuring the cattle as point sources resulted in more accurate CH(4) emissions than assuming a uniform area release from the pen surface. The results indicate that the bLS dispersion technique using cattle as point sources can be used to accurately measure enteric CH(4) from cattle and to evaluate the impact of dietary mitigation strategies. PMID- 19643742 TI - Retraction. Bone morphogenetic protein-7 induces telomerase inhibition, telomere shortening, breast cancer cell senescence, and death via Smad3. PMID- 19643745 TI - Field-scale cleanup of atrazine and cyanazine contaminated soil with a combined chemical-biological approach. AB - A former agrichemical dealership in western Nebraska was suspected of having contaminated soil. Our objective was to characterize and remediate the contaminated site by a combined chemical-biological approach. This was accomplished by creating contour maps of the on-site contamination, placing the top 60 cm of contaminated soil in windrows and mixing with a mechanical high speed mixer. Homogenized soil containing both atrazine [6-chloro-N-ethyl-N' isopropyl-1,3,5-triazine-2,4-diamine] and cyanazine {2-[[4-chloro-6-(ethylamino) 1,3,5-triazin-2-yl] amino]-2-methylpropanenitrile} was then used in laboratory investigations to determine optimum treatments for pesticide destruction. Iron suspension experiments verified that zerovalent iron (Fe(0)) plus ferrous sulfate (FeSO(4).7H(2)O) removed more than 90% of both atrazine and cyanazine within 14 d. Liquid chromatography/mass spectrometry (LC/MS) analysis of the atrazine solution after treating with Fe(0) and ferrous sulfate identified several degradation products commonly associated with biodegradation (i.e., deethlyatrazine (DEA), deisopropylatrazine (DIA), hydroxyatrazine (HA), and ammelines). Biological treatment evaluated emulsified soybean [Glycine max (L.) Merr.] oil (EOS) as a carbon source to stimulate biodegradation in static soil microcosms. Combining emulsified soybean oil with the chemical amendments resulted in higher destruction efficiencies (80-85%) and reduced the percentage of FeSO(4) needed. This chemical-biological treatment (Fe(0) + FeSO(4) + EOS, EOS Remediation, Raleigh, NC) was then applied with water to 275 m(3) of contaminated soil in the field. Windrows were tightly covered with clear plastic to increase soil temperature and maintain soil water content. Temporal sampling (0-342 d) revealed atrazine and cyanazine concentrations decreased by 79 to 91%. These results provide evidence that a combined chemical-biological approach can be used for on-site, field-scale treatment of pesticide-contaminated soil. PMID- 19643746 TI - Estimation of postfire nutrient loss in the Florida everglades. AB - Postfire nutrient release into ecosystem via plant ash is critical to the understanding of fire impacts on the environment. Factors determining a postfire nutrient budget are prefire nutrient content in the combustible biomass, burn temperature, and the amount of combustible biomass. Our objective was to quantitatively describe the relationships between nutrient losses (or concentrations in ash) and burning temperature in laboratory controlled combustion and to further predict nutrient losses in field fire by applying predictive models established based on laboratory data. The percentage losses of total nitrogen (TN), total carbon (TC), and material mass showed a significant linear correlation with a slope close to 1, indicating that TN or TC loss occurred predominantly through volatilization during combustion. Data obtained in laboratory experiments suggest that the losses of TN, TC, as well as the ratio of ash total phosphorus (TP) concentration to leaf TP concentration have strong relationships with burning temperature and these relationships can be quantitatively described by nonlinear equations. The potential use of these nonlinear models relating nutrient loss (or concentration) to temperature in predicting nutrient concentrations in field ash appear to be promising. During a prescribed fire in the northern Everglades, 73.1% of TP was estimated to be retained in ash while 26.9% was lost to the atmosphere, agreeing well with the distribution of TP during previously reported wild fires. The use of predictive models would greatly reduce the cost associated with measuring field ash nutrient concentrations. PMID- 19643747 TI - Survival and growth of hardwoods in brown versus gray sandstone on a surface mine in West Virginia. AB - Surface mining in West Virginia removes the eastern deciduous forest and reclaiming the mined land to a productive forest must consider soil depth, soil physical and chemical properties, soil compaction, ground cover competition, and tree species selection. Our objective was to evaluate tree survival and growth in weathered brown sandstone and in unweathered gray sandstone. Brown and gray sandstone are often substituted when insufficient native topsoil is available for replacement. Three 2.8-ha plots were constructed with either 1.5 or 1.2 m of brown sandstone, or 1.5 m of gray sandstone at the surface. Half of each plot was compacted with a large dozer. Percent fines (<2 mm) in the upper 20 cm was 61% for brown sandstone and 34% in gray. Brown sandstone's pH was 5.1, while gray sandstone's pH was around 8.0. In March 2005, 2-yr-old seedlings of 11 hardwood species were planted. After 3 yr, tree survival was 86% on 1.5-m gray sandstone, 67% on 1.5-m brown sandstone, and 82% on 1.2-m brown sandstone. Survival was 78% on noncompacted and 79% on compacted areas. Average volume of all trees (height x diameter(2)) was significantly greater on brown sandstone (218 cm(3)) than gray sandstone (45 cm(3)) after 3 yr. Black locust (Robinia pseudoacacia L.) had the highest survival (100%) and significantly greater volume (792 cm(3)) than all other tree species. Survival of the other 10 species varied between 65% for tulip poplar (Liriodendron tulipifera L.) and 92% for redbud (Cercis canadensis L.), and volume varied between 36 cm(3) for white pine (Pinus strobes L.) and 175 cm(3) for tulip poplar. After 3 yr, brown sandstone appears to be a better topsoil material due to the much greater growth of trees, but tree growth over time as these topsoils weather will determine whether these trends continue. PMID- 19643748 TI - Hydrologic and biogeochemical controls of river subsurface solutes under agriculturally enhanced ground water flow. AB - The relative influences of hydrologic processes and biogeochemistry on the transport and retention of minor solutes were compared in the riverbed of the lower Merced River (California, USA). The subsurface of this reach receives ground water discharge and surface water infiltration due to an altered hydraulic setting resulting from agricultural irrigation. Filtered ground water samples were collected from 30 drive point locations in March, June, and October 2004. Hydrologic processes, described previously, were verified by observations of bromine concentrations; manganese was used to indicate redox conditions. The separate responses of the minor solutes strontium, barium, uranium, and phosphorus to these influences were examined. Correlation and principal component analyses indicate that hydrologic processes dominate the distribution of trace elements in the ground water. Redox conditions appear to be independent of hydrologic processes and account for most of the remaining data variability. With some variability, major processes are consistent in two sampling transects separated by 100 m. PMID- 19643749 TI - Nitrogen mass balance of a tile-drained agricultural watershed in East-Central Illinois. AB - Simple nitrogen (N) input/output balance calculations in agricultural systems are used to evaluate performance of nutrient management; however, they generally rely on extensive assumptions that do not consider leaching, denitrification, or annual depletion of soil N. We constructed a relatively complete N mass balance for the Big Ditch watershed, an extensively tile-drained agricultural watershed in east-central Illinois. We conducted direct measurements of a wide range of N pools and fluxes for a 2-yr period, including soil N mineralization, soybean N(2) fixation, tile and river N loads, and ground water and in-stream denitrification. Fertilizer N inputs were from a survey of the watershed and yield data from county estimates that were combined with estimated protein contents to obtain grain N. By using maize fertilizer recovery and soybean N(2) fixation to estimate total grain N derived from soil, we calculated the explicit change in soil N storage each year. Overall, fertilizer N and soybean N(2) fixation dominated inputs, and total grain export dominated outputs. Precipitation during 2001 was below average (78 cm), whereas precipitation in 2002 exceeded the 30-yr average of 97 cm; monthly rainfall was above average in April, May, and June of 2002, which flooded fields and produced large tile and riverine N loads. In 2001, watershed inputs were greater than outputs, suggesting that carryover of N to the subsequent year may occur. In 2002, total inputs were less than outputs due to large leaching losses and likely substantial field denitrification. The explicit change in soil storage (67 kg N ha(-1)) offsets this balance shortfall. Although 2002 was climatically unusual, with current production trends of greater maize grain yields with less fertilizer N, soil N depletion is likely to occur in maize/soybean rotations, especially in years with above-average precipitation or extremely wet spring periods. PMID- 19643750 TI - Nitrate leaching and nitrous oxide flux in urban forests and grasslands. AB - Urban landscapes contain a mix of land-use types with different patterns of nitrogen (N) cycling and export. We measured nitrate (NO(3)(-)) leaching and soil:atmosphere nitrous oxide (N(2)O) flux in four urban grassland and eight forested long-term study plots in the Baltimore, Maryland metropolitan area. We evaluated ancillary controls on these fluxes by measuring soil temperature, moisture, and soil:atmosphere fluxes of carbon dioxide on these plots and by sampling a larger group of forest, grass, and agricultural sites once to evaluate soil organic matter, microbial biomass, and potential net N mineralization and nitrification. Annual NO(3)(-) leaching ranged from 0.05 to 4.1 g N m(-2) yr(-1) and was higher in grass than forest plots, except in a very dry year and when a disturbed forest plot was included in the analysis. Nitrous oxide fluxes ranged from 0.05 to >0.3 g N m(-2) yr(-1), with few differences between grass and forest plots and markedly higher fluxes in wet years. Differences in NO(3)(-) leaching and N(2)O flux between forests and grasslands were not as high as expected given the higher frequency of disturbance and fertilization in the grasslands. Carbon dioxide flux, organic matter, and microbial biomass were as high or higher in urban grasslands than in forests, suggesting that active carbon cycling creates sinks for N in vegetation and soil in these ecosystems. Although urban grasslands export more N to the environment than native forests, they have considerable capacity for N retention that should be considered in evaluations of land-use change. PMID- 19643751 TI - Behavior of atrazine in limited irrigation cropping systems in colorado: prior use is important. AB - Glyphosate-resistant (GR) corn may be a major component of new cropping systems to optimize the use of limited irrigation water supply while sustaining production. Because atrazine is an important tool for residual weed control in GR corn, we examined atrazine binding to soil, dissipation, movement, and early season weed control in limited and full irrigation cropping systems. These systems included continuous corn under conventional tillage and full irrigation (CCC-FI) and under no-tillage and deficit irrigation (CCC-DI), a sunflower-wheat corn rotation under no-tillage and deficit irrigation (SWC-DI), and a wheat fallow-wheat-corn rotation under no tillage and natural precipitation (WFWC-NP). Crop rotation and herbicide use history influenced atrazine behavior more than amount or type of irrigation. Atrazine dissipated more rapidly in the top 30 cm of soil in the CCC-FI and CCC-DI plots (half-life [T(1/2)] = 3-12 d), which had received previous applications of the herbicide, compared with the SWC-DI and WFWC-NP plots, which had no history of atrazine use (T(1/2) = 15-22 d). Laboratory assays indicated that the different rates of degradation were at least partly due to differences in microbial degradation in the soil. Atrazine moved the most in the top 30 cm in the SWC-DI and WFWC-NP plots. This greater movement is probably due to the slower rate of atrazine degradation. Studies of the behavior of pre-emergence herbicides in new limited irrigation cropping systems must consider all characteristics of the systems, not just amount and timing of irrigation. PMID- 19643752 TI - Soil nitrate leaching in silvopastures compared with open pasture and pine plantation. AB - Wide acceptance of silvopasture as an alternative sustainable agricultural system in the southeastern United States will depend on an improved understanding of the tree-forage interactions and recognition of its environmental benefits. The objective of this study was to evaluate differences in soil nitrate leaching in different land-use systems, in north Florida. An 18-yr-old loblolly pine (Pinus taeda L.) plantation was thinned in the summer of 2002 to create a fifth-row thinned, nontraditional intensive pine plantation (FO), silvopastures (HE = fourth-row conventionally thinned with random tree distribution and DO = double row sets of trees with 15-m wide alleys), and an open pasture (PA). 'Argentine' bahiagrass (Paspalum notatum Flugge.) was established as understory vegetation in HE, DO, and PA. From 2004 to 2005 soil nitrate leaching was sampled and compared in the DO, HE, PA, and FO systems at 0.3 and 1.2 m depths after fertilizer application. Significant nitrate peaks were observed at 0.3 m depth after N fertilizer application in all systems. At the 1.2 m depth, the maximum nitrate concentrations were 67, 18, and 8 mg L(-1), in the forest plantation, open pasture, and both silvopastures, respectively. In general, reduced nitrate leaching at 1.2 m depth was observed in silvopastures compared with other land used systems. These results are not intended to have a direct bearing on traditional pine plantation management, but rather support the potential role of silvopasture systems in reducing nitrate losses from the soil. PMID- 19643753 TI - Gene and antigen markers of shiga-toxin producing E. coli from Michigan and Indiana river water: occurrence and relation to recreational water quality criteria. AB - The relation of bacterial pathogen occurrence to fecal indicator bacteria (FIB) concentrations used for recreational water quality criteria (RWQC) is poorly understood. This study determined the occurrence of Shiga-toxin producing Escherichia coli (STEC) markers and their relation to FIB concentrations in Michigan and Indiana river water. Using 67 fecal coliform (FC) bacteria cultures from 41 river sites in multiple watersheds, we evaluated the occurrence of five STEC markers: the Escherichia coli (EC) O157 antigen and gene, and the STEC virulence genes eaeA, stx1, and stx2. Simple isolations from selected FC cultures yielded viable EC O157. By both antigen and gene assays, EC O157 was detected in a greater proportion of samples exceeding rather than meeting FC RWQC (P < 0.05), but was unrelated to EC and enterococci RWQC. The occurrence of all other STEC markers was unrelated to any FIB RWQC. The eaeA, stx2, and stx1 genes were found in 93.3, 13.3, and in 46.7% of samples meeting FC RWQC and in 91.7, 0.0, and 37.5% of samples meeting the EC RWQC. Although not statistically significant, the percentage of samples positive for each STEC marker except stx1 was lower in samples that met, as opposed to exceeded, FIB RWQC. Viable STEC were common members of the FC communities in river water throughout southern Michigan and northern Indiana, regardless of FIB RWQC. Our study indicates that further information on the occurrence of pathogens in recreational waters, and research on alternative indicators of their occurrence, may help inform water-resource management and public health decision-making. PMID- 19643754 TI - Natural ferrihydrite as an agent for reducing turbidity caused by suspended clays. AB - Biologically impaired waters are often caused by the turbidity associated with elevated suspended sediment concentrations. Turbidity can be reduced by the addition of positively charged compounds that coagulate negatively charged particles in suspension, causing them to flocculate. This research was conducted to determine the effectiveness of ferrihydrite, a poorly crystalline Fe oxide, as a flocculating agent for suspended clays similar to those found in high-turbidity waters of the Mississippi delta. Clay concentrations of 100 mg L(-1) from a Dubbs silt loam (fine silty, mixed, active, thermic Typic Hapludalfs), a Forestdale silty clay loam (fine, smectitic, thermic Typic Hapludalfs), and a Sharkey clay (very fine, smectitic, thermic Chromic Epiaquerts) were suspended in 0.0005 mol L(-1) CaCl(2) solutions at pH 5, 6, 7, or 8. Natural ferrihydrite with a zero point of charge at pH 5.8 was acquired from a drinking water treatment facility and mixed with the suspension at concentrations of 0, 10, 25, and 50 mg L(-1). After settling periods of 24 and 48 h, percent transmittance was measured at a wavelength of 420 nm using a 3-mL sample collected at a depth of 2 cm. The greatest reductions in turbidity after 24-h equilibration were recorded for the pH 5 suspensions of the Dubbs (31%) and Forestdale (37%) clays at a ferrihydrite concentration of 10 mg L(-1) and for the Sharkey clay at a ferrihydrite concentration of 25 mg L(-1) (relative to the 0 ferrihydrite treatment). Water clarity for all samples further increased after 48 h. These results indicate that the effectiveness of ferrihydrite, as a means of reducing turbidity associated with suspended clays, is greatest at pH values below its zero point of charge. PMID- 19643755 TI - Identifying pathways and processes affecting nitrate and orthophosphate inputs to streams in agricultural watersheds. AB - Understanding nutrient pathways to streams will improve nutrient management strategies and estimates of the time lag between when changes in land use practices occur and when water quality effects that result from these changes are observed. Nitrate and orthophosphate (OP) concentrations in several environmental compartments were examined in watersheds having a range of base flow index (BFI) values across the continental United States to determine the dominant pathways for water and nutrient inputs to streams. Estimates of the proportion of stream nitrate that was derived from groundwater increased as BFI increased. Nitrate concentration gradients between groundwater and surface water further supported the groundwater source of nitrate in these high BFI streams. However, nitrate concentrations in stream-bed pore water in all settings were typically lower than stream or upland groundwater concentrations, suggesting that nitrate discharge to streams was not uniform through the bed. Rather, preferential pathways (e.g., springs, seeps) may allow high nitrate groundwater to bypass sites of high biogeochemical transformation. Rapid pathway compartments (e.g., overland flow, tile drains) had OP concentrations that were typically higher than in streams and were important OP conveyers in most of these watersheds. In contrast to nitrate, the proportion of stream OP that is derived from ground water did not systematically increase as BFI increased. While typically not the dominant source of OP, groundwater discharge was an important pathway of OP transport to streams when BFI values were very high and when geochemical conditions favored OP mobility in groundwater. PMID- 19643756 TI - Disinfection byproduct formation potentials of wetlands, agricultural drains, and rivers and the effect of biodegradation on trihalomethane precursors. AB - Trihalomethane (THM) precursors are a significant problem in the San Joaquin River (SJR) watershed, an important source of drinking water for >20 million people. Trihalomethane precursors diminish drinking water quality and are formed during natural decomposition of organic matter in aquatic systems. This study sought to identify sources of chlorine-reactive dissolved organic carbon (DOC) in the SJR watershed and to determine if wetlands were more important sources of THM precursors than nearby rivers and agricultural drains. The effects of biodegradation on DOC quality and quantity were investigated and analyzed across drainage type. Results show wetland drainage contained comparable bromide concentrations and organic carbon aromaticity but contained more than two times the average DOC concentrations found in agricultural drains and rivers. Wetland DOC did not have an increased propensity to form THMs when compared with the other drainage types, despite significantly higher wetland formation potentials. The higher formation potentials measured in wetland drainages were attributed to higher DOC concentrations; the positive correlation found between DOC and trihalomethane formation potentials (THMFPs) and the significantly higher wetland DOC concentrations suggest that increased wetland restoration could result in increased THMFPs in the SJR watershed. Wetland THM precursors were more resistant to biodegradation than THM precursors from agricultural and river samples. Results suggest that THM precursors in the SJR were from algae and were biodegraded. PMID- 19643757 TI - Phosphorus forms in conventional and organic dairy manure identified by solution and solid state p-31 NMR spectroscopy. AB - Organic dairy production has increased rapidly in recent years. Organic dairy cows (Bos taurus) generally eat different diets than their conventional counterparts. Although these differences could impact availability, utilization, and cycling of manure nutrients, little such information is available to aid organic dairy farmers in making nutrient and manure management decisions. In this study, we comparatively characterized P in organic and conventional dairy manure using solution and solid state (31)P NMR spectroscopic techniques. Phosphorus in both types of dairy manure was extracted with water, Na acetate buffer (100 mmol L(-1), pH 5.0) plus 20 mg Na dithionite mL(-1), or 0.025 mol L(-1) NaOH with 50 mmolL(-1) EDTA. Solution NMR analysis revealed that organic dairy manure contained about 10% more inorganic phosphate than conventional dairy manure. Whereas organic dairy manure did contain slightly more phytate P, it contained 30 to 50% less monoester P than conventional dairy manure. Solid state NMR spectroscopy revealed that mono-, di-, and trivalent metal P species with different stabilities were present in the two dairy manures. Conventional dairy manure contained relatively higher contents of soluble inorganic P species and stable metal phytate species. In contrast, organic dairy manure contained more Ca and Mg species of P. These results indicate that P transformation rates and quantities should be expected to differ between organic and conventional dairy manures. PMID- 19643758 TI - Airborne endotoxin concentrations at a large open-lot dairy in southern idaho. AB - Endotoxins are derived from gram-negative bacteria and are a potential respiratory health risk for animals and humans. To determine the potential for endotoxin transport from a large open-lot dairy, total airborne endotoxin concentrations were determined at an upwind location (background) and five downwind locations on three separate days. The downwind locations were situated at of the edge of the lot, 200 and 1390 m downwind from the lot, and downwind from a manure composting area and wastewater holding pond. When the wind was predominantly from the west, the average endotoxin concentration at the upwind location was 24 endotoxin units (EU) m(-3), whereas at the edge of the lot on the downwind side it was 259 EU m(-3). At 200 and 1390 m downwind from the edge of the lot, the average endotoxin concentrations were 168 and 49 EU m(-3), respectively. Average airborne endotoxin concentrations downwind from the composting site (36 EU m(-3)) and wastewater holding pond (89 EU m(-3)) and 1390 m from the edge of the lot were not significantly different from the upwind location. There were no significant correlations between ambient weather data collected and endotoxin concentrations over the experimental period. The downwind data show that the airborne endotoxin concentrations decreased exponentially with distance from the lot edge. Decreasing an individual's proximity to the dairy should lower their risk of airborne endotoxin exposure and associated health effects. PMID- 19643760 TI - Gene expression profiling reveals a downregulation in immune-associated genes in patients with AS. AB - OBJECTIVE: To identify differentially expressed genes in peripheral blood mononuclear cells (PBMCs) from patients with ankylosing spondylitis (AS) compared with healthy individuals. METHODS: RNA was extracted from PBMCs collected from 18 patients with active disease and 18 gender-matched and age-matched controls. Expression profiles of these cells were determined using microarray. Candidate genes with differential expressions were confirmed in the same samples using quantitative reverse transcription-PCR (qRT-PCR). These genes were then validated in a different sample cohort of 35 patients with AS and 18 controls by qRT-PCR. RESULTS: Microarray analysis identified 452 genes detected with 485 probes which were differentially expressed between patients with AS and controls. Underexpression of NR4A2, tumour necrosis factor AIP3 (TNFAIP3) and CD69 was confirmed. These genes were further validated in a different sample group in which the patients with AS had a wider range of disease activity. Predictive algorithms were also developed from the expression data using receiver-operating characteristic curves, which demonstrated that the three candidate genes have approximately 80% power to predict AS according to their expression levels. CONCLUSIONS: The findings show differences in global gene expression patterns between patients with AS and controls, suggesting an immunosuppressive phenotype in the patients. Furthermore, downregulated expression of three immune-related genes was confirmed. These candidate genes were also shown to be strong predictive markers for AS. PMID- 19643759 TI - Disparities in rheumatoid arthritis disease activity according to gross domestic product in 25 countries in the QUEST-RA database. AB - OBJECTIVE: To analyse associations between the clinical status of patients with rheumatoid arthritis (RA) and the gross domestic product (GDP) of their resident country. METHODS: The Quantitative Standard Monitoring of Patients with Rheumatoid Arthritis (QUEST-RA) cohort includes clinical and questionnaire data from 6004 patients who were seen in usual care at 70 rheumatology clinics in 25 countries as of April 2008, including 18 European countries. Demographic variables, clinical characteristics, RA disease activity measures, including the disease activity score in 28 joints (DAS28), and treatment-related variables were analysed according to GDP per capita, including 14 "high GDP" countries with GDP per capita greater than US$24,000 and 11 "low GDP" countries with GDP per capita less than US$11,000. RESULTS: Disease activity DAS28 ranged between 3.1 and 6.0 among the 25 countries and was significantly associated with GDP (r = -0.78, 95% CI -0.56 to -0.90, r(2) = 61%). Disease activity levels differed substantially between "high GDP" and "low GDP" countries at much greater levels than according to whether patients were currently taking or not taking methotrexate, prednisone and/or biological agents. CONCLUSIONS: The clinical status of patients with RA was correlated significantly with GDP among 25 mostly European countries according to all disease measures, associated only modestly with the current use of antirheumatic medications. The burden of arthritis appears substantially greater in "low GDP" than in "high GDP" countries. These findings may alert healthcare professionals and designers of health policy towards improving the clinical status of patients with RA in all countries. PMID- 19643761 TI - Phylogenetic evidence for extensive horizontal gene transfer of type III secretion system genes among enterobacterial plant pathogens. AB - This study uses sequences from four genes, which are involved in the formation of the type III secretion apparatus, to determine the role of horizontal gene transfer in the evolution of virulence genes for the enterobacterial plant pathogens. Sequences of Erwinia, Brenneria, Pectobacterium, Dickeya and Pantoea were compared (a) with one another, (b) with sequences of enterobacterial animal pathogens, and (c) with sequences of plant pathogenic gamma and beta proteobacteria, to evaluate probable paths of lateral exchange leading to the current distribution of virulence determinants among these micro-organisms. Phylogenies were reconstructed based on hrcC, hrcR, hrcJ and hrcV gene sequences using parsimony and maximum-likelihood algorithms. Virulence gene phylogenies were also compared with several housekeeping gene loci in order to evaluate patterns of lateral versus vertical acquisition. The resulting phylogenies suggest that multiple horizontal gene transfer events have occurred both within and among the enterobacterial plant pathogens and plant pathogenic gamma and beta proteobacteria. hrcJ sequences are the most similar, exhibiting anywhere from 2 to 50 % variation at the nucleotide level, with the highest degree of variation present between plant and animal pathogen sequences. hrcV sequences are conserved among plant and animal pathogens at the N terminus. The C-terminal domain is conserved only among the enterobacterial plant pathogens, as are the hrcC and hrcR sequences. Additionally, hrcJ and hrcV sequence phylogenies suggest that at least some type III secretion system virulence genes from enterobacterial plant pathogens are related more closely to those of the genus Pseudomonas, a conclusion neither supported nor refuted by hrcC or hrcR. PMID- 19643762 TI - Pseudomonas aeruginosa recognizes and responds aggressively to the presence of polymorphonuclear leukocytes. AB - Polymorphonuclear neutrophilic leukocytes (PMNs) play a central role in innate immunity, where they dominate the response to infections, in particular in the cystic fibrosis lung. PMNs are phagocytic cells that produce a wide range of antimicrobial agents aimed at killing invading bacteria. However, the opportunistic pathogen Pseudomonas aeruginosa can evade destruction by PMNs and thus cause persistent infections. In this study, we show that biofilm cells of P. aeruginosa recognize the presence of attracted PMNs and direct this information to their fellow bacteria through the quorum sensing (QS) signalling system. The bacteria respond to the presence of PMNs by upregulating synthesis of a number of QS-controlled virulence determinants including rhamnolipids, all of which are able to cripple and eliminate cells of the host defence. Our in vitro and in vivo analyses support a 'launch a shield' model by which rhamnolipids surround the biofilm bacteria and on contact eliminate incoming PMNs. Our data strengthen the view that cross-kingdom communication plays a key role in P. aeruginosa recognition and evasion of the host defence. PMID- 19643764 TI - Positive regulation of flhDC expression by OmpR in Yersinia pseudotuberculosis. AB - OmpR has been demonstrated to negatively regulate the expression of the flagellar master operon flhDC in a wide variety of bacterial species. Here we report the positive regulation of flhDC expression by OmpR in Yersinia pseudotuberculosis. A sigma(70)-dependent promoter was identified by primer extension analysis and an active region with two conserved OmpR-binding sites around the flhDC promoter was confirmed. To confirm the regulation of flhDC expression by OmpR, flhDC as well as the downstream flagellar genes fliA, flgD, flgA, flgM, fliC and flaA were fused to lacZ, and decreased expression of all these genes in an ompR mutant (Delta ompR) was detected. Furthermore, Delta ompR was defective in bacterial motility and flagella synthesis. This defect was due to the low level of expression of flhDC in Delta ompR since overproduction of FlhDC in Delta ompR restored bacterial motility. The importance of two conserved OmpR-binding sites around the flhDC promoter region in the regulation of flhDC expression by OmpR was demonstrated by the fact that mutation of either one or both sites significantly decreased the promoter activity in the wild-type but not in Delta ompR. The binding of OmpR to these two sites was also demonstrated by DNA mobility shift assay. The possible mechanism underlying this positive regulation in Y. pseudotuberculosis is discussed. To our knowledge, this is the first report to demonstrate that OmpR positively regulates flhDC expression. PMID- 19643765 TI - Influence of heterologous MreB proteins on cell morphology of Bacillus subtilis. AB - The prokaryotic cytoskeletal protein MreB is thought to govern cell shape by positioning the cell wall synthetic apparatus at growth sites in the cell. In rod shaped bacteria it forms helical filaments that run around the periphery of the rod during elongation. Gram-positive bacteria often contain more than one mreB gene. Bacillus subtilis has three mreB-like genes, mreB, mbl and mreBH, the first two of which have been shown to be essential under normal growth conditions. Expression of an mreB homologue from the closely related organism Bacillus licheniformis did not have any effect on cell growth or morphology. In contrast, expression of mreB from the phylogenetically more distant bacterium Clostridium perfringens produced shape defects and ultimately cell death, due to disruption of the endogenous MreB cytoskeleton. However, expression of either mreB(B. licheniformis) (mreB(Bl)) or mreB(C. perfringens) (mreB(Cp)) was sufficient to confer a rod shape to B. subtilis deleted for the three mreB isologues, supporting the idea that the three proteins have largely redundant functions in cell morphogenesis. Expression of mreBCD(Bl) could fully compensate for the loss of mreBCD in B. subtilis and led to the formation of rod-shaped cells. In contrast, expression of mreBCD(Cp) was not sufficient to confer a rod shape to B. subtilis Delta mreBCD, indicating that a complex of these three cell shape determinants is not enough for cell morphogenesis of B. subtilis. PMID- 19643763 TI - Genealogical typing of Neisseria meningitidis. AB - Despite the increasing popularity of multilocus sequence typing (MLST), the most appropriate method for characterizing bacterial variation and facilitating epidemiological investigations remains a matter of debate. Here, we propose that different typing schemes should be compared on the basis of their power to infer clonal relationships and investigate the utility of sequence data for genealogical reconstruction by exploiting new statistical tools and data from 20 housekeeping loci for 93 isolates of the bacterial pathogen Neisseria meningitidis. Our analysis demonstrated that all but one of the hyperinvasive isolates established by multilocus enzyme electrophoresis and MLST were grouped into one of six genealogical lineages, each of which contained substantial variation. Due to the confounding effect of recombination, evolutionary relationships among these lineages remained unclear, even using 20 loci. Analyses of the seven loci in the standard MLST scheme using the same methods reproduced this classification, but were unable to support finer inferences concerning the relationships between the members within each complex. PMID- 19643766 TI - Estimating the potential impacts of intervention from observational data: methods for estimating causal attributable risk in a cross-sectional analysis of depressive symptoms in Latin America. AB - BACKGROUND: The field of epidemiology struggles both with enhancing causal inference in observational studies and providing useful information for policy makers and public health workers focusing on interventions. Population intervention models, analogous to population attributable fractions, estimate the causal impact of interventions in a population, and are one option for understanding the relative importance of various risk factors. With population intervention parameters, risk factors are effectively standardised, allowing one to compare their values directly and determine which potential intervention may have the greatest impact on the outcome. METHODS: The difference between total effects and population intervention parameters was examined using naive, G computation and inverse probability of treatment weighting approaches. The differences between these parameters and the intuitions they provide were explored using data from a 2003 cross-sectional study in rural Mexico. RESULTS: The assumptions, specific analytic steps, limitations and interpretations of the total effects and population intervention parameters are discussed, and code is provided in Stata. CONCLUSION: Population intervention parameters are a valuable and straightforward approach in epidemiological studies for making causal inference from the data while also supplying information that is relevant for researchers, public health practitioners and policy makers. PMID- 19643767 TI - Heart failure with a normal ejection fraction: new developments. PMID- 19643768 TI - Simple versus complex stenting strategy for coronary artery bifurcation lesions in the drug-eluting stent era: a meta-analysis of randomised trials. AB - BACKGROUND: Coronary bifurcation lesions remain a challenge for interventional cardiologists and the optimal stenting strategy has not been established in the current drug-eluting stent (DES) era. This study compared two strategies for DES treatment of coronary bifurcation lesions: a simple stenting approach (stenting only the main vessel (MV) and provisional stenting of the side branch (SB) only when bailout of the SB is necessary) versus a complex stenting approach (routinely stenting not only MV but also SB). METHODS: Data sources included PubMed and conference proceedings. Prespecified criteria were met by five randomised studies comparing simple stenting strategy versus complex stenting strategy in 1553 patients with coronary bifurcation lesions. Studies reported the clinical and angiographic outcomes of efficacy and safety during a minimum of 6 months. RESULTS: The risks of follow-up myocardial infarction (MI) (relative ratio (RR) 0.54, 95% confidence interval (CI) 0.37 to 0.78, p = 0.001) and early (in-hospital or 30-day) MI (RR 0.52, 95% CI 0.35 to 0.78, p = 0.002) were markedly lower in patients treated with the simple strategy compared to the complex strategy. There were no significant differences between the two different strategies with respect to the rates of cardiac death (RR 0.68, 95% CI 0.21 to 2.25, p = 0.53), target lesion revascularisation (TLR) (RR 0.93, 95% CI 0.62 to 1.41, p = 0.74) or definite stent thrombosis (ST) (RR 0.50, 95% CI 0.19 to 1.32, p = 0.16). The restenosis risk of MV and SB did not differ between the simple strategy group and the complex strategy group (RR 1.15, 95% CI 0.66 to 2.00, p = 0.63 and RR 1.12, 95% CI 0.80 to 1.57, p = 0.50, respectively). CONCLUSIONS: Compared to the complex strategy for DES treatment of coronary bifurcation lesions, the simple strategy was associated with a lower risk of early MI and a similar rate of angiographic restenosis. Since the complex strategy could not improve the clinical or angiographic outcome, the simple strategy can be recommended as a preferred bifurcation stenting technique in the DES era. PMID- 19643769 TI - Impact of continuous positive airway pressure treatment on left atrial volume and function in patients with obstructive sleep apnoea assessed by real-time three dimensional echocardiography. AB - BACKGROUND: Obstructive sleep apnoea (OSA) has been reported as a predictor of left ventricle (LV) diastolic dysfunction and left atrium (LA) remodelling. The aim of this study is to evaluate the impact of OSA treatment with a continuous positive airway pressure device (CPAP) on the LA volume and function, as well as on the LV diastolic function. METHODS: In total, 56 OSA patients were studied. All patients underwent real-time three-dimensional (RT3DE) and two-dimensional echocardiogram with tissue Doppler evaluation in order to estimate LA volumes, function and LV diastolic performance. A total of 30 patients with an apnoea hypopnoea index greater than 20 were randomly selected to receive sham CPAP (n = 15) or effective CPAP (n = 15) for 24 weeks. They underwent echo examination on three different occasions: at baseline, after 12 weeks and 24 weeks of CPAP or sham CPAP. RESULTS: In the effective CPAP group we observed the following changes from the baseline to the 24-week echo evaluation: (a) a reduction in the E/E' ratio (10.3 (1.9) to 7.9 (1.3), p = 0.03); (b) an increase in the LA passive emptying fraction (28.8% (11.9%) to 46.8% (9.3%), p = 0.01); and (c) a reduction in the LA active emptying fraction (42.7% (11.5%) to 25.7 (15.7), p<0.01). In the sham group, there were no changes from the baseline to the 24-week echo. We found a positive correlation between 24 week/baseline LA active emptying volume and 24 week/baseline E/E' ratios (r = 0.40, p<0.05) and a negative correlation between 24 week/baseline LA passive emptying volume and 24 week/baseline E/E' ratios (r = -0.53, p<0.05). No significant changes were found on LA total emptying fraction. CONCLUSION: CPAP improved LV diastolic function and LA passive emptying, but not LA structural variables in OSA patients. TRIAL REGISTRATION NUMBER: NCT00768807. PMID- 19643770 TI - Childhood dairy and calcium intake and cardiovascular mortality in adulthood: 65 year follow-up of the Boyd Orr cohort. AB - BACKGROUND: Dairy consumption in childhood may have long-term effects on cardiovascular mortality through influencing the development of risk factors or programming effects. OBJECTIVE: To investigate whether dairy and calcium consumption in childhood is associated with adult mortality due to coronary heart disease (CHD), stroke and all causes. METHODS: In 1937-9, 4999 children in England and Scotland participated in a study of family food consumption, assessed from 7-day household food inventories. Cause of death was ascertained between 1948 and 2005 in 4374 traced cohort members with complete data. Per capita household intake estimates for dairy products and calcium were used as proxies for individual intake. RESULTS: No strong evidence that a family diet in childhood high in dairy products was associated with CHD or stroke mortality was found. However, childhood calcium intake was inversely associated with stroke mortality (multivariable adjusted hazard ratio (HR) for highest versus lowest calcium group: 0.41; 95% confidence interval (CI) 0.16 to 1.05; p for trend = 0.04), but not CHD mortality. All-cause mortality was lowest in those with the highest family dairy (HR = 0.77; 95% CI 0.61 to 0.98; p for trend = 0.04) and calcium intake (HR = 0.77, 95% CI 0.60 to 0.98; p for trend = 0.05). CONCLUSIONS: Children whose family diet in the 1930s was high in calcium were at reduced risk of death from stroke. Furthermore, childhood diets rich in dairy or calcium were associated with lower all-cause mortality in adulthood. Replication in other study populations is needed to determine whether residual confounding explains part of these findings. PMID- 19643771 TI - Mortality from cancer and other causes in the Balangero cohort of chrysotile asbestos miners. AB - OBJECTIVES: To provide further information on mortality from cancer and other causes among chrysotile asbestos miners several years after exposure ceased, we updated the analyses from the Balangero mine worker cohort with follow-up to the end of 2003. METHODS: The cohort included 1056 men, for a total of 34 432 man years of observation. We obtained employment data from factory personnel records, and ascertained vital status and causes of death through population registers and death certificates from municipal registration offices. We computed expected numbers of deaths and standardised mortality ratios (SMRs) for relevant causes using the province of Turin and national death rates, for each 5-year calendar period and age group. RESULTS: We found a significant excess mortality from pleural cancer only (4 deaths, SMR 4.67) and pleural and peritoneal cancers combined (5 deaths, SMR 3.16). All pleural and peritoneal cancer deaths occurred 30 or more years after first exposure. The SMRs were 1.27 for lung cancer (45 deaths), 1.82 for laryngeal cancer (8 deaths) and 1.12 for all cancers (142 deaths). Cumulative dust exposure and the various time factors considered did not show a clear pattern of risk associated with mortality from lung cancer. There were 57 deaths from cirrhosis (SMR 2.94) and 54 from accidents and violence (SMR 1.88). Overall, we observed a total of 590 deaths as compared to 412.9 expected (SMR 1.43). CONCLUSIONS: This updated analysis, with almost 60% of the cohort having died, confirmed the excess mortality from pleural and peritoneal cancers and from several alcohol-related causes. PMID- 19643772 TI - Molecular analysis of pericentrin gene (PCNT) in a series of 24 Seckel/microcephalic osteodysplastic primordial dwarfism type II (MOPD II) families. AB - Microcephalic osteodysplastic primordial dwarfism type II (MOPD II, MIM 210720) and Seckel syndrome (SCKL, MIM 210600) belong to the primordial dwarfism group characterised by intrauterine growth retardation, severe proportionate short stature, and pronounced microcephaly. MOPD II is distinct from SCKL by more severe growth retardation, radiological abnormalities, and absent or mild mental retardation. Seckel syndrome is associated with defective ATR dependent DNA damage signalling. In 2008, loss-of-function mutations in the pericentrin gene (PCNT) have been identified in 28 patients, including 3 SCKL and 25 MOPDII cases. This gene encodes a centrosomal protein which plays a key role in the organisation of mitotic spindles. The aim of this study was to analyse PCNT in a large series of SCKL-MOPD II cases to further define the clinical spectrum associated with PCNT mutations. Among 18 consanguineous families (13 SCKL and 5 MOPDII) and 6 isolated cases (3 SCKL and 3 MOPD II), 13 distinct mutations were identified in 5/16 SCKL and 8/8 MOPDII including five stop mutations, five frameshift mutations, two splice site mutations, and one apparent missense mutation affecting the last base of exon 19. Moreover, we demonstrated that this latter mutation leads to an abnormal splicing with a predicted premature termination of translation. The clinical analysis of the 5 SCKL cases with PCNT mutations showed that they all presented minor skeletal changes and clinical features compatible with MOPDII diagnosis. It is therefore concluded that, despite variable severity, MOPDII is a genetically homogeneous condition due to loss-of-function of pericentrin. PMID- 19643773 TI - Lack of interaction between raltegravir and cyclosporin in an HIV-infected liver transplant recipient. PMID- 19643774 TI - Molecular cloning and characterization of SmrA, a novel ABC multidrug efflux pump from Stenotrophomonas maltophilia. AB - OBJECTIVES: Stenotrophomonas maltophilia is an emerging nosocomial pathogen that can cause difficult-to-treat infections and exhibits significant degrees of poorly understood multidrug resistance (MDR). The aim of this study was to identify and characterize a multidrug ATP-binding cassette (ABC) efflux pump in S. maltophilia. METHODS: SmrA was identified in the S. maltophilia genome based on the detection of ABC transporter conserved motifs and alignment with experimentally proven MDR ABC transporters. The smrA gene was cloned and expressed in the hypersusceptible acrAB mutant Escherichia coli strain SM1411. The resistance to several antimicrobial agents was tested using Stokes' disc diffusion and broth microdilution MIC methods. Norfloxacin accumulation and efflux assays were performed using a fluorescence method with and without the efflux pump inhibitors sodium O-vanadate and reserpine. RESULTS: Cloning and expression of smrA in Escherichia coli conferred increased resistance to structurally unrelated compounds, including fluoroquinolones, tetracycline, doxorubicin and multiple dyes. Moreover, the expression of smrA in E. coli reduced norfloxacin uptake and enhanced its efflux, features that could be inhibited by the ABC efflux pump inhibitors. CONCLUSIONS: SmrA is a member of the ABC multidrug efflux pump family. The findings warrant further study of the role of this molecule in S. maltophilia isolates, to estimate the potential impact of this system in antimicrobial resistance. PMID- 19643775 TI - Intracellular metabolism of favipiravir (T-705) in uninfected and influenza A (H5N1) virus-infected cells. AB - OBJECTIVES: To determine the metabolism of favipiravir (T-705, 6-fluoro-3-hydroxy 2-pyrazinecarboxamide) to its ribosylated, triphosphorylated form (T-705 RTP) in uninfected and influenza A/Duck/MN/1525/81 (H5N1) virus-infected cells. Effects of treatment on intracellular guanosine triphosphate (GTP) pools and influenza virus-inhibitory activity were also assessed. METHODS: A strong anion exchange HPLC separation method with UV detection was used to quantify T-705 RTP and GTP levels in Madin-Darby canine kidney cells. Antiviral activity was determined by virus yield reduction assay. RESULTS: Accumulation of T-705 RTP in uninfected cells increased linearly from 3 to 320 pmol/10(6) cells in cells exposed to 1 1000 microM extracellular T-705 for 24 h, approaching maximum levels by 9 h. Virus infection did not result in greater T-705 RTP accumulation compared with uninfected cells. Catabolism of T-705 RTP occurred after removal of T-705 from the extracellular medium, with a half-life of decay of 5.6 +/- 0.6 h. Based upon these results, short-term incubation of T-705 with H5N1 virus-infected cells was predicted to provide an antiviral benefit. Indeed, 4-8 h 10-100 microM T-705 treatment of cells resulted in virus yield reductions, but less than continuous exposure. A 100-fold higher extracellular concentration of T-705 was required to inhibit intracellular GTP levels compared with ribavirin, which helps explain ribavirin's greater toxicity. CONCLUSIONS: The favourable intracellular metabolic properties of T-705 combined with its reduced cell-inhibitory properties make this compound an attractive candidate for treating human influenza virus infections. PMID- 19643776 TI - Determination of the pharmacodynamic activity of clinically achievable tigecycline serum concentrations against clinical isolates of Escherichia coli with extended-spectrum beta-lactamases, AmpC beta-lactamases and reduced susceptibility to carbapenems using an in vitro model. AB - BACKGROUND: Escherichia coli harbouring extended-spectrum beta-lactamases (ESBLs), AmpC beta-lactamases and reduced susceptibility to carbapenems (CRS) are increasing worldwide. This study assessed the in vitro pharmacodynamic activity of tigecycline against E. coli with ESBLs, AmpCs and CRS. METHODS: Nine E. coli isolates were studied, including three ESBL-producing isolates, three AmpC producing isolates and three isolates demonstrating CRS (ertapenem MIC > or = 0.12 mg/L). The pharmacodynamic model was inoculated with organisms at 1 x 10(6) cfu/mL and tigecycline dosed once every 24 h to simulate the fC(max) (free peak serum concentration) and t(1/2) (serum half-life) obtained after standard dosing of 100 mg intravenously every 24 h (fC(max), 0.15 mg/L; t(1/2), 42 h). Samples were collected over 48 h. RESULTS: For isolates with a tigecycline fAUC(24)/MIC of 2.0 (tigecycline MIC = 0.5 mg/L), tigecycline demonstrated bacteriostatic activity with < 1 log(10) reduction in bacterial growth compared with the initial inoculum at 12, 24 and 48 h. Against the two isolates for which the tigecycline fAUC(24)/MIC was 4.0 (tigecycline MIC = 0.25 mg/L), tigecycline demonstrated bacteriostatic activity with approximately 1.5 log(10) reduction in bacterial growth compared with the initial inoculum at 12, 24 and 48 h. Against the two isolates for which the tigecycline fAUC(24)/MIC was 8.0 (tigecycline MIC = 0.12 mg/L), tigecycline demonstrated bacteriostatic activity with approximately 2.0 log(10) reduction in bacterial growth compared with the initial inoculum at 12, 24 and 48 h. CONCLUSIONS: Tigecycline demonstrated approximately 1-2 log(10) killing against E. coli harbouring ESBLs, AmpC beta-lactamases and CRS when simulating clinically achievable serum concentrations, and represents a potential therapy for infections caused by these isolates. PMID- 19643777 TI - Novel strategies to treat antiretroviral-naive HIV-infected patients. AB - Although guidelines exist that provide recommended strategies for treating HIV infected patients who are naive to antiretroviral therapy, treatment needs to be tailored to individual circumstances. Here we discuss the current recommendations and the evidence used in their development, along with new and emerging treatment strategies. PMID- 19643778 TI - How Medicare could get better prices on prescription drugs. AB - Congress may reform drug pricing policies under Medicare Part D as part of a larger health reform effort. Currently, the "noninterference" provision prevents the government from negotiating drug prices on behalf of Medicare Part D prescription drug plans. Commonly considered reform proposals borrow ideas from Medicaid, either through returning dual eligibles to Medicaid drug pricing or by imposing mandatory rebates across the Part D population. We examine a menu of other options, including value-based pricing; expansion of generic and therapeutically equivalent substitution; increased formulary diversity; importation; and limited antitrust waivers. These latter options may reduce federal spending without direct government price negotiations. PMID- 19643779 TI - Three-dimensional ultrasonographic depiction of fetal abdominal blood vessels. AB - OBJECTIVE: The purpose of this study was to identify fetal abdominal vasculature with 3-dimensional (3D) ultrasonography and to describe a systematic method for analysis of volume data sets. METHODS: Three-dimensional volumes of the fetal abdomen were acquired prospectively in 30 patients between 15 and 34 weeks' gestation with color Doppler, high-definition (HD) flow, power Doppler, and B flow imaging. All volumes were analyzed offline by 2 examiners separately. The feasibility of identifying the fetal abdominal blood vessels was analyzed. A standardized approach was applied to identify specific vessels by correlating the images with known anatomic landmarks. RESULTS: The volumes were rotated into an anatomic orientation in the multiplanar mode, and then the vessels were identified in the following order: aorta (30 of 30), celiac trunk (29 of 30), superior mesenteric vein (28 of 30 and 26 of 30 for readers 1 and 2, respectively), superior mesenteric artery (29 of 30), left renal artery (25 of 30 and 26 of 30), right renal artery (27 of 30), common iliac arteries (30 of 30), umbilical arteries (26 of 27), external iliac arteries (20 of 22), umbilical vein (29 of 30), ductus venosus (30 of 30), hepatic vein (29 of 30), right portal vein (29 of 30), inferior vena cava (28 of 30), adrenal artery (2 of 30), hepatic artery (24 of 30 and 23 of 30), splenic artery (24 of 30 and 23 of 30), gastric artery (14 of 30 and 9 of 30), splenic vein (19 of 30 and 15 of 30), and renal vein (1 of 30). A step-by-step systematic approach to identify the abdominal vasculature from the ultrasonographic volume data set was developed. CONCLUSIONS: Fetal abdominal vessels can be easily visualized when a systematic analysis is performed on 3D data set volumes. Visualization of the vessels was optimal when volumes were acquired with HD flow imaging. PMID- 19643780 TI - Prenatal surveillance of bronchopulmonary sequestration using 3-dimensional ultrasonography. AB - OBJECTIVE: The purpose of this study was to assess the growth of fetal lung lesions using 3-dimensional ultrasonography (3DUS) and to note the clinical outcomes of infants with congenital bronchopulmonary sequestration (BPS) diagnosed prenatally. METHODS: Twenty-two cases of intrathoracic BPS diagnosed prenatally occurred between May 2005 and September 2008. The volume of the BPS lesion (V(mass)) and the volume of the fetal chest (V(chest)) were measured with the 3DUS software Virtual Organ Computer-Aided Analysis (VOCAL; GE Healthcare, Kretztechnik, Zipf, Austria). The clinical outcomes of all cases were recorded. RESULTS: Among 22 cases with fetal BPS, 8 were terminated, and 2 were lost to follow-up. The growth pattern of the BPS lesions was assessed in 12 live-born cases with 2 or 3 3DUS measurements per case. There was no statistically significant difference between the V(mass) (P = .859) and V(mass)/V(chest) (P = .078) at 19 to 24 weeks' gestational age (WGA) and greater than 24 to 30 WGA, but there was a statistically significant difference between the V(mass) (P = .010) and V(mass)/V(chest) (P = .008) at greater than 24 to 30 WGA and greater than 30 to 39 WGA. The lung lesion resolved spontaneously before birth in 4 fetuses and postnatally in 2 infants. All 12 fetuses survived to term without any prenatal intervention, were born without any evidence of neonatal respiratory impairment, and did not undergo surgical resection of the mass. CONCLUSIONS: Our data showed that fetuses with BPS had a favorable clinical outcome, and the pulmonary mass decreased during late pregnancy and resolved spontaneously. Three-dimensional ultrasonography with VOCAL provides a useful method for assessing the growth of pulmonary lesions. PMID- 19643781 TI - Supratentorial abnormalities in the Chiari II malformation, III: The interhemispheric cyst. AB - OBJECTIVE: Our clinical observations noted an interhemispheric "cyst," a protrusion of the posterior superior third ventricle, in fetuses with myelomeningocele (MMC). The study analyzed the frequency of this observation and features that influence its visualization. METHODS: We searched for cases of fetal MMC sonographically detected between 1999 and 2007. Intracranial findings were retrospectively reviewed with attention to the interhemispheric cistern. Additionally, we reviewed 25 fetuses without a central nervous system anomaly and 10 fetuses with ventriculomegaly but no MMC. RESULTS: Among 89 fetuses identified, the mean gestational age was 22 weeks 4 days. Thirty-eight (43%) had an interhemispheric cyst. The frequency was similar on sonograms judged to be well visualized compared with studies judged to be suboptimally visualized. The degree of ventriculomegaly, timing of diagnosis, and severity of the Chiari II malformation did not appear to influence the frequency of the finding. Among fetuses without a central nervous system anomaly, no interhemispheric cysts were detected; a cyst was detected in 1 of 10 fetuses with ventriculomegaly. Interhemispheric cysts were more likely to be detected in fetuses with the Chiari II malformation than fetuses with ventriculomegaly but without the Chiari II malformation (P = .04). CONCLUSIONS: Interhemispheric cysts are a common supratentorial feature of the Chiari II malformation. Their presence appears to be unrelated to other features of the Chiari II malformation. Although interhemispheric cysts are seen in other abnormal fetuses, their striking prevalence in the Chiari II malformation should lead to a thorough examination for MMC. PMID- 19643783 TI - Basic versus detailed sonography: what do we miss? AB - OBJECTIVE: The purpose of this study was to evaluate the impact of restrictive versus routine use of "detailed" second-trimester sonography. METHODS: Records of singleton pregnancies undergoing evaluation from 2004 to 2008 were reviewed. A detailed examination (Current Procedural Terminology [CPT] code 76811) was routinely performed on all patients. Major structural abnormalities were categorized on the basis of whether the structure would be included in a "basic" examination (CPT code 76805). Risk factors for anomalies were identified. The Fisher exact test and Student t test were used for statistical comparison. RESULTS: Major anomalies were identified in 218 patients, 75 of whom elected to undergo abortion. In 88 patients (40.4%), the abnormal structure would not be included in a basic examination. Risk factors were not more prevalent in those with anomalies requiring a detailed examination for diagnosis or in those patients who chose to undergo abortion. CONCLUSIONS: Restricting detailed evaluation to those with risk factors would have prevented detection of a substantial proportion of anomalies. PMID- 19643782 TI - Interobserver reproducibility of transabdominal 3-dimensional sonography of the fetal brain. AB - OBJECTIVE: The purpose of this study was to assess the interobserver reproducibility of transabdominal 3-dimensional (3D) fetal neurosonography. METHODS: This was a prospective observational study. We studied 23 consecutive singleton pregnancies between 18 and 23 weeks' gestation. All cases had normal fetal neurosonographic examination findings, which were confirmed after birth. A 3D sonographic volume of the fetal head was acquired transabdominally by a single operator using an axial approach. Fetal brain anatomy was later analyzed offline by 2 different operators. Axial, sagittal, and coronal views of the fetal brain were obtained to perform a detailed evaluation of the fetal brain. Each operator defined the scanning planes obtained as adequate or inadequate. Results were evaluated with 2 x 2 tables and the Cohen kappa coefficient to assess interobserver agreement. RESULTS: Good-quality multiplanar images were obtained in 23 of 23 cases. The rate of adequate visualization was 100% for all of the axial planes, with kappa values of 1.00. For sagittal and coronal planes, the rate of visualization ranged between 78% and 91%, with kappa values ranging between 0.61 and 0.83. CONCLUSIONS: Transabdominal 3D sonography of the fetal brain at 18 to 23 weeks' gestation has an acceptable degree of interobserver reproducibility. PMID- 19643784 TI - Is sonographic assessment of fetal weight influenced by formula selection? AB - OBJECTIVE: Several published formulas exist for the determination of estimated fetal weight (EFW), with limited data on their comparative accuracies. The aims of our study were to assess and compare the performance of different EFW formulas in predicting actual birth weight (BW) in an urban population. METHODS: Patients with an EFW determined within 7 days of delivery were considered eligible for the study. Fourteen published formulas, derived from populations comparable to ours, were used to recalculate EFWs from the same initial measurements. The accuracy of the EFWs obtained from the different formulas were compared by percentage error methods using bias and precision and Bland-Altman limits of agreement methods. Sensitivity and specificity for prediction of being small for gestational age (SGA) were calculated. RESULTS: Eighty-one fetuses were included in the study. Formula C of Hadlock et al [Hadlock C; log(10) BW = 1.335 - 0.0034(abdominal circumference [AC])(femur length [FL]) + 0.0316(biparietal diameter) + 0.0457(AC) + 0.1623(FL); Am J Obstet Gynecol 1985; 151:333-337] had the best performance according to the bias and precision method. Bland-Altman limits of agreement confirmed these results. Among the formulas, the sensitivity for detection of SGA ranged from 72% to 100%, and specificity was 41% to 88%. Hadlock C had the optimal sensitivity/specificity trade-off for detection of SGA. CONCLUSIONS: Fourteen formulas showed considerable variation of bias and precision in our population as well as a wide range of sensitivities and specificities for SGA. The choice of the appropriate formula for EFW in a given population should be based on objective and explicit criteria. Consideration of bias and precision for the formula in the population being assessed is critical and may affect clinical care. PMID- 19643785 TI - Maternal obesity limits the ultrasound evaluation of fetal anatomy. AB - OBJECTIVE: The purpose of this study was to evaluate the effect of maternal habitus on adequate visualization of fetal anatomy during a standard second trimester ultrasound examination. METHODS: This was a retrospective cohort study of singleton pregnancies at 18 to 24 weeks that underwent sonography over a 5 year period. Pregnancies complicated by an indication for targeted sonography were excluded. Standard ultrasound examinations were performed according to American Institute of Ultrasound in Medicine criteria. Ten anatomic components were evaluated for adequacy of visualization: atria of the cerebral ventricles, posterior fossa, midline face, 4-chamber view of the heart, spine, ventral wall, umbilical cord vessels, stomach, kidneys, and bladder. The body mass index (BMI) was based on the patient's weight at the first prenatal visit. RESULTS: Of 10,112 women who underwent a standard ultrasound examination, 2% were underweight; 38% were of normal weight; 34% were overweight; and 26% were obese. Visualization of fetal anatomy decreased significantly with increasing maternal BMI for the complete survey as well as for each individual component with the exception of the fetal bladder (all P < .001). Among those with a normal or underweight BMI, an overweight BMI, and class 1, 2, and 3 obesity, all 10 anatomic components were adequately visualized at the initial examination in 72%, 68%, 57%, 41%, and 30% of cases, respectively (P < .001). CONCLUSIONS: Increasing maternal BMI limits visualization of fetal anatomy during a standard ultrasound examination at 18 to 24 weeks. In obese women, the fetal anatomy survey could be completed during the initial examination in only 50% of cases. Counseling may need to be modified to reflect the limitations of sonography in obese women. PMID- 19643786 TI - Retained products of conception: spectrum of color Doppler findings. AB - OBJECTIVE: The purpose of this study was to characterize color Doppler imaging features of retained products of conception (RPOC) with gray scale correlation. METHODS: Clinically suspected cases of RPOC between January 2005 and February 2008 were reviewed. Patient data and relevant color Doppler and gray scale features were recorded. RESULTS: A total of 269 patients referred for sonographic evaluation for RPOC were identified. Thirty-five patients had confirmed pathologic diagnoses, 28 of whom had RPOC. In those with RPOC, 5 (18%) were avascular (type 0); 6 (21%) had minimal vascularity (type 1); 12 (43%) had moderate vascularity (type 2); and 5 (18%) had marked vascularity (type 3). Peak systolic velocities ranged from 10 to 108 cm/s (average, 36.1 cm/s). Resistive indices in arterial waveforms ranged from 0.33 to 0.7 (average, 0.5). Five (45%) of the patients with type 0 vascularity had RPOC; 6 (86%) of those with type 1 had RPOC; and 17 (100%) of those with types 2 and 3 had RPOC. An echogenic mass had a moderate positive predictive value (80%) but low sensitivity (29%) for RPOC. CONCLUSIONS: Color Doppler evaluation of the endometrium is helpful in determining the presence of RPOC. Endometrial vascularity is highly correlated with RPOC, whereas the lack of vascularity can be seen in both intrauterine clots and avascular RPOC. PMID- 19643787 TI - Three-dimensional power Doppler angiography of cyclic ovarian blood flow. AB - OBJECTIVE: The purpose of this study was to assess the vascular indices generated by 3-dimensional (3D) power Doppler angiography by evaluating the cyclic changes in the vascularity of normal ovaries, including those that were ovulating, nonovulating, and hormonally suppressed. METHODS: In this prospective longitudinal observational study, a cohort of premenopausal regularly menstruating women with no known ovarian disease underwent 3D power Doppler imaging every 2 to 3 days for the duration of 1 menstrual cycle. Four indices were generated: vascularization index (VI), flow index (FI), vascularization-flow index (VFI), and mean grayness. Comparisons of vascularity were made between ovulating, nonovulating, and hormonally suppressed ovaries. Normal ranges were established and graphed longitudinally. RESULTS: Eighteen participants (36 ovaries) ages 28 to 45 years underwent an average of 10 examinations, yielding 368 acquired ovarian volumes for analysis. Seven participants used hormonal contraception. The VI, FI, and VFI were closely correlated (Pearson product moment correlation coefficients, 0.52-0.95). The vascular indices of ovulating ovaries were significantly higher than those of nonovulating ovaries (VI, FI, and VFI, all P < .001), with the largest discrepancies during the luteal phase. Hormonally suppressed ovaries had significantly lower vascularity throughout the cycle (VI, P < .002; FI, P < .001; VFI, P < .007). The vascular indices of all groups appeared to drop during the late follicular period and then rise again. CONCLUSIONS: The VI would suffice as the principal vascular parameter for 3D power Doppler analysis. Preovulatory scans may be more useful for distinguishing pathologic vascularization. Hormonally suppressed ovaries have significantly lower vascularity throughout the cycle. Normal-appearing ovaries with vascular indices above the normal ranges established by these data may warrant further investigation. PMID- 19643788 TI - Postabortion Doppler evaluation of the uterus: incidence and causes of myometrial hypervascularity. AB - OBJECTIVE: The aim of this study was to investigate the incidence and causes of uterine hypervascular lesions showing low-impedance, high-velocity flow on color Doppler sonography (CDS) after first-trimester dilation and curettage (D&C). METHODS: This was a prospective study of 65 consecutive women who underwent first trimester termination of pregnancy. Color Doppler sonography of the uterus was performed on days 3 and 10 after D&C. If the myometrial hypervascularity (MH) persisted on day 10, a second D&C was performed, and then the patients were followed with weekly Doppler examinations. RESULTS: In 16 of 65 women (24.6%), MH was detected with CDS on day 3 after D&C. In 3 cases, MH resolved spontaneously by postabortion day 10. In the remaining 13 patients, the second D&C performed on day 10 revealed retained products of conception (RPOC) in 8 patients (61.5%), a hydatidiform mole in 2 (15.4%), endometritis in 1 (7.7%), and no abnormality in 2 (15.4%). Complete resolution of the MH occurred in all cases. The mean period to the resolution of MH after the second D&C +/- SD was 16.54 +/- 11.06 days (range, 7-48 days). Univariate analysis revealed that gestational age at D&C (P = .012) and a history of any uterine surgery (P = .044) were significantly associated with postabortion MH. On binary logistic regression analysis, gestational age at D&C was the only independent predictive factor for MH (P = .016; odds ratio, 1.47; 95% confidence interval, 1.08-2.02). CONCLUSIONS: The presence of hypervascular areas within the myometrium is a common finding in the postabortion period, and in most cases, the cause of this finding is RPOC. PMID- 19643789 TI - Three-dimensional sonographic characteristics of deep endometriosis. AB - OBJECTIVE: The purpose of this presentation is to investigate the potential role of 3-dimensional (3D) sonography in the assessment of deep endometriosis. METHODS: Cases of deep endometriosis are presented to illustrate the spectrum of appearances obtained with 3D sonography. In addition, we evaluate the possible role of other functions included in 3D equipment, such as the niche mode and tomographic ultrasound imaging (TUI). RESULTS: Three-dimensional image rendering could allow a good analysis of the endometriotic nodule; in fact, in all presented cases, this reconstruction seems to clearly show the irregular shapes and borders of the lesions. This technique allows unrestricted access to an infinite number of viewing planes, which can be very useful for correctly locating lesions within the pelvis and evaluating the relationship with other organs. The stored 3D volumes can be reassessed and compared by the same or different examiners over time. This characteristic may be relevant for monitoring the effect of medical therapies over time. In the niche mode, sonographic imaging is represented as a "cut-open" view of the internal aspect of the nodule and its surrounding tissue. This additional function, which is associated with TUI, could be particularly useful for evaluation of the extension of a nodule in the rectovaginal septum, the depth of infiltration, and the relationship with the rectosigmoid junction or ureter. CONCLUSIONS: In the near future, 3D sonography in deep infiltrating endometriosis could be an interesting mode of research with positive effects in everyday clinical practice. PMID- 19643790 TI - Compact ultrasound for improving maternal and perinatal care in low-resource settings: review of the potential benefits, implementation challenges, and public health issues. AB - OBJECTIVE: Ultrasound imaging, a front-line diagnostic tool for perinatal care, is rarely available in the developing world, where maternal and newborn mortality rates are starkly higher than elsewhere. The development of portable and inexpensive medical ultrasound machines (compact ultrasound) offers the possibility of broader use of ultrasound. Our objective was to assess the potential benefits and challenges of deploying compact ultrasound in developing countries for improving obstetric health. METHODS: Existing literature on perinatal care, compact ultrasound, and issues in the deployments of medical technology in low-resource settings was reviewed. Anecdotal evidence was assessed, and the authors' field experiences in Nicaragua and Mali were evaluated as a template for wider deployments. RESULTS: Few published studies directly concerned with compact ultrasound in low-resource settings were found. These, however, in combination with available anecdotal data, support the view that compact ultrasound in less-developed regions is feasible and would result in a relatively low-cost improvement in perinatal care. CONCLUSIONS: The development of lightweight, portable, and relatively inexpensive ultrasound systems offers a great opportunity for reducing maternal and neonatal mortality in low-resource settings. Evidence-based analysis of compact ultrasound deployments as a public health response to obstetric needs in less-developed countries has been hampered by limited data in 3 key areas: maternal and perinatal mortality and morbidity in these settings, evaluations of compact ultrasound systems as reliable alternatives to full-sized systems, and the lack of outcomes data based on actual deployments of compact ultrasound for this purpose. Field trials of compact ultrasound on a scale commensurate with public health interventions should be undertaken. PMID- 19643791 TI - Monosomy 18p presenting with holoprosencephaly and increased nuchal translucency in the first trimester: report of 2 cases. AB - OBJECTIVE: The purpose of this series is to describe the first-trimester sonographic findings leading to the diagnosis of monosomy 18p. METHODS: The sonographic appearance of 2 cases of monosomy 18p, detected as part of first trimester sonographic screening for aneuploidy at this institution, was reviewed. RESULTS: Increased nuchal translucency thickness, alobar holoprosencephaly, and facial defects were detected in both cases. Chromosomal analysis by chorionic villus sampling revealed de novo del(18p) in 1 case and monosomy 18p as the result of an 18q isochromosome in the other. CONCLUSIONS: Increased nuchal translucency thickness in association with brain and face anomalies on a first trimester scan allowed the early diagnosis of monosomy 18p. Fetuses with holoprosencephaly can be readily identified in the first trimester by examining a cross section of the fetal head looking for the "butterfly" sign. Prenatal karyotyping provides important information regarding the etiology and risk of recurrence in these cases. PMID- 19643792 TI - Prenatal diagnosis of congenital lobar emphysema: case report and review of the literature. PMID- 19643793 TI - Prenatal detection of an extra-adrenal neuroblastoma with hepatic metastases. PMID- 19643794 TI - Prenatal sonographic features of fetal atelosteogenesis type 1. PMID- 19643795 TI - Prenatal diagnosis of benign extreme hyperlordosis. PMID- 19643796 TI - Complete right heart flow reversal: pathognomonic recipient twin circular shunt in twin-twin transfusion syndrome. PMID- 19643797 TI - Umbilical artery hypoplasia in twin-twin transfusion syndrome complicated by discordant umbilical artery Doppler findings in the donor twin: a diagnostic dilemma. PMID- 19643798 TI - Pelvic arteriovenous malformation: an important differential diagnosis of a complex adnexal mass. PMID- 19643799 TI - Subinvolution of the placental site. PMID- 19643800 TI - Tonic-clonic seizures in a fetus with Pena-Shokeir syndrome. PMID- 19643801 TI - What is the role of sonography in the diagnosis of ovarian hyperthecosis? PMID- 19643802 TI - Apico-aortic valved conduit as an alternative for aortic valve re-replacement in severe prosthesis-patient mismatch. AB - Off-pump implantation of an apico-aortic bioprothesis-valved conduit in a 75-year old female symptomatic patient with severe prosthesis-patient mismatch secondary to a previous aortic valve replacement, calcified ascending aorta, tight adhesion with the sternum, was successfully conducted to relieve the left ventricle from severe aortic stenosis. PMID- 19643803 TI - Sentinel node mapping and micrometastasis in patients with clinical stage IA non small cell lung cancer. AB - Many evidences suggest that prognosis of non-small cell lung cancer (NSCLC) with lymph node micrometastases (LNMM) is poor compared with those without LNMM. Therefore, it is better to evaluate LNMM through immunohistochemistry (IHC) of serial sectioning of all dissected lymph nodes. However, this labor-intensive approach is impossible in a practical setting. Therefore, we examined whether we are able to efficiently diagnose LNMM using the sentinel node (SN) mapping. Fifty one patients with clinical T1N0M0 NSCLC were enrolled in this study. SNs were then detected intraoperatively. After SN mapping, lobectomy and hilar and mediastinal lymph node dissection were performed. Metastases of all dissected lymph nodes were examined by hematoxylin and eosin (H&E) staining and immunohistochemical cytokeratin staining. SN detection rate was 80.4% (41/51). Average number of SNs was 1.8+/-1.1 in a patient. Lymph node metastases were diagnosed in two patients using H&E staining. LNMM were found only in SNs of two patients. On the other hand, micrometastasis was not found in non-SN. According to these results, two patients with clinical T1N0M0 NSCLC migrated to T1N1M0. Evaluation of micrometastases of all dissected lymph nodes may be substituted by evaluating micrometastases of SNs. We believe that further studies are warranted to determine the most useful clinical applications. PMID- 19643804 TI - Anti-Mullerian hormone and inhibin B levels as markers of premature ovarian aging and transition to menopause in type 1 diabetes mellitus. AB - BACKGROUND: Serum anti-Mullerian hormone (AMH) levels decrease early during the transition to menopause and women with type 1 diabetes mellitus (DM1) experience menopause at a younger age. We hypothesized that older women with DM1 will have lower AMH levels than controls. METHODS: We studied ovarian function in women with DM1 (n = 66) and healthy controls (n = 58), all <45 years old. Steroids, gonadotrophins, AMH and inhibin B levels were measured during the follicular phase. RESULTS: Piece-wise regression analysis demonstrated that AMH levels begin to decrease at 33 years of age in both groups. This age limit was used to compare data in both groups. AMH levels were lower in DM1 women than in controls >33 years (4.1 +/- 4.2 versus 9.5 +/- 7.9 pmol/l, mean +/- SD, P = 0.006). A higher proportion of women with DM1 showed AMH levels in the menopausal range compared with controls (16.7% versus 3.4%, respectively, P = 0.02). For all patients, those with DM1 exhibited lower inhibin B levels than controls (89.3 +/- 51.7 versus 113.2 +/- 76.0 ng/ml, P < 0.05). FSH and estradiol were similar in both groups. Regression analysis showed an earlier decline in AMH levels in women with DM1 than controls. Even after age adjustment, DM1 was a significant factor for the determination of inhibin B and AMH levels. CONCLUSIONS: Lower AMH levels in women with DM1 during the fourth decade of life suggest the presence of an earlier decline in the ovarian follicle pool in these women. Further studies are needed to evaluate the mechanism of this complication. PMID- 19643805 TI - Health impact assessment of quality wine production in Hungary. AB - Alcohol-related health outcomes show strikingly high incidence in Hungary. The effects of alcohol consumption are influenced not only by the quantity, but also the quality of drinks; therefore, wine production can have an important effect on public health outcomes. Nevertheless, the Hungarian wine sector faces several vital problems and challenges influenced by the country's accession to the European Union and by the need for restructuring. A comprehensive health impact assessment (HIA) based on the evaluation of the Hungarian legislation related to the wine sector has been carried out, aiming to assess the impact of the production of quality wine versus that of table wine, using a range of public health and epidemiological research methods and data as well as HIA guidelines. The study finds that the toxic effects of alcohol can be reduced with an increased supply of quality wine and with decreased overall consumption due to higher cost, although this might drive some people to seek illegal sources. Quality wine production allows for improved use of land, creates employment opportunities and increases the incomes of producers and local communities; however, capital-scarce producers unable to manage restructuring may lose their source of subsistence. The supply of quality wine can promote social relations, contribute to a healthy lifestyle and reduce criminality related to alcohol's influence and adulteration. In general, the production and supply of quality wine can have an overall positive impact on health. Nevertheless, because of the several possible negative effects expected without purposeful restructuring, recommendations for the maximization of favourable outcomes and suggestions for monitoring the success of the analysis have been provided. PMID- 19643806 TI - Spontaneously beating cardiomyocytes derived from white mature adipocytes. AB - AIMS: Adipose stromal cells and dissociated brown adipose tissue have been shown to generate cardiomyocyte-like cells. However, it is not clear whether white mature adipocytes have the same potential, even though a close relationship has been found between adipocytes and vascular endothelial cells, another cardiovascular cell type. The objective of this study was to examine if white adipocytes would be able to supply cardiomyocytes. METHODS AND RESULTS: We prepared a highly purified population of lipid-filled adipocytes from mice, 6-7 weeks of age. When allowed to lose lipids, the adipocytes assumed a fibroblast like morphology, so-called dedifferentiated fat (DFAT) cells. Subsequently, 10 15% of the DFAT cells spontaneously differentiated into cardiomyocyte-like cells, in which the cardiomyocyte phenotype was identified by morphological observations, expression of cardiomyocyte-specific markers, and immunocytochemical staining. In addition, electrophysiological studies revealed pacemaker activity in these cells, and functional studies showed that a beta adrenergic agonist stimulated the beating rate, whereas a beta-antagonist reduced it. In vitro treatment of newly isolated adipocytes or DFAT cells with inhibitors of bone morphogenetic proteins (BMP) and Wnt signalling promoted the development of the cardiomyocyte phenotype as determined by the number or beating colonies of cardiomyocyte-like cells and expression of troponin I, a cardiomyocyte-specific marker. Inhibition of BMP was most effective in promoting the cardiomyocyte phenotype in adipocytes, whereas Wnt-inhibition was most effective in DFAT cells. CONCLUSION: White mature adipocytes can differentiate into cardiomyocyte-like cells, suggesting a link between adipocyte and cardiomyocyte differentiation. PMID- 19643807 TI - Cetuximab-induced aseptic meningitis. PMID- 19643808 TI - Oxygen sensitivity of a nitrogenase-like protochlorophyllide reductase from the cyanobacterium Leptolyngbya boryana. AB - Dark-operative protochlorophyllide (Pchlide) oxido-reductase (DPOR) is a nitrogenase-like enzyme that catalyzes Pchlide reduction, the penultimate step of chlorophyll a biosynthesis. DPOR is distributed widely among oxygenic phototrophs such as cyanobacteria, green algae and gymnosperms. To determine how DPOR operates in oxygenic photosynthetic cells, we constructed two shuttle vectors for overexpression of Strep-tagged L-protein (ChlL) and Strep-tagged NB-protein (ChlN ChlB) in Leptolyngbya boryana (formerly Plectonema boryanum) and introduced them into mutants lacking chlL and chlB. Both transformants restored the ability to produce chlorophyll in the dark. The DPOR activity was reconstituted by L-protein and NB-protein purified from the transformants under anaerobic conditions. L protein activity disappeared within 5 min of exposure to air while NB-protein activity persisted for >30 min in an aerobic condition, indicating that the L protein of DPOR components is the primary target of oxygen in cyanobacterial cells. These results suggested that the DPOR from an oxygenic photosynthetic organism did not acquire oxygen tolerance during evolution; but that the cyanobacterial cell developed a mechanism to protect DPOR from oxygen. PMID- 19643810 TI - Cell-type specific properties of pyramidal neurons in neocortex underlying a layout that is modifiable depending on the cortical area. AB - To understand sensory representation in cortex, it is crucial to identify its constituent cellular components based on cell-type-specific criteria. With the identification of cell types, an important question can be addressed: to what degree does the cellular properties of neurons depend on cortical location? We tested this question using pyramidal neurons in layer 5 (L5) because of their role in providing major cortical output to subcortical targets. Recently developed transgenic mice with cell-type-specific enhanced green fluorescent protein labeling of neuronal subtypes allow reliable identification of 2 cortical cell types in L5 throughout the entire neocortex. A comprehensive investigation of anatomical and functional properties of these 2 cell types in visual and somatosensory cortex demonstrates that, with important exceptions, most properties appear to be cell-type-specific rather than dependent on cortical area. This result suggests that although cortical output neurons share a basic layout throughout the sensory cortex, fine differences in properties are tuned to the cortical area in which neurons reside. PMID- 19643811 TI - Association of a novel mitochondrial protein M19 with mitochondrial nucleoids. AB - We have identified a novel mitochondrial protein, termed M19, by proteomic analysis of mitochondrial membrane proteins from HeLa cells. M19 is highly conserved among vertebrates, and possesses no homologous domains with other known proteins. By northern and western blotting, mouse M19 was shown to be expressed in various tissues, and to be especially abundant in the brain. Human M19 (hM19) is present in mitochondria, and protease-protection experiment showed it to be sublocalized in the matrix space. Carboxy-terminally tagged hM19 appeared as spotted signals within mitochondria and co-localized with signals arising from mitochondrial DNA (mtDNA), suggesting the inclusion of M19 in the mtDNA-protein complex (mitochondrial nucleoids). Fractionation of mitochondrial nucleoids from HeLa cells revealed that hM19 has a similar distribution pattern like that of known nucleoid components, such as mtSSB and PHBs, and surely exists in the nucleoid fraction. Furthermore, expression of M19 is closely related to the amount of mtDNA, because it was down-regulated in mtDNA-depleted rho(0) HeLa cells. These results indicate that M19 associates with the nucleoid and likely regulates the organization and metabolism of mtDNA. PMID- 19643812 TI - Molecular pathogenesis of protein misfolding diseases: pathological molecular environments versus quality control systems against misfolded proteins. AB - Diverse human diseases, including various neurodegenerative disorders and amyloidoses, are thought to result from the misfolding and aggregation of disease causative proteins, and thus are collectively called protein misfolding diseases. Natively folded disease-causative proteins generally undergo a beta-sheet conformational transition through an energetically unfavourable process, and further polymerize into amyloid fibrils. In the case of beta(2)-microglobulin related amyloidosis, an extracellular protein misfolding disease, many kinds of biological molecules including glycosaminoglycans, proteoglycans and lipids partially unfold beta(2)-microglobulin and catalyse its subsequent nucleus formation. After amyloid fibrils are formed, these biological molecules stabilize the beta(2)-microglobulin fibrils. In the polyglutamine neurodegenerative diseases, an intracellular protein misfolding disease, molecular chaperones as well as the ubiquitin-proteasome and autophagy-lysosome protein degradation systems, which are called the protein quality control systems, strictly regulate protein misfolding, aggregation and disease progression. A family of extracellular chaperones also binds to misfolded proteins and inhibit amyloid fibril formation in the extracellular space. Protein misfolding and aggregation may be an ideal therapeutic target for protein misfolding diseases in general. PMID- 19643813 TI - Relationship between TP53 tumour suppressor gene mutations and smoking-related bulky DNA adducts in a lung cancer study population from Hungary. AB - Lung cancer rate in Hungary is one of the highest in the world among men and also very high among women, for reasons not clearly understood yet. The aim of the study was to explore characteristics of DNA damage and TP53 gene mutations in lung cancer from Hungary. Tissue samples from 104 lung resections for lung cancer patients, both men and women, operated on for non-small cell lung cancer, specifically, primary squamous cell carcinoma or adenocarcinoma were studied. Of the cases, 37% smoked up to the surgery, 24% stopped smoking within 1 year before the surgery, 26% stopped smoking more than a year before the surgery and 13% never smoked. TP53 mutations were detected by denaturant gradient gel electrophoresis, automated capillary electrophoresis single-strand conformation polymorphism and sequencing. Bulky DNA adduct levels were determined by (32)P post-labelling in non-tumorous lung tissue. In total, 45% (47/104) of the cases carried TP53 mutation. The prevalence of TP53 mutations was statistically significantly associated with duration of smoking, tumour histology and gender. Smokers had approximately twice as high bulky adduct level as the combined group of former- and never-smokers (10.9 +/- 6.5 versus 5.5 +/- 3.4 adducts/10(8) nucleotides). The common base change G --> T transversion (8/43; 19%) was detected exclusively in smokers. For the first time, we demonstrate that most carriers of G --> T transversions had also a high level of bulky DNA adducts in their non-tumourous lung tissue. Our study provides evidence for a high burden of molecular alterations occurring concurrently in the lung of lung cancer patients. PMID- 19643809 TI - The effect of strict adherence to a high-fiber, high-fruit and -vegetable, and low-fat eating pattern on adenoma recurrence. AB - Individual differences in dietary intake are thought to account for substantial variation in cancer incidence. However, there has been a consistent lack of effect for low-fat, high-fiber dietary interventions and risk of colorectal cancer. These inconsistencies may reflect the multistage process of cancer as well as the range and timing of dietary change. Another potential reason for the lack of effect is poor dietary adherence among participants in these trials. The authors examined the effect of strict adherence to a low-fat, high-fiber, high fruit and -vegetable intervention over 4 years among participants (n = 1,905) in the US Polyp Prevention Trial (1991-1998) on colorectal adenoma recurrence. There was a wide range of individual variation in the level of compliance among intervention participants. The most adherent participants, defined as "super compliers" (n = 210), consistently reported that they met or exceeded each of the 3 dietary goals at all 4 annual visits. Multivariate logistic regression models were used to estimate the association between dietary adherence and adenoma recurrence. The authors observed a 35% reduced odds of adenoma recurrence among super compliers compared with controls (odds ratio = 0.65, 95% confidence interval: 0.47, 0.92). Findings suggest that high compliance with a low-fat, high fiber diet is associated with reduced risk of adenoma recurrence. PMID- 19643814 TI - Evaluation of imaging plates as recording medium for images of negatively stained single particles and electron diffraction patterns of two-dimensional crystals. AB - We evaluated imaging plates (IPs) and the DITABIS Micron scanner for their use in recording images of negatively stained single-particle specimens and electron diffraction patterns of two-dimensional crystals. We first established the optimal imaging and read-out conditions for images of negatively stained single particle specimens using the signal-to-noise ratio of the images as the evaluation criterion. We found that images were best recorded on IPs at a magnification of 67,000x, read out with a gain setting of 20,000 and a laser power setting of 30% with subsequent binning over 2 x 2 pixels. Our results show that for images of negatively stained specimens, for which the resolution is limited to approximately 20 A, IPs are a good alternative to EM film. We also compared IPs with a 2K x 2K Gatan charge-coupled device (CCD) camera for their use in recording electron diffraction patterns of sugar-embedded two-dimensional crystals. Diffraction patterns of aquaporin-0 recorded on IPs and with the CCD camera showed reflections beyond 3 A and had similar R(Friedel) as well as R(merge) values. IPs can thus be used to collect diffraction patterns, but CCD cameras are more convenient and remain the best option for recording electron diffraction patterns. PMID- 19643815 TI - The genetic basis of melanism in the gray squirrel (Sciurus carolinensis). AB - The black squirrel is a melanic variant of the gray squirrel (Sciurus carolinensis). We found 3 coat color variants in the gray squirrel: the wild-type gray, a jet-black, and a brown-black phenotype. These 3 morphs are due to varying distributions of eumelanin and phaeomelanin pigment in hairs. The melanocortin 1 receptor (MC1R) plays a central role in regulating eumelanin and phaeomelanin production. We sequenced the MC1R gene for all 3 coat color phenotypes and found a 24 base-pair deletion. The gray phenotype was homozygous for the wild-type allele E(+), the jet-black phenotype was homozygous for the MC1R-Delta24 allele E(B), and the brown-black phenotype was heterozygous for the E(+) and E(B) alleles. We conclude that melanism in gray squirrels is associated with the MC1R Delta24 E(B) allele at amino acid positions 87-94 and that this allele is incompletely dominant to the wild-type allele. We predict that the MC1R-Delta24 E(B) allele encodes a constitutively active or hyperactive receptor. PMID- 19643816 TI - The modern RNP world of eukaryotes. AB - Eukaryote gene expression is mediated by a cascade of RNA functions that regulate, process, store, transport, and translate RNA transcripts. The RNA network that promotes this cascade depends on a large cohort of proteins that partner RNAs; thus, the modern RNA world of eukaryotes is really a ribonucleoprotein (RNP) world. Features of this "RNP infrastructure" can be related to the high cytosolic density of macromolecules and the large size of eukaryote cells. Because of the densely packed cytosol or nucleoplasm (with its severe restriction on diffusion of macromolecules), partitioning of the eukaryote cell into functionally specialized compartments is essential for efficiency. This necessitates the association of RNA and protein into large RNP complexes including ribosomes and spliceosomes. This is well illustrated by the ubiquitous spliceosome for which most components are conserved throughout eukaryotes and which interacts with other RNP-based machineries. The complexes involved in gene processing in modern eukaryotes have broad phylogenetic distributions suggesting that the common ancestor of extant eukaryotes had a fully evolved RNP network. Thus, the eukaryote genome may be uniquely informative about the transition from an earlier RNA genome world to the modern DNA genome world. PMID- 19643817 TI - Peroxisome-proliferator activator receptor-gamma activation decreases attachment of endometrial cells to peritoneal mesothelial cells in an in vitro model of the early endometriotic lesion. AB - The aim of this study was to investigate whether peroxisome proliferator activated receptor (PPAR)-gamma activation has an effect on the attachment of endometrial cells to peritoneal mesothelial cells in a well-established in vitro model of the early endometriotic lesion. The endometrial epithelial cell line EM42 and mesothelial cell line LP9 were used for this study. EM42 cells, LP9 cells or both were treated with the PPAR-gamma agonist ciglitazone (CTZ) at varying concentrations (10, 20 and 40 microM) x 48 h with subsequent co-culture of EM42 and LP9 cells. The rate of EM42 attachment and invasion through LP9 cells was then assessed and compared with control (EM42 and LP9 cells co-cultured without prior treatment with CTZ). Next, attachment of CTZ-treated and untreated EM42 cells to hyaluronic acid (HA), a cell adhesion molecule (CAM) on peritoneal mesothelial cells, were assessed. Although there was no difference in EM42 attachment when LP9 cells alone were treated with CTZ, treatment of EM42 cells with 40 microM CTZ decreased EM42 attachment to LP9 cells by 27% (P < 0.01). Treatment of both EM42 and LP9 cells with 40 microM CTZ decreased EM42 attachment to LP9 by 37% (P < 0.01). Treatment of EM42 cells with 40 microM CTZ decreased attachment to HA by 66% (P = 0.056). CTZ did not decrease invasion of EM42 cells through the LP9 monolayer. CTZ may inhibit EM42 cell proliferation. In conclusion, CTZ significantly decreased EM42 attachment to LP9 cells and HA in an in vitro model of the early endometriotic lesion. PMID- 19643818 TI - Seasonal increase in olfactory receptor neurons of the Japanese toad, Bufo japonicus, is paralleled by an increase in olfactory sensitivity to isoamyl acetate. AB - Japanese toads (Bufo japonicus) migrate to and from breeding sites in the early spring, possibly guided by olfactory cues. We previously showed that the electrical activity of olfactory receptor neurons (ORNs) in the toads was enhanced in the breeding period. We undertook morphological and physiological studies of the olfactory epithelium to determine whether any cellular substrate of the epithelium underlies the enhanced electrical activity of ORNs. The ORNs of the toads were labeled by antiserum to olfactory marker protein (OMP), and the morphology of the labeled cells and their distribution in the epithelium were examined throughout the year. The OMP-positive cells, distributed mainly in the basal and intermediate layers of the epithelium, were most numerous in the early breeding period. Cell proliferation in the epithelium detected by 5-bromo-2' deoxyuridine labeling was most elevated in this period. The electrical activity of ORNs was examined by recording the electroolfactogram (EOG) in the toads throughout the year. Statistical analysis showed a positive correlation between the density of OMP-positive cells in the epithelium and the amplitude of the EOG responses. A greater number of ORNs in the breeding period possibly aids the toads in migrating to their breeding sites. PMID- 19643819 TI - Interaction between cytochrome P450 1A2 genetic polymorphism and cigarette smoking on the risk of hepatocellular carcinoma in a Japanese population. AB - Limited epidemiological evidence suggests that genetic polymorphisms of drug metabolizing enzymes such as cytochrome P450 (CYP), glutathione S-transferase (GST) and N-acetyltransferase (NAT) may be involved in tobacco-related hepatocarcinogenesis. We conducted a case-control study, including 209 incident cases with hepatocellular carcinoma (HCC) and two different control groups [275 hospital controls and 381 patients with chronic liver disease (CLD) without HCC], to investigate whether CYP1A1, CYP1A2, CYP2A6, CYP2E1, GSTM1 and NAT2 polymorphisms are related to the risk of HCC with any interaction with cigarette smoking. Overall, no significant associations with HCC were observed for any genotypes against either control group. However, we found a significant interaction (P = 0.0045) between CYP1A2 -3860G>A polymorphism and current smoking on HCC risk when we compared HCC cases with CLD patients; adjusted odds ratios [ORs; and 95% confidence intervals (CIs)] for G/A and A/A genotypes relative to G/G genotype were 0.28 (0.12-0.66) and 0.18 (0.04-0.94), respectively, among current smokers (P trend = 0.002), as compared with 1.28 (0.80-2.06) and 0.76 (0.34-1.71), respectively, among never/former smokers (P trend = 0.96). Similarly, in CYP1A2 G/G genotype, significant risk increase was observed for current smoking (OR = 4.08, 95% CI = 2.02-8.25) or more recent cigarette use (e.g. pack-years during last 5 years, P trend = 0.0003) but not in G/A and A/A genotypes combined (OR for current smoking = 1.39, 95% CI = 0.63-3.03; P trend for pack-years during last 5 years = 0.40). These results suggest that the CYP1A2 -3860G>A polymorphism modifies the smoking-related HCC risk among CLD patients. PMID- 19643820 TI - The human homolog of the Drosophila headcase protein slows down cell division of head and neck cancer cells. AB - The human homolog of the Drosophila headcase (HECA) belongs to a new class of cell differentiation regulators. In Drosophila, the HECA protein regulates the proliferation and differentiation of cells during adult morphogenesis. There is growing evidence that HECA plays an important role in human carcinogenesis. In different tumor entities, an altered HECA expression was found (colorectal, pancreatic and renal cancer). Colorectal cancer studies also suggested HECA as a marker for early disease stages. Therefore, we speculated whether human HECA affects cell cycle progression and proliferation in head and neck cancer cells. In vivo, we found a distinct HECA protein expression in basal and superficial cells of a healthy oral epithelium via immunohistochemistry, whereas in tissues of oral squamous cell carcinoma (OSCC), a weaker staining was observed, particularly in basal cells. In vitro, mRNA and protein expression analyses of OSCC cell lines exhibited that HECA expression correlates with the state of cellular differentiation. In further investigations, we overexpressed HECA in the OSCC cell line PCI 13 and performed functional assays. HECA-overexpressing OSCC cells revealed a significant extended doubling time (up to 45%, 17 h) and yielded a lower number of proliferating cells (up to 30%) than controls. Flow cytometry analyses have shown that HECA-overexpressing OSCC cells forced to hold in the G(2)/M-Phase. In summary, our results show that human HECA slows down cell division of OSCC cells and may therefore act as a tumor suppressor in head and neck cancer. PMID- 19643822 TI - Survival after heart surgery continues to improve after publication of mortality data. PMID- 19643821 TI - Urinary bladder carcinogenesis induced by chronic exposure to persistent low-dose ionizing radiation after Chernobyl accident. AB - Urinary bladder urothelium as well as cells in the microenvironment of lamina propria (endothelial elements, fibroblasts and lymphocytes) demonstrate a number of responses to chronic persistent long-term, low-dose ionizing radiation (IR). Thus, oxidative stress occurs, accompanied by up-regulation of at least two signaling pathways (p38 mitogen-activated protein kinase and nuclear factor kappaB cascades) and activation of growth factor receptors, in the bladder urothelium of people living in Cesium 137-contaminated areas of Ukraine, resulting in chronic inflammation and the development of proliferative atypical cystitis, so-called Chernobyl cystitis, which is considered a possible pre neoplastic condition in humans. Furthermore, significant alterations in regulation of cell cycle transitions are associated with increased cell proliferation, along with up-regulated ubiquitination and sumoylation processes as well as inefficient DNA repair (base and nucleotide excision repair pathways) in the affected urothelium. The microenvironmental changes induced by chronic long-term, low-dose IR also appear to promote angiogenesis and remodeling of the extracellular matrix that could facilitate invasion as well as progression of pre existing initiated cells to malignancy. Based on the available findings, new strategies have been developed for predicting and treatment of Chernobyl cystitis a first step in urinary bladder carcinogenesis in humans. PMID- 19643824 TI - End of life decisions and quality of care before death. PMID- 19643826 TI - Long-term oxygen therapy: aligning the clinician and patient perspective to maximize patient benefit. PMID- 19643825 TI - Euthanasia and other end of life decisions and care provided in final three months of life: nationwide retrospective study in Belgium. AB - OBJECTIVE: To explore the relation between the care provided in the final three months of life and the prevalence and types of end of life decisions in Belgium. Design Two year nationwide retrospective study, 2005-6 (SENTI-MELC study). SETTING: Data collection via the sentinel network of general practitioners, an epidemiological surveillance system representative of all general practitioners in Belgium. SUBJECTS: 1690 non-sudden deaths in practices of the sentinel general practitioners. MAIN OUTCOME MEASURES: Non-sudden deaths of patients (aged >1 year) reported each week. Reported care provided in the final three months of life and the end of life decisions made. Multivariable regression analysis controlled for age, sex, cause, and place of death. RESULTS: Use of specialist multidisciplinary palliative care services was associated with intensified alleviation of symptoms (odds ratio 2.1, 95% confidence interval 1.6 to 2.6), continuous deep sedation forgoing food/fluid (2.9, 1.7 to 4.9), and the total of decisions explicitly intended to shorten life (1.5, 1.1 to 2.1) but not with euthanasia or physician assisted suicide in particular. To a large extent receiving spiritual care was associated with higher frequencies of euthanasia or physician assisted suicide than receiving little spiritual care (18.5, 2.0 to 172.7). CONCLUSIONS: End of life decisions that shorten life, including euthanasia or physician assisted suicide, are not related to a lower use of palliative care in Belgium and often occur within the context of multidisciplinary care. PMID- 19643827 TI - Self-management for breathlessness in COPD: the role of pulmonary rehabilitation. AB - Most of the effort of controlling breathlessness happens at home. Therefore, it is important to explore how patients and carers respond to breathlessness, what their self-care entails and what they experience as helpful. Data were collected from a purposive sample of 18 chronic obstructive pulmonary disease patients through participant observation during outpatient consultations and in-depth interviews at a large hospital and in the community in London. Data were analysed with the Grounded Theory approach. As information regarding the management of breathlessness was lacking and access to treatment was difficult, patients reverted to alternative strategies. Some patients developed considerable expertise and managed their symptoms competently within the limits of current care. Patients who coped successfully were involved in pulmonary rehabilitation and had adopted this as a way of life. Benefits and challenges to participation in these programmes were identified. Those patients who self-manage maintain an acceptable quality of life through self-acquired expertise relating to symptoms, medication and help-seeking. Well-being needs to be understood not as the end point, but as a precarious balance needing skillful maintenance and hard work. The findings have implications for notions such as adherence, patient involvement and responsibility in the management of chronic obstructive pulmonary disease. PMID- 19643828 TI - Long-term oxygen therapy: review from the patients' perspective. AB - Chronic respiratory conditions are responsible for increasing numbers of patients in need of long-term oxygen therapy (LTOT). However, many patients do not use their oxygen as prescribed. Unless we can assist these patients in living with oxygen therapy, optimal clinical outcomes will not be achieved. We conducted a meta-synthesis of qualitative research studies. We included any qualitative study that focused on the psychosocial nature or experience of patients prescribed LTOT. Four research studies met the conditions of our search. We performed a rigorous methodological protocol for meta-synthesis as described by the Joanna Briggs Institute. A total of 12 findings formulated four themes. These themes included the following: adapting oxygen to life's circumstances, living in a restricted world, self-management is fostered by oxygen, and submission and dependency. From the four thematic categories established, meta-synthesis resulted in two major results: persons prescribed oxygen rationalize its use while negotiating lifestyle interference and physical restrictions and the drive to care for one's self is conflicted. This meta-synthesis showed that each oxygen user faces tremendous physical, psychological, and emotional challenges. They strive to adapt and maintain mastery but eventually oxygen dependency results. These challenges affect the patient's ability to adhere to their treatment guidelines. These barriers and challenges are seldom addressed and are under treated. Clinicians involved in LTOT need to be aware and work with the patients to facilitate their use of oxygen. Inclusion of the patients' perspective can guide practice and assist with the development of new interventions and management strategies. PMID- 19643829 TI - The prognostic value of C-reactive protein in long-term care patients requiring prolonged mechanical ventilation. AB - C-reactive protein (CRP), a biomarker of inflammation, has predicted mortality in end-stage respiratory failure and in the critically ill patients. Our aim was to investigate if CRP can predict morbidity and mortality in patients requiring prolonged mechanical ventilation. A prospective study conducted in a ventilator weaning unit of a skilled nursing facility over 13 months included 98 patients older than 18 years of age requiring mechanical ventilation via tracheostomy. Serum CRP and albumin levels were tested on admission. Age, gender, body mass index (BMI), and diagnoses causing respiratory failure were recorded. The outcomes measured were as follows: hospitalization, weaned from mechanical ventilation, and death. Our population had a median age of 77 years and the median BMI, albumin, and mean CRP were 26 kg/m(2), 2.25 g/dL, and 5.75 mg/dL, respectively. The most common diseases leading to respiratory failure were pulmonary, neurologic, and cardiac. The patients with the empiric cutoff CRP of <2 mg/dL (n = 14) had 0% hospitalization rate at 2 weeks and 7% at 30 days, whereas the patients with CRP > or = 2 mg/dL (n = 84) had 26% hospitalization rate at 2 weeks and 38% at 30 days. Mortality for the patients with CRP > or = 2 mg/dL was 26% at 60 days, whereas the CRP < 2 mg/dL patients had no mortality at 60 days (P = 0.034). The patients who survived 60 days (n = 70) had significantly lower median CRP levels than the nonsurvivors (4.1 mg/dL vs 8.5 mg/dL, P = 0.009). The area under the receiver operating characteristic (ROC) curve for CRP levels predicting 2-week hospitalization was not large at 0.617 and the optimum CRP cutoff point was >2.7 mg/dL. The sensitivity and negative predictive value of the 2-week hospitalization outcome were equally high at 96%. The area under the ROC curve for 60-day survival was 0.691, and its optimum CRP cutoff point was >3.7 mg/dL with 85% sensitivity and 91% negative predictive value. CRP was not able to predict weaning success in this setting where the 60-day weaning rate was 9%. A CRP level of < or =2.7 mg/dL may be used to screen for patients who are not likely to develop acute illness requiring early 2-week rehospitalization, and a CRP level of < or =3.7 mg/dL may be used to predict 60-day survival in patients with respiratory failure requiring prolonged mechanical ventilation in the long term care setting. PMID- 19643830 TI - Can a chronic disease management pulmonary rehabilitation program for COPD reduce acute rural hospital utilization? AB - Chronic obstructive pulmonary disease (COPD) imposes a costly burden on healthcare. Pulmonary rehabilitation (PR) is the best practice to better manage COPD to improve patient outcomes and reduce acute hospital care utilization. To evaluate the impact of a once-weekly, eight-week multidisciplinary PR program as an integral part of the COPD chronic disease management (CDM) Program at Kyabram District Health Services. The study compared two cohorts of COPD patients: CDM-PR Cohort (4-8 weeks) and Opt-out Cohort (0-3 weeks) between February 2006 and March 2007. The CDM-PR Program involved multidisciplinary patient education and group exercise training. Nonparametric statistical tests were used to compare acute hospital care utilization 12 months before and after the introduction of CDM-PR. The number of patients involved in the CDM-PR Cohort was 29 (n = 29), and that in the Opt-out Cohort was 24 (n = 24). The CDM-PR Cohort showed significant reductions in cumulative acute hospital care utilization indicators (95% emergency department presentations, 95% inpatient admissions, 99% length of stay; effect sizes = 0.62-0.66, P < 0.001) 12 months after the introduction of the CDM Program; in contrast, changes in the cumulative indicators were statistically insignificant for the Opt-out Cohort (emergency department presentations decreased by 5%, inpatient admissions decreased by 12%, length of stay increased by 30%; effect size = 0.14-0.40, P > 0.05). Total costs associated with the hospital care utilization decreased from $130,000 to $7,500 for the CDM-PR Cohort and increased from $77,700 to $101,200 for the Opt-out Cohort. Participation in the CDM-PR for COPD patients can significantly reduce acute hospital care utilization and associated costs in a small rural health service. PMID- 19643831 TI - Providing reviews of evidence to COPD patients: controlled prospective 12-month trial. AB - The aim of this study was to evaluate a novel patient-held manual designed to reduce the evidence-practice gap in chronic obstructive pulmonary disease (COPD). The intervention manual contained summaries of research evidence. It was developed using current best practice for patient information materials and designed to cause discussion of evidence between patient and doctor. A controlled before-and-after study was employed in two similar but geographically separate regions of metropolitan Adelaide, South Australia. Participants had moderate to severe COPD, with 249 included at baseline and 201 completing the study. Evidence based COPD management was measured using an indicator with three components: rates of influenza vaccination, bone density testing, and pulmonary rehabilitation. A survey of behavioral steps leading to practice change was conducted with the trial. Analysis, by median split of socioeconomic disadvantage, showed significant difference between study arms for only one component of the indicator of evidence-based practice, enrollment in pulmonary rehabilitation and only for the most socioeconomically disadvantaged stratum. For both socioeconomic strata, more intervention participants than control participants reported remembering being given the information material, reading part or all, and finding it very or quite helpful. Other significant differences were restricted to the stratum of greatest socioeconomic disadvantage: reading all of the material, learning from it, referring back, and talking to a doctor about a topic from the material. Above 90% of all participants who received the manual reported reading from it, 42% reported discussing topics with a doctor, but only 10% reported treatment change attributable to the manual. We have found that people with COPD will read an evidence manual developed using current best practice. However, the study demonstrated improvement for only one of the three components of an indicator of evidence-based disease management for only the most socioeconomically disadvantaged stratum of participants. Future interventions should be designed to better translate reading uptake into evidence-based disease management. PMID- 19643833 TI - Cor pulmonale. AB - The term "cor pulmonale" is still popular but there is presently no consensual definition and it seems more appropriate to define the condition by the presence of pulmonary hypertension (PH) resulting from diseases affecting the structure and/or the function of the lungs: PH results in right ventricular enlargement and may lead with time to right heart failure (RHF). Chronic obstructive pulmonary disease (COPD) is the first cause of cor pulmonale, far before idiopathic pulmonary fibrosis and obesity-hypoventilation syndrome. In chronic respiratory disease (CRD) PH is "pre-capillary," due to an increase of pulmonary vascular resistance (PVR). The first cause of increased PVR is chronic long-standing alveolar hypoxia which induces pulmonary vascular remodeling. The main characteristic of PH in CRD and particularly in COPD is its mild to moderate degree, resting pulmonary artery mean pressure (PAP) in a stable state of the disease usually ranging between 20 and 35 mmHg. However, PH may worsen during exercise, sleep, and exacerbations of the disease. These acute increases in afterload can favor the development of RHF. A minority (<5%) of COPD patients exhibit severe or "disproportionate" PH (PAP >40 mmHg), the mechanism of which is not well understood. At present long-term oxygen therapy (LTOT) is the logical treatment of PH since alveolar hypoxia is considered to be the major determinant of the elevation of PAP and PVR. LTOT stabilizes or at least attenuates and sometimes reverses the progression of PH, but PAP seldom returns to normal. Vasodilators (prostacyclin, endothelin receptor antagonists, sildenafil, nitric oxide) could be considered in patients with severe PH but controlled studies in this field are presently lacking. PMID- 19643834 TI - Effects of hand cycle training on physical capacity in individuals with tetraplegia: a clinical trial. AB - BACKGROUND: Regular physical activity is important for people with tetraplegia to maintain fitness but may not always be easily integrated into daily life. In many countries, hand cycling has become a serious option for daily mobility in people with tetraplegia. However, little information exists regarding the suitability of this exercise mode for this population. OBJECTIVE: The purpose of this study was to evaluate the effects of a structured hand cycle training program in individuals with chronic tetraplegia. DESIGN: Pretraining and posttraining outcome measurements of physical capacity were compared. SETTING: Structured hand cycle interval training was conducted at home or in a rehabilitation center in the Netherlands. PARTICIPANTS: Twenty-two patients with tetraplegia (American Spinal Injury Association Impairment Scale classification A-D) at least 2 years since injury participated. INTERVENTION: The intervention was an 8- to 12-week hand cycle interval training program. MEASURES: Primary outcomes of physical capacity were: peak power output (POpeak) and peak oxygen uptake (Vo(2)peak), as determined in hand cycle peak exercise tests on a motor-driven treadmill. Secondary outcome measures were: peak muscle strength (force-generating capacity) of the upper extremities (as assessed by handheld dynamometry), respiratory function (forced vital capacity and peak expiratory flow) and participant reported shoulder pain. RESULTS: Significant improvements following a mean of 19 (SD=3) sessions of hand cycle training were found in POpeak (from 42.5 W [SD=21.9] to 50.8 W [SD=25.4]), Vo(2)peak (from 1.32 L.min(-1) [SD=0.40] to 1.43 L.min(-1) [SD=0.43]), and mechanical efficiency, as reflected by a decrease in submaximal oxygen uptake. Except for shoulder abduction strength, no significant effects were found on the secondary outcomes. LIMITATIONS: Common health complications, such as urinary tract infections, bowel problems, and pressure sores, led to dropout and nonadherence. CONCLUSION: Patients with tetraplegia were able to improve their physical capacity through regular hand cycle interval training, without participant-reported shoulder-arm pain or discomfort. PMID- 19643835 TI - Strategies to promote evidence-based practice in pediatric physical therapy: a formative evaluation pilot project. AB - BACKGROUND: The physical therapy profession has been perceived as one that bases its practice largely on anecdotal evidence and that uses treatment techniques for which there is little scientific support. Physical therapists have been urged to increase evidence-based practice behaviors as a means to address this perception and to enhance the translation of knowledge from research evidence into clinical practice. However, little attention has been paid to the best ways in which to support clinicians' efforts toward improving evidence-based practice. OBJECTIVES: The purpose of this study was to identify, implement, and evaluate the effectiveness of strategies aimed at enhancing the ability of 5 pediatric physical therapists to integrate scientific research evidence into clinical decision making. DESIGN: This study was a formative evaluation pilot project. METHODS: The participants in this study collaborated with the first author to identify and implement strategies and outcomes aimed at enhancing their ability to use research evidence during clinical decision making. Outcome data were analyzed with qualitative methods. RESULTS: The participants were able to implement several, but not all, of the strategies and made modest self-reported improvements in evidence-based practice behaviors, such as reading journal articles and completing database searches. They identified several barriers, including a lack of time, other influences on clinical decision making, and a lack of incentives for evidence-based practice activities. CONCLUSIONS: The pediatric physical therapists who took part in this project had positive attitudes toward evidence-based practice and made modest improvements in this area. It is critical for the profession to continue to investigate optimal strategies to aid practicing clinicians in applying research evidence to clinical decision making. PMID- 19643836 TI - Use of likelihood ratios can improve the clinical usefulness of enzyme immunoassays for the diagnosis of small-vessel vasculitis. PMID- 19643837 TI - Proximity ligation measurement of the complex between prostate specific antigen and alpha1-protease inhibitor. AB - BACKGROUND: Prostate specific antigen (PSA)-alpha1-protease inhibitor complex (PSA-API) is a minor form of PSA in serum. It may be useful for prostate cancer (PCa) diagnosis, but its specific detection is hampered by nonspecific background. To avoid this, we developed an immunoassay for PSA-API based on proximity ligation. METHODS: We used a monoclonal antibody (mAb) to total PSA (tPSA) to capture PSA, while using another anti-tPSA mAb together with an anti API mAb as probes. We measured PSA-API by quantification of amplified DNA strands conjugated to the probes. We measured serum PSA-API in 84 controls and 55 men with PCa who had PSA concentrations of 4.0-10 microg/L. RESULTS: The detection limit of the assay was 6.6 ng/L. The proportion of PSA-API to tPSA (%PSA-API) tended to be lower in men with PCa (2.8%) than without cancer (3.3%) but was not statistically significant (P = 0.363). When used alone, %PSA-API [area under the curve (AUC) 0.546] did not improve detection of PCa, whereas %fPSA (AUC 0.710) and the sum of %fPSA and %PSA-API (AUC 0.723) did. At 90% diagnostic sensitivity, the diagnostic specificity for cancer was not significantly better for %f PSA + %PSA-API than for %fPSA alone (36% vs 30%). CONCLUSIONS: Proximity ligation eliminated nonspecific background, enabling accurate measurement of PSA-API in serum specimens with moderately increased tPSA. The combined use of %PSA-API and %fPSA provided a modest improvement for PCa detection, but based on the current study cohort, it is uncertain whether the improvement has clinical utility. . PMID- 19643838 TI - Design and optimization of reverse-transcription quantitative PCR experiments. AB - BACKGROUND: Quantitative PCR (qPCR) is a valuable technique for accurately and reliably profiling and quantifying gene expression. Typically, samples obtained from the organism of study have to be processed via several preparative steps before qPCR. METHOD: We estimated the errors of sample withdrawal and extraction, reverse transcription (RT), and qPCR that are introduced into measurements of mRNA concentrations. We performed hierarchically arranged experiments with 3 animals, 3 samples, 3 RT reactions, and 3 qPCRs and quantified the expression of several genes in solid tissue, blood, cell culture, and single cells. RESULTS: A nested ANOVA design was used to model the experiments, and relative and absolute errors were calculated with this model for each processing level in the hierarchical design. We found that intersubject differences became easily confounded by sample heterogeneity for single cells and solid tissue. In cell cultures and blood, the noise from the RT and qPCR steps contributed substantially to the overall error because the sampling noise was less pronounced. CONCLUSIONS: We recommend the use of sample replicates preferentially to any other replicates when working with solid tissue, cell cultures, and single cells, and we recommend the use of RT replicates when working with blood. We show how an optimal sampling plan can be calculated for a limited budget. . PMID- 19643839 TI - Implications of increased C-reactive protein for cardiovascular risk stratification in black and white men and women in the US. AB - BACKGROUND: We evaluated prevalence and correlates of increased high-sensitivity C-reactive protein (hsCRP) in a large population of blacks and whites, and the impact of hsCRP measurement on coronary heart disease risk reclassification. METHODS: We studied 19 080 participants of the REGARDS (REasons for Geographic And Racial Differences in Stroke) study (age >45 years, without vascular diagnoses, and living dispersed across the US). A total of 8309 nondiabetic participants not using lipid-lowering medications were classified into 4 risk categories based on the Framingham vascular disease risk score. Participants with hsCRP <1 mg/L were reclassified to the next lower risk group, and those with hsCRP >3 mg/L to the next higher risk group. We also assessed reclassification of risk based on the Reynolds vascular risk score, incorporating hsCRP and family history. RESULTS: Overall, 40% of participants had hsCRP >3 mg/L. Blacks, women, and obese people were at highest risk for increased hsCRP. Among nondiabetic women at 5%-20% Framingham vascular predicted risk, hsCRP data led to reclassification of 48% to a higher risk group and 19% to a lower risk group. For men, these percentages were 24% and 40%. Blacks were more often reclassified to a higher risk group than whites. Reynolds vascular risk score data led to reclassification of 85% of women and 67% of men, almost exclusively to a lower risk group than the Framingham vascular score. CONCLUSIONS: In this national study, a majority of participants, especially blacks and women, were reclassified to a different 10-year vascular risk category on the basis of hsCRP testing after risk assessment. With the inclusion of hsCRP testing data, the Reynolds risk score classified the population differently than the new Framingham vascular score. . PMID- 19643840 TI - uPA+/+-SCID mouse with humanized liver as a model for in vivo metabolism of exogenous steroids: methandienone as a case study. AB - BACKGROUND: Adequate detection of designer steroids in the urine of athletes is still a challenge in doping control analysis and requires knowledge of steroid metabolism. In this study we investigated whether uPA(+/+)-SCID mice carrying functional primary human hepatocytes in their liver would provide a suitable alternative small animal model for the investigation of human steroid metabolism in vivo. METHODS: A quantitative method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed and validated for the urinary detection of 7 known methandienone metabolites. Application of this method to urine samples from humanized mice after methandienone administration allowed for comparison with data from in vivo human samples and with reported methandienone data from in vitro hepatocyte cultures. RESULTS: The LC-MS/MS method validation in mouse and human urine indicated good linearity, precision, and recovery. Using this method we quantified 6 of 7 known human methandienone metabolites in the urine of chimeric mice, whereas in control nonchimeric mice we detected only 2 metabolites. These results correlated very well with methandienone metabolism in humans. In addition, we detected 4 isomers of methandienone metabolites in both human and chimeric mouse urine. One of these isomers has never been reported before. CONCLUSIONS: The results of this proof-of-concept study indicate that the human liver-uPA(+/+)-SCID mouse appears to be a suitable small animal model for the investigation of human-type metabolism of anabolic steroids and possibly also for other types of drugs and medications. PMID- 19643841 TI - Cardiac autonomic dysfunction is associated with white matter lesions in patients with mild cognitive impairment. AB - BACKGROUND: Cardiac autonomic dysfunction has been associated with cognitive impairment, but the underlying pathogenesis is complex and cerebral white matter lesions (WMLs) might be implicated. METHODS: Time and frequency heart rate variability (HRV) and visual rating of WMLs were carried out in 42 patients with mild cognitive impairment. RESULTS: After adjustment for relevant demographic and clinical characteristics, including left ventricular mass, reduced HRV indices of parasympathetic (root mean square of successive difference of RR intervals, RMSSD) and sympathetic modulation (low-frequency [LF] power) were associated with increased WML score (RMSSD: B -0.30, 95% CI -0.52 to -0.08, p = .01; LF: B -0.24, 95% CI -0.46 to -0.02, p = .05). In a multiple-adjusted model, RMSSD was the major independent predictor of WMLs (B -0.35, 95% CI -0.57 to -0.13, p = .002). CONCLUSION: The evidence for an independent association of cardiac autonomic dysfunction with WMLs might suggest its role in the pathogenesis of WMLs. PMID- 19643843 TI - Free energy calculations of glycosaminoglycan-protein interactions. AB - Glycosaminoglycans (GAGs) are complex highly charged linear polysaccharides that have a variety of roles in biological processes. We report the first use of molecular dynamics (MD) free energy calculations using the MM/PBSA method to investigate the binding of GAGs to protein molecules, namely the platelet endothelial cell adhesion molecule 1 (PECAM-1) and annexin A2. Calculations of the free energy of the binding of heparin fragments of different sizes reveal the existence of a region of low GAG-binding affinity in domains 5-6 of PECAM-1 and a region of high affinity in domains 2-3, consistent with experimental data and ligand-protein docking studies. A conformational hinge movement between domains 2 and 3 was observed, which allows the binding of heparin fragments of increasing size (pentasaccharides to octasaccharides) with an increasingly higher binding affinity. Similar simulations of the binding of a heparin fragment to annexin A2 reveal the optimization of electrostatic and hydrogen bonding interactions with the protein and protein-bound calcium ions. In general, these free energy calculations reveal that the binding of heparin to protein surfaces is dominated by strong electrostatic interactions for longer fragments, with equally important contributions from van der Waals interactions and vibrational entropy changes, against a large unfavorable desolvation penalty due to the high charge density of these molecules. PMID- 19643842 TI - A randomized trial of two forms of therapeutic activity to improve walking: effect on the energy cost of walking. AB - BACKGROUND: Therapeutic activities to improve mobility often include walking practice and exercises to improve deficits in endurance, strength, and balance. Because walking may also be energy inefficient in people with decreased mobility, another approach is to reduce energy cost by improving timing and coordination (TC) of movement. METHODS: This pilot randomized trial of older adults with slow and variable gait offered two types of therapeutic activity over 12 weeks. One addressed Walking, Endurance, Balance, and Strength (WEBS) and the other focused on TC. Outcomes were energy cost of walking and measures of mobility. RESULTS: Of 50 participants (mean age, 77.2 +/- 5.5 years, 65% women), 47 completed the study. Baseline gait speed was 0.85 +/- 0.13 m/s and energy cost of walking was 0.30 +/- 0.10 mL/kg/m, nearly twice normal. Both interventions increased gait speed (TC by 0.21 m/s and WEBS by 0.14 m/s, p < .001). TC reduced the energy cost of walking 0.10 +/- 0.03 mL/kg/m more than WEBS (p < .001) and reduced the modified Gait Abnormalities Rating Scale 1.5 +/- 0.6 more points than WEBS (p < .05). TC had a 9.8 +/- 3.5 points greater gain than WEBS in self-reported confidence in walking (p < .01). CONCLUSIONS: In older adults with slow and variable gait, activity focused on TC reduced the energy cost of walking and improved confidence in walking more than WEBS while generating at least equivalent gains in mobility. To optimize mobility, future larger studies should assess various combinations of TC and WEBS over longer periods of time. PMID- 19643845 TI - The ideal graft of the future: a prospect of messianic proportions? PMID- 19643844 TI - Genetic and biochemical modulation of sialic acid O-acetylation on group B Streptococcus: phenotypic and functional impact. AB - Group B Streptococcus (GBS) is an important human pathogen and a model system for studying the roles of bacterial glycosylation in host-microbe interactions. Sialic acid (Sia), expressed prominently in the GBS capsular polysaccharide (CPS), mimics mammalian cell surface Sia and can interact with host Sia-binding proteins to subvert immune clearance mechanisms. Our earlier work has shown that GBS partially O-acetylates CPS Sia residues and employs an intracellular O acetylation/de-O-acetylation cycle to control the final level of this surface Sia modification. Here, we examine the effects of point mutations in the NeuD O acetyltransferase and NeuA O-acetylesterase on specific glycosylation phenotypes of GBS, pinpointing an isogenic strain pair that differs dramatically in the degree of the O-acetyl modification (80% versus 5%) while still expressing comparable levels of overall sialylation. Using these strains, higher levels of O acetylation were found to protect GBS CPS Sia against enzymatic removal by microbial sialidases and to impede engagement of human Siglec-9, but not to significantly alter the ability of GBS to restrict complement C3b deposition on its surface. Additional experiments demonstrated that pH-induced migration of the O-acetyl modification from the 7- to 9-carbon position had a substantial impact on GBS-Siglec-9 interactions, with 7-O-acetylation exhibiting the strongest interference. These studies show that both the degree and position of the GBS O acetyl modification influence Sia-specific interactions relevant to the host pathogen relationship. We conclude that native GBS likely expresses a phenotype of intermediate Sia O-acetylation to strike a balance between competing selective pressures present in the host environment. PMID- 19643846 TI - Importance of strain imaging in cardiac rehabilitation. AB - Cardiac rehabilitation improves the subjective condition of the patient; but are there associated structural and functional cardiac adaptations? The study group consisted of 39 patients with an inferior infarction and 21 patients with an anterior infarction, treated by surgical revascularization followed by 4 months of cardiac rehabilitation. Maximal exercise testing and Doppler echocardiography were performed before and after the rehabilitation program. Performance capacity was significantly improved after cardiac rehabilitation, but left ventricular function remained unchanged on Doppler imaging. Only by analyzing the subgroups using strain imaging significant differences were noted after cardiac rehabilitation: patients with an inferior infarction exhibited improved strain values in the anterior wall; those with an anterior infarction had improved strain values in the inferior wall. Strain values in the infarcted regions were worse after cardiac rehabilitation. Strain imaging indicated that cardiac rehabilitation could bring about improvements in cardiac function exclusively in the healthy non-infarcted myocardium, while there were signs of further deterioration of myocardial function in the highly ischemic zones. PMID- 19643847 TI - Impact of coronary disease after aortic valve replacement. AB - Left ventricular dimensions tend to reduce after aortic valve replacement in patients with aortic stenosis. Whether concomitant coronary artery disease has an influence on postoperative ventricular dimensions has not been evaluated. Between 1998 and 2002, 112 patients underwent aortic valve replacement for aortic stenosis; 68 had isolated aortic valve replacement, and 44 had combined coronary artery bypass grafting. Left ventricular dimensions were assessed by echocardiography preoperatively and at 3 and 12 months postoperatively. Transvalvular mean gradient, left ventricular end-diastolic diameter, and left ventricular mass index decreased significantly postoperatively, while left ventricular ejection fraction improved. Preoperative left ventricular dimensions in patients with isolated aortic stenosis were worse than in those with aortic stenosis and coronary artery disease. After aortic valve replacement with coronary artery bypass, left ventricular mass index regression was less than that after valve replacement alone, and there was no improvement in ejection fraction. This suggests that coronary artery disease has a negative impact on postoperative myocardial recovery. PMID- 19643849 TI - Effect on the brain of two techniques of myocardial protection. AB - This study compared the occurrence of intraoperative microemboli and postoperative changes in neuropsychological performance in 195 patients undergoing coronary artery bypass grafting who were randomized to intermittent crossclamp fibrillation or cardioplegic arrest. Cerebral microemboli were recorded from cannulation to 15 min after decannulation, using transcranial Doppler in 166 patients. Microemboli in relation to 9 surgical events were also noted. Neuropsychological change scores were obtained by comparing cognitive performance preoperatively with that at 6-8 weeks after surgery. The median number of microemboli detected was 105 (range, 9-1,757) in the fibrillation group, and 110 (range, 1-1,306) in the cardioplegia group, with no significant difference between groups. There was also no significant difference between groups in the generation of microemboli during any of the surgical events. Neuropsychological tests were completed postoperatively by 177 participants, with no significant differences in performance found between the 2 groups. Given the equivalence of the effect of intermittent crossclamp fibrillation and cardioplegic arrest on microemboli and neuropsychology, consideration of which form of myocardial protection to employ should perhaps focus more on which method affords most protection to the heart. PMID- 19643848 TI - Impact of gender on outcome after coronary artery bypass surgery. AB - Following recent studies concerning the increased risk of coronary artery bypass surgery for women, the impact of sex is still a controversial issue. Between 1996 and 2006, 9,527 men and 3,079 women underwent isolated coronary artery bypass in our institute. To adjust for dissimilarities in preoperative risk profiles, propensity score-based matching was applied. Before adjustment, clinical outcomes in terms of operative mortality, arrhythmias, intensive care unit stay, and maximum creatine kinase-MB levels were significantly different for men and women. After balancing the preoperative characteristics, including height, no significant differences in clinical outcomes were observed. However, there was decreased use of internal mammary artery, less total arterial revascularization, and increasing creatine kinase-MB levels with decreasing height. This study supports the theory that female sex per se does not increase operative risk, but shorter height, which is more common in women, affects the outcome, probably due to technical difficulties in shorter patients with smaller internal mammary arteries and coronary vessels. Thus women may especially benefit from sequential arterial grafting. PMID- 19643850 TI - Scimitar syndrome: experience with 6 patients. AB - Scimitar syndrome is a rare congenital anomaly characterized by anomalous pulmonary venous drainage to the inferior vena cava, causing a left-to-right shunt. Six patients with scimitar syndrome were diagnosed in our hospital between 2002 and 2008. There were 4 girls and 2 boys; 4 < 5 kg in weight, 2 < 8 kg in weight. Scimitar syndrome was suspected in 5 cases because of dextroversion, and diagnosed by color Doppler echocardiography in all 6 when a scimitar vein was detected entering the inferior vena cava. Computed tomography confirmed the diagnosis in all patients. Two patients had horseshoe lung, 2 had a unilobar right lung, 1 had a hypoplastic right lung, and 1 had a hypoplastic right lower lobe. Three patients had severe pulmonary arterial hypertension, 2 had moderate pulmonary arterial hypertension, and one had normal pulmonary arterial pressure. All patients had lower respiratory tract infections, volume loss of the right lung, a normal or hyperinflated left lung, dextroversion of the heart, and scimitar arteries from the descending aorta. Pneumonectomy was performed in 3 patients, lobectomy in 1, ligation of anomalous vessels in 1, and 1 died before surgery. PMID- 19643851 TI - Is age over 70 years a risk factor for pneumonectomy? AB - The lengthening of life expectancy has led to more surgical procedures in elderly patients. The aim of this work was to determine whether age >70 years is a risk factor for pneumonectomy. All cases of pneumonectomy from January 1999 to December 2006 were retrospectively reviewed. The 40 patients aged >70 years were compared with a group of 70 patients aged 40-68 years matched for sex, physical status, respiratory function, side of pneumonectomy, and pathologic stage. Postoperatively, significantly more older patients had atrial fibrillation (24% vs. 5.6%). There was a low incidence of respiratory complications in both groups, and reduced respiratory function did not increase respiratory morbidity. Thirty day mortality was not significantly different (2.5% in older vs. 1.4% in younger patients), but long-term mortality rates evaluated at December 31, 2007 were 50% for those aged <70 years (35 patients) and 72.5% for the older group. Although age is a risk factor for morbidity and mortality in pneumonectomy, the risk is acceptable. PMID- 19643852 TI - Leaflet suspension and subvalvular annuloplasty in aortic valve prolapse. AB - We have utilized the combined techniques of subvalvular annuloplasty and leaflet suspension since 1999 to repair prolapsing aortic valves. We reviewed our short term results to assess perioperative echocardiographic changes and repair durability. Nineteen patients (15 men and 4 women; mean age, 60.7 years) underwent this operation between July 1999 and June 2002. All were interviewed to establish their latest functional status, reoperation and survival rates. After a mean follow-up of 40.1 months, all patients were alive and in New York Heart Association functional class I. The echocardiographic grade of aortic regurgitation decreased from 3.2 preoperatively to 1.6 at follow-up. Left ventricular end-diastolic dimension shortened significantly from 6.2 to 5.2 cm. Left ventricular end-systolic dimension decreased from 4.1 to 3.3 cm. Annulus size was also significantly less at 2.2 cm from 2.5 cm preoperatively. At 48 months, freedom from reoperation was 88.9% +/- 7.4%. The follow-up was 100% complete. Repair of a prolapsing aortic valve with leaflet suspension and subvalvular annuloplasty is a good procedure and the short-term results are satisfying. PMID- 19643853 TI - Can chest trauma patients provide breath sample with Lion SD-400 Alcometer? AB - Various investigators have addressed the minimum lung function required to activate breathalyzers, and the impact of comorbid respiratory illness. We postulated that subjects with significant chest trauma may have difficulty in providing an adequate breathalyzer sample. A prospective self-controlled study of 20 patients who underwent thoracotomy was conducted between August 2005 and December 2005, using a Lion Alcometer SD-400. The mean age of the patients was 69.3 years (range, 37-83 years). Preoperatively, their mean forced expiratory volume was 1.97 L (range, 1.19-2.46 L), and peak expiratory flow rate was 240 L min(-1) (range, 126-520 L min(-1)). Postoperatively, mean forced expiratory volume was 1.14 L (range, 0.34-2.2 L) and peak expiratory flow rate was 179 L min(-1) (range, 36-492 L min(-1)). These decreases were highly significant. All patients activated the breathalyzer device preoperatively, but only 2 (10%) could activate it postoperatively. Extrapolating this to patients with chest injury, most may find it impossible to activate breathalyzers. PMID- 19643854 TI - Establishment of rat model of cardiopulmonary bypass in pulmonary hypertension. AB - An experimental model of cardiopulmonary bypass in rats with pulmonary hypertension is necessary to understand underlying mechanisms and develop protective strategies. Male Sprague-Dawley rats were randomly divided into a sham group, cardiopulmonary bypass group, pulmonary hypertension group, and pulmonary hypertension with cardiopulmonary bypass group. Both groups with pulmonary hypertension received a subcutaneous injection of monocrotaline 60 mg x kg(-1) on day 0. Cardiopulmonary bypass was instituted in one of them 21 days later. The sham and pulmonary hypertension control groups underwent cannulation only. Cardiopulmonary bypass was conducted for 60 min at a flow rate of 100 mL x kg(-1) x min(-1). Hemodynamic investigations, blood gas analysis, interleukin-6, tumor necrosis factor-alpha, and survival studies were performed subsequently. Time dependent increases of serum interleukin-6 and tumor necrosis factor-alpha were found after cardiopulmonary bypass in both groups. This model allows the study of multiple organ pathophysiological processes after cardiopulmonary bypass in rats with pulmonary hypertension, as well as the evaluation of possible protective strategies. PMID- 19643855 TI - Squamous cell carcinoma of the lung in association with sarcoidosis. AB - A 76-year-old man who was known to have sarcoidosis, developed a lung tumor. He had previously undergone cardiac and abdominal vascular surgery, at which sarcoidosis was confirmed by lymph node biopsy. A right lower lobectomy was carried out. Postoperative pathology showed limited disease, but cancer recurred 1 year later. Issues regarding the combination of sarcoidosis and a malignant tumor are discussed. PMID- 19643856 TI - Surgical repair of mitral and tricuspid valves after cardiac transplantation. AB - A 43-year-old man underwent mitral valve repair for mitral valve insufficiency due to infective endocarditis, and tricuspid valve repair for iatrogenic chordal rupture due to multiple endomyocardial biopsies after orthotopic cardiac transplantation. Valve repair using no artificial material is feasible, instead of valve replacement, to decrease the risk of recurrent infective endocarditis and enable further biopsies. PMID- 19643857 TI - Emergency surgical embolectomy for pulmonary emboli after failed thrombolysis. AB - A 34-year-old man presented in cardiogenic shock secondary to massive pulmonary embolism. Surgical embolectomy was performed after failed thrombolysis. Intraoperatively, a right atrial lesion and pulmonary emboli were removed. Histopathology revealed myxoma complicated by pulmonary emboli. The patient made a good recovery. This case suggests that surgical embolectomy should be considered as first-line treatment for all patients with acute massive pulmonary embolism, and not reserved for those with severe hemodynamic compromise or failed conservative management. PMID- 19643858 TI - Middle lobectomy after pneumonectomy. AB - A 59-year-old man underwent a successful middle lobectomy to treat metastasis from a pulmonary adenocarcinoma resected previously by left pneumonectomy. PMID- 19643859 TI - Adult patent ductus arteriosus: successful surgery with mitral valvuloplasty. AB - The development of left ventricular dysfunction is a serious complication of longstanding patent ductus arteriosus. An 80-year-old woman who underwent patent ductus arteriosus ligation 13 years previously developed congestive heart failure and mitral regurgitation. She underwent surgical repair with transpulmonary ductus closure and mitral valve annuloplasty under cardiopulmonary bypass. She made a full recovery with improved left ventricular function. PMID- 19643860 TI - Coronary-to-pulmonary artery collateral in tetralogy of Fallot. AB - Angiography in a 14-year-old boy with cyanosis since birth confirmed the diagnosis of tetralogy of Fallot with a subaortic ventricular septal defect, large overriding aorta, severe pulmonary stenosis, and a large collateral arising from the left circumflex artery. The collateral was isolated and ligated at its origin, and the patient underwent an uneventful repair with ventricular septal defect patch closure, infundibular resection, pulmonary valvotomy, and right ventricular outflow tract reconstruction with an autologous pericardial patch. PMID- 19643862 TI - Primary tuberculous sternal osteomyelitis: a clinical rarity. AB - Primary tuberculous sternal osteomyelitis is a rare condition, presenting as painful swelling and discharging sinuses over the chest wall. Diagnosis is based on radiological findings and histological examination of debrided infected tissues, with specific cultures for mycobacteria. Two cases were successfully treated by surgical debridement and reconstruction using pectoralis major muscle flaps, followed by antituberculous therapy. PMID- 19643861 TI - Carinoplasty with telescope anastomosis for tuberculous bronchial stenosis. AB - A 25-year-old women developed severe stenosis of the right main bronchus after medical treatment for pulmonary tuberculosis in the right upper lobe. She underwent a right upper sleeve lobectomy with partial excision of the right main bronchus and right side of the carina. Reconstruction was performed using telescopic anastomosis between the carina and intermediate bronchus. Her symptoms improved immediately. PMID- 19643864 TI - Traumatic extrapleural haematoma imitating pericardial and pleural pathology. PMID- 19643863 TI - Video-assisted surgery for lung cancer. State of the art and personal experience. AB - This paper reviews the role of videothoracoscopy in lung cancer, highlighting its utility in definitive staging, diagnosis, and treatment. We show exploratory videothoracoscopy to be the perfect technique for last-minute staging, looking for tumor invasion, especially parietal T3 and vascular T4 (due to videopericardioscopy), management of solitary pulmonary nodules, and the possibility of radical treatment with video-assisted thoracoscopic lobectomy. We perform an overview of the literature and analyze our experience of 1,381 patients with lung cancer. In 1,277 of them, the final decision on resectability was made by exploratory videothoracoscopy, including 91 by videopericardioscopy (only 30 were considered non-resectable on videopericardioscopy). Solitary pulmonary nodules were diagnosed in 382 cases (190 were cancer), and we performed 260 major lung resections by video-assisted thoracoscopic surgery (22 pneumonectomies, 238 lobectomies/bilobectomies). PMID- 19643865 TI - Solitary intrapulmonary nodular amyloidoma. PMID- 19643866 TI - Severely protruding descending aortic atheroma. PMID- 19643867 TI - Left ventricular aneurysm. PMID- 19643869 TI - Pandoraea thiooxydans sp. nov., a facultatively chemolithotrophic, thiosulfate oxidizing bacterium isolated from rhizosphere soils of sesame (Sesamum indicum L.). AB - A facultatively chemolithoautotrophic, thiosulfate-oxidizing, Gram-negative, aerobic, motile, rod-shaped bacterial strain, designated ATSB16(T), was isolated from rhizosphere soils of sesame (Sesamum indicum L.). 16S rRNA gene sequence analysis demonstrated that this strain was closely related to Pandoraea pnomenusa LMG 18087(T) (96.7 % similarity), P. pulmonicola LMG 18016(T) (96.5 %), P. apista LMG 16407(T) (96.2 %), P. norimbergensis LMG 18379(T) (96.1 %) and P. sputorum LMG 18819(T) (96.0 %). Strain ATSB16(T) shared 96.0-96.4 % sequence similarity with four unnamed genomospecies of Pandoraea. The major cellular fatty acids of the strain ATSB16(T) were C(17 : 0) cyclo (33.0 %) and C(16 : 0) (30.6 %). Q-8 was the predominant respiratory quinone. The major polar lipids were phosphatidylmethylethanolamine, diphosphatidylglycerol, phosphatidylethanolamine and two unidentified aminophospholipids. Hydroxyputrescine and putrescine were the predominant polyamines. The genomic DNA G+C content of the strain was 64.0 mol%. On the basis of the results obtained from this study, strain ATSB16(T) represents a novel species of the genus Pandoraea, for which the name Pandoraea thiooxydans sp. nov. is proposed. The type strain is ATSB16(T) (=KACC 12757(T) =LMG 24779(T)). PMID- 19643870 TI - Jeotgalibacillus salarius sp. nov., isolated from a marine saltern, and reclassification of Marinibacillus marinus and Marinibacillus campisalis as Jeotgalibacillus marinus comb. nov. and Jeotgalibacillus campisalis comb. nov., respectively. AB - A Gram-variable, motile and rod-shaped bacterial strain, ASL-1(T), was isolated from a marine saltern located on the coast of the Yellow Sea, Korea. A neighbour joining phylogenetic tree based on 16S rRNA gene sequences showed that strain ASL 1(T) clustered with Jeotgalibacillus alimentarius YKJ-13(T) and that this cluster joined the clade comprising the type strains of two Marinibacillus species. Strain ASL-1(T) exhibited 16S rRNA gene sequence similarity values of 97.3 % to J. alimentarius YKJ-13(T) and 96.5 % to the type strains of Marinibacillus marinus and Marinibacillus campisalis. The chemotaxonomic properties of strain ASL-1(T) were similar to those of one or two of the genera Jeotgalibacillus and Marinibacillus. The peptidoglycan type was A1alpha linked directly through L lysine as the diamino acid. Strain ASL-1(T) contained MK-7 as the predominant menaquinone with the presence of a significant amount of MK-8. The predominant fatty acid was anteiso-C(15 : 0). The DNA G+C content was 42.9 mol%. Differential phenotypic properties, together with the phylogenetic and genetic distinctiveness, revealed that strain ASL-1(T) could be differentiated from J. alimentarius and the two Marinibacillus species. On the basis of the data presented, strain ASL-1(T) represents a novel species within the genus Jeotgalibacillus, for which the name Jeotgalibacillus salarius sp. nov. is proposed. The type strain is ASL-1(T) (=KCTC 13257(T)=CCUG 56751(T)). It is also proposed that Marinibacillus marinus and Marinibacillus campisalis be reclassified as Jeotgalibacillus marinus comb. nov. (type strain 581(T)=DSM 1297(T)=ATCC 29841(T)=CCUG 28884(T)=CIP 103308(T)=LMG 6930(T)) and Jeotgalibacillus campisalis comb. nov. (type strain SF-57(T)=KCCM 41644(T)=JCM 11810(T)), respectively. PMID- 19643872 TI - Transfer of Bacillus mucilaginosus and Bacillus edaphicus to the genus Paenibacillus as Paenibacillus mucilaginosus comb. nov. and Paenibacillus edaphicus comb. nov. AB - Bacillus mucilaginosus and Bacillus edaphicus were reclassified based on their 16S rRNA and gyrB gene sequences, DNA-DNA hybridization, fatty acid methyl esters and other taxonomic characteristics. Phylogenetic analysis based on 16S rRNA and gyrB gene sequences indicated that strains of B. mucilaginosus and B. edaphicus were members of the genus Paenibacillus, with over 90.4 % and 70.3 % sequence similarity, respectively. Their DNA G+C contents were 54.5-56.8 mol%. The DNA-DNA relatedness values of B. edaphicus VKPM B-7517(T) with B. mucilaginosus KNP414 and B. mucilaginosus CGMCC 1.236 were 89.2 % and 88.7 %, respectively. The major isoprenoid quinone of B. mucilaginosus and B. edaphicus was MK-7 (94.1-95.7 %). The peptidoglycan type was A1gamma (meso-diaminopimelic acid) and the major polar lipids were phosphatidylglycerol and diphosphatidylglycerol. The major fatty acids were anteiso-C(15 : 0), C(16 : 1)omega11c and C(16 : 0). Phenotypic features and fatty acid profiles supported the similarity of B. mucilaginosus and B. edaphicus to Paenibacillus validus CCTCC 95016(T) and confirmed their relationship with members of the genus Paenibacillus. Therefore, it is proposed that Bacillus mucilaginosus and Bacillus edaphicus be transferred to the genus Paenibacillus as Paenibacillus mucilaginosus comb. nov. (type strain HSCC 1605(T)=VKPM B-7519(T)=VKM B-1480D(T)=CIP 105815(T)=KCTC 3870(T)) and Paenibacillus edaphicus comb. nov. (type strain VKPM B-7517(T)=DSM 12974(T)=CIP 105814(T)), respectively. PMID- 19643871 TI - Anaerosphaera aminiphila gen. nov., sp. nov., a glutamate-degrading, Gram positive anaerobic coccus isolated from a methanogenic reactor treating cattle waste. AB - A strictly anaerobic, mesophilic and aminolytic strain (WN036(T)) was isolated from a methanogenic reactor treating waste from cattle farms. Cells were Gram positive cocci, often occurred in pairs and were non-motile. Although spore formation was not confirmed by microscopic observation of cells, the strain produced thermotolerant cells. The optimum temperature for growth was 35-37 degrees C and the optimum pH was 6.7. Oxidase, catalase and nitrate-reducing activities were negative. The novel strain did not ferment carbohydrates and grew in PY medium without additional substrates. The strain utilized l-glutamate, l glutamine, l-histidine and l-arginine as growth substrates. Major fermentation products were acetate and butyrate with a small amount of propionate. The genomic DNA G+C content was 32.5 mol%. The major cellular fatty acids were C(17 : 1)omega8, C(18 : 1)omega7 DMA and C(16 : 0). The diagnostic diamino acid of the cell-wall peptidoglycan was lysine. Glutamic acid, glycine, alanine and aspartic acid were also detected in the cell-wall peptidoglycan. On the basis of 16S rRNA gene sequences, the most closely related species to strain WN036(T) were Peptoniphilus asaccharolyticus ATCC 14965(T) (89.8 %) and Peptoniphilus indolicus ATCC 29427(T) (89.6 %). Based on the differences in the phenotypic and phylogenetic characteristics of strain WN036(T) compared with those of closely related species, a novel genus and species, Anaerosphaera aminiphila gen. nov., sp. nov., is proposed. The type strain is WN036(T) (=JCM 15094(T)=DSM 21120(T)). PMID- 19643873 TI - Brevundimonas naejangsanensis sp. nov., a proteolytic bacterium isolated from soil, and reclassification of Mycoplana bullata into the genus Brevundimonas as Brevundimonas bullata comb. nov. AB - A Gram-negative, motile and rod-shaped bacterial strain, BIO-TAS2-2(T), of the class Alphaproteobacteria, was isolated from a soil in Korea and studied using a polyphasic taxonomic approach. Strain BIO-TAS2-2(T) grew optimally at pH 7.5-8.5 and 30 degrees C and in the presence of 0-1.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain BIO-TAS2 2(T) fell within the clade comprising species of the genus Brevundimonas, forming a coherent cluster with Brevundimonas terrae KSL-145(T) and Brevundimonas diminuta LMG 2089(T). It exhibited 16S rRNA gene sequence similarity values of 96.0-98.7 % to members of the genus Brevundimonas and Mycoplana bullata IAM 13153(T). Strain BIO-TAS2-2(T) contained Q-10 as the predominant ubiquinone and cyclo-C(18 : 1)omega7c and C(16 : 0) as the major fatty acids. The DNA G+C content was 67.0 mol%. Strain BIO-TAS2-2(T) exhibited DNA-DNA relatedness levels of 12-19 % with the type strains of phylogenetically related Brevundimonas species and M. bullata. The novel strain could be differentiated from Brevundimonas species and M. bullata by differences in phenotypic characteristics. On the basis of phenotypic, phylogenetic and genetic data, strain BIO-TAS2-2(T) is considered to represent a novel species of the genus Brevundimonas, for which the name Brevundimonas naejangsanensis sp. nov. is proposed. The type strain is BIO-TAS2-2(T) (=KCTC 22631(T)=CCUG 57609(T)). In this study, it is also proposed that Mycoplana bullata be transferred to the genus Brevundimonas as Brevundimonas bullata comb. nov. (type strain TK0051(T)=ATCC 4278(T)=DSM 7126(T)=JCM 20846(T)=LMG 17157(T)). PMID- 19643874 TI - Kineosporia mesophila sp. nov., isolated from surface-sterilized stems of Tripterygium wilfordii. AB - An endophytic actinomycete strain, designated YIM 65293(T), was isolated from a surface-sterilized stem sample of Tripterygium wilfordii collected from Yunnan province, south-west China, and its taxonomic position was investigated. The chemical and morphological properties of the organism were consistent with those of the genus Kineosporia. Phylogenetic analysis indicated that the levels of 16S rRNA gene sequence similarity between strain YIM 65293(T) and other type strains of recognized members of the genus Kineosporia were 97.0-98.2 %. However, the DNA DNA hybridization values, in combination with differences in phenotypic characteristics, revealed that the strain differed from recognized species of the genus Kineosporia. Therefore, strain YIM 65293(T) represents a novel species of the genus Kineosporia, for which the name Kineosporia mesophila sp. nov. is proposed. The type strain is YIM 65293(T) (=CCTCC AA 208061(T)=DSM 45271(T)). PMID- 19643875 TI - Leeuwenhoekiella palythoae sp. nov., a new member of the family Flavobacteriaceae. AB - The taxonomic status of a novel, heterotrophic, strictly aerobic, gliding and yellow-orange-pigmented bacterium (strain KMM 6264(T)), associated with the coral Palythoa, was determined. The 16S rRNA gene sequence analysis indicated that strain KMM 6264(T) clustered with the recognized species of the genus Leeuwenhoekiella of the family Flavobacteriaceae with 96.4-98.2 % sequence similarity. DNA-DNA reassociation levels between the isolate and the type strains of Leeuwenhoekiella species were 15-22 %. The DNA G+C content was 41.2 mol%. The phylogenetic evidence and the results of genomic and phenotypic analyses showed that the isolate should be classified as a member of a novel species of the genus Leeuwenhoekiella, for which the name Leeuwenhoekiella palythoae sp. nov. is proposed. The type strain is KMM 6264(T) (=KCTC 22020(T)=LMG 24856(T)). PMID- 19643876 TI - Aidingimonas halophila gen. nov., sp. nov., a moderately halophilic bacterium isolated from a salt lake. AB - Two Gram-negative, facultatively anaerobic, catalase-positive, oxidase-negative, non-motile, rod-shaped and moderately halophilic bacterial strains, designated YIM 90637(T) and BH 017, were isolated from a salt lake in Xinjiang province, north-west China, and subjected to a polyphasic taxonomic study. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the two novel isolates were affiliated with the family Halomonadaceae; the two strains shared 100 % sequence similarity, but showed similarities of 94.7 % with the type strain of Modicisalibacter tunisiensis, 93.2-94.7 % with members of the genus Chromohalobacter, 93.2-95.0 % with members of the genus Halomonas and less than 92.0 % with other members of the family Halomonadaceae. However, DNA-DNA relatedness data and phenotypic properties demonstrated that strains YIM 90637(T) and BH 017 were representatives of the same species. The major fatty acids were C(19 : 0) cyclo omega8c and C(16 : 0.) The relative amount of C(19 : 0) cyclo omega8c was notably higher than that found in most species of the family Halomonadaceae for which fatty acid composition has been determined. The genomic DNA G+C content was 57.2-57.5 mol% and the only respiratory quinone was ubiquinone 9. Based on evidence from the polyphasic taxonomic study, it was concluded that the two strains should be classified as representatives of a novel species in a new genus, for which name Aidingimonas halophila gen. nov., sp. nov. is proposed; the type strain of Aidingimonas halophila is YIM 90637(T) (=KCTC 12885(T)=CCTCC AB 207002(T)). PMID- 19643877 TI - Herbidospora osyris sp. nov., isolated from surface-sterilized tissue of Osyris wightiana Wall. ex Wight. AB - An endophytic actinomycete, strain YIM 65070(T), was isolated from surface sterilized tissue of Osyris wightiana Wall. ex Wight collected from Yunnan province, south-west China, and characterized by using a polyphasic approach. Strain YIM 65070(T) had morphological and chemotaxonomic markers that were consistent with its classification in the genus Herbidospora. Phylogenetic analysis based on almost complete 16S rRNA gene sequences indicated that strain YIM 65070(T) was phylogenetically very closely related to Herbidospora cretacea IFO 15474(T). DNA-DNA hybridization experiments confirmed the separate genomic status of strains YIM 65070(T) and H. cretacea DSM 44071(T). Moreover, strain YIM 65070(T) could be distinguished from H. cretacea DSM 44071(T) by differences in several phenotypic characteristics such as tolerance to NaCl, degradation activity, utilization of sole carbon and nitrogen sources and the cellular fatty acid contents. On the basis of phenotypic and phylogenetic evidence, strain YIM 65070(T) was identified as a novel species of the genus Herbidospora, for which the name Herbidospora osyris sp. nov. is proposed, with YIM 65070(T) (=CCTCC AA 208019(T)=DSM 45214(T)) as the type strain. PMID- 19643878 TI - Gordonia hankookensis sp. nov., isolated from soil. AB - A Gram-positive, aerobic and non-motile bacterial strain, designated ON-33(T), was subjected to a study based on a polyphasic approach to determine its exact taxonomic position. Strain ON-33(T) grew optimally at pH 7.0-7.5 and 30 degrees C. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain ON-33(T) fell within the clade comprising Gordonia species, clustering with Gordonia soli CC-AB07(T), with which it exhibited 16S rRNA gene sequence similarity of 98.5 %. The chemotaxonomic properties of strain ON-33(T) were consistent with those shared by members of the genus Gordonia. The peptidoglycan type was based on meso-diaminopimelic acid and the whole-cell sugars were arabinose and galactose. The predominant menaquinone was MK-9(H(2)). The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The major fatty acids were C(16 : 0), iso-C(15 : 0) 2-OH and/or C(16 : 1)omega7c, 10-methyl C(18 : 0) and C(18 : 1)omega9c. The DNA G+C content was 66.9 mol%. Strain ON-33(T) exhibited a DNA-DNA relatedness value of 13 % to G. soli DSM 44995(T) and could be differentiated from G. soli by differences in phenotypic characteristics. On the basis of the data obtained, strain ON-33(T) is considered to represent a novel species of the genus Gordonia, for which the name Gordonia hankookensis sp. nov., is proposed. The type strain is ON-33(T) (=KCTC 19599(T)=CCUG 57507(T)). PMID- 19643879 TI - Sphingobium vermicomposti sp. nov., isolated from vermicompost. AB - Strain VC-230(T) was isolated from homemade vermicompost produced from kitchen waste. The isolate was a Gram-negative-staining, catalase- and oxidase-positive, motile rod-shaped bacterium able to grow at 15-37 degrees C and pH 6-8. On the basis of 16S rRNA gene sequence analysis, strain VC-230(T) was determined to belong to the family Sphingomonadaceae by its clustering with type strains of the genus Sphingobium, with Sphingobium chlorophenolicum ATCC 33790(T) (97.7 %) and Sphingobium herbicidovorans DSM 11019(T) (97.4 %) as its closest neighbours. The polar lipid pattern, the presence of spermidine and ubiquinone 10, the predominance of the cellular fatty acids C(18 : 1)omega7c/9t/12t, C(16 : 1)omega7c and C(16 : 0) and the G+C content of the genomic DNA supported the affiliation of this organism to the genus Sphingobium. The phylogenetic, chemotaxonomic, phenotypic and DNA-DNA hybridization analyses verify that strain VC-230(T) represents a novel species, for which the name Sphingobium vermicomposti sp. nov. is proposed. The type strain is VC-230(T) (=CCUG 55809(T) =DSM 21299(T)). PMID- 19643880 TI - Desulfocurvus vexinensis gen. nov., sp. nov., a sulfate-reducing bacterium isolated from a deep subsurface aquifer. AB - A novel anaerobic, chemo-organotrophic bacterium, designated VNs36(T), was isolated from a well that collected water from a deep saline aquifer used for underground gas storage at a depth of 830 m in the Paris Basin, France. Cells were curved motile rods or vibrios (3.0-5.0x0.5 microm). Strain VNs36(T) grew at temperatures between 20 and 50 degrees C (optimum 37 degrees C) and at pH values between 5.0 and 9.0 (optimum 6.9). It did not require salt for growth, but tolerated up to 20 g NaCl l(-1) (optimum 2 g l(-1)). In the presence of sulfate, strain VNs36(T) used lactate, formate and pyruvate as carbon and energy sources. The main fermentation products from lactate were acetate, H(2) and CO(2). Sulfate, thiosulfate and sulfite were used as electron acceptors, but not sulfur. The genomic DNA G+C content of strain VNs36(T) was 67.2 mol%. Phylogenetic analysis of the 16S rRNA gene sequence indicated that strain VNs36(T) was affiliated with the family Desulfovibrionaceae within the class Deltaproteobacteria. On the basis of 16S rRNA gene sequence comparisons, DNA G+C content and the absence of desulfoviridin in cell extracts, it is proposed that strain VNs36(T) be assigned to a new genus, Desulfocurvus gen. nov., as a representative of a novel species, Desulfocurvus vexinensis sp. nov. The type species of this genus is Desulfocurvus vexinensis with the type strain VNs36(T) (=DSM 17965(T)=JCM 14038(T)). PMID- 19643881 TI - Microbispora siamensis sp. nov., a thermotolerant actinomycete isolated from soil. AB - An actinomycete, strain DMKUA 245(T), isolated from soil, was investigated using a polyphasic approach. The isolate formed longitudinally paired spores on the tips of short sporophores that branched alternately from aerial hyphae. The morphological and chemotaxonomic properties clearly demonstrated that the new isolate belonged to the genus Microbispora. 16S rRNA gene sequence analysis supported the assignment of the novel strain to the genus Microbispora. The gene sequence similarity values between the novel strain and the closely related species Microbispora corallina, Microbispora rosea subsp. rosea, Microbispora rosea subsp. aerata and Microbispora amethystogenes were 98.4 %, 97.4 %, 97.0 % and 96.9 %, respectively. The DNA-DNA hybridization values and some physiological and biochemical properties indicated that strain DMKUA 245(T) could be distinguished from its phylogenetically closest relatives. Based on these genotypic and phenotypic data, strain DMKUA 245(T) represents a novel species in the genus Microbispora for which the name Microbispora siamensis sp. nov. is proposed. The type strain is strain DMKUA 245(T) (=BCC 14407(T)=NBRC 104113(T)). In addition, DNA-DNA relatedness values in reciprocal hybridization experiments showed that M. amethystogenes was a separate genomic species from M. rosea subsp. rosea. A combination of genotypic and phenotypic data supported the classification of M. amethystogenes as a separate species. PMID- 19643882 TI - Hoyosella altamirensis gen. nov., sp. nov., a new member of the order Actinomycetales isolated from a cave biofilm. AB - A novel actinomycete, strain OFN S31(T), was isolated from a complex biofilm in the Altamira Cave, Spain. A polyphasic study was carried out to clarify the taxonomic position of this strain. Phylogenetic analysis with 16S rRNA gene sequences of representatives of the genera Corynebacterium, Dietzia, Gordonia, Millisia, Mycobacterium, Nocardia, Rhodococcus, Segniliparus, Skermania, Tsukamurella and Williamsia indicated that strain OFN S31(T) formed a distinct taxon in the 16S rRNA gene tree that was more closely associated with the Mycobacterium clade. The type strain of Mycobacterium fallax was the closest relative of strain OFN S31(T) (95.6 % similarity). The cell wall contained meso diaminopimelic acid, arabinose and galactose, which are characteristic components of cell-wall chemotype IV of actinomycetes. The sugars of the peptidoglycan were acetylated. The polar lipid pattern was composed of phosphatidylinositol, phosphatidylglycerol, phosphatidylethanolamine and diphosphatidylglycerol. Strain OFN S31(T) is characterized by the absence of mycelium and mycolic acids. Strain OFN S31(T) had MK-8 as the major menaquinone. The DNA G+C content was 49.3 mol%, the lowest found among all taxa included in the suborder Corynebacterineae. Based on morphological, chemotaxonomic, phenotypic and genetic characteristics, strain OFN S31(T) is considered to represent a novel species of a new genus, for which the name Hoyosella altamirensis gen. nov., sp. nov. is proposed. The type strain of Hoyosella altamirensis is strain OFN S31(T) (=CIP 109864(T) =DSM 45258(T)). PMID- 19643883 TI - Thiothrix caldifontis sp. nov. and Thiothrix lacustris sp. nov., gammaproteobacteria isolated from sulfide springs. AB - Five strains of filamentous, sulfur-oxidizing bacteria were isolated from sulfur mats of different sulfide springs from various regions of the Northern Caucasus, Russia. A phylogenetic analysis based on 16S rRNA gene sequence comparison showed that all of the isolates are affiliated with the filamentous, colourless, sulfur oxidizing bacteria of the genus Thiothrix within the Gammaproteobacteria and are closely related to Thiothrix fructosivorans. All strains are capable of growing heterotrophically, lithoautotrophically with thiosulfate or sulfide as the sole energy source and mixotrophically. Strains G1(T), G2, P and K2 are able to fix molecular nitrogen, but strain BL(T) is not. Randomly amplified polymorphic DNA (RAPD)-PCR analysis was used to assess the level of genetic relationships among the Thiothrix isolates. The Nei and Li similarity index revealed high genetic similarity among strains G1(T), G2, P and K2 (above 75 %), indicating that they are closely related. In combination with physiological and morphological data, strains G1(T), G2, P and K2 can be considered as members of the same species. The lowest genetic similarity (approx. 20 %) was reached between strain BL(T) and the other isolated Thiothrix strains. Strains BL(T) and G1(T) shared 35 % DNA-DNA relatedness and showed 51 and 53 % relatedness, respectively, to Thiothrix fructosivorans ATCC 49749. On the basis of this polyphasic analysis, strains G1(T), G2, P and K2 represent a novel species within the genus Thiothrix, for which the name Thiothrix caldifontis sp. nov. is proposed, with strain G1(T) (=DSM 21228(T) =VKM B-2520(T)) as the type strain. In addition, strain BL(T) represents a second novel species, Thiothrix lacustris sp. nov., with strain BL(T) (=DSM 21227(T) =VKM B-2521(T)) as the type strain. PMID- 19643884 TI - Carnobacterium jeotgali sp. nov., isolated from a Korean traditional fermented food. AB - A Gram-positive, facultatively anaerobic bacterium, designated strain MS3(T), was isolated from a traditional Korean fermented food made with freshwater shrimp. Strain MS3(T) was able to grow at 4-37 degrees C, at pH 5.5-9.0 and in the presence of 0-5 % (w/v) NaCl. Optimal growth occurred at 30 degrees C, at pH 8.5 and in the presence of 2 % NaCl. The strain was catalase- and oxidase-negative. It was able to metabolize various carbohydrates as energy sources. 16S rRNA gene sequence analysis showed that strain MS3(T) was most closely related to Carnobacterium pleistocenium FTR1(T) (98.95 % similarity), but the level of DNA DNA relatedness between the two taxa was less than 16.0 %. The genomic G+C content of strain MS3(T) was 43.9 mol% and the major fatty acid components were C(16 : 0), C(16 : 1)omega9c and C(18 : 1)omega9c. On the basis of its genotypic, physiological and biochemical characteristics, strain MS3(T) is considered to represent a novel species of the genus Carnobacterium, for which the name Carnobacterium jeotgali sp. nov. is proposed. The type strain is MS3(T) (=KCTC 13251(T)=JCM 15539(T)). PMID- 19643885 TI - Shewanella chilikensis sp. nov., a moderately alkaliphilic gammaproteobacterium isolated from a lagoon. AB - A Gram-negative, motile, rod-shaped, facultatively anaerobic bacterium was isolated from sediment of Chilika Lagoon, a brackish water lagoon in India. The strain, designated JC5(T), was able to grow in the presence of 0-8.0 % NaCl and at pH 7.0-10.0. The isolate was positive for oxidase and catalase and exhibited alpha-haemolysis. The major fatty acids were iso-C(15 : 0) (18.3 %), C(16 : 0) (11.3 %), C(17 : 1)omega8c (13.1 %) and a summed feature, C(16 : 1)omega7c and/or C(16 : 1)omega6c (15.1 %). The genomic DNA G+C content was 54.6 mol%. A phylogenetic tree based on the 16S rRNA gene sequences showed that strain JC5(T) forms a lineage within the genus Shewanella and is closely related to Shewanella haliotis DW01(T) (98.0 %), Shewanella algae ATCC 51192(T) (97.6 %) and Shewanella marina C4(T) (95.8 %). Further, genomic DNA-DNA hybridization of strain JC5(T) with S. haliotis DW01(T) and S. algae ATCC 51192(T) showed relatedness of only 42 and 23 %, respectively. On the basis of phenotypic and molecular genetic evidence, strain JC5(T) represents a novel species of the genus Shewanella, for which the name Shewanella chilikensis sp. nov. is proposed. The type strain is JC5(T) (=CCUG 57101(T) =NBRC 105217(T) =KCTC 22540(T)). PMID- 19643886 TI - Virgibacillus salinus sp. nov., a moderately halophilic bacterium from sediment of a saline lake. AB - A novel, moderately halophilic, Gram-positive bacterium, designated strain XH 22(T), was isolated from sediment of a saline lake located near Xilinhot, Inner Mongolia Autonomous Region, China. Cells were rod-shaped, endospore-forming and motile. The isolate was able to grow in the presence of 3-20 % (w/v) total salts (optimum, 10 %, w/v), and at 15-40 degrees C (optimum, 37 degrees C) and pH 6.0 10.0 (optimum, pH 7.5). Strain XH-22(T) had diaminopimelic acid in the cell-wall peptidoglycan, MK-7 as the predominant menaquinone, and anteiso-C(15 : 0), C(16 : 0) and iso-C(14 : 0) as major fatty acids. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, a glycolipid and two unidentified phospholipids. The DNA G+C content of strain XH-22(T) was 38.8 mol%. 16S rRNA gene sequence analysis revealed that the novel strain was affiliated with the genus Virgibacillus. Levels of 16S rRNA gene sequence similarity between strain XH-22(T) and the type strains of recognized Virgibacillus species ranged from 97.6 % (with Virgibacillus carmonensis) to 94.9 % (with Virgibacillus koreensis). Levels of DNA-DNA relatedness between strain XH-22(T) and V. carmonensis DSM 14868(T) and Virgibacillus necropolis DSM 14866(T) were 32 and 28 %, respectively. Strain XH-22(T) could be differentiated from recognized Virgibacillus species based on phenotypic characteristics, chemotaxonomic differences, phylogenetic analysis and genotypic features. On the basis of these results, strain XH-22(T) is considered to represent a novel species of the genus Virgibacillus, for which the name Virgibacillus salinus sp. nov. is proposed. The type strain is XH-22(T) (=CCM 7562(T)=CECT 7439(T)=DSM 21756(T)). PMID- 19643887 TI - Isolation of the anaerobic thermoacidophilic crenarchaeote Acidilobus saccharovorans sp. nov. and proposal of Acidilobales ord. nov., including Acidilobaceae fam. nov. and Caldisphaeraceae fam. nov. AB - An anaerobic acidophilic, hyperthermophilic archaeon, designated strain 345 15(T), was isolated from an acidic hot spring of Kamchatka (Russia). Cells of strain 345-15(T) were regular or irregular cocci, 1-2 mum in diameter, with flagella. Strain 345-15(T) grew optimally at 80-85 degrees C and pH 3.5-4.0 and fermented a wide range of carbohydrates, including polysaccharides. Acetate, ethanol and lactate were the fermentation products. Growth was stimulated by elemental sulfur and thiosulfate, which were reduced to hydrogen sulfide. The G+C content of the DNA was 54.5 mol%. The 16S rRNA gene sequence analysis indicated that strain 345-15(T) belonged to the genus Acidilobus. The level of DNA-DNA hybridization between strain 345-15(T) and Acidilobus aceticus 1904(T) was 61 %. Thus, strain 345-15(T) was considered as representing a novel species of the genus Acidilobus, with the name Acidilobus saccharovorans sp. nov. (type strain, 345-15(T)=DSM 16705(T)=VKM B-2471(T)), which shared the main morphological and physiological properties of the genus but differed by the presence of flagella and the spectrum of substrates utilized. Phylogenetic analysis showed that the genus Acidilobus, with its species Acidilobus aceticus, Acidilobus saccharovorans sp. nov. and 'Acidilobus sulfurireducens', and the genus Caldisphaera, represented by Caldisphaera lagunensis and 'Caldisphaera draconis', formed a separate cluster that adjoins the cluster formed by the species of the order Desulfurococcales. Members of the Acidilobus-Caldisphaera cluster are thermophilic, organotrophic anaerobic cocci that can be distinguished from all species of the order Desulfurococcales on the basis of acidophily. Based on these considerations, we propose a new family, Acidilobaceae fam. nov., to accommodate the subcluster of hyperthermophiles represented by the genus Acidilobus, a new family, Caldisphaeraceae fam. nov., for the subcluster of extreme thermophiles represented by the genus Caldisphaera, and a new order, Acidilobales ord. nov., to accommodate the two new families. PMID- 19643888 TI - Sphingobium chinhatense sp. nov., a hexachlorocyclohexane (HCH)-degrading bacterium isolated from an HCH dumpsite. AB - A yellow-pigmented, hexachlorocyclohexane (HCH)-degrading bacterium, strain IP26(T), was isolated from an HCH dumpsite and subjected to a polyphasic analysis in order to determine its taxonomic position. Strain IP26(T) showed maximum 16S rRNA gene sequence similarity with Sphingobium francense Sp+(T) (98.5 %), Sphingobium japonicum UT26(T) (98.4 %) and Sphingobium indicum B90A(T) (98.2 %). Phylogenetic analysis based on 16S rRNA gene sequences also showed that strain IP26(T) formed a cluster with these three HCH-degrading strains. Chemotaxonomic data (major polyamine, spermidine; major quinone, ubiquinone with ten isoprene units; major polar lipids, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, diphosphatidylglycerol, phosphotidylcholine; and presence of 2-hydroxy fatty acid) supported inclusion of strain IP26(T) in the genus Sphingobium. However, the results of DNA-DNA hybridization and morphological and biochemical tests clearly allowed phenotypic and genotypic differentiation of strain IP26(T) from recognized species of the genus Sphingobium. Strain IP26(T) thus represents a novel species of the genus Sphingobium for which the name Sphingobium chinhatense sp. nov. is proposed. The type strain is IP26(T) (=MTCC8598(T) =CCM 7432(T)). PMID- 19643889 TI - Rhizobium tibeticum sp. nov., a symbiotic bacterium isolated from Trigonella archiducis-nicolai (Sirj.) Vassilcz. AB - Isolated from root nodules of Trigonella archiducis-nicolai (Sirj.) Vassilcz. grown in Tibet, China, cells of the bacterial strains CCBAU 85039(T) and CCBAU 85027 were Gram-negative, aerobic, motile, non-spore-forming rods that formed colonies that were semi-translucent and opalescent on yeast extract-mannitol agar. In numerical taxonomy, SDS-PAGE analysis of whole-cell proteins and DNA-DNA hybridization, the two strains were very similar and were different from reference strains of defined Rhizobium species. In the phylogeny based on 16S rRNA gene sequences, they were most similar to Rhizobium etli CFN 42(T) (98.2 % similarity) and R. leguminosarum USDA 2370(T) (97.6 %). Sequence analyses of the housekeeping genes recA, atpD and glnII and the 16S-23S rRNA intergenic spacer, phenotypic characteristics and cellular fatty acid profiles strongly suggested that these two strains represented a novel species within Rhizobium. Cross nodulation tests and sequencing of nifH and nodA genes showed that these two strains were symbiotic bacteria that nodulated Trigonella archiducis-nicolai, Medicago lupulina, Medicago sativa, Melilotus officinalis, Phaseolus vulgaris and Trigonella foenum-graecum. Based on the results, the novel species Rhizobium tibeticum sp. nov. is described to accommodate the two strains. The type strain is CCBAU 85039(T) (=LMG 24453(T) =CGMCC 1.7071(T)). The DNA G+C content of this strain is 59.7 mol% (T(m)). PMID- 19643890 TI - Janibacter hoylei sp. nov., Bacillus isronensis sp. nov. and Bacillus aryabhattai sp. nov., isolated from cryotubes used for collecting air from the upper atmosphere. AB - Three novel bacterial strains, PVAS-1(T), B3W22(T) and B8W22(T), were isolated from cryotubes used to collect air samples at altitudes of between 27 and 41 km. Based on phenotypic characteristics, chemotaxonomic features, DNA-DNA hybridization with the nearest phylogenetic neighbours and phylogenetic analysis based on partial 16S rRNA gene sequences (PVAS-1(T), 1196 nt; B3W22(T), 1541 nt; B8W22(T), 1533 nt), the three strains were identified as representing novel species, and the names proposed are Janibacter hoylei sp. nov. (type strain PVAS 1(T) =MTCC 8307(T) =DSM 21601(T) =CCUG 56714(T)), Bacillus isronensis sp. nov. (type strain B3W22(T) =MTCC 7902(T) =JCM 13838(T)) and Bacillus aryabhattai sp. nov. (type strain B8W22(T) =MTCC 7755(T) =JCM 13839(T)). PMID- 19643891 TI - Brachymonas chironomi sp. nov., isolated from a chironomid egg mass, and emended description of the genus Brachymonas. AB - A Gram-negative, aerobic, chemo-organotrophic, catalase- and oxidase-positive strain, designated AIMA4(T), was isolated from a chironomid (Diptera; Chironomidae) egg mass which was sampled from a waste stabilization pond in northern Israel. Phylogenetic analysis based on the 16S rRNA gene placed strain AIMA4(T) in the genus Brachymonas (class Betaproteobacteria). Strain AIMA4(T) shared 16S rRNA gene sequence similarity values of 96.9 % with Brachymonas denitrificans JCM 9216(T) and <95.7 % with the type strains of other genera. Strain AIMA4(T) was found to be a non-motile coccobacillus or rod that did not grow under anaerobic conditions and did not produce acid from carbohydrates. Growth was observed at salinities from 0 to 2.5 % (w/v) NaCl, at pH values from 5.0 to 9.0 and at temperatures from 18 to 37 degrees C. The major fatty acids (>10 %) of strain AIMA4(T) were C(16 : 1)omega7c, C(16 : 0) and C(18 : 1)omega7c. Phosphatidylethanolamine, phosphatidylglycerol and phosphatidylserine were the predominant components of the polar lipids. The major ubiquinone was Q-8. On the basis of phenotypic properties and phylogenetic distinctiveness, strain AIMA4(T) (=LMG 24400(T)=DSM 19884(T)) was classified in the genus Brachymonas as the type strain of a novel species for which the name Brachymonas chironomi sp. nov. is proposed. PMID- 19643892 TI - Piscibacillus halophilus sp. nov., a moderately halophilic bacterium from a hypersaline Iranian lake. AB - A Gram-positive, moderately halophilic bacterium, designated strain HS224(T), was isolated from the hypersaline lake Howz-Soltan in Iran. Cells of strain HS224(T) were rod-shaped, motile and produced oval endospores. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain HS224(T) was affiliated to the genus Piscibacillus, exhibiting 98.5 % sequence similarity to the type strain of Piscibacillus salipiscarius. Strain HS224(T) was also related closely to the type strains of Aquisalibacillus elongatus (98.0 % 16S rRNA gene sequence similarity), Filobacillus milosensis (97.9 %) and Tenuibacillus multivorans (97.0 %). Strain HS224(T) was able to grow at NaCl concentrations of 1-20 % (w/v), with optimum growth occurring at 10 % (w/v) NaCl. The optimum temperature and pH for growth were 35 degrees C and pH 7.5. Major polar lipids were phosphatidylglycerol and diphosphatidylglycerol, the isoprenoid quinone was MK-7 and the peptidoglycan type was A1gamma, with meso-diaminopimelic acid as the diagnostic diamino acid; these characteristics were shared with P. salipiscarius. The major cellular fatty acids of strain HS224(T) were anteiso-C(15 : 0), iso-C(15 : 0), anteiso-C(17 : 0) and iso-C(16 : 0). The G+C content of the DNA was 37.5 mol%. The level of DNA-DNA relatedness between strain HS224(T) and P. salipiscarius JCM 13188(T) was 30.8 %. It is evident from the genotypic, chemotaxonomic and phenotypic data presented that strain HS224(T) represents a novel species of the genus Piscibacillus, for which the name Piscibacillus halophilus sp. nov. is proposed. The type strain is HS224(T) (=CCM 7596(T)=DSM 21633(T)=JCM 15721(T)=LMG 24786(T)). PMID- 19643893 TI - Actinocatenispora rupis sp. nov., isolated from cliff soil, and emended description of the genus Actinocatenispora. AB - A novel actinomycete, designated strain CS5-AC17(T), was isolated from cliff soil in the Republic of Korea. Cells of the organism were aerobic and catalase- and oxidase-negative. Substrate mycelium was well developed and was pale to strong yellow. Spore chains were borne on rudimentary aerial mycelium. The spores (0.4 0.5x0.9-1.6 microm) were smooth surfaced and cylindrical. Growth occurred at 25 42 degrees C, at pH 5.1-12.1 and in the presence of up to 4 % NaCl. Phylogenetic analyses based on 16S rRNA gene sequences indicated that the isolate was closely related to members of the genus Actinocatenispora in the family Micromonosporaceae. The phylogenetic neighbours were Actinocatenispora thailandica TT2-10(T) (97.7 % 16S rRNA gene sequence similarity) and Actinocatenispora sera KV-744(T) (97.6 %). The diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. The major respiratory quinones were MK-9(H(4)), MK-9(H(6)) and MK-9(H(8)). The polar lipids contained phosphatidylethanolamine and phosphatidylinositol with a small amount of phosphatidylglycerol. The DNA G+C content was 74.3 mol%. DNA-DNA relatedness values between strain CS5-AC17(T) and its phylogenetically closest relatives were 6.1-7.1 % (A. thailandica DSM 44816(T)) and 21.5-27.6 % (A. sera NRRL B 24477(T)). On the basis of the phenotypic features and the DNA-DNA hybridization data, strain CS5-AC17(T) (=DSM 45178(T)=NRRL B-24660(T)) represents a novel species of the genus Actinocatenispora, for which the name Actinocatenispora rupis sp. nov. is proposed. PMID- 19643894 TI - Streptomyces thinghirensis sp. nov., isolated from rhizosphere soil of Vitis vinifera. AB - A novel actinomycete, strain S10(T), was isolated from rhizosphere soil of wild Vitis vinifera in Thinghir, Ouarzazate Province, Southern Morocco. The taxonomic status of this strain was established using a polyphasic approach. Strain S10(T) had white-grey aerial mycelium with long, spiral spore chains bearing smooth surfaced spores and produced a yellow diffusible pigment. Chemotaxonomic analyses showed that the cell wall of strain S10(T) contained ll-diaminopimelic acid and glycine. Phylogenetic analysis based on the almost complete 16S rRNA gene sequence indicated that strain S10(T) belonged to the Group I streptomycetes, branching off next to Streptomyces marokkonensis LMG 23016(T) from the Streptomyces violaceoruber group. DNA-DNA relatedness and phenotypic data distinguished strain S10(T) from the phylogenetically closest related type strains. It is therefore proposed that strain S10(T) (=CCMM B35(T)=DSM 41919(T)) represents the type strain of a novel species of the genus Streptomyces, for which the name Streptomyces thinghirensis sp. nov. is proposed. PMID- 19643895 TI - Maribaculum marinum gen. nov., sp. nov., isolated from deep seawater. AB - A taxonomic study was carried out on strain P38(T), which was isolated from an enriched polycyclic aromatic hydrocarbon-degrading consortium from a deep seawater sample collected from the Indian Ocean. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain P38(T) formed a distinct evolutionary lineage within the family Hyphomonadaceae. Strain P38(T) was most closely related to members of the genera Hyphomonas (92.3-93.5 % 16S rRNA gene sequence similarity), Hirschia (88.8 %), Maricaulis (88.3-88.6 %), Hellea (87.5 %), Oceanicaulis (87.4 %) and Robiginitomaculum (86.7 %) of the family Hyphomonadaceae. The DNA G+C content of strain P38(T) was 61.0 mol% and the predominant cellular fatty acids were C(16 : 0) (20 %), C(17 : 0) (5.7 %), C(18 : 1)omega7c (37.7 %), C(18 : 0) (6.3 %) and C(18 : 1)omega7c 11-methyl (7.1 %). Strain P38(T) was distinguishable from members of phylogenetically related genera by differences in several phenotypic properties. On the basis of the phenotypic and phylogenetic data, strain P38(T) represents a novel species of a new genus, for which the name Maribaculum marinum gen. nov., sp. nov. is proposed. The type strain of Maribaculum marinum is P38(T) (=CCTCC AB 208227(T)=LMG 24711(T)=MCCC 1A01086(T)). PMID- 19643896 TI - Gynumella flava gen. nov., sp. nov., isolated from the rhizosphere of rice (Oryza sativa L.) managed under a no-tillage regime. AB - A bacterial strain designated YC6842T, isolated from the rhizosphere of rice (Oryza sativa L.) managed under no-tillage practice in Jinju, Korea, was characterized using polyphasic taxonomic approach. Cells of the strain were Gram negatively stained, aerobic, rod-shaped and motile by multiple polar flagella. It grew at a temperature of 20 to 40 degrees C (optimum at 28 degrees C). Growth occurred between pH 6.0 and 10.0, with an optimum of pH 7.0-8.0. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strain represented a separate clade within the family Xanthomonadaceae. It showed the highest 16S rRNA gene sequence similarity with Dyella yeojuensis R2A16-10T (93.6 %). The DNA G+C content was 62.6 mol%. Q-8 was the major quinone. Major polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylcholine (PC) and phosphatidylglycerol (PG). Phylogenetic analysis, biochemical and physiological characteristics strongly supported the genotypic and phenotypic differentiation of the strain YC6842T from the validly published genera of the family Xanthomonadaceae. Therefore, it is proposed that the strain YC6842T represents a novel species within a novel genus, with the name Gynumella flava gen. nov., sp. nov. The type strain is YC6842T (= KCTC 22443T = DSM 21636T). PMID- 19643897 TI - Nocardioides ginsengisoli sp. nov., isolated from soil of a ginseng field. AB - A Gram-positive, rod-shaped, non-spore-forming bacterium (Gsoil 1124(T)) was isolated from soil of a ginseng field of Pocheon province in South Korea, and was characterized in order to determine its taxonomic position. On the basis of 16S rRNA gene sequence similarity, strain Gsoil 1124(T) was shown to belong to the family Nocardioidaceae and related to Nocardioides simplex (98.2 % 16S rRNA gene sequence similarity), Nocardioides aromaticivorans (98.1 %), Nocardioides nitrophenolicus (97.7 %) and Nocardioides kongjuensis (97.5 %). The sequence similarity with any other species with validly published names within the genus Nocardioides was less than 94.5 %. Strain Gsoil 1124(T) was characterized chemotaxonomically as having ll-2,6-diaminopimelic acid in the cell-wall peptidoglycan, MK-8(H(4)) as the predominant menaquinone and iso-C(16 : 0), C(18 : 0), C(16 : 0), and C(18 : 1)omega9c as the major fatty acids. The G+C content of the genomic DNA was 70.2 mol%. The chemotaxonomic properties and phenotypic characteristics supported the affiliation of strain Gsoil 1124(T) to the genus Nocardioides. The results of physiological and biochemical tests, and the low level of DNA-DNA relatedness allowed genotypic differentiation of strain Gsoil 1124(T) from recognized Nocardioides species. Therefore, strain Gsoil 1124(T) is considered to represent a novel species, for which the name Nocardioides ginsengisoli sp. nov. is proposed, with the type strain Gsoil 1124(T) (=KCTC 19135(T)=CCUG 52478(T)=DSM 17921(T)). PMID- 19643898 TI - Saccharopolyspora tripterygii sp. nov., an endophytic actinomycete isolated from the stem of Tripterygium hypoglaucum. AB - An endophytic actinomycete, designated strain YIM 65359(T), was isolated from a surface-sterilized stem sample of Tripterygium hypoglaucum collected from Yunnan province, south-west China. The morphological and chemotaxonomic properties of the new isolate were consistent with those of members of the genus Saccharopolyspora. Analysis of 16S rRNA gene sequences revealed that the new isolate was most closely related to 'Saccharopolyspora endophytica' YIM 61095 (98.6 %), Saccharopolyspora flava AS4.1520(T) (97.6 %) and Saccharopolyspora spinosa DSM 44228(T) (97.0 %). The results of DNA-DNA hybridizations (57.5 %, 44.9 % and 48.5 %, respectively) with the above micro-organisms, in combination with differences in the biochemical and physiological characteristics, suggested that strain YIM 65359(T) should be classified as a novel species of the genus Saccharopolyspora. The name Saccharopolyspora tripterygii sp. nov. is proposed for this novel species, with YIM 65359(T) (=CCTCC AA 208062(T)=DSM 45269(T)) as the type strain. PMID- 19643900 TI - Pseudomonas pelagia sp. nov., isolated from a culture of the Antarctic green alga Pyramimonas gelidicola. AB - Two Gram-negative, strictly aerobic bacterial strains, designated CL-AP6(T) and CL-AP22, were isolated from a culture of a green alga, Pyramimonas gelidicola, established from the Antarctic. Cells of the strains were straight rods and motile by means of a single polar flagellum. The strains grew with 0.5-8 % (w/v) NaCl (optimum, 1-2 %) and at 4-33 degrees C (optimum, 25 degrees C) and pH 6.5 9.1 (optimum, pH 7.5-8.1). The two strains shared 98.8 % 16S rRNA gene sequence similarity. Analysis of the 16S rRNA gene sequences of strains CL-AP6(T) and CL AP22 revealed that they were members of the genus Pseudomonas and were most closely related to Pseudomonas xiamenensis C10-2(T) (95.5-95.8 % sequence similarity) and next to Pseudomonas pertucinogena NBRC 14163(T) (95.1-95.5 % sequence similarity) and to other members of the genus Pseudomonas (<95.2 % sequence similarity). Phylogenetic analyses based on the 16S rRNA gene sequences showed that strain CL-AP6(T) formed a robust clade with strain CL-AP22, and that this clade clustered tightly with the nearest clade containing P. xiamenensis and P. pertucinogena. The major isoprenoid quinone of strains CL-AP6(T) and CL-AP22 was Q-9 and the major cellular fatty acids were C(18 : 1)omega7c (40.2-41.6 %), summed feature 3 (C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH; 26.3-26.8 %), C(16 : 0) (13.7-13.9 %) and C(12 : 0) (5.8-6.2 %). The genomic DNA G+C contents of strains CL-AP6(T) and CL-AP22 were 59.1 and 57.2 mol%, respectively. DNA-DNA hybridization experiments revealed high relatedness values (98.5+/-0.5 %; mean+/ sem, n=2) between strains CL-AP6(T) and CL-AP22, indicating that the two strains constituted a single species. However, the two strains differed phenotypically from P. xiamenensis by their inability to grow without NaCl, temperature range for growth, hydrolysis of starch and production of certain enzymes. The phylogenetic analysis and physiological and biochemical data showed that strains CL-AP6(T) and CL-AP22 should be classified as representing a novel species in the genus Pseudomonas, for which the name Pseudomonas pelagia sp. nov. is proposed. The type strain is CL-AP6(T) (=KCCM 90073(T)=JCM 15562(T)). PMID- 19643899 TI - Bacillus neizhouensis sp. nov., a halophilic marine bacterium isolated from a sea anemone. AB - A novel Gram-stain-positive, slightly halophilic, facultatively alkaliphilic, non motile, catalase- and oxidase-positive, endospore-forming, rod-shaped, aerobic bacterium, strain JSM 071004(T), was isolated from a sea anemone collected from Neizhou Bay in the South China Sea. Growth occurred with 0.5-10 % (w/v) total salts (optimum 2-4 %) and at pH 6.5-10.0 (optimum pH 8.5) and 4-30 degrees C (optimum 25 degrees C). meso-Diaminopimelic acid was present in the cell-wall peptidoglycan. The predominant respiratory quinone was menaquinone 7 (MK-7) and the polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The major cellular fatty acids were anteiso-C(15 : 0) and iso-C(15 : 0). The genomic DNA G+C content was 39.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain JSM 071004(T) belongs to the genus Bacillus, being related most closely to the type strain of Bacillus agaradhaerens (sequence similarity 97.3 %), followed by the type strains of Bacillus cellulosilyticus (96.2 %), Bacillus clarkii (96.1 %) and Bacillus polygoni (96.0 %). The combination of phylogenetic analysis, DNA-DNA hybridization, phenotypic characteristics and chemotaxonomic data support the proposal that strain JSM 071004(T) represents a novel species of the genus Bacillus, for which the name Bacillus neizhouensis sp. nov. is proposed, with JSM 071004(T) (=CCTCC AB 207161(T) =DSM 19794(T) =KCTC 13187(T)) as the type strain. PMID- 19643901 TI - Parasegetibacter luojiensis gen. nov., sp. nov., a member of the phylum Bacteroidetes isolated from a forest soil. AB - A novel golden-yellow-coloured strain, designated RHYL-37(T), was isolated from a soil sample from a forest of Euphrates poplar (Populus euphratica) in Xinjiang, China. The cells were strictly aerobic, Gram-staining-negative, heterotrophic, non-spore-forming rods that were motile by gliding. Growth occurred at 17-37 degrees C (optimum, 30 degrees C), at pH 5.0-9.0 (optimum, pH 7.0) and with 0-1 % NaCl (w/v; optimum, 0 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that the novel isolate formed a cluster with members of the genera Segetibacter, Terrimonas, Niastella, Niabella and Chitinophaga in the family 'Chitinophagaceae' in the phylum Bacteroidetes. Sequence similarities with the type strains of recognized species ranged from 90.6 to 94.0 %. The predominant isoprenoid quinone was MK-7 and the major cellular fatty acids were iso-C(15 : 0), iso-C(15 : 1), C(16 : 0) and iso-C(17 : 0) 3-OH. The DNA G+C content was 39.7 mol%. On the basis of the phylogenetic, physiological and chemotaxonomic data, strain RHYL-37(T) represents a novel genus and species in the family 'Chitinophagaceae', for which the name Parasegetibacter luojiensis gen. nov., sp. nov. is proposed. The type strain of Parasegetibacter luojiensis is RHYL-37(T) (=CCTCC AB 208240(T)=KCTC 22561(T)). PMID- 19643902 TI - Kosmotoga olearia gen. nov., sp. nov., a thermophilic, anaerobic heterotroph isolated from an oil production fluid. AB - A novel thermophilic, heterotrophic bacterium, strain TBF 19.5.1(T), was isolated from oil production fluid at the Troll B oil platform in the North Sea. Cells of strain TBF 19.5.1(T) were non-motile rods with a sheath-like structure, or toga. The strain was Gram-negative and grew at 20-80 degrees C (optimum 65 degrees C), pH 5.5-8.0 (optimum pH 6.8) and NaCl concentrations of 10-60 g l(-1) (optimum 25 30 g l(-1)). For a member of the order Thermotogales, the novel isolate is capable of unprecedented growth at low temperatures, with an optimal doubling time of 175 min (specific growth rate 0.24 h(-1)) and a final optical density of >1.4 when grown on pyruvate at 37 degrees C. Various carbohydrates, proteinaceous compounds and pyruvate served as growth substrates. Thiosulfate, but not elemental sulfur, enhanced growth of the isolate. Sulfate also enhanced growth, but sulfide was not produced. The strain grew in the presence of up to approximately 15 % oxygen, but only if cysteine was included in the medium. Growth of the isolate was inhibited by acetate, lactate and propionate, while butanol and malate prevented growth. The major fermentation products formed on maltose were hydrogen, carbon dioxide and acetic acid, with traces of ethanol and propionic acid. The G+C content of the genomic DNA was 42.5 mol%. Phylogenetic analyses of the 16S and 23S rRNA gene sequences as well as 29 protein-coding ORFs placed the strain within the bacterial order Thermotogales. Based on the phylogenetic analyses and the possession of a variety of physiological characteristics not previously found in any species of this order, it is proposed that the strain represents a novel species of a new genus within the family Thermotogaceae, order Thermotogales. The name Kosmotoga olearia gen. nov., sp. nov. is proposed. The type strain of Kosmotoga olearia is TBF 19.5.1(T) (=DSM 21960(T) =ATCC BAA-1733(T)). PMID- 19643903 TI - Marinobacterium maritimum sp. nov., a marine bacterium isolated from Arctic sediment. AB - A Gram-negative, aerobic, rod-shaped, motile, marine bacterium, strain AR11(T), was isolated from Arctic marine sediment. Strain AR11(T) grew with 0.5-7 % NaCl and at 7-37 degrees C and pH 5.5-9.0. It utilized propionate, 3-hydroxybenzoate, l-proline, acetate, d- and l-lactate, l-alanine, malate and phenylacetic acid. Alkaline phosphatase, esterase lipase (C8), leucine arylamidase and acid phosphatase activity tests were positive. Acid was produced from 5-ketogluconate and aesculin. Strain AR11(T) possessed C(16 : 0) (22.0 %), summed feature 4 (C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH; 28.1 %) and summed feature 7 (one or more of C(18 : 1)omega7c, omega9t and omega12t; 34.0 %) as the major cellular fatty acids. The major ubiquinone was Q-8. Comparative 16S rRNA gene sequence studies showed that strain AR11(T) belonged to the Gammaproteobacteria and was most closely related to Marinobacterium stanieri DSM 7027(T), Marinobacterium halophilum mano11(T) and Marinobacterium georgiense KW-40(T) (97.8, 97.0 and 96.7 % similarity, respectively). The G+C content of the genomic DNA of strain AR11(T) was 57.9 mol%. DNA-DNA relatedness data indicated that strain AR11(T) represented a distinct species that was separated from M. stanieri DSM 7027(T), M. halophilum KCTC 12240(T) and M. georgiense JCM 21667(T). On the basis of evidence from this polyphasic study, it is proposed that strain AR11(T) (=KCTC 22254(T)=JCM 15134(T)) represents the type strain of a novel species, Marinobacterium maritimum sp. nov. PMID- 19643904 TI - Chryseobacterium piscicola sp. nov., isolated from diseased salmonid fish. AB - Eight bacterial strains isolated from diseased rainbow trout (n=5) and Atlantic salmon (n=3) were characterized by phenotypic and molecular taxonomic methods. The isolates were negative for the Gram-reaction, non-motile, rod-shaped and catalase- and oxidase-positive. Colonies on solid media were yellow, smooth, shiny and circular with regular edges. Growth occurred at 4-28 degrees C (optimum, 15 degrees C) and with 0-3 % NaCl (optimum, 0.5 %). Analysis of the 16S rRNA gene sequence allocated the micro-organisms to the genus Chryseobacterium, with Chryseobacterium soldanellicola PSD1-4(T) and Chryseobacterium soli JS6-6(T) as their closest relatives (96.9 and 97.1 % sequence similarity, respectively). The levels of DNA-DNA hybridization towards these nearest phylogenetic neighbours were below 17.1 %. The DNA G+C contents of strains VQ-6316s(T) and VQ-4836s were 32.5 and 32.3 mol%, respectively. The predominant menaquinone was MK-6 and the major fatty acids were iso-C(15 : 0), anteiso-C(15 : 0), iso-C(17 : 1)omega9c, iso-C(17 : 0) 3-OH and summed feature 3 (comprising C(16 : 1)omega7c and/or C(16 : 1)omega7t and/or iso-C(15 : 0) 2-OH). The eight isolates were classified as representatives of a novel species, Chryseobacterium piscicola sp. nov., with strain VQ-6316s(T) (=CECT 7357(T)=DSM 21068(T)) as the type strain. PMID- 19643905 TI - Mesorhizobium shangrilense sp. nov., isolated from root nodules of Caragana species. AB - Five strains of bacteria isolated from nodules of Caragana bicolor and Caragana erinacea in Yunnan Province of China were classified within the genus Mesorhizobium in the class Alphaproteobacteria. The highest degree of 16S rRNA gene sequence similarity was determined to be to Mesorhizobium loti LMG 6125(T) (99.7 %) and Mesorhizobium ciceri UPM-Ca7(T) (99.7 %). Polyphasic taxonomic methods including SDS-PAGE of whole-cell soluble proteins, comparative housekeeping sequence analysis of atpD, glnII and recA, fatty acid profiles and a series of phenotypic and physiological tests allowed us to cluster the five strains into a coherent group while differentiating them from all previously established Mesorhizobium species. The DNA-DNA relatedness between the representative strain CCBAU 65327(T) and the type strains of M. loti and M. ciceri was 26.5 and 23.4 %, respectively, clearly indicating that strain CCBAU 65327(T) represents a novel species for which we propose the name Mesorhizobium shangrilense sp. nov. Strain CCBAU 65327(T) (=LMG 24762(T) =HAMBI 3050(T)) is designated as the type strain, and could nodulate Caragana microphylla, Caragana intermedia, Glycyrrhiza uralensis, Astragalus adsurgens, Vigna unguiculata, Vigna radiata and Phaseolus vulgaris in cross-nodulation tests. PMID- 19643906 TI - Rhizobium alkalisoli sp. nov., isolated from Caragana intermedia growing in saline-alkaline soils in the north of China. AB - Three rhizobial strains (CCBAU 01393(T), CCBAU 01389 and CCBAU 03239) isolated from nodules of Caragana intermedia grown in saline-alkaline soils in the north of China had identical 16S rRNA genes that showed 99.7 and 99.5 % sequence similarities with those of Rhizobium huautlense SO2(T) and Rhizobium galegae USDA 4128(T), respectively. Phylogenies of the housekeeping genes atpD, recA and glnII confirmed their distinct position, differing from recognized Rhizobium species. SDS-PAGE of whole-cell soluble proteins and a series of phenotypic and physiological tests allowed us to differentiate the novel group from all closely related recognized Rhizobium species. The levels of DNA-DNA relatedness between strain CCBAU 01393(T) and R. huautlense SO2(T) and R. galegae USDA 4128(T) were 34.9 and 20.5 %, respectively. Therefore, we propose that strains CCBAU 01393(T), CCBAU 01389 and CCBAU 03239 represent a novel species, Rhizobium alkalisoli sp. nov., with strain CCBAU 01393(T) (=LMG 24763(T)=HAMBI 3051(T)) as the type strain. This strain could form effective nodules on Caragana microphylla, Phaseolus vulgaris and Vigna radiata. PMID- 19643907 TI - Gilvimarinus chinensis gen. nov., sp. nov., an agar-digesting marine bacterium within the class Gammaproteobacteria isolated from coastal seawater in Qingdao, China. AB - A taxonomic study was performed on strain QM42(T), which was isolated from coastal seawater from an aquaculture site near Qingdao, China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain QM42(T) was a member of the class Gammaproteobacteria. Cells of strain QM42(T) were Gram-negative, yellow, aerobic and rod-shaped. The strain formed a distinct phyletic line with less than 91 % 16S rRNA gene sequence similarity to its closest relatives with validly published names within the class Gammaproteobacteria. The genomic DNA G+C content was 51.9 mol%. The major fatty acids were C(16 : 1)omega7c/iso-C(15 : 0) 2-OH, C(18 : 1)omega7c and C(16 : 0). Based on data from a polyphasic chemotaxonomic, physiological and biochemical study, strain QM42(T) is considered to represent a novel genus and species, for which the name Gilvimarinus chinensis gen. nov., sp. nov., is proposed. The type strain is QM42(T) (=CGMCC 1.7008(T)=DSM 19667(T)). PMID- 19643909 TI - Genetic differences in fruit-set patterns are determined by differences in fruit sink strength and a source : sink threshold for fruit set. AB - BACKGROUND AND AIMS: Fruit set in indeterminate plant species largely depends on the balance between source and sink strength. Plants of these species show fluctuations in fruit set during the growing season. It was tested whether differences in fruit sink strength among the cultivars explained the differences in fruit-set patterns. METHODS: Capsicum was chosen as a model plant. Six cultivars with differences in fruit set, fruit size and plant growth were evaluated in a greenhouse experiment. Fruit-set patterns, generative and vegetative sink strength, source strength and the source : sink ratio at fruit set were determined. Sink strength was quantified as potential growth rate. Fruit set was related to total fruit sink strength and the source : sink ratio. The effect of differences observed in above-mentioned parameters on fruit-set patterns was examined using a simple simulation model. KEY RESULTS: Sink strengths of individual fruits differed greatly among cultivars. Week-to-week fruit set in large-fruited cultivars fluctuated due to large fluctuations in total fruit sink strength, but in small-fruited cultivars, total fruit sink strength and fruit set were relatively constant. Large variations in week-to-week fruit set were correlated with a low fruit-set percentage. The source : sink threshold for fruit set was higher in large-fruited cultivars. Simulations showed that within the range of parameter values found in the experiment, fruit sink strength and source : sink threshold for fruit set had the largest impact on fruit set: an increase in these parameters decreased the average percentage fruit set and increased variation in weekly fruit set. Both were needed to explain the fruit-set patterns observed. The differences observed in the other parameters (e.g. source strength) had a lower effect on fruit set. CONCLUSIONS: Both individual fruit sink strength and the source : sink threshold for fruit set were needed to explain the differences observed between fruit-set patterns of the six cultivars. PMID- 19643908 TI - Relationships among plants, soils and microbial communities along a hydrological gradient in the New Jersey Pinelands, USA. AB - BACKGROUND AND AIMS: Understanding the role of different components of hydrology in structuring wetland communities is not well developed. A sequence of adjacent wetlands located on a catenary sequence of soils and receiving the same sources and qualities of water is used to examine specifically the role of water-table median position and variability in affecting plant and microbial community composition and soil properties. METHODS: Two replicates of three types of wetland found adjacent to each other along a hydrological gradient in the New Jersey Pinelands (USA) were studied. Plant-community and water-table data were obtained within a 100-m(2) plot in each community (pine swamp, maple swamp and Atlantic-white-cedar swamp). Monthly soil samples from each plot were analysed for soil moisture, organic matter, extractable nitrogen fractions, N mineralization rate and microbial community composition. Multivariate ordination methods were used to compare patterns among sites within and between data sets. KEY RESULTS: The maple and pine wetlands were more similar to each other in plant community composition, soil properties and microbial community composition than either was to the cedar swamps. However, maple and pine wetlands differed from each other in water-table descriptors as much as they differed from the cedar swamps. All microbial communities were dominated by Gram-positive bacteria despite hydrologic differences among the sites. Water-table variability was as important as water-table level in affecting microbial communities. CONCLUSIONS: Water tables affect wetland communities through both median level and variability. Differentiation of both plant and microbial communities are not simple transforms of differences in water-table position, even when other hydrologic factors are kept constant. Rather, soil genesis, a result of both water-table position and geologic history, appears to be the main factor affecting plant and microbial community similarities. PMID- 19643910 TI - Profound hypokalaemia mimicking acute myocardial infarction. PMID- 19643911 TI - Grave's disease and acquired hyposplenism. PMID- 19643912 TI - Aprataxin, poly-ADP ribose polymerase 1 (PARP-1) and apurinic endonuclease 1 (APE1) function together to protect the genome against oxidative damage. AB - Aprataxin, defective in the neurodegenerative disorder ataxia oculomotor apraxia type 1 (AOA1), is a DNA repair protein that processes the product of abortive ligations, 5' adenylated DNA. In addition to its interaction with the single strand break repair protein XRCC1, aprataxin also interacts with poly-ADP ribose polymerase 1 (PARP-1), a key player in the detection of DNA single-strand breaks. Here, we reveal reduced expression of PARP-1, apurinic endonuclease 1 (APE1) and OGG1 in AOA1 cells and demonstrate a requirement for PARP-1 in the recruitment of aprataxin to sites of DNA breaks. While inhibition of PARP activity did not affect aprataxin activity in vitro, it retarded its recruitment to sites of DNA damage in vivo. We also demonstrate the presence of elevated levels of oxidative DNA damage in AOA1 cells coupled with reduced base excision and gap filling repair efficiencies indicative of a synergy between aprataxin, PARP-1, APE-1 and OGG1 in the DNA damage response. These data support both direct and indirect modulating functions for aprataxin on base excision repair. PMID- 19643913 TI - The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver. AB - Genome-wide association studies have identified a number of signals for both Type 2 Diabetes and related quantitative traits. For the majority of loci, the transition from association signal to mutational mechanism has been difficult to establish. Glucokinase (GCK) regulates glucose storage and disposal in the liver where its activity is regulated by glucokinase regulatory protein (GKRP; gene name GCKR). Fructose-6 and fructose-1 phosphate (F6P and F1P) enhance or reduce GKRP-mediated inhibition, respectively. A common GCKR variant (P446L) is reproducibly associated with triglyceride and fasting plasma glucose levels in the general population. The aim of this study was to determine the mutational mechanism responsible for this genetic association. Recombinant human GCK and both human wild-type (WT) and P446L-GKRP proteins were generated. GCK kinetic activity was observed spectrophotometrically using an NADP(+)-coupled assay. WT and P446L-GKRP-mediated inhibition of GCK activity and subsequent regulation by phosphate esters were determined. Assays matched for GKRP activity demonstrated no difference in dose-dependent inhibition of GCK activity or F1P-mediated regulation. However, the response to physiologically relevant F6P levels was significantly attenuated with P446L-GKRP (n = 18; P 1 cartilage abnormality on CT were found to be reliable indicators of neoplastic cartilage invasion in patients with laryngeal carcinoma. PMID- 19643919 TI - Association of white matter hyperintensity measurements on brain MR imaging with cognitive status, medial temporal atrophy, and cardiovascular risk factors. AB - BACKGROUND AND PURPOSE: White matter hyperintensities (WMHs) are frequently characterized as markers of cerebrovascular disease, whereas medial temporal atrophy (MTA) is a recognized marker of Alzheimer disease (AD). Our purpose was to test the reliability of a visual rating system (VRS) in evaluating WMHs and MTA and in distinguishing healthy from cognitively impaired subjects. MATERIALS AND METHODS: Subjects (n = 192) enrolled in the Florida Alzheimer's Disease Research Center were diagnosed with no cognitive impairment, nonamnestic mild cognitive impairment (na-MCI), amnestic MCI (a-MCI), or probable AD. The severity of WMHs was assessed on T2-weighted fluid-attenuated inversion recovery axial MR images, and the severity of MTA was evaluated on 1.5-mm-thick coronal MR images by using a computer-based visual rating system. Cardiovascular risk factor scores were calculated as the sum of 10 independent cardiovascular risk factors. RESULTS: WMH and MTA scores were greater in subjects with probable AD, relative to those with no cognitive impairment and na-MCI. MTA scores differentiated subjects with a-MCI from those with no cognitive impairment and na-MCI. The total WMH score was significantly related to MTA (r = 0.39; P < .001) but not to cardiovascular risk factor scores (r = 0.07; P = not significant). The overall correct classification rate of probable AD versus no cognitive impairment by using MTA scores was 81.8%, improving to 86.5% when combined with WMH scores. CONCLUSIONS: Both MTA and WMH scores distinguished subjects with no cognitive impairment and probable AD. Combining MTA and WMH scores improved the correct classification rate, whereas WMH scores were significantly related to MTA scores, but not to cardiovascular risk factor scores. This finding suggests that among subjects with a-MCI and probable AD, WMHs on MR images are primarily associated with neurodegenerative disease. PMID- 19643921 TI - Is all "communicating" hydrocephalus really communicating? Prospective study on the value of 3D-constructive interference in steady state sequence at 3T. AB - BACKGROUND AND PURPOSE: 3D-constructive interference in steady state (3D-CISS) sequence has been used to assess the CSF pathways. The aim of this study was to investigate the additive value of 3D-CISS compared with conventional sequences in the diagnosis of obstructive membranes in hydrocephalus. MATERIALS AND METHODS: A total of 134 patients with hydrocephalus underwent MR imaging examination with a 3T unit consisting of turbo spin-echo, 3D-CISS, and cine phase-contrast (cine PC) sequences. 3D-CISS was used to assess obstructive membranes in CSF pathways compared with other sequences. Cine PC, follow-up imaging, and surgical findings were used to confirm obstructive membranes. RESULTS: Comparing the number of noncommunicating cases by using the conventional and 3D-CISS images, we found 26 new cases (19.4%) of 134 cases that were previously misdiagnosed as communicating hydrocephalus by conventional images. 3D-CISS sequence identified obstructive membranes invisible in other sequences, which facilitated selection of neuroendoscopy in the treatment of 31 patients (23.1%) in total who would have been otherwise treated with shunt insertion. These patients included 26 newly diagnosed noncommunicating cases after demonstration of intraventricular and/or fourth ventricular outlet membranes and 5 cases of communicating hydrocephalus with obstructing cisternal membranes. There were obstructions of the foramina of Luschka in 22 of 26 newly found noncommunicating cases. CONCLUSIONS: Conventional sequences are insensitive to obstructive membranes in CSF pathways, especially in the fourth ventricular exit foramina and the basal cisterns. 3D-CISS sequence, revealing these obstructive membranes, can alter patient treatment and prognosis. PMID- 19643922 TI - The anatomic variations of the circle of Willis in preterm-at-term and term-born infants: an MR angiography study at 3T. AB - BACKGROUND AND PURPOSE: It has been shown that the brain of a preterm infant develops differently from that of a term infant, but little is known about the neonatal cerebrovascular anatomy. Our aims were to establish reference data for the prevalence of the anatomic variations of the neonatal circle of Willis (CoW) and to explore the effect of prematurity, MR imaging abnormality, vascular related abnormality, laterality, and sex on these findings. MATERIALS AND METHODS: We scanned 103 infants with an optimized MR angiography (MRA) protocol. Images were analyzed for different variations of the CoW, and results were compared for the following: 1) preterm-at-term and term-born infants, 2) infants with normal and abnormal MR imaging, 3) infants with and without a vascular related abnormality, 4) boys and girls, and 5) left- and right-sided occurrence. RESULTS: The most common anatomic variation was absence/hypoplasia of the posterior communicating artery. Preterm infants at term had a higher prevalence of a complete CoW and a lower prevalence of anatomic variations compared with term-born infants; this finding was significant for the anterior cerebral artery (P = .02). There was increased prevalence of variations of the major cerebral arteries in those infants with vascular-related abnormalities, statistically significant for the posterior cerebral artery (P = .004). There was no statistically significant difference between boys and girls and left/right variations. CONCLUSIONS: Prematurity is associated with more complete CoWs and fewer anatomic variations. In vascular-related abnormalities, more variations involved major arterial segments, but fewer variations occurred in the communicating arteries. Overall reference values of the variations match those of the general adult population. PMID- 19643920 TI - Voxel-based analysis of T2 hyperintensities in white matter during treatment of childhood leukemia. AB - BACKGROUND AND PURPOSE: White matter (WM) hyperintensities on T2-weighted MR imaging are the most common imaging manifestation of neurotoxic effects of therapy for central nervous system (CNS) prophylaxis in childhood acute lymphoblastic leukemia (ALL). This study uses voxel-based analyses (VBA) of T2 weighted imaging of patients during treatment to identify which WM regions are preferentially damaged. MATERIALS AND METHODS: Two sets of conventional T2 weighted axial images were acquired on a 1.5T MR imaging scanner from 197 consecutive patients (85 female, 112 male; aged 1.0-18.9 years) enrolled on an institutional ALL treatment protocol. Images were acquired after completion of induction therapy and after the final of the 4 courses of intravenous high-dose methotrexate in consolidation therapy (3.9 +/- 0.8 months apart). Voxel-wise statistical testing of the incremental change between normalized longitudinal T2 images was performed with radiologist reading (normal or abnormal) and treatment risk-group as covariates. RESULTS: Two highly significant bilateral clusters of T2 signal intensity change were identified in both 1-group and 2-group analyses. The regions were symmetric in size, shape, and average signal intensity. Increased T2-weighted signal intensity from these regions both within and between examinations were nonlinear functions of age at examination, and the difference between the examinations was greater for older subjects who received more intense therapy. CONCLUSIONS: These analyses identified specific WM tracts involving predominantly the anterior, superior, and posterior corona radiata and superior longitudinal fasciculus, which were at increased risk for the development of T2 weighted hyperintensities during therapy for childhood ALL. These vulnerable regions may be the cause of subsequent cognitive difficulties consistently observed in survivors. PMID- 19643923 TI - CT angiography source images predict final infarct extent in patients with basilar artery occlusion. AB - BACKGROUND AND PURPOSE: The posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) is a 10-point grading system to quantify ischemic changes in the posterior circulation. We analyzed whether pc-ASPECTS on CT angiography (CTA) source images (CTASI) predicted the final infarct extent and hemorrhagic transformation (HT) rate in patients with basilar artery occlusion. MATERIALS AND METHODS: A pc-ASPECTS score of 10 indicates absence of visible ischemic changes in the posterior circulation, and pc-ASPECTS score of 0 indicates ischemic changes in the midbrain, pons, and bilateral thalami, posterior circulation territories, and cerebellar hemispheres. We retrospectively studied patients with basilar artery occlusion on CTA within 24 hours from symptom onset. We applied pc ASPECTS to noncontrast CT (NCCT), CTASI, and follow-up images by 3-reader consensus and assessed HT on follow-up images. We calculated Spearman correlation coefficients and performed linear regression analysis. Final infarct extent and HT rates were compared across dichotomized CTASI pc-ASPECTS groups (>/= 8 vs < 8). RESULTS: Among 43 patients, median (range) onset to CTA time was 5.0 hours (range, 0.7-24 hours). Pc-ASPECTS on CTASI (r = 0.75; P < .001) but not NCCT (r = 0.29; P = .063) correlated with pc-ASPECTS on follow-up scans. Linear regression demonstrated a significant positive relationship between pc-ASPECTS on CTASI and follow-up scans (R(2) = 0.58; P < 01). Median follow-up pc-ASPECTS was lower in patients with a CTASI pc-ASPECTS < 8 compared with patients with a CTASI pc ASPECTS of 8 or more, respectively (P < .001). HT rates were 27.3% vs 9.5%, respectively (P = .24). None of 8 patients without thrombolysis had HT on follow up scans. CONCLUSIONS: The extent of hypoattenuation on CTASI predicts the final infarct extent in patients with basilar artery occlusion. PMID- 19643924 TI - Subsequent fracture after percutaneous vertebroplasty can be predicted on preoperative multidetector row CT. AB - BACKGROUND AND PURPOSE: Subsequent fracture is often seen after percutaneous vertebroplasty. The purpose of this prospective study was to evaluate preoperative multidetector row CT (MDCT) for the prediction of subsequent fractures after vertebroplasty. MATERIALS AND METHODS: This study included 26 consecutive patients (18 women and 8 men) with osteoporotic compression fractures (58 vertebrae). A 64-section MDCT with multiplanar reformation was obtained 1 day before the procedure. Subsequent MR imaging was used to evaluate new fractures at least 3 months after treatment on a routine basis or if there was recurrent pain. We used logistic regression analysis with MDCT findings and clinical data for statistical evaluation according to the location of new fractures. RESULTS: Subsequent fractures were noted at 14 adjacent vertebrae (12.1%) in 13 patients and at 14 remote vertebrae in 6 patients (23.1%). Subsequent fractures in adjacent vertebrae tended to occur in small vertebrae before treatment (P < .05). Steroid medication and low CT value in nonfractured vertebrae were associated with subsequent fractures in remote vertebrae (P < .05). Further collapse of the treated vertebral bodies was noted in 10 patients (11 vertebrae [19.0%]) without specific findings (P > .05). CONCLUSIONS: The small size of the treated vertebrae may relate to subsequent fractures in adjacent vertebrae. Steroid use and low CT value of nonfractured vertebrae on preoperative MDCT can be associated with subsequent fractures in remote vertebrae. PMID- 19643925 TI - Smaller gray matter volumes in frontal and parietal cortices of solvent abusers correlate with cognitive deficits. AB - BACKGROUND AND PURPOSE: Abuse of toluene-containing organic solvents by inhalation is a prevalent practice among adolescents. Long-term abuse of toluene causes cognitive deficits. The mechanism of cognitive deficits induced by long term toluene abuse has not yet been defined. In the current study, we assessed the effects of chronic toluene abuse on cortical gray matter volume and the association between cognitive impairment and cortical gray matter volume distribution in chronic toluene abusers. MATERIALS AND METHODS: Fifteen toluene abusers and 20 healthy control subjects matched in sex, age, education level, and handedness were investigated by structural MR imaging. The cognitive states of the subjects were assessed by using the third edition of the Wechsler Intelligence Scale for Children (WISC-III). The voxel-based comparison and correlation analyses of MR images were performed by using SPM5 software. RESULTS: The voxel-based morphometric analysis revealed that toluene abusers had significantly lower gray matter volumes in the bilateral frontotemporal and right parietal cortices. In addition, the lower gray matter volumes in the frontal and parietal regions correlated with the duration of toluene abuse. There was a positive correlation between the WISC performance scale scores and gray matter volumes in the frontal and parietal cortices of the abusers. CONCLUSIONS: The results of the current study demonstrate that chronic toluene abusers have smaller gray matter volumes than nonabusers in various regions of the brain. Moreover, the cognitive deficits are associated with the lower gray matter volumes in the frontal and parietal cortices of chronic toluene abusers. PMID- 19643926 TI - Health-related quality of life in CKD Patients: correlates and evolution over time. AB - BACKGROUND AND OBJECTIVES: Very few large-scale studies have investigated the determinants of health-related quality of life (HRQOL) in chronic kidney disease (CKD) patients not on dialysis or the evolution of HRQOL over time. DESIGN AND SETTING: A prospective evaluation was undertaken of HRQOL in a cohort of 1186 CKD patients cared for in nephrology clinics in North America. Baseline and follow-up HRQOL were evaluated using the validated Kidney Disease Quality Of Life instrument. RESULTS: Baseline measures of HRQOL were reduced in CKD patients in proportion to the severity grade of CKD. Physical functioning score declined progressively with more advanced stages of CKD and so did the score for role physical. Female gender and the presence of diabetes and a history of cardiovascular co-morbidities were also associated with reduced HRQOL (physical composite score: male: 41.0 +/- 10.2; female: 37.7 +/- 10.8; P < 0.0001; diabetic: 37.3 +/- 10.6; nondiabetic: 41.6 +/- 10.2; P < 0.0001; history of congestive heart failure, yes: 35.4 +/- 9.7; no: 40.3 +/- 10.6; P < 0.0001; history of myocardial infarction, yes: 36.1 +/- 10.0; no: 40.2 +/- 10.6; P < 0.0001). Anemia and beta blocker usage were also associated with lower HRQOL scores. HRQOL measures declined over time in this population. The main correlates of change over time were age, albumin level and co-existent co-morbidities. CONCLUSIONS: These observations highlight the profound impact CKD has on HRQOL and suggest potential areas that can be targeted for therapeutic intervention. PMID- 19643928 TI - Plasma apelin levels in obstructive sleep apnea and the effect of continuous positive airway pressure therapy. AB - Apelin is a peptide hormone with cardiovascular and glucose homeostasis properties, and obstructive sleep apnea (OSA) is complicated by cardiovascular and metabolic comorbidities. Plasma apelin has not been previously assessed in OSA. We investigated the response of plasma apelin to a 2-h 75 g oral glucose tolerance test (OGTT) and the effect of 3 months compliant continuous positive airway pressure (CPAP) therapy in 15 obese males with newly diagnosed OSA. Plasma apelin and serum cortisol were recorded 10 minutely, while serum insulin and glucose were measured 30 minutely. Ten subjects had plasma apelin measured at intervals across a 24-h period to investigate for circadian variation in apelin levels, and this was repeated following 3 months compliant CPAP therapy. Fasting (0.342+/-0.038 vs 0.288+/-0.024 ng/ml, P=0.04), 30 min (0.399+/-0.035 vs 0.312+/ 0.036 ng/ml, P=0.007) and 120 min (0.402+/-0.030 vs 0.259+/-0.024 ng/ml, P<0.001) apelin levels were reduced following CPAP. The area under curve for apelin OGTT response was lower post-CPAP (44.1+/-3.3 vs 35.8+/-2.3 ng/ml per min, P<0.001). Mean OGTT apelin levels showed a significant treatment effect (P=0.006) and a time effect (P<0.001), and the effect of time was different pre- versus post-CPAP (P=0.005). No significant variability in apelin levels existed across the 24-h period at diagnosis. Lower levels were evident overnight following treatment (P=0.004). Improvements in insulin and glucose parameters and reduced cortisol levels were found post-CPAP. In summary, untreated OSA was associated with elevated plasma apelin levels, altered apelin secretory dynamics in response to oral glucose and lack of an apparent circadian variability, which was restored following CPAP. PMID- 19643927 TI - Interferon for hepatitis C virus in hemodialysis--an individual patient meta analysis of factors associated with sustained virological response. AB - BACKGROUND AND OBJECTIVES: Hepatitis C virus (HCV) infection is prevalent in hemodialysis patients and causes excess mortality. Interferon (IFN) treatment of chronic HCV infection in hemodialysis patients results in high sustained virological response (SVR) rates 6 mo after treatment. The authors aimed to identify factors associated with SVR in hemodialysis patients through analysis of individual patient data obtained from systematic review of published literature. DESIGN, SETTING, PARTICIPANTS & MEASUREMENTS: Medline was searched from 1966 through February 2009, and prospective studies describing IFN treatment of hemodialysis patients with chronic HCV infection with published individual patient data were included. To identify factors associated with SVR, logistic regression was applied with adjustment for study. RESULTS: Twenty studies of IFN treatment provided data on 428 patients. Overall SVR was 45% and in univariate analyses was higher with: 1) three million units or higher three times weekly of IFN; 2) treatment for at least 6 mo; 3) treatment completion; 4) lower baseline HCV RNA; 5) female gender; and 6) early virological negativity. Although limited by missing data, these relationships persisted in multivariate regression. CONCLUSIONS: SVR is more likely with larger IFN dose, longer treatment duration, treatment completion, female gender, lower HCV RNA and early virological negativity. For appropriate treatment candidates, regimens should consist of three million units of IFN three times weekly for at least 6 mo, with patients encouraged to complete the full course. PMID- 19643929 TI - Distinct roles for basal and induced COX-2 in podocyte injury. AB - Transgenic mice that overexpress cyclooxygenase-2 (COX-2) selectively in podocytes are more susceptible to glomerular injury by adriamycin and puromycin (PAN). To investigate the potential roles of COX-2 metabolites, we studied mice with selective deletion of prostanoid receptors and generated conditionally immortalized podocyte lines from mice with either COX-2 deletion or overexpression. Podocytes that overexpressed COX-2 were virtually indistinguishable from wild-type podocytes but were significantly more sensitive to PAN-induced injury, produced more prostaglandin E(2) and thromboxane B(2), and had greater expression of prostaglandin E(2) receptor subtype 4 (EP(4)) and thromboxane receptor (TP). Treatment of COX-2-overexpressing podocytes with a TP antagonist reduced apoptosis, but treatment with an EP(4) antagonist did not. In contrast, podocytes from COX-2-knockout mice exhibited increased apoptosis, markedly decreased cell adhesion, and prominent stress fibers. In vivo, selective deletion of podocyte EP(4) did not alter the increased sensitivity to adriamycin induced injury observed in mice overexpressing podocyte COX-2. In contrast, genetic deletion of TP in these mice prevented adriamycin-induced injury, with attenuated albuminuria and foot process effacement. These results suggest that basal COX-2 may be important for podocyte survival, but overexpression of podocyte COX-2 increases susceptibility to podocyte injury, which is mediated, in part, by activation of the thromboxane receptor. PMID- 19643930 TI - Urinary peptidome may predict renal function decline in type 1 diabetes and microalbuminuria. AB - One third of patients with type 1 diabetes and microalbuminuria experience an early, progressive decline in renal function that leads to advanced stages of chronic kidney disease and ESRD. We hypothesized that the urinary proteome may distinguish between stable renal function and early renal function decline among patients with type 1 diabetes and microalbuminuria. We followed patients with normal renal function and microalbuminuria for 10 to 12 yr and classified them into case patients (n = 21) with progressive early renal function decline and control subjects (n = 40) with stable renal function. Using liquid chromatography matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, we identified three peptides that decreased in the urine of patients with early renal function decline [fragments of alpha1(IV) and alpha1(V) collagens and tenascin-X] and three peptides that increased (fragments of inositol pentakisphosphate 2-kinase, zona occludens 3, and FAT tumor suppressor 2). In renal biopsies from patients with early nephropathy from type 1 diabetes, we observed increased expression of inositol pentakisphosphate 2-kinase, which was present in granule-like cytoplasmic structures, and zona occludens 3. These results indicate that urinary peptide fragments reflect changes in expression of intact protein in the kidney, suggesting new potential mediators of diabetic nephropathy and candidate biomarkers for progressive renal function decline. PMID- 19643931 TI - The orphan nuclear receptor SHP attenuates renal fibrosis. AB - The accumulation of extracellular matrix proteins is a common feature of fibrotic kidney diseases. Accumulating evidence suggests that TGF-beta and plasminogen activator inhibitor type 1 (PAI-1) promote the development of renal fibrosis by stimulating the generation and inhibiting the removal of matrix proteins. The small heterodimer partner (SHP) represses PAI-1 expression in the liver by inhibiting TGF-beta signaling, but whether SHP inhibits renal fibrosis is unknown. Here, unilateral ureteral obstruction (UUO) markedly increased the expression of PAI-1, type I collagen, and fibronectin but decreased SHP gene expression. Moreover, in kidneys of SHP-/- mice, the expression of PAI-1, type I collagen, fibronectin and alpha-smooth muscle actin (alpha-SMA) were higher compared with those in kidneys of wild-type mice. In addition, loss of SHP accelerated renal fibrosis after UUO. Adenovirus-mediated overexpression of SHP in cultured rat mesangial cells and renal tubular epithelial cells inhibited TGF beta-stimulated expression of PAI-1, type I collagen, and fibronectin. SHP inhibited TGF-beta- and Smad3-stimulated PAI-1 promoter activities as well as TGF beta-stimulated binding of Smad3 to its consensus response element on the PAI-1 promoter. Similarly, in vivo, adenovirus-mediated overexpression of SHP in the kidney inhibited the expression of UUO-induced PAI-1, type I collagen, fibronectin, and alpha-SMA. In summary, SHP attenuates renal fibrosis in obstructive nephropathy, making its pathway a possible therapeutic target for chronic kidney disease. PMID- 19643933 TI - Helicobacter pylori oipA, vacA and dupA genetic diversity in individual hosts. AB - Helicobacter pylori putative virulence factors can undergo a continuously evolving mechanism as an approach to bacterial adaptation to the host changing environment during chronic infection. oipA, vacA and dupA genetic diversity among isolates from multiple biopsies (niches) from the antrum and corpus of 40 patients was investigated. A set of 229 isolates was examined. Direct DNA sequence analysis of amplified fragments was used to study oipA 'on/off' expression status as well as the presence of C or T insertion in jhp0917 that originates a continuous (jhp0917-jhp0918) dupA gene. vacA alleles were identified by multiplex PCR. Different inter-niches oipA CT repeat patterns were observed in nine patients; in six of these, 'on' and 'off' mixed patterns were found. In three of these nine patients, different vacA alleles were also observed in a single host. Inter-niche dupA differences involved the absence and presence of jhp0917 and/or jhp0918 or mutations in dupA, including those that may originate a non-functional gene, and they were also present in two patients with mixed oipA CT patterns and in another seven patients. Evidence of mixed infection was observed in two patients only. In conclusion, oipA and dupA genes showed similar inter-niche variability, occurring in approximately 1/4 patients. Conversely, vacA allele microevolution seemed to be a less common event, occurring in approximately 1/10 patients, probably due to the mechanism that this gene evolves 'in vivo'. PMID- 19643934 TI - Role of biofilm formation in the persistent colonization of Haemophilus influenzae in children from northern India. AB - The human nasopharynx is a major ecological niche for Haemophilus influenzae colonization. Establishment of infection is critically dependent on the persistence of bacteria in the nasopharynx. Various factors are presumed to mediate this persistence and the influence of biofilm formation has been under scrutiny for a long time. In a prospective population-based study, the nasopharyngeal colonization pattern of 250 children <2 years old was traced to gain further insights into the phenomenon. The association between biofilm formation and persistence was delineated by quantitative biofilm assay, while the true nature of biofilm formers was further evaluated by electron microscopy studies. H. influenzae isolates obtained in this study, when analysed by phenotypic and genotypic means, revealed a clonal distribution of strains within the population. The biofilm formation ability of the isolates was found to be significantly associated with bacterial persistence (P<0.001). The isolates having biofilm formation ability were found to be 7.1 times more likely to persist in the nasopharynx than non-biofilm formers. This study provides direct evidence indicating the intricate relationship between biofilm formation and the persistence of bacteria. Our results emphasize the need to evaluate the potential for biofilm formation before designing preventive and therapeutic strategies. PMID- 19643932 TI - Considerations in the statistical analysis of hemodialysis patient survival. AB - The association of hemodialysis dosage with patient survival is controversial. Here, we tested the hypothesis that methods for survival analysis may influence conclusions regarding dialysis dosage and mortality. We analyzed all-cause mortality by proportional hazards and accelerated failure time regression models in a cohort of incident hemodialysis patients who were followed for 9 yr. Both models identified age, race, heart failure, physical functioning, and comorbidity scores as important predictors of patient survival. Using proportional hazards, there was no statistically significant association between mortality and Kt/V (hazard ratio 0.72; 95% confidence interval 0.45 to 1.14). In contrast, using accelerated failure time models, each 0.1-U increment of Kt/V improved adjusted median patient survival by 3.50% (95% confidence interval 0.20 to 7.08%). Proportional hazard models also yielded less accurate estimates for median survival. These findings are consistent with an additive damage model for the survival of patients who are on hemodialysis. In this conceptual model, the assumptions of the proportional hazard model are violated, leading to underestimation of the importance of dialysis dosage. These results suggest that future studies of dialysis adequacy should consider this additive damage model when selecting methods for survival analysis. Accelerated failure time models may be useful adjuncts to the Cox model when studying outcomes of dialysis patients. PMID- 19643935 TI - Changes in the prevalence of asthma in adults since 1966: the Busselton health study. AB - Asthma prevalence has increased worldwide; although less so in developed countries recently. This study assessed changes in the prevalence of asthma and related symptoms in the Busselton community since 1966. Cross-sectional respiratory health surveys of Busselton adults were conducted in 1966, 1969, 1972, 1975, 1981, 1990 and 2005-2007. Logistic regression models were used to estimate prevalence rates of asthma, respiratory symptoms, smoking, airway hyperresponsiveness (AHR) and atopy and to make comparisons in 2005-2007 and previous survey years. Asthma was defined as ever having doctor-diagnosed asthma (DDA). The prevalence of DDA was around 6% from 1966 to 1975, 8% in 1981 and rose to 19% in 2005-2007. From 1981 to 2005-2007, smoking prevalence declined and obesity and atopy increased but changes in these variables explained only a small part of the increase in DDA. Wheeze and cough/phlegm increased but AHR, breathlessness and doctor-diagnosed bronchitis remained relatively stable over the same period. These observations indicate that the increase in DDA is partly explained by increased symptoms and atopy. The lack of changes in AHR and doctor diagnosed bronchitis suggests that factors such as diagnostic transfer and increased awareness of asthma have also contributed to the rise in prevalence of DDA. PMID- 19643936 TI - Inspiratory muscle dysfunction in patients with severe obstructive sleep apnoea. AB - Repetitive inspiratory effort against an obstructed airway and intermittent hypoxia may be deleterious to the inspiratory muscles in patients with obstructive sleep apnoea (OSA). We investigated muscular dysfunction by comparing the strength, endurance and fatigability of inspiratory muscles and knee extensors in patients with newly diagnosed severe OSA compared with matched controls. The measurements included strength and endurance tests of both muscles, and a fatigue trial with simultaneous surface electromyography of the diaphragm and the vastus lateralis during voluntary contractions and in response to magnetic stimulation. To our knowledge, this is the first investigation to assess peripheral muscle performance in severe OSA patients versus controls. Patients in the OSA group exhibited significantly lower strength and endurance in both muscles than the control group. The fatigue index decreased significantly exclusively in the inspiratory muscles of OSA patients. Magnetic stimulation evoked compound muscle action potential latencies increased and the amplitudes decreased significantly in the diaphragm, but not in the vastus lateralis after a fatigue test in the OSA group. In conclusion, a significantly lower functional performance was shown for both inspiratory muscles and knee extensors in the OSA group. However, higher fatigability was only seen in the inspiratory muscles of patients with severe OSA. PMID- 19643937 TI - A randomised trial of home energy efficiency improvement in the homes of elderly COPD patients. AB - A randomised trial of 178 patients in Aberdeen, UK with a previous hospital admission for chronic obstructive pulmonary disease (COPD) was carried out in order to determine whether improving home energy efficiency improves health related quality of life in COPD patients. 118 patients were randomised and 60 agreed to monitoring only. Energy efficiency upgrading was carried out in 42% of homes randomised to intervention. Independent energy efficiency action was taken by 15% of control participants and 18% in the monitoring group. The main outcome measures were respiratory and general health status, home energy efficiency and hospital admissions. Intention-to-treat analysis found no difference in outcomes between the two groups. In 45 patients, who had energy efficiency action independent of original randomisation, there were significant improvements in respiratory symptom scores (adjusted mean 9.0, 95% CI 2.5-15.5), decreases in estimated annual fuel costs (- pound65.3, 95% CI - pound31.9- - pound98.7) and improved home energy efficiency rating (1.1, 95% CI 0-1.4). COPD patients are unlikely to take up home energy efficiency upgrading, if offered. Secondary "pragmatic" analysis suggests that those who do take action may achieve clinically significant improvement in respiratory health, which is not associated with an increase in indoor warmth. PMID- 19643938 TI - Toll-like receptor 7 function is reduced in adolescents with asthma. AB - Anti-viral innate immune responses may be impaired in asthma, although the mechanisms are not well understood. Toll-like receptors (TLRs) 7 and 3 are particularly relevant for initiating responses to common respiratory viruses, as they recognise single-stranded viral RNA and double-stranded viral RNA, respectively. The aim of the present study was to investigate TLR7 and TLR3 function in 14-yr-old adolescents with asthma. Blood mononuclear cells obtained from 17 atopic asthmatics, 29 atopic, non-asthmatics and 21 healthy, non-atopic individuals, were stimulated with the TLR7 agonist imiquimod and the TLR3 agonist poly I:C. Expression of anti-viral molecules was measured by real-time PCR. Concentrations of interferon-gamma-inducible cytokine protein (IP)-10 and interleukin (IL)-6 were measured by ELISA. TLR7-induced myxovirus resistance protein A and 2'5' oligoadenylate synthetase mRNA expression and protein levels of IP-10 were significantly lower in asthma subjects compared with healthy subjects (p = 0.041, p = 0.003 and p = 0.001 respectively). There was a significant negative correlation between total serum immunoglobulin E and IP-10 following TLR7 stimulation. However, TLR3-induced responses did not vary with asthma or atopy. IL-10 mRNA and IL-6 protein synthesis were similar in asthmatic and control subjects. In conclusion, TLR7 function is reduced in adolescents with asthma and this may contribute to susceptibility to respiratory viral infections. PMID- 19643939 TI - Variability and effects of bronchial colonisation in patients with moderate COPD. AB - Sputum and lung function were periodically assessed in stable moderate chronic obstructive pulmonary disease (COPD) outpatients to determine relationships between bronchial colonisation and inflammation. Relationships between potentially pathogenic microorganism (PPM) typology, bronchial inflammation (neutrophilia, tumour necrosis factor-alpha, interleukin (IL)-1beta, IL-6, IL-8, IL-10 and IL-12) and post-bronchodilator decline in forced expiratory volume in 1 s (FEV(1)) were analysed. PPMs periodically showing the same molecular profile using pulse field gel electrophoresis were considered long-term persistent. Bronchial colonisation was observed in 56 out of 79 follow-up examinations (70.9%) and was mainly due to Haemophilus influenzae, Pseudomonas aeruginosa and enterobacteria (n = 47). These PPMs were all related to sputum neutrophilia (p< or =0.05, Chi-squared test), and H. influenzae was related to higher levels of IL 1beta (p = 0.005) and IL-12 (p = 0.01), with a dose-response relationship (Spearman's correlation coefficient of 0.38 for IL-1beta (p = 0.001), and of 0.32 for IL-12 (p = 0.006)). Haemophilus parainfluenzae was not associated with an identifiable inflammatory response. Long-term persistence of the same strain was observed in 12 examinations (21.4%), mainly due to P. aeruginosa or enterobacteria. A neutrophilic bronchial inflammatory response was associated with a statistically significant decline in FEV(1) during follow-up (OR 2.67, 95% CI 1.07-6.62). A load-related relationship to bronchial inflammation in moderate COPD was observed for colonisation by H. influenzae, but not for colonisation by H. parainfluenzae. PMID- 19643940 TI - Single nucleotide polymorphisms in matrix metalloproteinase genes and lung cancer chemotherapy response and prognosis. AB - The prognosis for lung cancer patients treated with chemotherapy is poor. Single nucleotide polymorphisms (SNPs) in matrix metalloproteinase (MMP) genes could influence treatment outcome by altering apoptotic pathways. Eight SNPs with known or suspected phenotypic effect in six genes (MMP1, MMP2, MMP3, MMP7, MMP9 and MMP12) were investigated. For 349 Caucasian patients with primary lung cancer, receiving first-line chemotherapy, three different endpoints were analysed: response after the second cycle, progression free survival (PFS) and overall survival (OS). The prognostic value of the SNPs was analysed using multiple logistic regression for all patients and histology-, stage- and treatment specific subgroups. Hazard ratio estimates for PFS and OS were calculated using Cox regression methods. None of the investigated polymorphisms modified response significantly in the whole patient population. However, tumour stage IIIB variant allele carriers of MMP2 C-735T showed a significantly worse response. PFS was significantly prolonged in MMP1 G-1607GG variant allele carriers and OS in small cell lung cancer patients carrying the MMP12 A-82G variant allele. In conclusion, this study identified SNPs in MMP1, MMP2, MMP7 and MMP12 for further investigation as possible predictors of chemotherapy outcome in lung cancer patients. PMID- 19643941 TI - Rapid reduction in hospitalisations after an intervention to manage severe asthma. AB - Asthma is the third cause of hospitalisations due to clinical illnesses in Brazil. The Programme for Control of Asthma in Bahia (ProAR) leads an initiative in Salvador City (Brazil) to manage severe asthma for free. The aim of this study was to identify trends in asthma hospitalisation in the entire city and to evaluate the impact of ProAR. Information on asthma hospitalisations from 1998 to 2006 was collected. We analysed trends in Salvador (2.8 million inhabitants) before and after ProAR, taking pneumonia and myocardial infarction into account for local comparison. As an external control we obtained information on asthma from Recife, which is the most comparable Brazilian city. In Salvador, asthma hospital admissions declined by 82.3% (1998-2006). A greater proportion of this reduction (74%) occurred after 2003, in parallel with the implementation of ProAR. The reduction in asthma admissions in Recife was smaller. The rates of hospitalisation in 2006 were 2.25 per 10,000 inhabitants in Salvador and 17.06 in Recife. In Salvador, we found an inverse correlation between the provision of medication for asthma and hospitalisation (-0.801; p<0.0001). A rapid reduction in asthma admissions in the entire city of Salvador was associated with ProAR, a public health intervention targeting severe asthma. PMID- 19643942 TI - Systemic inflammatory markers in COPD: results from the Bergen COPD Cohort Study. AB - Chronic obstructive pulmonary disease (COPD) is considered an inflammatory pulmonary disorder with systemic inflammatory manifestations. The aim of this study was to assess the systemic levels of six inflammatory mediators in a large cohort of COPD patients and controls. 409 COPD patients and 231 healthy subjects, aged 40-75 yrs, were included from the first phase of the Bergen COPD Cohort Study. All COPD patients were clinically diagnosed by a physician, and had a forced expiratory volume in 1 s/forced vital capacity ratio less than 0.7 and a smoking history of >10 pack-yrs. The plasma levels of C-reactive protein (CRP), soluble tumour necrosis factor receptor (sTNFR)-1, osteoprotegrin, neutrophil activating peptide-2, CXCL16 and monocyte chemoattractant protein-4 were determined by ELISA. After adjustment for all known confounders, COPD patients had significantly lower levels of osteoprotegrin than subjects without COPD (p<0.05), and higher levels of CRP (p<0.01). Among COPD patients, CRP was elevated in patients with frequent exacerbations (p<0.05). sTNFR-1 and osteoprotegrin were both related to Global Initiative for Chronic Obstructive Lung Disease stage and frequency of exacerbations in the last 12 months (p<0.05). In addition, sTNFR-1 was significantly associated with important comorbidities such as hypertension and depression (p<0.05). The present study confirms that certain circulating inflammatory mediators are an important phenotypic feature of COPD. PMID- 19643943 TI - Disproportionate elevation of N-terminal pro-brain natriuretic peptide in scleroderma-related pulmonary hypertension. AB - N-terminal pro-brain natriuretic peptide (NT-proBNP) is a marker of neurohormonal activation that is useful in the diagnosis and prognosis of various forms of pulmonary arterial hypertension (PAH). We sought to characterise and compare NT proBNP in a cohort of PAH related to systemic sclerosis (PAH-SSc) and idiopathic PAH (IPAH) patients. NT-proBNP levels, collected from PAH-SSc and IPAH patients followed prospectively, were compared and correlated with haemodynamic variables. Cox proportional hazard models were created to assess the predictive value of NT proBNP. 98 patients (55 PAH-SSc, 43 IPAH) were included. Haemodynamics were similar, except for lower mean pulmonary arterial pressure in PAH-SSc. NT-proBNP levels were significantly higher in PAH-SSc (3,419+/-3,784 versus 1,393+/-1,633 pg x mL(-1); p<0.01) and were more closely related to haemodynamics in PAH-SSc than IPAH. 28 patients died. NT-proBNP predicted survival (hazard ratio (HR) 3.18; p<0.01) in the overall cohort; however, when stratified by group, predicted survival only in PAH-SSc (HR 3.07, p<0.01 versus 2.02, p = 0.29 in IPAH). This is the first description showing NT-proBNP levels are 1) significantly higher in PAH SSc than IPAH despite less severe haemodynamic perturbations, and 2) stronger predictors of survival in PAH-SSc, suggesting that neurohormonal regulation may differ between PAH-SSc and IPAH. Future studies to define pertinent mechanisms are warranted. PMID- 19643944 TI - Maintaining benefits following pulmonary rehabilitation: a randomised controlled trial. AB - The aim of this study was to determine if weekly, supervised, outpatient-based exercise plus unsupervised home exercise following an 8-week pulmonary rehabilitation programme would maintain functional exercise capacity and quality of life at 12 months better than standard care of unsupervised home exercise training. Chronic obstructive pulmonary disease (COPD) subjects completed an 8 week pulmonary rehabilitation programme, were randomised to an intervention group (IG) of weekly, supervised, exercise plus home exercise or to a control group (CG) of unsupervised home exercise and followed for 12 months. Outcome measurements at baseline (after pulmonary rehabilitation), and 3, 6 and 12 months included the 6-min walk test and St George's Respiratory Questionnaire (SGRQ). 59 subjects with moderate COPD (Global Initiative for Chronic Obstructive Lung Disease stage II) were recruited and 48 subjects completed the study. 12-month mean difference showed no significant change from baseline in 6-min walk distance (IG -11 m, 95% CI -21-10 m; CG -6 m, 95% CI -34-11 m) or total SGRQ score (IG 3, 95% CI -0.8-7; CG -3, 95% CI -7-3). 12 months following pulmonary rehabilitation both weekly, supervised, outpatient-based exercise plus unsupervised home exercise and standard care of unsupervised home exercise successfully maintained 6-min walk distance and quality of life in subjects with moderate COPD. PMID- 19643945 TI - Analysis of home support and ventilator malfunction in 1,211 ventilator-dependent patients. AB - Risk management is an important aspect of home ventilation (HV). We examined the nature of calls to a home support helpline to identify patient/equipment problems and strategies to minimise risk for patients, healthcare teams and manufacturers. From 1,211 adult and paediatric patients with neuromuscular disease, chronic obstructive pulmonary disease or chest wall disease receiving HV, all calls to a dedicated respiratory support telephone hotline between January 1, 2006 and June 30, 2006 were analysed. 1,199 patients received noninvasive ventilation, 12 tracheostomy ventilation; 149 had two ventilators for 24-h ventilator dependency. There was a mean of 528 daytime calls per month and 14 calls a month at night. Following 188 calls, a home visit was performed; these identified a technical problem that could either be solved in the patient's home in 64% or required replacement or new parts in 22% of cases. In 25 calls in which no mechanical fault was identified, 13 patients were either found to be unwell or required hospital admission. Patients using HV have a substantial requirement for assistance, with most technical problems being resolved simply. Where no fault can be found during an equipment check, the patient themselves may be unwell and should receive early clinical evaluation. The patient may have mistaken clinical deterioration for an equipment problem. PMID- 19643946 TI - Long-term effects of a partially supervised conditioning programme in cystic fibrosis. AB - Little is known about the long-term persistence of positive effects induced by a physical conditioning programme in cystic fibrosis. Therefore, this study determined the effects of a 6-month conditioning programme on peak oxygen uptake (primary outcome) and other markers of fitness, physical activity, anthropometry, lung function and quality of life (secondary outcomes), 18 and 24 months after the programme was initiated. Patients with cystic fibrosis aged 12-40 yrs were randomly assigned to an intervention (n = 23) and a control (n = 15) group. The intervention group consented to add 3 h of sports per week for > or =6 months to their previous activities. Controls were asked to maintain their level of activity for 12 months. Patients were seen at baseline and after 3, 6, 12, 18 and 24 months. There was no significant difference between groups at baseline. The intervention induced positive effects on peak oxygen uptake (difference in changes from baseline to the 18- and 24-month assessments between groups: 3.72+/ 1.23 mL.min(-1).kg(-1); p<0.01), maximal workload (0.37+/-0.11 W.kg(-1); p<0.01), vigorous physical activity (1.63+/-0.82 h.week(-1); p<0.05), forced vital capacity (6.06+/-2.87% predicted; p<0.05) and perceived health (9.89+/-4.72; p<0.05). A home-based partially supervised physical conditioning programme can improve physical fitness, lung function and perceived health long after the intervention has ended. PMID- 19643947 TI - SCH527123, a novel CXCR2 antagonist, inhibits ozone-induced neutrophilia in healthy subjects. AB - SCH527123 is a novel, selective CXC chemokine receptor 2 antagonist that inhibits neutrophil activation and modulates neutrophil trafficking in animal models, characteristics that may be beneficial in the treatment of conditions with unbalanced pulmonary neutrophilia, such as chronic obstructive pulmonary disease. The purpose of this proof-of-principle study was to determine whether SCH527123 inhibits ozone-induced neutrophil recruitment in healthy humans. In a randomised, double-blind, placebo-controlled, three-way crossover study, oral SCH527123 (50 mg once daily, 4 days), prednisolone (50 mg once), or placebo was alternated with 2-week washouts. 18 healthy ozone responders (>20% increase in sputum neutrophils) underwent ozone challenge tests (250 ppb, 3 h intermittent exercise) 1 h after the last treatment dose. Sputum was induced at 3 h post-challenge. After SCH527123 treatment, the ozone challenge resulted in significantly lower sputum neutrophil counts (0.13x10(6).mL(-1)) compared with prednisolone (0.84x10(6).mL(-1); p<0.001) or placebo (2.98x10(6).mL(-1); p<0.001). Comparable results were obtained for total cell count, percentage of sputum neutrophils, and for interleukin-8 and myeloperoxidase in sputum supernatant. Post-challenge, SCH527123 inhibited neutrophilia in peripheral blood but significantly less than in sputum. All treatments were safe and well tolerated. SCH527123 causes significant attenuation of ozone-induced airway neutrophilia in healthy subjects. Further evaluation in a large trial of patients with pulmonary disorders is warranted. PMID- 19643948 TI - Pulmonary hypertension in patients with combined pulmonary fibrosis and emphysema syndrome. AB - This study aims to describe the haemodynamic and survival characteristics of patients with pulmonary hypertension in the recently individualised syndrome of combined pulmonary fibrosis and emphysema. A retrospective multicentre study was conducted in 40 patients (38 males; age 68+/-9 yrs; 39 smokers) with combined pulmonary fibrosis and emphysema, and pulmonary hypertension at right heart catheterisation. Dyspnoea was functional class II in 15%, III in 55% and IV in 30%. 6-min walk distance was 244+/-126 m. Forced vital capacity was 86+/-18%, forced expiratory volume in 1 s 78+/-19%, and carbon monoxide diffusion transfer coefficient 28+/-16% of predicted. Room air arterial oxygen tension was 7.5+/-1.6 kPa (56+/-12 mmHg). Mean pulmonary artery pressure was 40+/-9 mmHg, cardiac index 2.5+/-0.7 L x min(-1) x m(-2) and pulmonary vascular resistance 521+/-205 dyn x s x cm(-5). 1-yr survival was 60%. Higher pulmonary vascular resistance, higher heart rate, lower cardiac index and lower carbon monoxide diffusion transfer were associated with shorter survival. Patients with combined pulmonary fibrosis and emphysema syndrome and pulmonary hypertension confirmed by right heart catheterisation have a dismal prognosis despite moderately altered lung volumes and flows and moderately severe haemodynamic parameters. PMID- 19643949 TI - Endobronchial ultrasound-guided transbronchial needle aspiration for identifying EGFR mutations. AB - The presence of somatic mutations of the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) gene in patients with advanced nonsmall cell lung cancer (NSCLC) correlates with a good response to tyrosine kinase inhibitors. The usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for the detection of EGFR mutations in cells recovered from malignant mediastinal nodes in patients with NSCLC was assessed. All patients with lung adenocarcinoma or unspecified NSCLC referred for staging with EBUS-TBNA were included. Nodes with a short-axis diameter of >5 mm were sampled, and genomic DNA from metastatic tumour cells was obtained for analysis of exons 19 and 21. The impact of sampling on management was assessed. EGFR gene analysis of the EBUS TBNA sample was feasible in 26 (72.2%) out of the 36 patients with lymph node metastasis. Somatic mutations of the EGFR gene were detected in tissue obtained through EBUS-TBNA in two (10%) out of 20 patients with metastasic lung adenocarcinoma. Malignant tissue samples obtained by EBUS-TBNA from patients with nodal metastasis of NSCLC are suitable for the detection of EGFR mutations in most cases, and this technique demonstrates mutated neoplastic cells in a tenth of patients with adenocarcinoma. PMID- 19643950 TI - Barriers to achieving care at home at the end of life: transferring patients between care settings using patient transport services. AB - Enabling patients to be cared for in their preferred location often involves journeys between care settings. The challenge of ensuring journeys are timely and safe emerged as an important issue in an evaluation of palliative care services, which informed a service redesign programme in three areas of the United Kingdom by the Marie Curie Cancer Care 'Delivering Choice Programme'. This article explores perceptions of service users and key stakeholders of palliative care services about problems encountered in journeys between care settings during end of-life care. This article draws on data from interviews with stakeholders (n = 44), patients (n = 16), carers (n = 19) and bereaved carers (n = 20); and focus groups (n = 9) with specialist nurses. Data were gathered in three areas of the United Kingdom. Data were analysed using a framework approach. Transport problems between care settings emerged as a key theme. Four particular problems were identified: (1) urgent need for transport due to patients' rapidly changing condition; (2) limited time to organise transfers; (3) the management of specialist equipment and (4) the need to clarify the resuscitation status of patients. Partnership working between Ambulance Services and secondary care is required to develop joint protocols of care to ensure timely and safe transportation between care settings of patients, who are near their end of life. Commissioning of services should be responsive to the complexities of patients' needs and those of their families. PMID- 19643951 TI - Reliability and validity of Japanese version of the McGill Quality of Life Questionnaire assessed by application in palliative care wards. AB - The McGill Quality of Life Questionnaire (MQOL), which consists of 16 items constructing physical, psychological, existential and support subscales and one item of overall quality of life (QOL), has been developed to assess QOL of terminal cancer patients. To examine if MQOL Japanese version (MQOL-J) is applicable, it was administered to 83 terminal cancer patients in palliative care wards several days after admission and then 7 to 10 days after the first interview. Cronbach's alpha coefficient for four subscales was 0.584-0.860. Sixteen items were classified into four factors by factor analysis, similar to the original English version. The results indicated that psychological and existential domains of the MQOL-J significantly related to overall QOL. Existential and support domains as well as overall QOL were significantly improved between the first and second interviews, although performance status assessed by Eastern Cooperative Oncology Group worsened. It is suggested that MQOL-J can reflect perceived health status of terminal cancer patients. PMID- 19643952 TI - Reporting end-of-life practice: can we trust doctors to be honest? PMID- 19643953 TI - Interstitial cells of Cajal generate spontaneous transient depolarizations in the rat gastric fundus. AB - Intracellular recordings were made from isolated circular muscle bundles of rat gastric fundus. The majority of cells generated an ongoing discharge of electrical activity that were 15 min) resulted in the spread of dye between CSMC, between ICC-IM, and between CSMC and ICC-IM. Two types of STDs were observed, regularly occurring continuous STDs and irregular noisy bursting STDs. The amplitude of STDs varied between the two types of STDs. Single units summed to develop STDs with a maximum amplitude of 30 mV. Sodium nitroprusside (3 microM) induced membrane hyperpolarization and abolished unitary potentials generated by CSMC. In contrast, the amplitude of STDs generated by ICC-IM was increased with membrane hyperpolarization. Hyperpolarization induced by pinacidil (10 microM) also increased the amplitude of STDs and enhanced dV/dt(max). These observations indicate that STDs generated in ICC-IM spread passively to the adjacent CSMC to evoke the discharge of unitary potentials in the gastric fundus. PMID- 19643954 TI - Upregulation of activin signaling in experimental colitis. AB - Several lines of studies have suggested that activins are critical mediators of inflammation and tissue repair. As activins and their receptors are expressed in the gastrointestinal tract, we tested the hypothesis that activin signaling is involved in the development of colitis by using two murine models of colitis induced by dextran sodium sulfate (DSS) or in mdr1a-/- mice. By immunohistochemistry, expression of activins was found increased in both models and correlated with the severity of inflammation. Activin expression was observed in macrophages as well as in some nonmacrophage cells. Furthermore, while activin receptors are normally expressed in colonic epithelial cells, their expression was further increased in both epithelial cells and inflammatory cells in inflamed colonic mucosa. Moreover, in vitro studies showed that activin A inhibited proliferation and induced apoptosis of intestinal epithelial cells, and this growth inhibition was largely reversed by administration of the activin inhibitor, follistatin. Because we also observed an increased number of apoptotic epithelial cells in both colitis models, the upregulation of activins occurring in colitis could be involved both in the inflammatory process and in growth inhibition of the intestinal epithelium. Importantly, in vivo administration of follistatin attenuated inflammatory cell infiltration during colitis. Rectal bleeding was reduced, and the integrity of epithelium was preserved in the DSS/follistatin-treated group compared with the group treated with DSS alone. Bromodeoxyuridine incorporation studies showed an increase in proliferative epithelial cells in the DSS/follistatin-treated group, suggesting that follistatin accelerates epithelial cell proliferation/repair during colitis. Overall, our results reveal that activin signaling may play an important role in the pathogenesis and resolution of colitis. These findings suggest new therapeutic options in inflammatory bowel diseases. PMID- 19643955 TI - Luminal L-glutamate enhances duodenal mucosal defense mechanisms via multiple glutamate receptors in rats. AB - Presence of taste receptor families in the gastrointestinal mucosa suggests a physiological basis for local and early detection of a meal. We hypothesized that luminal L-glutamate, which is the primary nutrient conferring fundamental umami or proteinaceous taste, influences mucosal defense mechanisms in rat duodenum. We perfused the duodenal mucosa of anesthetized rats with L-glutamate (0.1-10 mM). Intracellular pH (pH(i)) of the epithelial cells, blood flow, and mucus gel thickness (MGT) were simultaneously and continuously measured in vivo. Some rats were pretreated with indomethacin or capsaicin. Duodenal bicarbonate secretion (DBS) was measured with flow-through pH and CO(2) electrodes. We tested the effects of agonists or antagonists for metabotropic glutamate receptor (mGluR) 1 or 4 or calcium-sensing receptor (CaSR) on defense factors. Luminal L-glutamate dose dependently increased pH(i) and MGT but had no effect on blood flow in the duodenum. L-glutamate (10 mM)-induced cellular alkalinization and mucus secretion were inhibited by pretreatment with indomethacin or capsaicin. L-glutamate effects on pH(i) and MGT were mimicked by mGluR4 agonists and inhibited by an mGluR4 antagonist. CaSR agonists acidified cells with increased MGT and DBS, unlike L-glutamate. Perfusion of L-glutamate with inosinate (inosine 5' monophosphate, 0.1 mM) enhanced DBS only in combination, suggesting synergistic activation of the L-glutamate receptor, typical of taste receptor type 1. L leucine or L-aspartate had similar effects on DBS without any effect on pH(i) and MGT. Preperfusion of L-glutamate prevented acid-induced cellular injury, suggesting that L-glutamate protects the mucosa by enhancing mucosal defenses. Luminal L-glutamate may activate multiple receptors and afferent nerves and locally enhance mucosal defenses to prevent subsequent injury attributable to acid exposure in the duodenum. PMID- 19643957 TI - Dichoptic multifocal pupillography reveals afferent visual field defects in early type 2 diabetes. AB - PURPOSE: Multifocal pupillographic perimetry was used to examine differences in the visual fields of 23 subjects with early type 2 diabetes (T2D) and 23 age- and sex-matched control subjects. METHODS: Independent stimuli were delivered to 44 regions of each eye while pupil responses were recorded with infrared cameras. The stimuli were presented in 8 segments of 30 seconds, and both eyes of each subject were tested twice. The direct and consensual responses provided 88 responses per eye. The diagnostic power of the method was then examined by applying receiver operator analysis to the peak regional contraction amplitudes, time to peaks, and linear combinations of those. RESULTS: Dichoptic multifocal pupillography provided response amplitudes with a median z-score of 2.63 +/- 0.26 (SE). The diagnostic performance (expressed as areas under ROC plots) of the eight subjects (32 fields) who had had T2D for at least 10 years was 0.87 +/- 0.06 (mean +/- SE) for response amplitude deviations from normative data, rising to 0.95 +/- 0.04 when between-eye symmetry was considered. Mean pupil size did not have diagnostic power. Comparison of direct and consensual response fields indicated that the observed localized field defects were afferent. CONCLUSIONS: Reasonable diagnostic power was obtained, especially for the 16 eyes that had had T2D for more than 10 years, inferring that even in the near absence of visible diabetic retinopathy, some retinal damage had been sustained. This result, if confirmed in a wider group, suggests the that the method may be clinically useful in screening for early damage to the retina in T2D diabetes. PMID- 19643956 TI - Cultivated human conjunctival epithelial transplantation for total limbal stem cell deficiency. AB - PURPOSE: To determine the feasibility of cultivated conjunctiva as a viable epithelial sheet for transplantation and corneal resurfacing in eyes with limbal stem cell deficiency (LSCD). METHODS: Human corneal epithelial (HCE) and human conjunctival epithelial (HCjE) cells were cultivated on human amniotic membrane (AM) to confluence and then air lifted to allow further stratification and differentiation. Denuded AM and cultivated HCE and cultivated HCjE cells were then transplanted into 18 eyes of rabbits with induced LSCD. The cultivated and engrafted epithelia were examined by transmission electron microscopy (TEM) and immunohistochemistry. Two weeks after transplantation, the eyes were examined by slit lamp biomicroscopy and scored on epithelial integrity, corneal haze, and corneal neovascularization. RESULTS: Both cultivated and engrafted HCjE sheets demonstrated confluent epithelial sheets with five to six layers of well stratified epithelium. TEM examination of engrafted HCjE revealed numerous microvilli, desmosomes, and hemidesmosomes, identical with in vivo corneal epithelium. Immunohistochemical analysis of both HCjE and HCE cells showed the presence of CK3, CK4, and CK12, with absence of Muc5AC. Clinical outcomes for eyes receiving HCjE transplants and HCE transplants were comparable, with most having transparent, smooth corneas, free of epithelial defects. CONCLUSIONS: The study showed that microscopically, HCjE cells have features similar to HCE cells, with clinically equivalent outcomes. The ex vivo cultivation of conjunctiva to form transplantable epithelial sheets for corneal replacement is a promising new treatment modality in patients with LSCD. PMID- 19643958 TI - Function of MYO7A in the human RPE and the validity of shaker1 mice as a model for Usher syndrome 1B. AB - PURPOSE: To investigate the function of MYO7A in human RPE cells and to test the validity of using shaker1 RPE in preclinical studies on therapies for Usher syndrome 1B by comparing human and mouse cells. METHODS: MYO7A was localized by immunofluorescence. Primary cultures of human and mouse RPE cells were used to measure melanosome motility and rod outer segment (ROS) phagocytosis and digestion. MYO7A was knocked down in the human RPE cells by RNAi to test for a mutant phenotype in melanosome motility. RESULTS: The distribution of MYO7A in the RPE of human and mouse was found to be comparable, both in vivo and in primary cultures. Primary cultures of human RPE cells phagocytosed and digested ROSs with kinetics comparable to that of primary cultures of mouse RPE cells. Melanosome motility was also comparable, and, after RNAi knockdown, consisted of longer-range fast movements characteristic of melanosomes in shaker1 RPE. CONCLUSIONS: The localization and function of MYO7A in human RPE cells is comparable to that in mouse RPE cells. Although shaker1 retinas do not undergo degeneration, correction of mutant phenotypes in the shaker1 RPE represents a valid preclinical test for potential therapeutic treatments. PMID- 19643960 TI - Functional changes in the retina during and after acute intraocular pressure elevation in mice. AB - PURPOSE: To examine retinal function using the full-field electroretinogram (ERG) during and after acute intraocular pressure (IOP) elevation in wild-type mice. METHODS: IOP was elevated by anterior chamber cannulation in wild-type C57/BL6 mice. The pressure-function relationship was determined by IOP elevation in steps from baseline to 80 mm Hg. The rate of functional recovery was assessed for 60 minutes after an IOP spike of 50 mm Hg for 30 minutes. During and immediately after IOP elevation, scotopic ERG signals were recorded in response to dim and bright flashes (-4.54, -2.23, and 0.34 log cd x s x m(-2)) and analyzed for photoreceptoral (a-wave), ON-bipolar (b-wave), oscillatory potentials (OPs), and scotopic threshold responses (positive [p]STR/negative [n] STR). A full ERG protocol was collected 2 days before and 7 days after the single 50-mm Hg IOP spike. RESULTS: The pSTR was most sensitive to IOP elevation with 50% amplitude loss (mu) at 41 mm Hg (mu, 95% confidence limits (CL): 37.7, 45.6) followed by nSTR at 45 mm Hg (95% CL: 41.0, 49.1). pSTR was significantly more sensitive than the b-wave (95% CL: 41.4, 49.1), a-wave (95% CL: 47.6, 55.3), and OPs (95% CL: 49.6, 59.2). pSTR showed slower recovery immediately after the 50 mm Hg spike compared with the b-wave (P = 0.02). One week after the 50-mm Hg spike, pSTR ( 30% +/- 6%, P < 0.001) and OP (-27% +/- 2%, P < 0.001) amplitudes were reduced, whereas other components were unaffected. CONCLUSIONS: The STR in mice is more sensitive to acute IOP elevation and recovers slower than other ERG components. Reduction in pSTR and OP amplitude at 1 week suggests persistent impairment of inner retinal function can occur after a single IOP spike. PMID- 19643959 TI - Detection of differentially expressed wound-healing-related glycogenes in galectin-3-deficient mice. AB - PURPOSE: A prior study showed that exogenous galectin-3 (Gal-3) stimulates re epithelialization of corneal wounds in wild-type (Gal-3(+/+)) mice but, surprisingly, not in galectin-3-deficient (Gal-3(-/-)) mice. In an effort to understand why the injured corneas of Gal-3(-/-) mice are unresponsive to exogenous Gal-3, the present study was designed to determine whether genes encoding the enzymes that regulate the synthesis of glycan ligands of Gal-3 are differentially expressed in Gal-3(-/-) corneas compared with the Gal-3(+/+) corneas. METHODS: Glycogene microarray technology was used to identify differentially expressed glycosyltransferases in healing Gal-3(+/+) and Gal-3(-/ ) corneas. RESULTS: Of approximately 2000 glycogenes on the array, the expression of 8 was upregulated and that of 14 was downregulated more than 1.3-fold in healing Gal-3(-/-) corneas. A galactosyltransferase, beta3GalT5, which has the ability to synthesize Gal-3 ligands was markedly downregulated in healing Gal-3( /-) corneas. The genes for polypeptide galactosaminyltransferases (ppGalNAcT-3 and -7) that are known to initiate O-linked glycosylation and N-aspartyl-beta glucosaminidase, which participates in the removal of N-glycans, were found to be upregulated in healing Gal-3(-/-) corneas. Microarray data were validated by qRT PCR. CONCLUSIONS: Based on the known functions of the differentially expressed glycogenes, it appears that the glycan structures on glycoproteins and glycolipids, synthesized as a result of the differential glycogene expression pattern in healing Gal-3(-/-) corneas may lead to the downregulation of specific counterreceptors for Gal-3. This may explain, at least in part, why, unlike healing Gal-3(+/+) corneas, the healing Gal-3(-/-) corneas are unresponsive to the stimulatory effect of exogenous Gal-3 on re-epithelialization of corneal wounds. PMID- 19643961 TI - Aberration control and vision training as an effective means of improving accommodation in individuals with myopia. AB - PURPOSE: To test the efficacy of a novel dual treatment for improving accommodative accuracy and dynamics in young persons with myopia. METHODS: Ninety three young persons with myopia (mean spherical equivalent, -3.0 +/- 1.8 D; age 16.8 +/- 2.1 years; spherical aberration +0.06 +/- 0.04 microm) participated in the study. Custom-designed soft contact lenses were used to alter ocular SA to 0.10 microm to improve accommodative accuracy and reduce any lag of accommodation. A vision training regimen was performed for 18 minutes per day for up to 6 weeks to improve speed of dynamic accommodation. Control groups had contact lenses with no added SA and/or no exercises. To avoid any effects of natural levels of negative aberration on the results of the study, all participants who had negative SA were excluded. RESULTS: The treatment contact lenses produced a significant reduction in lag of accommodation (P < 0.05) at all proximal viewing distances measured. The vision training measurement and treatment resulted in a significant increase in distance facility rate for all groups compared with their own baselines (P < 0.05). Near facility rate improved in the vision training treatment group only compared with its baseline (P < 0.05). Both positive and negative response times for distant viewing were significantly shorter in all groups after training compared with their baseline values (P < 0.05). At near, the positive response times were decreased significantly (P < 0.05) in both groups, whereas the negative response times decreased significantly only in the vision training treatment group. CONCLUSIONS: After 3 months, the dual treatments (altering SA and vision training) used in the study were effective in modifying accommodation. The static accommodative response to targets at proximal distances was increased by the altered SA contact lenses and rates of dynamic accommodation improved with vision training. PMID- 19643962 TI - Optical characterization of Bangerter foils. AB - PURPOSE: Optical penalization is emerging as an alternative to patching for the treatment of amblyopia. Bangerter foils offer a form of optical penalization that is distinctly different from standard techniques making use of atropine or spectacle lens manipulation, or both, to produce defocus. The authors examined the optical properties of Bangerter foils and compared them with the effect of defocus. METHODS: Bangerter foils were evaluated on an optical bench to calculate point spread and modulation transfer functions. Retinal images through the foils were also simulated and qualitatively compared with those with defocus and Gaussian blur. Subjective visual acuity and contrast sensitivity were compared in two subjects wearing spectacles with foils and with simple defocus. RESULTS: The optical characteristics of the Bangerter foils do not correspond well with their labeled density designation. Bangerter foils and defocus affect the modulation transfer function similarly, with more attenuation of mid-range spatial frequencies than low spatial frequencies. However, Bangerter foils do not exhibit spurious resolution and phase shifts, as does defocus. CONCLUSIONS: The blur resulting from Bangerter filters is qualitatively different from defocus. Whether this difference is of any consequence when these two methods of optical penalization are used for amblyopia treatment remains to be investigated. PMID- 19643963 TI - Regulation of cross-linked actin network (CLAN) formation in human trabecular meshwork (HTM) cells by convergence of distinct beta1 and beta3 integrin pathways. AB - PURPOSE: To determine the beta1/beta3 integrin-mediated pathways that regulate cross-linked actin network (CLAN) formation in human trabecular meshwork (HTM) cells. CLANs form in glaucomatous and steroid-treated TM cells, which may contribute to reducing outflow facility through the TM. METHODS: Expression of CD47 (an alphavbeta3 integrin coreceptor/thrombospondin-1 receptor) and integrins alphavbeta3 and beta1 was assessed by FACS. CLANs were induced by plating cells on fibronectin (a beta1 integrin ligand) in the absence or presence of the beta3 integrin-activating mAb AP-5 and were identified by phalloidin labeling. The role of Src kinases, PI-3 kinase (PI-3K), Rac1, and CD47 was determined by incubating cells with the inhibitors PP2 and EPA (Src kinases), LY294002 (PI-3K), or NSC23766 (Rac1). Tiam1 and Trio siRNAs and dominant-negative Tiam1 were used to determine which Rac1-specific guanine nucleotide exchange factor was involved. The role of CD47 was determined using the thrombospondin-1-derived agonist peptide 4N1K and the CD47 function blocking antibody B6H12.2. RESULTS: HTM cells expressed CD47 and integrins alphavbeta3 and beta1. beta3 Integrin or CD47 activation significantly increased CLAN formation over beta1 integrin-induced levels, whereas anti-CD47 mAb B6H12.2 inhibited this increase. PP2, NSC23766, and Trio siRNA decreased beta3-induced CLAN formation by 72%, 45%, and 67%, respectively, whereas LY294002 and dominant negative Tiam1 had no effect. LY294002 decreased beta1 integrin-mediated CLAN formation by 42%, and PP2 completely blocked it. CONCLUSIONS: Distinct beta1 and alphavbeta3 integrin signaling pathways converge to enhance CLAN formation. beta1-Mediated CLAN formation was PI-3K dependent, whereas beta3-mediated CLAN formation was CD47 and Rac1/Trio dependent and might have been regulated by thrombospondin-1. Both integrin pathways were Src dependent. PMID- 19643966 TI - Association of the lumican gene functional 3'-UTR polymorphism with high myopia. AB - PURPOSE: The lumican gene (LUM) encodes a major extracellular component of the fibrous mammalian sclera. Alteration in the expression levels of extracellular matrix components may influence scleral shape, which in turn could affect visual acuity. Single-nucleotide polymorphisms (SNPs) in the LUM gene were determined in an investigation of whether LUM gene polymorphisms correlate with high myopia. METHODS: Sequences spanning all three exons, intron-exon boundaries, and promoter regions were determined in 50 normal individuals. Five SNPs were identified, one of which was found to be a newly identified polymorphism. Genomic DNA was prepared from peripheral blood obtained from 201 patients with high myopia and 86 control subjects. Genotypes of the SNPs -1554 T/C (rs3759223), -628 A/ (rs17018757), -59 CC/-(rs3832846), c.601 T/C (rs17853500), and the novel SNP c.1567 C>T were determined by polymerase chain reaction. RESULTS: Of the five SNPs, one showed a significant difference between patients and control subjects (c.1567 C>T, P = 0.0016). Haplotype analysis revealed a significantly higher presence of polymorphisms in patients with myopia (P < 0.0001). Moreover, the c.1567 T polymorphism was determined to have lower reporter gene activity than that of c.1567 C. CONCLUSIONS: These observations suggest that LUM gene polymorphisms contribute to the development of high myopia. PMID- 19643964 TI - Dual involvement of caspase-4 in inflammatory and ER stress-induced apoptotic responses in human retinal pigment epithelial cells. AB - PURPOSE: To investigate the functional involvement of caspase-4 in human retinal pigment epithelial (hRPE) cells. METHODS: Expression and activation of caspase-4 in hRPE cells were measured after stimulation with proinflammatory agents IL 1beta (2 ng/mL), TNF-alpha (20 ng/mL), lipopolysaccharide (1000 ng/mL), interferon-gamma (500 U/mL), or monocyte coculture in the absence or presence of immunomodulating agent cyclosporine (3 or 30 ng/mL), dexamethasone (10 microM), or IL-10 (100 U/mL) and endoplasmic reticulum (ER) stress inducer thapsigargin (25 nM) or tunicamycin (3 or 10 microM). The onset of ER stress was determined by expression of GRP78. The involvement of caspase-4 in inflammation and apoptosis was further examined by treating the cells with caspase-4 inhibitor Z-LEVD-fmk, caspase-1 and -4 inhibitor Z-YVAD-fmk, and pan-caspase inhibitor Z-VAD-fmk. RESULTS: Caspase-4 mRNA expression and protein activation were induced by all the proinflammatory agents and ER stress inducers tested in this study. Caspase-4 activation was blocked or reduced by dexamethasone and IL-10. Elevated ER stress by proinflammatory agents and ER stress inducers was shown by increased expression of the ER stress marker GRP78. The induced caspase-4 and caspase-3 activities by tunicamycin and the stimulated IL-8 protein expression by IL-1beta were markedly reduced by caspase-4 inhibitor Z-LEVD-fmk. Although caspase-4 inhibitor Z-LEVD-fmk and caspase-1 and -4 inhibitor Z-YVAD-fmk reduced tunicamycin-induced hRPE apoptotic cell death by 59% and 86%, respectively, pan caspase inhibitor Z-VAD-fmk completely abolished the induced apoptosis. CONCLUSIONS: Caspase-4 is dually involved in hRPE proinflammatory and proapoptotic responses. Various proinflammatory stimuli and ER stress induce hRPE caspase-4 mRNA synthesis and protein activation. ER stress-induced hRPE cell death is caspase and, in part, caspase-4 dependent. PMID- 19643967 TI - The structural relationship between the microvasculature, neurons, and glia in the human retina. AB - PURPOSE: To develop a new technique for detailed study of the spatial distribution of retinal and choroidal microvasculature and their relationship to neurons and glial cells at the cellular level in human cadaveric eyes. METHODS: Twenty-six human donor eyes were used. Wherever possible, the central retinal artery and a branch of the posterior ciliary artery were individually cannulated and perfused with oxygenated Ringer's solution with 0.5% bovine serum albumin. The perfusion pressure was continuously monitored. Once residual blood was washed out, the perfusate solutions were switched to fixative, membrane-permeabilizing solution and selected labeling solutions. The eyes were then immersion fixed and the retina and choroid flat-mounted for immunolabeling and confocal imaging before cryosectioning. The microstructures of vascular, glial, and neuronal cells in the retina and the stroma in the choroid were studied. RESULTS: The retinal microvasculature was fully perfused and stained by cannulation of the central retinal artery. Regional distribution of choroidal vasculature perfusion was dependent on the specific feeder artery cannulated. The detailed spatial relationship between endothelial cells, glial cells, and neurons at the cellular and subcellular levels was identified with confocal microscopy and immunohistochemical labeling of retinal sections. In the choroid, endothelial cells were clearly identifiable down to the level of the intracellular cytoarchitecture of the choriocapillaris, along with their relationship to Bruch's membrane and the feeding and drainage vessels. CONCLUSIONS: A microperfusion fixation and staining technique has been developed that allows studies of the structural relationships of vascular, glial, and neuronal elements at the cellular level in human donor eyes. PMID- 19643965 TI - CREB1/ATF1 activation in photoreceptor degeneration and protection. AB - PURPOSE: The cAMP response element binding protein 1 (CREB1) and activating transcription factor 1 (ATF1) are closely related members of the bZIP superfamily of transcription factors. Both are activated in response to a wide array of stimuli, including cellular stress. This study was conducted to assess the CREB1/ATF1 pathway in photoreceptor disease and protection. METHODS: The expression levels of p-CREB1, CREB1, and ATF1 were examined by immunoblot and immunohistochemistry in normal canine retina and retinas of several canine models of retinal degeneration (rcd1, rcd2, erd, prcd, XLPRA1, XLPRA2, T4R RHO). Humans retinas affected with age-related macular degeneration (AMD) were also examined. p-CREB1/ATF1 immunolabeling was assessed in normal and rcd1 dogs treated with ciliary neurotrophic factor (CNTF), to examine the effect of a neuroprotective stimulus on activation of CREB1/ATF1. RESULTS: Native CREB1 and ATF1 as well as phosphorylated CREB1/ATF1 was examined in normal canine retina by immunoblot. The p-CREB1 antibody identified phosphorylated CREB1 and ATF1 and labeled the inner retina only in normal dogs. In degenerate canine and human retinas, strong immunolabeling appeared in rod and cone photoreceptors, indicating increased expression of native CREB1 and ATF1, as well as increased phosphorylation of these proteins. Retinal protection by CNTF in rcd1 dogs was accompanied by a significant increase in the number of p-CREB1/ATF1-labeled photoreceptor nuclei. CONCLUSIONS: Positive association of CREB1/ATF1 phosphorylation with photoreceptor protection suggests that it may contribute to an innate protective response. These data identify a signaling mechanism in rods and cones of potential importance for therapies of RP and AMD. PMID- 19643968 TI - Inhibition of protein kinase C is not sufficient to prevent or reverse effects of VEGF165 on claudin-1 and permeability in microvascular retinal endothelial cells. AB - PURPOSE: Pathogenesis of diabetic macular edema is driven by deregulated expression of VEGF. A study of long-term exposure of immortalized bovine retinal endothelial cells (iBRECs) to VEGF(165) clearly confirmed the role of the tight junction protein claudin-1, which almost completely disappeared within 24 hours, an effect that was completely reversed by addition of the VEGF-binding Fab fragment ranibizumab. This study was conducted to investigate whether the VEGF(165)-induced loss of claudin-1 is regulated by protein kinase C (PKC) and indeed affects the barrier function of iBRECs. METHODS: The effects of various PKC inhibitors on claudin-1 expression and cellular localization in iBRECs treated with VEGF(165) for up to 2 days were studied by Western blot analyses and immunofluorescence microscopy. The permeability of the cell layers was determined by transendothelial electrical resistance measurements. RESULTS: Activation of PKC led to decreased expression of claudin-1, which was blocked by inhibitors of PKCdelta. However, none of the PKC inhibitors significantly affected VEGF(165) induced effects on cellular localization or expression of claudin-1. Also VEGF(165)-induced higher permeability of iBREC layers could be reversed or prevented by ranibizumab but not by PKC inhibitors. In addition, low claudin-1 expression and its delocalization from the plasma membrane were significantly associated with elevated permeability. CONCLUSIONS: In iBRECs, PKC isoforms are not crucially involved in the VEGF(165)-initiated signal transduction that affects permeability and expression of claudin-1. This finding is in contrast to published results concerning only short-term effects of VEGF(165). The results also confirmed that claudin-1 is a highly relevant component of functional tight junctions in retinal endothelial cells. PMID- 19643969 TI - Identification of a novel sodium-coupled oligopeptide transporter (SOPT2) in mouse and human retinal pigment epithelial cells. AB - PURPOSE: A sodium-coupled oligopeptide transporter (SOPT1) was described originally in ARPE-19 cells. The transporter is inducible by HIV-1 Tat. Recent studies of conjunctival epithelial cells have identified a second oligopeptide transporter (SOPT2). This study was conducted to determine whether the newly discovered SOPT2 is expressed in ARPE-19 cells, to examine whether the new transporter is also inducible by HIV-1 Tat, and to find out whether this transporter is expressed in primary RPE cells. METHODS: The transport activity of SOPT2 was monitored in control and Tat-expressing ARPE-19 cells and in primary mouse and human fetal RPE cells by the uptake of the synthetic opioid peptide DADLE ((H-Tyr-D-Ala-Gly-Phe-D-Leu-OH) and by its susceptibility to inhibition by small peptides. Substrate selectivity was examined by competition studies and kinetic parameters were determined by saturation analysis. RESULTS: ARPE-19 cells express DADLE uptake activity that is inhibited by small peptides, indicating expression of SOPT2 in these cells. The activity of SOPT2 is induced by HIV-1 Tat. SOPT2 accepts endogenous and synthetic opioid peptides as substrates, but nonpeptide opiate antagonists are excluded. An 11-amino-acid HIV-1 Tat peptide also serves as a high-affinity substrate for the transporter. Primary cultures of mouse and human fetal RPE cells express SOPT2. The transporter is partially Na(+) dependent with comparable substrate selectivity and inhibitor specificity in the presence and absence of Na(+). CONCLUSIONS: ARPE-19 cells as well as primary mouse and human fetal RPE cells express the newly discovered oligopeptide transporter SOPT2, and the transporter is induced by HIV-1 Tat in ARPE-19 cells. PMID- 19643970 TI - Heterozygous loss-of-function variants in CYP1B1 predispose to primary open-angle glaucoma. AB - PURPOSE: Although primary congenital glaucoma (PCG)-associated CYP1B1 mutations in the heterozygous state have been evaluated for association with primary open angle glaucoma (POAG) in several small studies, their contribution to the occurrence of POAG is still controversial. The present study was conducted to determine whether heterozygous functionally characterized CYP1B1 mutations are associated with the disease in a large cohort of German patients with POAG. METHODS: The frequency of CYP1B1 variants on direct sequencing of the entire coding region was compared in 399 unrelated German patients with POAG (270, POAG; 47, JOAG; and 82, NTG) and 376 control subjects without any signs of glaucoma on ophthalmic examination. In vitro functional assays were performed and relative enzymatic activity of the CYP1B1 variants embedded in their respective background haplotypes and not previously unambiguously classified were determined, to assess their possible causative role. RESULTS: Apart from known polymorphic variants, 11 amino acid substitutions in CYP1B1 reported before, both in PCG and POAG cases, were identified. After in vitro functional assay, variants P52L and R368H showed marked reduction of activity, confirming their role as loss-of-function mutations similar to previously determined variants G61E, N203S, and G329V. In contrast, variants G168D, A443G, and A465V showed no relevant effects and were thus classified as polymorphisms. Overall, seven functionally impaired variants were present in 13 (3.6%) patients and in 1 (0.2%) control subject (P = 0.002, OR = 5.4). Reanalysis of previous studies reporting CYP1B1 mutations in patients with POAG based on updated functional validation showed a significant excess of carriers among patients compared to controls (OR = 3.85; P = 2.3 x 10(-7)). CONCLUSIONS: Heterozygous CYP1B1 mutations with absent or reduced relative enzymatic activity can be considered a risk factor for POAG. PMID- 19643971 TI - Normative measurements of the Chinese extraocular musculature by high-field magnetic resonance imaging. AB - PURPOSE: To establish the normal measurements of diameter and cross-sectional area of the Chinese extraocular muscles (EOMs) and optic nerve-sheath complex (ON) as seen on high-field (3-Tesla; 3T) magnetic resonance imaging (MRI). METHODS: Coronal 3T MRI of the orbit (TR, 700 ms; TE, 15 ms; FOV, 160 mm; matrix, 256 x 256; slice thickness, 1 mm; and slice gap, 0) was performed on 80 normal Chinese volunteers. T1-weighted images were analyzed with computer-assisted segmentation. The diameter and the cross-sectional area of EOMs and the ON were measured from the image plane at the posterior aspect of the globe and at 7 mm behind the globe. The maximum diameter of EOM was measured from their respective reconstructed images. RESULTS: The normal measurement (mean +/- SD) of diameter at the posterior aspect of the globe: medial rectus (MR), 3.6 +/- 0.4 mm; inferior rectus (IR), 3.7 +/- 0.8 mm; lateral rectus (LR), 2.3 +/- 0.5 mm; superior oblique (SO), 2.4 +/- 0.6 mm; and the ON, 5.4 +/- 0.7 mm. The normal measurement of diameter 7 mm behind the globe: MR, 3.2 +/- 0.6 mm; IR, 3.9 +/- 0.8 mm; LR, 4.0 +/- 0.8 mm; SO, 2.2 +/- 0.7 mm; and ON, 4.2 +/- 0.5 mm. The normal measurement of cross-sectional area at the posterior aspect of the globe: superior muscle group (SMG), 28.2 +/- 6.5 mm(2); MR, 25.5 +/- 3.2 mm(2); IR, 26.9 +/- 7.2 mm(2); LR, 17.3 +/- 3.9 mm(2); SO, 10.5 +/- 3.5 mm(2); and ON, 27.6 +/- 6.1 mm(2). The normal measurement of cross-sectional area 7 mm behind the globe: SMG, 24.1 +/- 6.6 mm(2); MR, 19.1 +/- 4.6 mm(2); IR, 29.5 +/- 6.6 mm(2); LR, 32.3 +/- 6.5 mm(2); SO, 9.7 +/- 3.9 mm(2); and ON, 17.1 +/- 2.9 mm(2). The normal measurement of maximum diameter: SMG, 4.8 +/- 1.1 mm; MR, 5.1 +/- 0.9 mm; IR, 5.4 +/- 1.0 mm; and LR, 4.5 +/- 0.9 mm. CONCLUSIONS: The Chinese 3T MRI EOMs and ON normative data may be useful in determining pathologic enlargement of the EOMs and ON in various orbital conditions. (ClinicalTrials.gov number, NCT00348413.). PMID- 19643972 TI - Proteomics of uveal melanomas suggests HSP-27 as a possible surrogate marker of chromosome 3 loss. AB - PURPOSE: To compare the proteomic profiles of primary uveal melanomas, with and without loss of chromosome 3. METHODS: Frozen specimens from three uveal melanomas with disomy 3 and from four tumors with monosomy 3, according to fluorescence in situ hybridization (FISH) analysis, were subjected to high resolution, two-dimensional (2-D) gel electrophoresis. The protein expression profiles of the two uveal melanoma cytogenetic groups were compared: Proteins that differed significantly were excised and analyzed by tandem mass spectrometry. Differentially expressed proteins were further analyzed with Western blot analysis. An independent cohort of 41 formalin-fixed, paraffin embedded (FFPE) uveal melanomas, whose chromosome 3 status had been determined by multiplex ligation-dependent probe amplification (MLPA), was examined for the appropriate antigens by immunohistochemistry. RESULTS: Four protein spots were 1.5-fold (Student's t-test, P < 0.05) differentially expressed in the two uveal melanoma types: two spots were overexpressed in the disomy 3 group compared with the monosomy 3 group, whereas two spots were underexpressed. Identification of the four spots yielded nine proteins. Western blot analysis confirmed the results for heat shock protein (HSP)-27, vimentin, and pyruvate dehydrogenase beta (PDHB), with a statistical significance for the first two proteins. HSP-27 was significantly downregulated, whereas vimentin was upregulated in the monosomy 3 tumors (Student's t-test, P = 0.003 and P = 0.005, respectively). Immunohistochemistry confirmed low-to-negative HSP-27 protein expression in monosomy 3 uveal melanomas (Student's t-test; P = 0.011). CONCLUSIONS: Low-to negative HSP-27 protein expression in uveal melanoma correlates strongly with monosomy 3. Further validation is necessary to determine whether immunohistochemical assessment of HSP-27 expression correlates with metastatic mortality. PMID- 19643973 TI - Correlation of light-flicker-induced retinal vasodilation and retinal vascular caliber measurements in diabetes. AB - PURPOSE: Subtle changes in retinal vascular caliber have been shown to predict diabetic retinopathy and other diabetic complications. This study was undertaken to investigate whether retinal vascular caliber correlates with light-flicker induced retinal vasodilation, a measure of endothelial function. METHODS: The participants were 224 persons with diabetes (85 type 1 and 139 type 2) and 103 persons without diabetes (controls). Flicker-induced retinal vasodilation (percentage increase over baseline diameter) was measured with a vessel analyzer. Retinal vascular caliber was measured from digital retinal photographs according to a standardized, validated protocol. Data from both right and left eyes were used and modeled with generalized estimating equations to account for correlation between eyes. RESULTS: In persons with diabetes, after adjustment for age and sex, reduced flicker-induced vasodilation was associated with wider retinal vascular caliber. Eyes with the lowest tertiles of flicker-induced arteriolar dilation had wider arteriolar caliber (5.40 mum; 95% confidence interval [CI], 1.76-9.05) and eyes with the lowest tertiles of flicker-induced venular dilation had corresponding wider venular caliber (12.4 mum; 95% CI, 6.48-18.2), respectively, than eyes with the highest tertile of vasodilation. These associations persisted after further adjusting for diabetes duration, systolic blood pressure, fasting glucose, lipids, body mass index, current smoking, and presence of diabetic retinopathy. No associations were evident in persons without diabetes. CONCLUSIONS: Changes in retinal vascular caliber (wider arterioles and venules) are associated with impaired flicker-induced vasodilation in persons with diabetes. Determining whether endothelial dysfunction explains the link between retinal vascular caliber and risks of diabetic microvascular complications calls for further study. PMID- 19643974 TI - The effect of trabeculectomy on ocular pulse amplitude. AB - PURPOSE: To investigate whether trabeculectomy, besides its intraocular pressure (IOP)-lowering effect, has an effect on ocular pulse amplitude (OPA); and to determine whether OPA changes are influenced by IOP changes. METHODS: Forty-eight patients with glaucoma (48 eyes) scheduled for unilateral first-time trabeculectomy were prospectively enrolled from October 2007 to April 2008. The eye undergoing trabeculectomy was considered the study eye, whereas the nonsurgical fellow eye was used as the control eye. OPA, IOP, blood pressure, and heart rate were measured before and 4 weeks after trabeculectomy by means of Pascal dynamic contour tonometry (DCT), Goldmann applanation tonometry (GAT), and sphygmomanometry. A regression model for repeated measures was used. RESULTS: Preoperative GAT, DCT, and OPA were 20.92 +/- 8.55, 21.33 +/- 7.06, and 3.23 +/- 1.58 mm Hg, respectively. One month after trabeculectomy, GAT, DCT, and OPA were 11.23 +/- 5.03, 14.45 +/- 4.79, and 2.12 +/- 1.07 mm Hg, respectively. There was a significant decrease in OPA after filtration surgery in the study eye compared with the control eye (P < 0.0001). Changes in OPA were correlated with changes in IOP (Spearman rho = 0.49, P = 0.0004). When the IOP change caused by filtration surgery was taken into account, no significant difference in effect on OPA after trabeculectomy was demonstrated in the study eye compared with the control eye (P = 0.18). CONCLUSIONS: OPA changes correlated strongly with IOP changes. There was no evidence of an effect of filtration surgery on OPA when the concomitant IOP decrease after trabeculectomy was taken into account. PMID- 19643975 TI - Mechanisms of corneal tissue cross-linking in response to treatment with topical riboflavin and long-wavelength ultraviolet radiation (UVA). AB - PURPOSE: Treatment of de-epithelialized human corneas with riboflavin (RF) + long wavelength ultraviolet light (UVA; RFUVA) increases corneal stroma tensile strength significantly. RFUVA treatment retards the progression of keratoconus, perhaps by cross-linking of collagen molecules, but exact molecular mechanisms remain unknown. Research described here tested possible chemical mechanisms of cross-linking. METHODS: Corneas of rabbits and spiny dogfish sharks were de epithelialized mechanically, subjected to various chemical pretreatments, exposed to RFUVA, and then subjected to destructive tensile stress measurements. Tensile strength was quantified with a digital force gauge to measure degree of tissue cross-linking. RESULTS: For both rabbit and shark corneas, RFUVA treatment causes significant cross-linking by mechanism(s) that can be blocked by the presence of sodium azide. Conversely, such cross-linking is greatly enhanced in the presence of deuterium oxide (D(2)O), even when RF is present at only one tenth the currently used clinical concentrations. Blocking carbonyl groups preexisting in the stroma with 2,4-dinitrophenylhydrazide or hydroxylamine blocks essentially all corneal cross-linking. In contrast, blocking free amine groups preexisting in the stroma with acetic anhydride or ethyl acetimidate does not affect RFUVA corneal cross-linking. When both carbonyl groups are blocked and singlet oxygen is quenched, no RFUVA cross-linking occurs, indicating the absence of other cross linking mechanisms. CONCLUSIONS: RFUVA catalyzes cross-linking reactions that require production of singlet oxygen ((1)O(2)), whose half-life is extended by D(2)O. Carbonyl-based cross-linking reactions dominate in the corneal stroma, but other possible reaction schemes are proposed. The use of D(2)O as solution media for RF would enable concentration decreases or significant strength enhancement in treated corneas. PMID- 19643976 TI - Incorporating receptor flexibility in the molecular design of protein interfaces. AB - The success of antibody-based pharmaceuticals has led to a resurgence in interest in computational structure-based design. Most efforts to date have been on the redesign of existing interfaces. These efforts have mostly neglected the inherent flexibility of the receptor that is critical for binding. In this work, we extend on a previous study to perform a series of designs of protein binding interfaces by incorporating receptor flexibility using an ensemble of conformers collected from explicit-solvent molecular dynamics (MD) simulations. All designer complexes are subjected to 30 ns of MD in explicit solvent to assess for stability for a total of 480 ns of dynamics. This is followed by end-point free energy calculations whereby intermolecular potential energy, polar and non-polar solvation energy and entropy of ligand and receptor are subtracted from that of the complex and averaged over 320 snapshots collected from each of the 30 ns MD simulations. Our initial effort consisted of redesigning the interface of three well-studied complexes, namely barnase-barstar, lysozyme-antibody D1.3 and trypsin-BPTI. The design was performed with flexible backbone approach. MD simulations revealed that all three complexes remained stable. Interestingly, the redesigned trypsin-BPTI complex was significantly more favorable than the native complex. This was attributed to the favorable electrostatics and entropy that complemented the already favorable non-polar component. Another aspect of this work consisted of grafting the surface of three proteins, namely tenascin, CheY and MBP1 to bind to barnase, trypsin and lysozyme. The process was initially performed using fixed backbone, and more than 300 ns of the explicit-solvent MD simulation revealed some of the complexes to dissociate over the course of the trajectories, whereas others remained stable. Free energy calculations confirmed that the non-polar component of the free energy as computed by summing the van der Waals energy and the non-polar solvation energy was a strong predictor of stability. Four complexes (two stable and two unstable) were selected, and redesigned using multiple conformers collected from the MD simulation. The resulting designer systems were then immersed in explicit solvent and 30 ns of MD was carried out on each. Interestingly, those complexes that were initially stable remained stable, whereas one of the unstable complexes became stable following redesign with flexible backbone. Free energy calculations showed significant improvements in the affinity for most complexes, revealing that the use of multiple conformers in protein design may significantly enhance such efforts. PMID- 19643978 TI - Prescribing errors in a pediatric clinic. AB - OBJECTIVE: This project was completed to determine the frequency and type of prescribing errors occurring in a pediatric clinic. STUDY DESIGN: Records for all patient encounters in the pediatric acute care clinic from February through April 2007 were reviewed. Prescriptions entered into the electronic medical records (EMR) were reviewed the day after they were written. RESULTS: A total of 3523 records containing 1802 new prescriptions were reviewed. Prescribing errors were found in 175 prescriptions (9.7%). The most common type of error was an incomplete prescription (42%), followed by dosing errors (34%). Anti-infectives were most commonly written in error followed by anti-inflammatories. CONCLUSIONS: Prescribing errors were commonly identified in a pediatric clinic utilizing electronic medical records. Incomplete prescriptions and dosing errors were the most commonly occurring errors. Recognizing the types of errors has been beneficial for developing educational programs intended to decrease prescribing errors and recommending improvements to the EMR system and its utilization. PMID- 19643979 TI - Preterm premature rupture of membranes: clinical outcomes of late-preterm infants. AB - OBJECTIVE: To determine gestational age-specific neonatal outcomes of late preterm infants delivered as a consequence of premature rupture of membranes (PROM). METHODS: Retrospective cohort study of infants born to women delivered electively due to preterm PROM between 34(0/7) and 36(6/7) weeks of gestation. Neonatal outcomes were compared between those delivered at 34(0/7) to 34( 6/7) weeks, at 35(0/7) to 35(6/7) weeks, and at 36( 0/7) to 36(6/7) weeks. RESULTS: 192 infants were identified. The 34(0/7) to 34(6/7) week infants had significantly higher neonatal intensive care admission rate (72.5%) compared to those at 35( 0/7) to 35(6/7) weeks (22.8%) and at 36 to 36(6/7) weeks (17.8%) (P < .05). Neonatal respiratory distress syndrome was significantly higher at 34(0/7) to 34(6/7) weeks (35.4%) compared with 35(0/7) to 35(6/7) week and 36(0/7) to 36( 6/7) week infants (10.5% and 4.1%; P < .05). The longest hospitalization occurred in the 34(0/7) to 34(6/7) week infants (248.5 +/- 20.0 hours). CONCLUSION: Substantial short-term morbidity occurred in late preterm infants. The greatest number of complications affected infants born at 34(0/7) to 34(6/7) weeks. PMID- 19643977 TI - Design, expression and characterization of mutants of fasciculin optimized for interaction with its target, acetylcholinesterase. AB - Predicting mutations that enhance protein-protein affinity remains a challenging task, especially for high-affinity complexes. To test our capability to improve the affinity of such complexes, we studied interaction of acetylcholinesterase with the snake toxin, fasciculin. Using the program ORBIT, we redesigned fasciculin's sequence to enhance its interactions with Torpedo californica acetylcholinesterase. Mutations were predicted in 5 out of 13 interfacial residues on fasciculin, preserving most of the polar inter-molecular contacts seen in the wild-type toxin/enzyme complex. To experimentally characterize fasciculin mutants, we developed an efficient strategy to over-express the toxin in Escherichia coli, followed by refolding to the native conformation. Despite our predictions, a designed quintuple fasciculin mutant displayed reduced affinity for the enzyme. However, removal of a single mutation in the designed sequence produced a quadruple mutant with improved affinity. Moreover, one designed mutation produced 7-fold enhancement in affinity for acetylcholinesterase. This led us to reassess our criteria for enhancing affinity of the toxin for the enzyme. We observed that the change in the predicted inter molecular energy, rather than in the total energy, correlates well with the change in the experimental free energy of binding, and hence may serve as a criterion for enhancement of affinity in protein-protein complexes. PMID- 19643980 TI - Variations in costs for the care of low-birth-weight infants among academic hospitals. AB - OBJECTIVES: To determine the relative role that academic hospitals (AHs) play in providing neonatal care for low-birth-weight infants within a single state and to determine if there are variations in inpatient costs for neonatal services among AHs. DESIGN: Retrospective analysis of hospital costs for low-birth-weight infants. SETTING: Cases were identified using 2003-2005 data from the Tennessee Hospital Discharge Data System. A specific focus was discharge data from the 5 AHs that support obstetrical residencies and have a neonatal intensive care unit. PARTICIPANTS: Cases included all discharged infants with a birth weight of <2500 grams. RESULTS: The 5 AHs discharged 18% of the total normal-birth-weight infants and 30% of the low-birth-weight infants for the entire state. AHs had higher costs associated with these infants than did other hospitals, with a single exception The difference in costs at this hospital was consistent with the finding of lower utilization rates of hospital services, a shorter average length of stay, and lower costs for infants insured by the state Medicaid program. CONCLUSION: Academic obstetrical hospitals discharged a disproportionately high percentage of low-birth-weight infants compared with other Tennessee hospitals. The lower costs observed in the Shelby County hospital indicates that other hospitals could potentially lower their costs for the care of low-birth-weight infants. PMID- 19643981 TI - A primer on screening data management. AB - A drug discovery startup company or academic lab entering the screening arena faces numerous challenges as it tries to manage the large quantity of data generated by a typical drug discovery screening campaign. Although there are sophisticated off-the-shelf software solutions available, their use requires substantial forethought and attention to detail if the data they capture are to be of sufficient quality to serve the various purposes to which it will be put. For newcomers to the field of screening data management in particular, the problem is compounded by a lack of literature covering the practical aspects of managing screening data. The authors provide some practical advice based on their experience of using a commercially available software suite. They discuss issues ranging from the organizational aspects to examples of how the form and content of metadata can have a big impact on whether results can be easily queried, pivoted, and reported. It is also hoped that their experiences might provide an opportunity for reflection to data management practitioners operating in established environments. PMID- 19643982 TI - Correction for interference by test samples in high-throughput assays. AB - In high-throughput biochemical assays performed in multiwell plates, the effect of test samples on the activity of the biochemical system is usually measured by optical means such as absorbance, fluorescence, luminescence, or scintillation counting. The test sample often causes detection interference when it remains in the well during the measurement. Interference may be due to light absorption, fluorescence quenching, sample fluorescence, chemical interaction of the sample with a detection reagent, or depression of the meniscus. A simple method is described that corrects for such interference well by well. The interference is measured in a separate artifact assay plate. An appropriate arithmetic correction is then applied to the measurement in the corresponding well of the activity assay plate. The correction procedure can be used for single-point screening or potency measurements on serial dilutions of test samples. PMID- 19643983 TI - Detailed analysis of p53 pathway defects in fludarabine-refractory chronic lymphocytic leukemia (CLL): dissecting the contribution of 17p deletion, TP53 mutation, p53-p21 dysfunction, and miR34a in a prospective clinical trial. AB - The prognosis of fludarabine (F)-refractory chronic lymphocytic leukemia (CLL) is very poor, and underlying mechanisms are only partly understood. To assess the contribution of p53 abnormalities to F-refractory CLL, we studied TP53 mutations in the CLL2H trial (subcutaneous alemtuzumab; n = 99). We found TP53 mutations in 37% of patients. Twelve of 67 (18%) patients without the 17p deletion showed a TP53 mutation and 50% showed evidence of uniparental disomy. A total of 75% of cases with TP53 mutation (without 17p-) showed clonal evolution/expansion. TP53 mutations had no impact on overall survival (P = .48). CLL with the 17p deletion or TP53 mutation showed very low miR-34a expression. To investigate the mechanisms underlying refractory CLL beyond p53, we studied cases without 17p /TP53 mutation in detail. In several paired samples before and after F-refractory disease, no change in p21/p53 induction was observed after DNA damage. Although TP53 mutations and 17p deletions are found in a high proportion of F-refractory CLL, more than half of the cases cannot be explained by p53 defects (deletion or mutation), and alternative mechanisms need to be investigated. Alemtuzumab is effective irrespective of genetic high-risk subgroups with TP53 mutations. These clinical trials are registered at www.clinicaltrials.gov as #NCT00274976. PMID- 19643984 TI - High Id1 expression is associated with poor prognosis in 237 patients with acute myeloid leukemia. AB - Inhibitors of differentiation (Id) are a group of dominant inhibitors of basic helix-loop-helix transcriptional factors, which promote excessive proliferation, and also protect cells against drug-induced apoptosis in mammalians. Recently, Id1 has been identified as a common downstream target of several constitutively activated oncogenic tyrosine kinase, such as FLT3 internal tandem duplication, in leukemia cells. We analyzed Id1 expression as possible prognostic factor in 237 acute myeloid leukemia (AML) patients. High Id1 expression was associated with older age (P = .009) and with FLT3 internal tandem duplication (P = .003). However, 61% of the patients in the group of FLT3(-) AML were Id1(+), suggesting that other tyrosine kinases are involved. In whole population, high Id1 expression independently predicted shorter disease-free survival (P = .05) and overall survival (P = .003). In young patients (age /= 18 years old, 70% male, 66% U.S.-born, 40% Black, 29% Hispanic, 19% White, and 12% Asian/Pacific Islander. The prevalence of each principal genetic group (GG) was 30% (GG1), 52% (GG2), and 18% (GG3). Multiple logistic regression analysis showed that GG1 participants were more likely to be Asian, male, and have a history of homelessness, as compared with participants with either GG2 or GG3 isolates. GG2 participants were more likely to be Hispanic, have streptomycin-resistant isolates, and be infected with HIV than either GG1 or GG3 participants. GG3 participants were more likely to be Black or Hispanic, report illicit drug use, and live in a congregative facility at the time of diagnosis, than GG1 or GG2 participants. Ethnicity and sociodemographic findings were significant, prompting additional research into social networks, genetic susceptibility, immunology, and virulence factors. PMID- 19644020 TI - Genotyping of frequent BRCA1/2 SNPs with unlabeled probes: a supplement to HRMCA mutation scanning, allowing the strong reduction of sequencing burden. AB - We previously validated mutation scanning for BRCA1 and 2 using high-resolution melting curve analysis (HRMCA). Due to recurrent single nucleotide polymorphisms (SNPs), a considerable amount of sequencing work remains after HRMCA, as melting curves for SNPs and deleterious mutations may be similar. Here, we present a simple approach for the optimization of SNP genotyping with HRMCA using unlabeled probes. Protocols were optimized for 14 frequent SNPs in BRCA1 and 2. Two probes contained an additional mismatch to detect a rare polymorphism a few nucleotides upstream. PCR was performed in the presence of LCgreenPlus and analyzed on a Lightscanner. Genotyping assays were optimized with five wild-type, heterozygous, and homozygous mutant samples. Sensitivity and specificity of the assays were evaluated with a blind screening of 95 samples. All unlabeled probes correctly genotyped the SNPs. A 1:5 asymmetric primer ratio produced sufficient probe strand duplexes to accurately genotype the SNP of interest. The most important parameter to optimize was the number of PCR cycles. By complementing our BRCA1/2 HRMCA with 14 unlabeled probe assays, we reduced the sequencing burden by three fold. Our simple approach for optimization can be used as a blueprint to design genotyping assays for other genes. This is one of the largest studies reported to date and the first that presents an approach combining genotyping and mutation scanning of two large polymorphic genes. PMID- 19644022 TI - Evaluation of 13q14 status in multiple myeloma by digital single nucleotide polymorphism technology. AB - Chromosome 13q deletions are common in multiple myeloma and other cancers, demonstrating the importance of this region in tumorigenesis. We used a novel single nucleotide polymorphism (SNP)-based technique, digital SNP (dSNP), to identify loss of heterozygosity (LOH) at chromosome 13q in paraffin-embedded bone marrow biopsies from 22 patients with multiple myeloma. We analyzed heterozygous SNPs at 13q for the presence of allelic imbalances and examined the results by sequential probability ratio analysis. Where possible, dSNP results were confirmed by fluorescence in situ hybridization. Using dSNP, we identified 13q LOH in 16/18 (89%) (95% Confidence Interval; 65%, 99%) patients without the need for neoplastic cell enrichment. In 8/16 (50%) cases, either partial or interstitial patterns of LOH were observed. Both fluorescence in situ hybridization and dSNP data proved concordant in just 3/9 cases. Five of the six discrepancies showed LOH by dSNP occurring beyond the boundaries of the fluorescence in situ hybridization probes. Our findings show that dSNP represents a useful technique for the analysis of LOH in archival tissue with minimal infiltration of neoplastic cells. The high-resolution screening afforded by the dSNP technology allowed for the identification of complex chromosomal rearrangements, resulting in either partial or interstitial LOH. Digital SNP represents an attractive approach for the investigation of tumors not suitable for genomic-array analysis. PMID- 19644024 TI - Rapid detection of KIT mutations in core-binding factor acute myeloid leukemia using high-resolution melting analysis. AB - The most frequent KIT mutations reported in core-binding factor acute myeloid leukemia are point mutations and insertions/deletions in exons 17 and 8. The vast majority of KIT mutation detection procedures are time-consuming, costly, or with a high lower limit of detection. High-resolution melting (HRM) is a gene scanning method that combines simplicity and rapid identification of genetic variants. We describe an HRM method for the simultaneous screening of exons 8 and 17 KIT mutations and report the results obtained in 69 core-binding factor acute myeloid leukemia patients. Mutation detection was compared with sequencing as the gold standard. The HRM method used high-resolution melting master reagents (Roche) and the LightCycler 480 (Roche) platform. HRM was reproducible, showed a lower limit of detection of 1%, and discriminated all patients with mutated KIT from controls without false positive or false negative results. Additionally, most of the mutations were differentiated from the other mutations. KIT mutations were present in 15.9% of patients, showing a higher incidence in inv(16) (25.8%) than in t(8;21) (7.9%). The presence of a KIT mutation was associated with a high white blood cell count, and adult patients with an exon 17 mutation had a higher incidence of relapse. These findings verify that HRM is a reliable, rapid, and sensitive method for KIT mutation screening. Furthermore, our study corroborates the unfavorable prognosis associated with exon 17 KIT mutations. PMID- 19644023 TI - Pharmacogenetics of solid tumors: directed therapy in breast, lung, and colorectal cancer: a paper from the 2008 william beaumont hospital symposium on molecular pathology. AB - Genetic variability in drug-metabolizing enzymes and signaling pathways affects chemotherapy-related toxicity and treatment outcome in cancer. In breast and colorectal cancer, polymorphisms in metabolic enzymes involved in tamoxifen and irinotecan therapies has led the U.S. Food and Drug Administration to address genetic factors relevant to patient consideration of treatment with these compounds. Tamoxifen therapeutic failure in breast cancer has been associated with reduced CYP2D6 activity due to inefficient activation of tamoxifen. Irinotecan toxicity in colorectal cancer is more common in patients with reduced activity UGT1A alleles, resulting in excessive exposure to the potent SN-38 metabolite. In colorectal and lung cancers, somatic mutations in the epidermal growth factor receptor and downstream signaling molecules have been associated with the therapeutic outcome of epidermal growth factor receptor-directed therapies. This review discusses the current knowledge regarding the utility of single gene-UGT1A1, CYP2D6, EGFR, and KRAS-or multigene analysis, for optimizing breast, colorectal, and lung cancer therapy. Current advances in these areas highlight how pharmacogenetics help personalized decision-making for patient management. PMID- 19644025 TI - Human papillomavirus genotyping using an automated film-based chip array. AB - The INFINITI HPV-QUAD assay is a commercially available genotyping platform for human papillomavirus (HPV) that uses multiplex PCR, followed by automated processing for primer extension, hybridization, and detection. The analytical performance of the HPV-QUAD assay was evaluated using liquid cervical cytology specimens, and the results were compared with those results obtained using the digene High-Risk HPV hc2 Test (HC2). The specimen types included Surepath and PreservCyt transport media, as well as residual SurePath and HC2 transport media from the HC2 assay. The overall concordance of positive and negative results following the resolution of indeterminate and intermediate results was 83% among the 197 specimens tested. HC2 positive (+) and HPV-QUAD negative (-) results were noted in 24 specimens that were shown by real-time PCR and sequence analysis to contain no HPV, HPV types that were cross-reactive in the HC2 assay, or low virus levels. Conversely, HC2 (-) and HPV-QUAD (+) results were noted in four specimens and were subsequently attributed to cross-contamination. The most common HPV types to be identified in this study were HPV16, HPV18, HPV52/58, and HPV39/56. We show that the HPV-QUAD assay is a user friendly, automated system for the identification of distinct HPV genotypes. Based on its analytical performance, future studies with this platform are warranted to assess its clinical utility for HPV detection and genotyping. PMID- 19644026 TI - Effects of acute hypoxia and hyperthermia on the permeability of the blood-brain barrier in adult rats. AB - Acute mountain sickness (AMS) develops within a few hours after arrival at high altitude and includes headache, anorexia, nausea, vomiting, and malaise. This afflicts 15-25% of the general tourist population at moderate altitudes. High altitude cerebral edema (HACE) is considered to be the end stage of severe AMS and has been suggested to be a vasogenic edema, raising the possibility that acute hypoxia may increase blood-brain barrier (BBB) permeability. At present, there are no good small-animal models to study this syndrome. We hypothesize 1) that acute hypoxia can damage the BBB and 2) that rat can be used as a model to study hypoxia-induced changes in BBB permeability, especially if hypoxia-induced hypothermia could be minimized with high ambient temperature (HAT). Male Wistar rats were exposed to 1, 2, and 7 days of hypobaric hypoxia (equivalent to 0.5 atm), and changes in the temperature and BBB permeability were studied. The extravasation of endogenous immunoglobulin G, a large molecule, did not increase during room temperature hypoxia but did increase when hypoxia was combined with HAT. Hypoxia caused a significant increase in the leakage of sodium fluorescein (mol wt 376 Da). The expression of endothelial barrier antigen (EBA), a protein associated with the BBB, was reduced to 50% between 24 and 48 h after exposure to hypoxia, and the loss was exacerbated by HAT. The values almost returned to control levels by 7 days, showing adaptation to hypoxia. Hypoxic rats exhibited sodium fluorescein leakage mainly in focal areas in the brain parenchyma. In conclusion, it is possible to have transient BBB damage through exposure to acute hypoxia, and this damage is exacerbated by increasing body temperature to more of a normothermic value. PMID- 19644027 TI - Muscle apoptosis is induced in pressure-induced deep tissue injury. AB - Pressure ulcer is a complex and significant health problem. Although the factors including pressure, shear, and ischemia have been identified in the etiology of pressure ulcer, the cellular and molecular mechanisms that contribute to the development of pressure ulcer are unclear. This study tested the hypothesis that the early-onset molecular regulation of pressure ulcer involves apoptosis in muscle tissue. Adult Sprague-Dawley rats were subjected to an in vivo protocol to mimic pressure-induced deep tissue injury. Static pressure was applied to the tibialis region of the right limb of the rats for 6 h each day on two consecutive days. The compression force was continuously monitored by a three-axial force transducer equipped in the compression indentor. The contralateral uncompressed limb served as intra-animal control. Tissues underneath the compressed region were collected for histological analysis, terminal dUTP nick-end labeling (TUNEL), cell death ELISA, immunocytochemical staining, and real-time RT-PCR gene expression analysis. The compressed muscle tissue generally demonstrated degenerative characteristics. TUNEL/dystrophin labeling showed a significant increase in the apoptotic muscle-related nuclei, and cell death ELISA demonstrated a threefold elevation of apoptotic DNA fragmentation in the compressed muscle tissue relative to control. Positive immunoreactivities of cleaved caspase-3, Bax, and Bcl-2 were evident in compressed muscle. The mRNA contents of Bax, caspase-3, caspase-8, and caspase-9 were found to be higher in the compressed muscle tissue than control. These results demonstrated that apoptosis is activated in muscle tissue following prolonged moderate compression. The data are consistent with the hypothesis that muscle apoptosis is involved in the underlying mechanism of pressure-induced deep tissue injury. PMID- 19644028 TI - An artificial neural network to estimate physical activity energy expenditure and identify physical activity type from an accelerometer. AB - The aim of this investigation was to develop and test two artificial neural networks (ANN) to apply to physical activity data collected with a commonly used uniaxial accelerometer. The first ANN model estimated physical activity metabolic equivalents (METs), and the second ANN identified activity type. Subjects (n = 24 men and 24 women, mean age = 35 yr) completed a menu of activities that included sedentary, light, moderate, and vigorous intensities, and each activity was performed for 10 min. There were three different activity menus, and 20 participants completed each menu. Oxygen consumption (in ml x kg(-1) x min(-1)) was measured continuously, and the average of minutes 4-9 was used to represent the oxygen cost of each activity. To calculate METs, activity oxygen consumption was divided by 3.5 ml x kg(-1) x min(-1) (1 MET). Accelerometer data were collected second by second using the Actigraph model 7164. For the analysis, we used the distribution of counts (10th, 25th, 50th, 75th, and 90th percentiles of a minute's second-by-second counts) and temporal dynamics of counts (lag, one autocorrelation) as the accelerometer feature inputs to the ANN. To examine model performance, we used the leave-one-out cross-validation technique. The ANN prediction of METs root-mean-squared error was 1.22 METs (confidence interval: 1.14-1.30). For the prediction of activity type, the ANN correctly classified activity type 88.8% of the time (confidence interval: 86.4-91.2%). Activity types were low-level activities, locomotion, vigorous sports, and household activities/other activities. This novel approach of applying ANNs for processing Actigraph accelerometer data is promising and shows that we can successfully estimate activity METs and identify activity type using ANN analytic procedures. PMID- 19644029 TI - Maturation and long-term hypoxia alters Ca2+-induced Ca2+ release in sheep cerebrovascular sympathetic neurons. AB - The contribution of sympathetic nerves arising from the superior cervical ganglia (SCG) toward the growth and function of cerebral blood vessels is pertinent throughout maturation as well as in response to cardiovascular stress imposed by high-altitude long-term hypoxia (LTH). The function of SCG sympathetic neurons is dependent on intracellular Ca2+ concentration ([Ca2+]i) signaling, which is strongly influenced by a process known as Ca(2+)-induced Ca2+ release (CICR) from the smooth endoplasmic reticulum (SER). In this study, we used the sheep SCG neuronal model to test the hypotheses that maturation decreases CICR and high altitude LTH depresses CICR in fetal SCG neurons but not in those of the adult. We found that the contribution of CICR to electric field stimulation (EFS)-evoked [Ca2+]i transients was greatest in SCG cells from normoxic fetuses and was abolished by LTH. The decline in CICR was associated with a reduction in sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) function in fetal SCG cells during LTH, reducing SER Ca2+ levels below the threshold needed for the coupling of Ca2+ influx and CICR. With respect to the maturation from the fetus to adult, the decrease in CICR may reflect both a reduction in the levels of ryanodine receptor isoforms 2 and 3 and SERCA function. In response to LTH and in contrast to the fetus, CICR function in adult SCG cells is maintained and may reflect alterations in other mechanisms that modulate the CICR process. As CICR is instrumental in the function of sympathetic neurons within the cerebrovasculature, the loss of this signaling mechanism in the fetus may have consequences for the adaptation to LTH in terms of fetal susceptibility to vascular insults. PMID- 19644030 TI - No major sex differences in muscle protein synthesis rates in the postabsorptive state and during hyperinsulinemia-hyperaminoacidemia in middle-aged adults. AB - Men have more muscle than women, but most studies evaluating sex differences in muscle protein metabolism have been unable to discern sexual dimorphism in basal muscle protein turnover rates in young and middle-aged adults. We hypothesized that the anabolic response to nutritional stimuli (i.e., amino acids and insulin) would be greater in young/middle-aged men than women. We therefore measured the rates of muscle protein synthesis (MPS) in 16 healthy individuals [8 men and 8 women, matched for age (mean +/- SE: 37.7 +/- 1.5 yr) and body mass index (25.2 +/- 0.7 kg/m2)] after an overnight fast (plasma insulin approximately 5 microU/ml and plasma phenylalanine approximately 60 microM) and during a hyperinsulinemic hyperaminoacidemic-euglycemic clamp (plasma insulin approximately 28 microU/ml; plasma phenylalanine approximately 110 microM; plasma glucose approximately 5.4 mM). The rates of MPS were not different between men and women (ANOVA main effect for sex; P = 0.49). During the clamp, the rate of MPS increased by approximately 50% (P = 0.003) with no difference in the increases from basal values between men and women (+0.019 +/- 0.004 vs. +0.018 +/- 0.010%/h, respectively; P = 0.93). There were also no differences between men and women in the basal concentrations of muscle phosphorylated Akt(Ser473), Akt(Thr308), mTOR(Ser2448), and p70s6k(Thr389) or in the hyperinsulinemia-hyperaminoacidemia-induced increases in phosphorylation of those signaling elements (P > or = 0.25). We conclude that there are no major differences in the rate of MPS and its intracellular control during basal conditions and during hyperinsulinemia-hyperaminoacidema between young and middle-aged adult men and women. PMID- 19644031 TI - Systemic hypoxia enhances exercise-mediated bactericidal and subsequent apoptotic responses in human neutrophils. AB - Phagocytosis and oxidative burst are critical host defense mechanisms in which neutrophils clear invading pathogens. Clearing phagocytic neutrophils by triggering apoptosis is an essential process for controlling inflammation. This study elucidates how various exercise bouts with/without hypoxia affected neutrophil bactericidal activity and subsequent apoptosis in humans. Fifteen sedentary males performed six distinct experimental tests in an air-conditioned normobaric hypoxia chamber: two normoxic exercises [strenuous exercise (SE; up to maximal O2 consumption) and moderate exercise (ME; 50% maximal O2 consumption for 30 min) while exposed to 21% O2], two hypoxic exercises (ME for 30 min while exposed to 12% and 15% O2), and two hypoxic exposures (resting for 30 min while exposed to 12% and 15% O2). The results showed that 1) plasma complement-C3a desArg/C4a desArg/C5a concentrations were increased, 2) expressions of L selectin/lymphocyte functin-associated antigen-1/Mac-1/C5aR on neutrophils were enhanced, 3) phagocytosis of neutrophils to Esherichia coli and release of neutrophil oxidant products by E. coli were elevated, and 4) E. coli-induced phosphotidylserine exposure or caspase-3 activation of neutrophils were promoted immediately and 2 h after both 12% O2 exposure at rest and with ME as well as normoxic SE. Although neither normoxic ME nor breathing 15% O2 at rest influenced these complement- and neutrophil-related immune responses, ME at both 12% and 15% O2 resulted in enhanced complement activation in the blood, expressions of opsonic/complement receptors on neutrophils, or the bactericidal activity and apoptosis of neutrophils. Moreover, the increased neutrophil oxidant production and apoptosis by normoxic SE and hypoxic ME were ameliorated by treating neutrophils with diphenylene iodonium (a NADPH oxidase inhibitor). Therefore, we conclude that ME at 12-15% O2 enhances bactericidal capacity and facilitates the subsequent apoptosis of neutrophils. PMID- 19644033 TI - Isometric contractions reduce plantar flexor moment, Achilles tendon stiffness, and neuromuscular activity but remove the subsequent effects of stretch. AB - The effects of isometric contractions and passive stretching on muscle-tendon mechanics and muscle activity were studied in 16 healthy human volunteers. First, peak concentric and passive ankle joint moment data were recorded on an isokinetic dynamometer with electromyographic monitoring of the triceps surae; real-time motion analysis of the lower leg and ultrasound imaging of the Achilles medial gastrocnemius muscle-tendon junction were simultaneously conducted. Second, the subjects performed six 8-s maximal voluntary isometric contractions (MVICs) before repeating the passive and active trials. Although there was no decrease in isometric joint moment after MVICs, peak concentric moment was significantly reduced (11.5%, P < 0.01). This was accompanied by, and correlated with (r = 0.90, P < 0.01), significant reductions in peak triceps surae electromyographic amplitude (21.0%, P < 0.01). Achilles tendon stiffness (10.9%, P < 0.01) and passive joint moment (4.9%, P < 0.01) were also significantly reduced. Third, the subjects performed three 60-s static plantar flexor stretches before being retested 2 and 30 min after stretch. The stretch protocol caused no significant change in any measure. At 30 min after stretching, significant recovery in concentric moment and muscle activity was detected at dorsiflexed joint angles, while Achilles tendon stiffness and passive joint moment remained significantly reduced. These data show that the performance of MVICs interrupts the normal stretch-induced losses in active and passive plantar flexor joint moment and neuromuscular activity, largely because concentric strength and tendon properties were already affected. Importantly, the decrease in Achilles tendon stiffness remained 30 min later, which may be an important etiological factor for muscle-tendon strain injury risk. PMID- 19644032 TI - Neuromuscular transmission failure and muscle fatigue in ankle muscles of the adult rat after spinal cord injury. AB - Current evidence suggests that significant morphological changes occur in nerve muscle connections caudal to spinal cord injury (SCI). To determine whether neuromuscular junction (NMJ) function is compromised after SCI, we investigated the contribution of NMJ failure to hindlimb muscle fatigue in control and spinalized adult rats. Repetitive supramaximal nerve stimulation was applied to two muscle-nerve preparations: medial gastrocnemius (MG)-tibial and tibialis anterior (TA)-peroneal. NMJ transmission failure was evident in control and SCI animals after repetitive stimulation. At 2 wk post-SCI, NMJ transmission failure was greater in SCI animals compared with controls, but the difference was not significant (P = 0.205 for the MG and P = 0.053 for the TA). At 6 wk post-SCI, there was a significant but small difference in NMJ transmission failure for the TA between control and spinal animals. These results demonstrate that, although there may be a mild decrement in NMJ function, NMJ transmission remains largely intact for supramaximal nerve stimulation. PMID- 19644034 TI - Breath-by-breath measurement of particle deposition in the lung of spontaneously breathing rats. AB - A number of deposition models for humans, as well as experimental animals, have been described. However, no breath-by-breath deposition measurement in rats has been reported to date. The objective of this study is to determine lung deposition of micrometer-sized particles as a function of breathing parameters in the adult rat lung. A new aerosol photometry system was designed to measure deposition of nonhygroscopic, 2-mum sebacate particles in anesthetized, intubated, and spontaneously breathing 90-day-old Wistar-Kyoto rats placed in a size-adjusted body plethysmograph box. Instrumental dead space of the system was minimized down to 310 microl (i.e., approximately 20% of respiratory dead space). The system allows continuous monitoring of particle concentration in the respired volume. Breathing parameters, such as respiratory rate (f), tidal volume (Vt), as well as inspiration/expiration times, were also monitored at different levels of anesthesia. The results showed that Vt typically varied between 1.5 and 4.0 ml for regular breathing and between 4.0 and 10.0 ml for single-sigh breaths; f ranged from 40 to 200 breaths/min. Corresponding deposition values varied between 5 and 50%, depending on breath-by-breath breathing patterns. The best fit of deposition (D) was achieved by a bilinear function of Vt and f and found to be D = 11.0 - 0.09.f + 3.75.Vt. We conclude that our approach provides more realistic conditions for the measurement of deposition than conventional models using ventilated animals and allows us to analyze the correlation between breath specific deposition and spontaneous breathing patterns. PMID- 19644037 TI - Strength training combined with plyometric jumps in adults: sex differences in fat-bone axis adaptations. PMID- 19644039 TI - Novel peptide antagonists of adrenomedullin and calcitonin gene-related peptide receptors: identification, pharmacological characterization, and interactions with position 74 in receptor activity-modifying protein 1/3. AB - Human adrenomedullin (AM) is a 52-amino acid peptide belonging to the calcitonin peptide family, which also includes calcitonin gene-related peptide (CGRP) and AM2. The two AM receptors, AM(1) and AM(2), are calcitonin receptor-like receptor (CL)/receptor activity-modifying protein (RAMP) (RAMP2 and RAMP3, respectively) heterodimers. CGRP receptors comprise CL/RAMP1. The only human AM receptor antagonist (AM(22-52)) is a truncated form of AM; it has low affinity and is only weakly selective for AM(1) over AM(2) receptors. To develop novel AM receptor antagonists, we explored the importance of different regions of AM in interactions with AM(1), AM(2), and CGRP receptors. AM(22-52) was the framework for generating further AM fragments (AM(26-52) and AM(30-52)), novel AM/alphaCGRP chimeras (C1-C5 and C9), and AM/AM(2) chimeras (C6-C8). cAMP assays were used to screen the antagonists at all receptors to determine their affinity and selectivity. Circular dichroism spectroscopy was used to investigate the secondary structures of AM and its related peptides. The data indicate that the structures of AM, AM2, and alphaCGRP differ from one another. Our chimeric approach enabled the identification of two nonselective high-affinity antagonists of AM(1), AM(2), and CGRP receptors (C2 and C6), one high-affinity antagonist of AM(2) receptors (C7), and a weak antagonist selective for the CGRP receptor (C5). By use of receptor mutagenesis, we also determined that the C-terminal nine amino acids of AM seem to be responsible for its interaction with Glu74 of RAMP3. We provide new information on the structure-activity relationship of AM, alphaCGRP, and AM2 and how AM interacts with CGRP and AM(2) receptors. PMID- 19644041 TI - Enhanced peroxisome proliferator-activated receptor-gamma expression in monocyte/macrophages from coronary artery disease patients and possible gender differences. AB - Peroxisome proliferator-activated receptor (PPAR) activation reduces inflammation and atherosclerosis, but recent evidence raised concerns about its beneficial clinical effects. However, the effects of gender on PPAR expression and basal cytokine release have not been investigated. In the present study, we evaluated PPAR-gamma and -alpha expression, as well as cytokine release, in monocyte/macrophages from 15 male and 15 female patients with coronary artery disease (CAD) in comparison with healthy controls. Both expression and activation of PPAR-alpha and PPAR-gamma proteins were evaluated by Western blot and electrophoretic mobility shift assay. Gene expression was evaluated by real-time polymerase chain reaction; cytokine release was measured by enzyme-linked immunosorbent assay. Monocyte/macrophages of CAD patients yielded a constitutively enhanced (approximately 10-fold; p < 0.001) protein expression of PPAR-gamma, but not PPAR-alpha, compared with healthy controls. Evaluation of PPAR-gamma gene expression showed a 60-fold increase in monocytes from CAD patients, compared with healthy donors. Moreover, monocytes spontaneously released higher amounts of proinflammatory cytokines than macrophages. It is interesting that monocytes from CAD females expressed significantly higher levels of PPAR-gamma protein compared with male patients (p < 0.05) and showed the lowest basal release of tumor necrosis factor-alpha. These results indicate that the expression of PPAR-gamma is significantly higher in CAD patients than in healthy donors and that, together with cytokine release, it seems to be gender related. In fact, CAD women demonstrated the highest PPAR-gamma expression and the lowest cytokine release. Such differences may, in part, modulate the response to PPAR-gamma activators. PMID- 19644040 TI - The role of alpha6-containing nicotinic acetylcholine receptors in nicotine reward and withdrawal. AB - The alpha6 nicotinic acetylcholine receptor (nAChR) subunit is involved in nicotine-stimulated dopamine release in the striatum. It is expressed in brain regions and coexpressed with nAChR subtypes implicated in nicotine dependence behaviors; hence, this subunit may play a role in nicotine dependence. Using the alpha6-selective antagonist alpha-conotoxin H9A;L15A (MII[H9A;L15A]), we determined the role of alpha6* nAChRs in the pharmacological and behavioral effects of nicotine. We measured effects of pretreatment with MII[H9A;L15A] on analgesia, locomotion, and body temperature after a single injection of nicotine. Effects of MII[H9A;L15A] on nicotine reward were measured using the conditioned place preference (CPP) paradigm. We further measured physical (somatic signs and hyperalgesia) and affective [anxiety-related behavior and conditioned place aversion (CPA)] nicotine withdrawal behaviors after extended nicotine exposure. Results showed that MII[H9A;L15A] did not block acute nicotine effects on the behaviors measured. Conversely, MII[H9A:l15A] blocked the expression of nicotine CPP, as well as withdrawal-associated CPA and anxiety-related behavior in the elevated plus maze, but not withdrawal-induced somatic signs or hyperalgesia. These results suggest a role for the alpha6 nAChR subunit in nicotine reward and affective nicotine withdrawal but not acute nicotine-induced or physical withdrawal behaviors. PMID- 19644042 TI - Neuroprotection by tosyl-polyamine derivatives through the inhibition of ionotropic glutamate receptors. AB - Tosyl-polyamine derivatives such as N-{4-[4-(guanidinobutylamino) butylamino]butyl}-4-methylbenzenesulfonamide trihydrochroride (TsHSPMG) have been found to strongly inhibit macroscopic currents through heteromeric N-methyl-D aspartate (NMDA) receptors (NR1/NR2A, NR1/NR2B) and Ca(2+)-permeable alpha-amino 3-hydroxy-5-methyl-4-isoxazolepropionic acid (homomeric glutamate receptor 1) receptors expressed in Xenopus laevis oocytes on voltage-clamp recording. In the present study, it was found that the inhibition of NMDA receptor activity induced by tosyl-polyamine derivatives was voltage-dependent. Some mutations located in the intracellular region of the channel pore, such as NR1 E621Q and NR2B W607L, reduced the inhibition by tosyl-polyamine derivatives, suggesting that tosyl polyamine derivatives penetrate deeply into the channel pore of NMDA receptors. The neuroprotective effects of tosyl-polyamine derivatives against cell injury caused by NMDA were investigated in cultured rat hippocampal neurons. Addition of 1 microM TsHSPMG to medium ablated the neurotoxicity induced by NMDA, and a similar effect was observed with 30 microM memantine. The neuroprotective effects of tosyl-polyamine derivatives on NMDA-induced seizures in mice were also assayed. Intracerebroventricular or intravenous injection of TsHSPMG (0.1 or 0.5 mg/kg) decreased the seizures induced by intraperitoneal injection of NMDA in mice. These findings indicate that tosyl-polyamine derivatives exhibit neuroprotective effects not only in primary cultured neurons but also in mice. PMID- 19644043 TI - The impact of obesity on oxygen desaturation during sleep-disordered breathing. AB - RATIONALE: Obesity increases the risk and severity of sleep-disordered breathing. The degree to which excess body weight contributes to blood oxygen desaturation during hypopneic and apneic events has not been comprehensively characterized. OBJECTIVES: To quantify the association between excess body weight and oxygen desaturation during sleep-disordered breathing. METHODS: A total of 750 adult participants in the Wisconsin Sleep Cohort Study were assessed for body mass index (BMI) (kg/m(2)) and sleep-disordered breathing. The amount of Sa(O(2)), duration, and other characteristics of 37,473 observed breathing events were measured during polysomnography studies. A mixed-effects linear regression model estimated the association of blood oxygen desaturation with participant-level characteristics, including BMI, gender, and age, and event-level characteristics, including baseline Sa(O(2)), change in Vt, event duration, sleep state, and body position. MEASUREMENTS AND MAIN RESULTS: BMI was positively associated with oxygen desaturation severity independent of age, gender, sleeping position, baseline Sa(O(2)), and event duration. BMI interacted with sleep state such that BMI predicted greater desaturation in rapid eye movement (REM) sleep than in non REM sleep. Each increment of 10 kg/m(2) BMI predicted a 1.0% (SE, 0.2%) greater mean blood oxygen desaturation for persons in REM sleep experiencing hypopnea events associated with 80% Vt reductions. CONCLUSIONS: Excess body weight is an important predictor of the severity of blood oxygen desaturation during apnea and hypopnea events, potentially exacerbating the impact of sleep-disordered breathing in obese patients. PMID- 19644045 TI - Efficacy and tolerability of budesonide/formoterol added to tiotropium in patients with chronic obstructive pulmonary disease. AB - RATIONALE: Budesonide/formoterol and tiotropium are commonly used maintenance treatments for patients with chronic obstructive pulmonary disease. Combining these medications may provide additional benefits. OBJECTIVES: To assess the efficacy and tolerability of budesonide/formoterol added to tiotropium in patients eligible for inhaled corticosteroid/long-acting beta(2)-agonist combination therapy. METHODS: In this 12-week, randomized, double-blind, parallel group, multicenter study, after a 2-week run-in, 660 subjects (75% male; mean age, 62 yr; FEV(1), 1.1 L; 38% predicted normal), 40 years of age or older, received tiotropium (18 microg once daily) plus either budesonide/formoterol (320/9 microg) (n = 329) or placebo (n = 331) twice daily. MEASUREMENTS AND MAIN RESULTS: Clinic predose (primary outcome) and postdose FEV(1), predose and postdose forced vital capacity and inspiratory capacity, and health status were measured. Other outcomes included daily measurements taken at home (pre- and postdose morning FEV(1) and peak expiratory flow, morning symptoms and activities, and morning reliever use), severe exacerbations, and tolerability. Over the treatment period, budesonide/formoterol plus tiotropium significantly increased predose FEV(1) by 6% (65 ml) and postdose by 11% (123 and 131 ml at 5 and 60 min postdose, respectively) versus tiotropium alone (both P < 0.001). Other outcomes all significantly improved with budesonide/formoterol plus tiotropium versus tiotropium alone. The number of severe exacerbations decreased by 62% (rate ratio, 0.38; 95% confidence interval, 0.25-0.57; P < 0.001). Both treatments were well tolerated. CONCLUSIONS: In patients with chronic obstructive pulmonary disease, budesonide/formoterol added to tiotropium versus tiotropium alone provides rapid and sustained improvements in lung function, health status, morning symptoms and activities, and reduces severe exacerbations. Clinical trial registered with www.clinicaltrials.gov (NCT00496470). PMID- 19644046 TI - Down-regulation of miR-133a contributes to up-regulation of Rhoa in bronchial smooth muscle cells. AB - RATIONALE: Augmented bronchial smooth muscle (BSM) contraction is one of the causes of bronchial hyperresponsiveness. The protein RhoA and its downstream pathways have now been proposed as a new target for asthma therapy. MicroRNAs (miRNAs) play important roles in normal and diseased cell functions, and a contribution of miR-133 to RhoA expression has been suggested in cardiomyocytes. OBJECTIVES: To make clear the mechanism(s) of up-regulation of RhoA observed in the BSMs of experimental asthma, the role of miR-133a in RhoA expression was tested. METHODS: Total proteins and RNAs (containing miRNAs) were extracted from cultured human BSM cells (hBSMCs) that were treated with antagomirs and/or IL-13, and bronchial tissues of BALB/c mice that were sensitized and repeatedly challenged with ovalbumin. RhoA protein and miR-133a were detected by immunoblotting and quantified real-time reverse transcriptase-polymerase chain reaction, respectively. MEASUREMENTS AND MAIN RESULTS: In hBSMCs, an up regulation of RhoA was observed when the function of endogenous miR-133a was inhibited by its antagomir. Treatment of hBSMCs with IL-13 caused an up regulation of RhoA and a down-regulation of miR-133a. In bronchial tissues of the repeatedly ovalbumin-challenged mice, a significant increase in RhoA was observed. Interestingly, the level of miR-133a was significantly decreased in BSMs of the challenged mice. CONCLUSIONS: These findings suggest that RhoA expression is negatively regulated by miR-133a in BSMs. IL-13 might, at least in part, contribute to the reduction of miR-133a. PMID- 19644047 TI - Decoy receptor 3 levels in peripheral blood predict outcomes of acute respiratory distress syndrome. AB - RATIONALE: Acute respiratory distress syndrome (ARDS), a serious inflammatory reaction to acute lung injury, is associated with high mortality rates. Decoy receptor (DcR) 3 is a soluble protein with immunomodulatory effects. Biomarkers that reliably predict outcomes in ARDS are not currently available. OBJECTIVES: Comparing DcR3 with the Acute Physiology and Chronic Health Evaluation (APACHE) II scores and three other plasma markers to explore the association of DcR3 and the clinical outcome in ARDS. METHODS: Eighty-eight patients with ARDS were studied. Baseline APACHE II scores and clinical data were recorded. Plasma levels of DcR3, soluble triggering receptor expressed on myeloid cells (sTREM)-1, tumor necrosis factor (TNF)-alpha, and IL-6 were measured on Day 1 and later time points, and correlated with the survival status on Day 28 after the onset of ARDS. For validation, 59 patients with ARDS from another medical center were studied. MEASUREMENTS AND MAIN RESULTS: Among the biomarkers evaluated, only DcR3 discriminated the survivors and nonsurvivors at all time points in the first week of ARDS. DcR3 independently associated with and best predicted the 28-day mortality of patients with ARDS. Plasma DcR3 levels most correlated to multiple organ dysfunction and ventilator dependence. Compared with survivors, the nonsurvivors had higher DcR3 levels regardless of the APACHE II scores. Kaplan Meier survival analysis showed higher mortality in patients with ARDS with higher DcR3 levels. The outcome prediction of patients with ARDS by plasma DcR3 levels was recapitulated by the validation cohort. CONCLUSIONS: High plasma DcR3 levels correlate with development of multiple-organ dysfunction and independently predict the 28-day mortality in patients with ARDS. PMID- 19644048 TI - The prevalence of nonadherence in difficult asthma. AB - RATIONALE: With the advent of new and expensive therapies for severe refractory asthma, targeting the appropriate patients is important. An important issue is identifying nonadherence with current therapies. The extent of nonadherence in a population with difficult asthma has not been previously reported. OBJECTIVES: To examine the prevalence of nonadherence to corticosteroid medication in a population with difficult asthma referred to a Specialist Clinic and to examine the relationship of poor adherence to asthma outcome. METHODS: General practitioner prescription refill records for the previous 6 months for inhaled combination therapy and short-acting beta-agonists were compared with initial prescriptions and expressed as a percentage. Blood plasma prednisolone and cortisol assay levels were used to examine the utility of these measures in assessing adherence to oral prednisolone. Patient demographics, hospital admissions, lung function, oral prednisolone courses, and quality of life data were analyzed to indentify the variables associated with reduced medication adherence. MEASUREMENTS AND MAIN RESULTS: A total of 182 patients were assessed. Sixty-three patients (35%) filled 50% or fewer inhaled medication prescriptions; 88% admitted poor adherence with inhaled therapy after initial denial. Twenty-one percent of patients filled more than 100% of presciptions, and 45% of subjects filled between 51 and 100% of prescriptions. Twenty-three of 51 patients (45%) prescribed oral steroids were found to be nonadherent. CONCLUSIONS: A significant proportion of patients with difficult-to-control asthma remained nonadherent to corticosteroid therapy. Objective surrogate and direct measures of adherence should be performed as part of a difficult asthma assessment and are important before prescibing expensive novel biological therapies. PMID- 19644050 TI - Preventive effects of heregulin-beta1 on macrophage foam cell formation and atherosclerosis. AB - RATIONALE: Human heregulins, neuregulin-1 type I polypeptides that activate proliferation, differentiation, and survival of glial cells, neurons, and myocytes, are expressed in macrophage foam cells within human coronary atherosclerotic lesions. Macrophage foam cell formation, characterized by cholesterol ester accumulation, is modulated by scavenger receptor class A (SR A), acyl-coenzyme A:cholesterol acyltransferase (ACAT)1, and ATP-binding cassette transporter (ABC)A1. OBJECTIVE: The present study clarified the roles of heregulins in macrophage foam cell formation and atherosclerosis. METHODS AND RESULTS: Plasma heregulin-beta(1) levels were significantly decreased in 31 patients with acute coronary syndrome and 33 patients with effort angina pectoris compared with 34 patients with mild hypertension and 40 healthy volunteers (1.3+/ 0.3, 2.0+/-0.4 versus 7.6+/-1.4, 8.2+/-1.2 ng/mL; P<0.01). Among all patients with acute coronary syndrome and effort angina pectoris, plasma heregulin-beta(1) levels were further decreased in accordance with the severity of coronary artery lesions. Expression of heregulin-beta(1) was observed at trace levels in intracoronary atherothrombosis obtained by aspiration thrombectomy from acute coronary syndrome patients. Heregulin-beta(1), but not heregulin-alpha, significantly reduced acetylated low-density lipoprotein-induced cholesterol ester accumulation in primary cultured human monocyte-derived macrophages by reducing SR-A and ACAT1 expression and by increasing ABCA1 expression at both mRNA and protein levels. Heregulin-beta(1) significantly decreased endocytic uptake of [(125)I]acetylated low-density lipoprotein and ACAT activity, and increased cholesterol efflux to apolipoprotein (Apo)A-I from human macrophages. Chronic infusion of heregulin-beta(1) into ApoE(-/-) mice significantly suppressed the development of atherosclerotic lesions. CONCLUSIONS: This study provided the first evidence that heregulin-beta(1) inhibits atherogenesis and suppresses macrophage foam cell formation via SR-A and ACAT1 downregulation and ABCA1 upregulation. PMID- 19644051 TI - Chronic hypoxia activates the Akt and beta-catenin pathways in human macrophages. AB - OBJECTIVE: Macrophage activation contributes importantly to the pathogenesis of inflammatory diseases including atherosclerosis. Macrophages exist chronically under moderate hypoxia (2% to 5% O(2)) in inflamed tissues such as atherosclerotic plaques. However, macrophage phenotypes in such environments remain incompletely understood. This study tested the hypothesis that chronic moderate hypoxia induces macrophage activation and explored the underlying mechanisms. METHODS AND RESULTS: We cultured primary human macrophages derived from peripheral blood monocytes in moderate hypoxia (2% O(2) tension) or normoxia (21% O(2)) for 10 days. Moderate hypoxia did not affect macrophage differentiation assessed via expression levels of scavenger receptor A. Chronic moderate hypoxia, but not normoxia, activated Akt and inactivated GSK-3beta, a negative effector of Akt, thus allowing nuclear translocation of beta-catenin. 2% O(2) tension increased accumulation of hypoxia-inducible factors 1 alpha (HIF-1 alpha) transiently at 3 to 5 days. Hypoxia induced mRNA expression of the beta catenin-associated genes: MMP-7, CD44, and c-Myc. RNAi of TCF7L2, a cofactor of beta-catenin, suppressed MMP-7 expression induced by hypoxia. Inhibition of Akt phosphorylation with LY294002 abolished hypoxia-induced GSK-3beta inactivation, beta-catenin activation, and MMP-7 expression. Macrophages under hypoxia were more resistant for oxLDL-induced apoptosis. Moreover, phospho-Akt colocalized with MMP-7 and CD44 expression in macrophages of human atherosclerotic plaques. CONCLUSIONS: Chronic moderate hypoxia induces macrophage activation via the Akt and beta-catenin pathways, providing new insight into the pathogenesis of inflammatory diseases. PMID- 19644052 TI - Carotid intima-media thickness, systemic inflammation, and incidence of heart failure hospitalizations. AB - OBJECTIVE: This study explored the relationships between carotid intima-media thickness (IMT), plasma levels of C-reactive protein (CRP), and incidence of heart failure hospitalizations. METHODS AND RESULTS: Men and women from the general population (n=4691), without history of myocardial infarction or stroke, were examined. Incidence of hospitalizations attributable to heart failure was studied over a mean follow-up of 13 years. A total of 75 subjects were hospitalized with a primary diagnosis of heart failure. Adjusted for risk factors, the hazards ratios (95% CI) were 1.00, 0.98 (0.36 to 2.7), 1.9 (0.80 to 4.6), and 2.7 (1.1 to 6.2), respectively, for the 1st, 2nd, 3rd, and 4th quartiles of IMT (P for trend=0.003). The HR associated with CRP levels >or=3 mg/L (versus <1 mg/L) was 2.0 (95% CI: 1.06 to 3.9) after adjustments for risk factors. There was a significant interaction between IMT and CRP on heart failure incidence (P=0.028). Subjects with CRP >or=3 mg/L and IMT in the 4th quartile had an adjusted HR of 3.7 (1.9 to 7.1) compared to those with CRP <3 mg/L and IMT in quartile 1 to 3. CONCLUSIONS: High IMT and high CRP are both independent risk factors for incidence of heart failure requiring hospitalization. The joint exposure to both risk factors substantially increases the risk. PMID- 19644053 TI - Interplay between human adipocytes and T lymphocytes in obesity: CCL20 as an adipochemokine and T lymphocytes as lipogenic modulators. AB - OBJECTIVE: Adipose tissue (AT) plays a major role in the low-grade inflammatory state associated with obesity. The aim of the present study was to characterize the human AT lymphocytes (ATLs) and to analyze their interactions with adipocytes. METHODS AND RESULTS: Human ATL subsets were characterized by flow cytometry in subcutaneous ATs from 92 individuals with body mass index (BMI) ranging from 19 to 43 kg/m(2) and in paired biopsies of subcutaneous and visceral AT from 45 class II/III obese patients. CD3(+) ATLs were composed of effector and memory CD4(+) helper and CD8(+) cytotoxic T cells. The number of ATLs correlated positively with BMI and was higher in visceral than subcutaneous AT. Mature adipocytes stimulated the migration of ATLs and released the chemokine CCL20, the receptor of which (CCR6) was expressed in ATLs. The expression of adipocyte CCL20 was positively correlated with BMI and increased in visceral compared to subcutaneous adipocytes. ATLs expressed inflammatory markers and released interferon gamma (IFN gamma). Progenitor and adipocyte treatment with ATL conditioned media reduced the insulin-mediated upregulation of lipogenic enzymes, an effect involving IFN gamma. CONCLUSIONS: Therefore, crosstalk occurs between adipocytes and lymphocytes within human AT involving T cell chemoattraction by adipocytes and modulation of lipogenesis by ATLs. PMID- 19644054 TI - Role of bone marrow-derived cells in the genetic control of restenosis. AB - OBJECTIVE: Angiographic indexes of restenosis after coronary stent placement in patients show a bimodal pattern suggesting the existence of two populations with different risk of restenosis. This is reflected in the arterial remodeling response of inbred mouse strains arguing for a genetic control of the mechanisms leading to lumen narrowing. As bone marrow-derived cells (BMCs) contribute to vascular healing after arterial injury, we investigated the role of BMCs in the genetic control of restenosis. METHODS AND RESULTS: 129X1/SvJ mice developed significantly more neointima and late lumen loss compared to C57BL/6 mice. Gene expression analysis of intimal tissue revealed major differences in the expression of inflammatory and hematopoietic stem and progenitor cell-associated genes in response to arterial injury. In 129X1/SvJ mice stronger mobilization of lin(-)sca-1(+)CXCR4(+) cells was observed after vascular injury. Bone marrow transplantation identified the extent of neointima formation as clearly dependent on the genetic background of BMCs (ie, mice with 129X1/SvJ BMCs developed more intimal hyperplasia). The inflammatory response and the recruitment of BMCs to the site of arterial injury were significantly increased in mice with 129X1/SvJ BMCs. CONCLUSIONS: The genetically controlled mechanisms leading to lumen narrowing in vascular remodeling are dependent on mobilization and recruitment capacities of particular BMCs. PMID- 19644055 TI - NADPH oxidase 4: walking the walk with Poldip2. PMID- 19644056 TI - Why don't they beat?: Cripto, apelin/APJ, and myocardial differentiation. PMID- 19644049 TI - Prevalence and factors of intensive care unit conflicts: the conflicus study. AB - RATIONALE: Many sources of conflict exist in intensive care units (ICUs). Few studies recorded the prevalence, characteristics, and risk factors for conflicts in ICUs. OBJECTIVES: To record the prevalence, characteristics, and risk factors for conflicts in ICUs. METHODS: One-day cross-sectional survey of ICU clinicians. Data on perceived conflicts in the week before the survey day were obtained from 7,498 ICU staff members (323 ICUs in 24 countries). MEASUREMENTS AND MAIN RESULTS: Conflicts were perceived by 5,268 (71.6%) respondents. Nurse-physician conflicts were the most common (32.6%), followed by conflicts among nurses (27.3%) and staff-relative conflicts (26.6%). The most common conflict-causing behaviors were personal animosity, mistrust, and communication gaps. During end of-life care, the main sources of perceived conflict were lack of psychological support, absence of staff meetings, and problems with the decision-making process. Conflicts perceived as severe were reported by 3,974 (53%) respondents. Job strain was significantly associated with perceiving conflicts and with greater severity of perceived conflicts. Multivariate analysis identified 15 factors associated with perceived conflicts, of which 6 were potential targets for future intervention: staff working more than 40 h/wk, more than 15 ICU beds, caring for dying patients or providing pre- and postmortem care within the last week, symptom control not ensured jointly by physicians and nurses, and no routine unit-level meetings. CONCLUSIONS: Over 70% of ICU workers reported perceived conflicts, which were often considered severe and were significantly associated with job strain. Workload, inadequate communication, and end-of-life care emerged as important potential targets for improvement. PMID- 19644059 TI - Angiotensin receptor blockers and stroke therapy: it is all about the blood pressure. PMID- 19644058 TI - Hypoxic preconditioning-induced cerebral ischemic tolerance: role of microvascular sphingosine kinase 2. AB - BACKGROUND AND PURPOSE: The importance of bioactive lipid signaling under physiological and pathophysiological conditions is progressively becoming recognized. The disparate distribution of sphingosine kinase (SphK) isoform activity in normal and ischemic brain, particularly the large excess of SphK2 in cerebral microvascular endothelial cells, suggests potentially unique cell- and region-specific signaling by its product sphingosine-1-phosphate. The present study sought to test the isoform-specific role of SphK as a trigger of hypoxic preconditioning (HPC)-induced ischemic tolerance. METHODS: Temporal changes in microvascular SphK activity and expression were measured after HPC. The SphK inhibitor dimethylsphingosine or sphingosine analog FTY720 was administered to adult male Swiss-Webster ND4 mice before HPC. Two days later, mice underwent a 60 minute transient middle cerebral artery occlusion and at 24 hours of reperfusion, infarct volume, neurological deficit, and hemispheric edema were measured. RESULTS: HPC rapidly increased microvascular SphK2 protein expression (1.7+/-0.2 fold) and activity (2.5+/-0.6-fold), peaking at 2 hours, whereas SphK1 was unchanged. SphK inhibition during HPC abrogated reductions in infarct volume, neurological deficit, and ipsilateral edema in HPC-treated mice. FTY720 given 48 hours before stroke also promoted ischemic tolerance; when combined with HPC, even greater (and dimethylsphingosine-reversible) protection was noted. CONCLUSIONS: These findings indicate hypoxia-sensitive increases in SphK2 activity may serve as a proximal trigger that ultimately leads to sphingosine-1 phosphate-mediated alterations in gene expression that promote the ischemia tolerant phenotype. Thus, components of this bioactive lipid signaling pathway may be suitable therapeutic targets for protecting the neurovascular unit in stroke. PMID- 19644060 TI - Angiotensin receptor blockers should be regarded as first-line drugs for stroke prevention in both primary and secondary prevention settings: no. PMID- 19644057 TI - Mechanisms of transendothelial migration of leukocytes. AB - A great deal of progress has been made recently in understanding the molecules and mechanisms that regulate transendothelial migration of leukocytes, or diapedesis, a critical step in the inflammatory response. This review focuses mainly on the active role of the endothelial cell in this process as it occurs at endothelial cell borders. It discusses some of the many molecules that have been reported to play a role in transendothelial migration and asks why so many molecules seem to be involved. The concept is emerging that diapedesis itself can be dissected into sequential steps controlled by specific molecule(s) at the endothelial cell border. Several mechanisms have been shown to play a critical role in transendothelial migration including signals derived from clustering of apically disposed intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, disruption or loosening of adherens junctions, and targeted recycling of platelet/endothelial cell adhesion molecule and other molecules from the recently described lateral border recycling compartment. A hypothesis that integrates the various known mechanisms is proposed. PMID- 19644061 TI - Angiotensin receptor blockers should be regarded as first-line drugs for stroke prevention in both primary and secondary prevention settings: yes. PMID- 19644062 TI - Gene variation of the transient receptor potential cation channel, subfamily M, member 7 (TRPM7), and risk of incident ischemic stroke: prospective, nested, case control study. AB - BACKGROUND AND PURPOSE: Transient receptor potential cation channel, subfamily M, member 7 (TRPM7), has been implicated in ischemic brain damage, a major source of morbidity and mortality in westernized society. We hypothesized that TRPM7 gene variation might play a role in the risk of ischemic stroke. METHODS: From a group of DNA samples collected at baseline in a prospective cohort of 14 916 initially healthy American men, we assessed 16 TRPM7 tag-single-nucleotide polymorphisms (SNPs) (dbSNP: rs11854949, rs4775899, rs11635825, rs12905120, rs16973487, rs7173321, rs7163283, rs17520378, rs17520350, rs4775892, rs7174839, rs17645523, rs3109894, rs616256, rs11070795, and rs313158) from 245 white men who subsequently had an incident ischemic stroke and from 245 age- and smoking habit matched white men who remained free of reported vascular disease during follow-up (controls). RESULTS: All SNPs examined were in Hardy-Weinberg equilibrium. Overall allele, genotype, and haplotype distributions were similar between cases and controls. Marker-by-marker conditional logistic-regression analysis, adjusted for potential risk factors, showed no evidence for an association between any of the SNPs tested and ischemic stroke. Further investigation with an Entropy Blocker-defined, haplotype-based approach showed similar null findings. Prespecified analysis limited to participants without baseline diabetes and hypertension (ie, low-risk group) again showed similar null findings. CONCLUSIONS: The present prospective investigation provides no evidence of a role for the TRPM7 gene in the risk of incident ischemic stroke. PMID- 19644063 TI - Carotid intimal medial thickness predicts cognitive decline among adults without clinical vascular disease. AB - BACKGROUND AND PURPOSE: Though clinical cardiovascular and cerebrovascular diseases are established risk factors for cognitive decline and dementia, less is known about the relations between vascular health and cognition among individuals without these diseases. Carotid intimal medial thickness (IMT), a measure of subclinical vascular disease, is associated with concurrent decrements in cognitive function, but relatively little research has examined longitudinal relations between carotid IMT and prospective cognitive decline. METHODS: We examined relations of carotid IMT to prospective trajectories of cognitive function among 538 (aged 20 to 93, 39% male, 66% white) participants in the Baltimore Longitudinal Study of Aging (BLSA) free of known cardiovascular, cerebrovascular, and neurological disease. Participants underwent initial carotid ultrasonography and repeat neuropsychological testing on up to 8 occasions over up to 11 years of follow-up. Mixed-effects regression analyses were adjusted for age, gender, race, education, mean arterial pressure, body mass index, total cholesterol, smoking, depressive symptoms, and cardiovascular medication use. RESULTS: Individuals with greater carotid IMT displayed accelerated decline in performance over time on multiple tests of verbal and nonverbal memory, as well as a test of semantic association fluency and executive function. CONCLUSIONS: Carotid IMT predicts accelerated cognitive decline, particularly in the domain of memory, among community-dwelling individuals free of vascular and neurological disease. PMID- 19644065 TI - Lesion patterns and stroke mechanisms in concurrent atherosclerosis of intracranial and extracranial vessels. AB - BACKGROUND AND PURPOSE: Concurrent atherosclerosis of the intracranial and extracranial cerebrovascular system is common in Asians. The typical lesion patterns and the mechanisms of stroke in patients with concurrent stenoses are unclear. This study aimed to determine these stroke features of such patients in Hong Kong. METHODS: We conducted a cross-sectional cohort study in a university hospital from January 2002 to December 2003. Consecutive Chinese patients with acute ischemic stroke underwent CT brain, MRI brain (with MR angiography and diffusion-weighted imaging sequences), and carotid duplex. RESULTS: In total, 251 patients were included in the analysis. Of these, 109 (43%) had concurrent stenoses. Patients who had concurrent stenoses, as compared with those without concurrent stenoses, had more symptomatic stenoses (84% versus 58%; OR, 4.0; 95% CI, 2.1 to 7.3; P<0.001), more concomitant perforating artery infarct, pial infarct, and borderzone infarct (14% versus 4%; OR, 3.6; 95% CI, 1.4 to 9.7; P=0.007), more multiple diffusion-weighted imaging lesions (55% versus 37%; OR, 2.1; 95% CI, 1.3 to 3.4; P=0.005), and more infarcts in the territory of the leptomeningeal branches of middle cerebral artery (26% versus 13%; OR, 2.2; 95% CI, 1.2 to 4.3; P=0.01). In multivariate regression analysis, smoking; prior stroke; the presence of concomitant pial infarct, pial infarct, and borderzone infarcts; multiple diffusion-weighted imaging lesions; and symptomatic stenoses were significantly associated with concurrent stenoses. Among patients with concurrent stenoses, those who had tandem lesions, as compared with those who had nontandem lesions, had more perforating artery infarct and borderzone infarcts (27% versus 8%; OR, 4.3; 95% CI, 0.9 to 19.8; P=0.04); more concomitant pial infarct, pial infarct, and borderzone infarcts (18% versus 0%; P=0.02), and more multiple diffusion-weighted imaging lesions (65% versus 23%; OR, 6.2; 95% CI, 2.2 to 17.2; P<0.001). Infarcts in the territory of middle cerebral artery leptomeningeal branches and symptomatic stenoses were more common in patients with tandem lesions. CONCLUSIONS: Concomitant perforating artery infarct, pial infarct, and borderzone infarcts; multiple diffusion-weighted imaging lesions, and infarcts in the leptomeningeal branches of the middle cerebral artery were more common in patients with concurrent stenoses, especially those with tandem lesions. This study suggested that the combination of hemodynamic compromise attributable to concurrent stenoses and artery-to-artery embolization is a common stroke mechanism in these patients. PMID- 19644064 TI - Association of plasma ADMA levels with MRI markers of vascular brain injury: Framingham offspring study. AB - BACKGROUND AND PURPOSE: Asymmetrical dimethylarginine (ADMA), an inhibitor of endothelial nitric oxide synthase, is a marker of endothelial dysfunction. Elevated circulating ADMA concentrations have been associated with systemic and carotid atherosclerosis, an elevated risk of developing stroke, and magnetic resonance imaging white-matter hyperintensities (WMHs). The relation of plasma ADMA to subclinical vascular brain injury has not been previously studied in a middle-aged, community-based sample. METHODS: In 2013 stroke-free Framingham offspring (mean+/-SD age, 58+/-9.5 years; 53% women), we related baseline plasma ADMA levels (1995-1998) to subsequent brain magnetic resonance imaging measures (1999-2004) of subclinical vascular injury: presence of silent brain infarcts (SBIs) and large white-matter hyperintensity volumes (LWMHs; defined as >1 SD above the age-specific mean). RESULTS: Prevalences of SBIs and LWMHs were 10.7% and 12.6%, respectively. In multivariable analyses adjusting for age, sex and traditional stroke risk factors, higher ADMA levels were associated with an increased risk of prevalent SBIs (odds ratio [OR] per 1-SD increase in ADMA=1.16; 95% CI, 1.01 to 1.33; P=0.04). We observed that participants in the upper 3 age specific quartiles (Qs) of plasma ADMA values had an increased prevalence of SBIs (OR for Q2-Q4 vs Q1=1.43; 95% CI, 1.00 to 2.04; P<0.05). The prevalence of SBIs in Q1and Q2-Q4 was 8.3% and 11.6%, respectively. The prevalence of LWMHs did not differ according to ADMA concentrations. CONCLUSIONS: Higher plasma ADMA values were associated with an increased prevalence of SBIs, after adjustment for traditional stroke risk factors. Thus, ADMA may be a potentially useful new biomarker of subclinical vascular brain injury, which is an important correlate of vascular cognitive impairment and risk of stroke. PMID- 19644066 TI - Effect of hyperthermia on prognosis after acute ischemic stroke. AB - BACKGROUND AND PURPOSE: Experimental studies have shown that hyperthermia is a determinant of poor outcome after ischemic stroke. Clinical studies evaluating the effect of temperature on poststroke outcome have, however, been limited by small sample sizes. We sought to evaluate the effect of temperature and timing of hyperthermia on outcome after ischemic stroke. METHODS: Data of 5305 patients in acute stroke trials from the Virtual International Stroke Trials Archive (VISTA) data set were analyzed. Data for temperatures at baseline, eighth, 24th, 48th, and 72nd hours, and seventh day were assessed in relation to outcome (poor versus good) based on the modified Rankin Scale at 3 months. Hyperthermia was defined as temperature >37.2 degrees C and poor outcome as 90-day modified Rankin Scale >2. Hazard ratios with 95% CIs were reported for hyperthermia in relation to the outcome. Logistic regression models, in relation to hyperthermia, were fitted for a set of preselected covariates at different time points to identify predictors/determinants of hyperthermia. RESULTS: The average age of patients was 68.0+/-11.9 years, 2380 (44.9%) were females, and 42.3% (2233) received thrombolysis using recombinant tissue plasminogen activator. After adjustment, hyperthermia was a statistically significant predictor of poor outcome. The hazard ratios (95% CI) for poor outcome in relation to hyperthermia at different time points were: baseline 1.2 (1.0 to 1.4), eighth hour 1.7 (1.2 to 2.2), 24th hour 1.5 (1.2 to 1.9), 48th hour 2.0 (1.5 to 2.6), 72nd hour 2.2 (1.7 to 2.9), and seventh day 2.7 (2.0 to 3.8). Gender, stroke severity (National Institutes of Health Stroke Scale score >16), white blood cell count, and antibiotic use were significantly associated with hyperthermia (P< or =0.01). CONCLUSIONS: Hyperthermia, in acute ischemic stroke, is associated with a poor clinical outcome. The later the hyperthermia occurs within the first week, the worse the prognosis. Severity of stroke and inflammation are important determinants of hyperthermia after ischemic stroke. In patients with acute ischemic stroke, aggressive measures to prevent and treat hyperthermia could improve the clinical outcomes. PMID- 19644067 TI - Apolipoprotein E genotype is related to progression of white matter lesion load. AB - BACKGROUND AND PURPOSE: The relationship between white matter lesions (WMLs) and the apolipoprotein E genotype has been controversial from cross-sectional studies and no longitudinal finding has been reported. We investigated whether the apolipoprotein E genotype influences baseline and evolution over 4-year follow-up of WML volumes in a population-based sample of 1779 nondemented subjects aged 65 to 80 years old at enrollment. METHODS: The sample consisted of 3C-Dijon study participants who had 2 cerebral MRIs, at entry and at 4-year follow-up. WML volumes were estimated using a fully automatic procedure. We performed analysis of covariance to evaluate the relationship between apolipoprotein E genotype and WML load and progression. RESULTS: Multivariable analyses showed that epsilon4epsilon4 individuals had both significantly higher WML volume at baseline and higher WML increase over 4-year follow-up than noncarriers and heterozygous of the epsilon4 allele for apolipoprotein E genotype. CONCLUSION: These findings suggest it might be important to take into account WML severity when assessing the relationship between apolipoprotein E and dementia. PMID- 19644068 TI - Do all age groups benefit from organized inpatient stroke care? AB - BACKGROUND AND PURPOSE: Organized inpatient stroke care consists of a multidisciplinary approach aimed at improving stroke outcomes. It is unclear whether elderly individuals benefit from these interventions to the same extent as younger patients. We sought to determine whether the reduction in mortality or institutionalization seen with organized stroke care was similar across all age groups. METHODS: This was a case-cohort study of patients with acute ischemic stroke seen between July 2003 and March 2005 and captured in the Registry of the Canadian Stroke Network. After stratifying by age category, we assessed for evidence of effect modification by age on the reduction in stroke fatality associated with stroke unit/organized care. RESULTS: Among 3631 patients with ischemic stroke, stroke case-fatality at 30 days was lower for patients admitted to a stroke unit compared with those admitted to general medical wards (10.2% versus 14.8%; P<0.0001 with an absolute risk reduction=4.6%, number needed to treat=22). All age groups achieved a similar benefit of stroke unit care versus general medical ward care (absolute risk reduction for 30-day stroke fatality was 4.5% for <60 years; 3.4% for 60 to 69 years; 5.3% for 70 to 79 years; and 5.5% for those >80 years). Increasing levels of organized care were associated with lower stroke fatality or institutionalization. The beneficial effect of stroke units/organized care on survival was seen even after adjustment for multiple prognostic factors and after excluding patients on palliative approach. There was no evidence of effect modification by age in any analyses. CONCLUSIONS: Stroke units and organized inpatient care reduce death or institutionalization with the same magnitude of effect across all age groups. PMID- 19644069 TI - Granulocyte-colony stimulating factor delays PWI/DWI mismatch evolution and reduces final infarct volume in permanent-suture and embolic focal cerebral ischemia models in the rat. AB - BACKGROUND AND PURPOSE: Granulocyte-colony stimulating factor (G-CSF) is used clinically to attenuate neutropenia after chemotherapy. G-CSF acts as a growth factor in the central nervous system, counteracts apoptosis, and is neuroprotective in rodent transient ischemia models. METHODS: We assessed the effect of G-CSF on ischemic lesion evolution in a rat permanent-suture occlusion model with diffusion- and perfusion-weighted magnetic resonance imaging and the neuroprotective effect of G-CSF in a rat embolic stroke model. RESULTS: With a constant perfusion deficit, vehicle-treated animals showed an expanding apparent diffusion coefficient lesion volume that matched the perfusion deficit volume at approximately 3 hours, with the 24-hour infarct volume equivalent to the perfusion deficit. In G-CSF-treated rats, the apparent diffusion coefficient lesion volume did not increase after treatment initiation, and the infarct volume at 24 hours reflected the initial apparent diffusion coefficient lesion volume. In the embolic model, we observed a significant decrease in infarct volume in G CSF-treated animals compared with the vehicle-treated group. CONCLUSIONS: These results confirm the potent neuroprotective activity of G-CSF in different focal ischemia models. The magnetic resonance imaging data demonstrate that G-CSF preserved the perfusion/diffusion mismatch. PMID- 19644070 TI - High-sensitivity C-reactive protein and lipoprotein-associated phospholipase A2 stability before and after stroke and myocardial infarction. AB - BACKGROUND AND PURPOSE: High-sensitivity C-reactive protein (hsCRP) and lipoprotein-associated phospholipase A2 (Lp-PLA2) are hypothesized to be biomarkers of systemic inflammation and risk of myocardial infarction (MI) and stroke. Little is known, however, about the stability of these markers over time, and in particular, about the effects of acute vascular events on these marker levels. METHODS: Serum samples were collected at 4 annual intervals in 52 stroke free participants from the Northern Manhattan Study (NOMAS) and assayed for hsCRP and Lp-PLA2 mass and activity levels using standard techniques. Log transformation of levels was performed as needed to stabilize the variance. Stability of marker levels over time was assessed using random effects models unadjusted and adjusted for demographics and other risk factors. In addition, samples from 37 initially stroke-free participants with stroke (n=17) or MI (n=20) were available for measurement before and after the vascular event (median 5 days, range 2 to 40 days). Levels before and after events were compared using nonparametric tests. RESULTS: HsCRP and Lp-PLA2 activity levels were stable over time, whereas Lp-PLA2 mass levels decreased on average 5% per year (P=0.0015). Using accepted thresholds to define risk categories of Lp-PLA2 mass, there was no significant change over time. HsCRP increased after stroke (from median 2.2 mg/L prestroke to 6.5 mg/L poststroke; P=0.0067) and MI (from median 2.5 mg/L pre-MI to 13.5 mg/L post-MI; P<0.0001). Lp-PLA2 mass and activity levels both decreased significantly after stroke and MI (for Lp-PLA2 mass, from median 210.0 ng/mL to 169.4 ng/mL poststroke, P=0.0348, and from median 233.0 ng/mL to 153.9 post-MI, P<0.0001). CONCLUSION: Lp-PLA2 mass levels decrease modestly, whereas hsCRP and Lp-PLA2 activity appear stable over time. Acutely after stroke and MI, hsCRP increases whereas Lp-PLA2 mass and activity levels decrease. These changes imply that measurements made soon after stroke and MI are not reflective of prestroke levels and may be less reliable for long-term risk stratification. PMID- 19644072 TI - Ecology. Barcoding of plants and fungi. PMID- 19644071 TI - Simvastatin and atorvastatin improve neurological outcome after experimental intracerebral hemorrhage. AB - BACKGROUND AND PURPOSE: This study investigates the effects of statin treatment on experimental intracerebral hemorrhage (ICH) using behavioral, histological, and MRI measures of recovery. METHODS: Primary ICH was induced in rats. Simvastatin (2 mg/kg), atorvastatin (2 mg/kg), or phosphate-buffered saline (n=6 per group) was given daily for 1 week. MRI studies were performed 2 to 3 days before ICH, and at 1 to 2 hours and 1, 2, 7, 14, and 28 days after ICH. The ICH evolution was assessed via hematoma volume measurements using susceptibility weighted imaging (SWI) and tissue loss using T2 maps and hematoxylin and eosin (H&E) histology. Neurobehavioral tests were done before ICH and at various time points post-ICH. Additional histological measures were performed with doublecortin neuronal nuclei and bromodeoxyuridine stainings. RESULTS: Initial ICH volumes determined by SWI were similar across all groups. Simvastatin significantly reduced hematoma volume at 4 weeks (P=0.002 versus control with acute volumes as baseline), whereas that for atorvastatin was marginal (P=0.09). MRI estimates of tissue loss (% of contralateral hemisphere) for treated rats were significantly lower (P=0.0003 and 0.001, respectively) than for control at 4 weeks. Similar results were obtained for H&E histology (P=0.0003 and 0.02, respectively). Tissue loss estimates between MRI and histology were well correlated (R2=0.764, P<0.0001). Significant improvement in neurological function was seen 2 to 4 weeks post-ICH with increased neurogenesis observed. CONCLUSIONS: Simvastatin and atorvastatin significantly improved neurological recovery, decreased tissue loss, and increased neurogenesis when administered for 1 week after ICH. PMID- 19644073 TI - Unprecedented restoration of a native oyster metapopulation. AB - Native oyster species were once vital ecosystem engineers, but their populations have collapsed worldwide because of overfishing and habitat destruction. In 2004, we initiated a vast (35-hectare) field experiment by constructing native oyster reefs of three types (high-relief, low-relief, and unrestored) in nine protected sanctuaries throughout the Great Wicomico River in Virginia, United States. Upon sampling in 2007 and 2009, we found a thriving metapopulation comprising 185 million oysters of various age classes. Oyster density was fourfold greater on high-relief than on low-relief reefs, explaining the failure of past attempts. Juvenile recruitment and reef accretion correlated with oyster density, facilitating reef development and population persistence. This reestablished metapopulation is the largest of any native oyster worldwide and validates ecological restoration of native oyster species. PMID- 19644075 TI - Reassessing the source of long-period comets. AB - We present numerical simulations to model the production of observable long period comets (LPCs) from the Oort Cloud, a vast reservoir of icy bodies surrounding the Sun. We show that inner Oort Cloud objects can penetrate Jupiter's orbit via a largely unexplored dynamical pathway, and they are an important, if not the dominant, source of known LPCs. We use this LPC production to place observationally motivated constraints on the population and mass of the inner Oort Cloud, which are consistent with giant planet formation theory. These constraints indicate that only one comet shower producing late Eocene bombardment levels has likely occurred since the Cambrian Explosion, making these phenomena an improbable cause of additional extinction events. PMID- 19644074 TI - Common regulatory variation impacts gene expression in a cell type-dependent manner. AB - Studies correlating genetic variation to gene expression facilitate the interpretation of common human phenotypes and disease. As functional variants may be operating in a tissue-dependent manner, we performed gene expression profiling and association with genetic variants (single-nucleotide polymorphisms) on three cell types of 75 individuals. We detected cell type-specific genetic effects, with 69 to 80% of regulatory variants operating in a cell type-specific manner, and identified multiple expressive quantitative trait loci (eQTLs) per gene, unique or shared among cell types and positively correlated with the number of transcripts per gene. Cell type-specific eQTLs were found at larger distances from genes and at lower effect size, similar to known enhancers. These data suggest that the complete regulatory variant repertoire can only be uncovered in the context of cell-type specificity. PMID- 19644077 TI - Gene banks for a warming planet. PMID- 19644076 TI - Enhancement of biodiversity and ecosystem services by ecological restoration: a meta-analysis. AB - Ecological restoration is widely used to reverse the environmental degradation caused by human activities. However, the effectiveness of restoration actions in increasing provision of both biodiversity and ecosystem services has not been evaluated systematically. A meta-analysis of 89 restoration assessments in a wide range of ecosystem types across the globe indicates that ecological restoration increased provision of biodiversity and ecosystem services by 44 and 25%, respectively. However, values of both remained lower in restored versus intact reference ecosystems. Increases in biodiversity and ecosystem service measures after restoration were positively correlated. Results indicate that restoration actions focused on enhancing biodiversity should support increased provision of ecosystem services, particularly in tropical terrestrial biomes. PMID- 19644078 TI - Particle physics. More bad connections may limit LHC energy or delay restart. PMID- 19644079 TI - Europe. Fix funding agency's 'original sin,' ERC review panel demands. PMID- 19644081 TI - Oysters booming on new reefs, but can they survive disease? PMID- 19644082 TI - Plant bar code soon to become reality. PMID- 19644084 TI - Science education. Universities begin to rethink first-year biology courses. PMID- 19644086 TI - Ecology. Saving a venomous ghost. PMID- 19644085 TI - Science education. Reshuffling graduate training. PMID- 19644087 TI - Astronomy. A quest for cosmic karma. PMID- 19644088 TI - China. Help wanted: 2000 leading lights to inject a spirit of innovation. PMID- 19644089 TI - Venezuelan science: government on course. PMID- 19644090 TI - Venezuelan science: a professor's defense. PMID- 19644091 TI - Mayas live on. PMID- 19644092 TI - Venezuelan science: making great strides. PMID- 19644093 TI - Comment on "Remeasuring the double helix". AB - Mathew-Fenn et al. (Reports, 17 October 2008, p. 446) reported unexpected distance fluctuations in short end-labeled DNA constructs and interpreted them as evidence for cooperative DNA stretching modes. We show that when accounting for a subtle linker leverage effect, their data can be understood within standard noncooperative DNA elasticity. PMID- 19644094 TI - Computing has changed biology--biology education must catch up. PMID- 19644095 TI - Mathematical biology education: beyond calculus. PMID- 19644096 TI - Neuroscience. Brain wiring by presorting axons. PMID- 19644097 TI - Geochemistry. Ironing out the oxidation of Earth's mantle. PMID- 19644098 TI - Astronomy. Probing the cold universe. PMID- 19644099 TI - Biochemistry. Nudging through a nucleosome. PMID- 19644101 TI - Computer science. Is your computer secure? PMID- 19644100 TI - Immunology. Dispensable but not irrelevant. PMID- 19644102 TI - The rise of restoration ecology. PMID- 19644103 TI - Nursing China's ailing forests back to health. PMID- 19644104 TI - Restoring a 'biological desert' on Borneo. PMID- 19644106 TI - Unleashing an army to repair alien-ravaged ecosystems. PMID- 19644105 TI - Bringing coral reefs back from the living dead. PMID- 19644107 TI - Addicted to rubber. PMID- 19644108 TI - Ecological restoration in the light of ecological history. AB - Ecological history plays many roles in ecological restoration, most notably as a tool to identify and characterize appropriate targets for restoration efforts. However, ecological history also reveals deep human imprints on many ecological systems and indicates that secular climate change has kept many targets moving at centennial to millennial time scales. Past and ongoing environmental changes ensure that many historical restoration targets will be unsustainable in the coming decades. Ecological restoration efforts should aim to conserve and restore historical ecosystems where viable, while simultaneously preparing to design or steer emerging novel ecosystems to ensure maintenance of ecological goods and services. PMID- 19644109 TI - Species invasions and the limits to restoration: learning from the New Zealand experience. AB - Species invasions impose key biotic thresholds limiting the success of ecological restoration projects. These thresholds may be difficult to reverse and will have long-term consequences for restoration because of invasion legacies such as extinctions; because most invasive species cannot be eliminated given current technology and resources; and because even when controlled to low levels, invasive species continue to exert substantial pressure on native biodiversity. Restoration outcomes in the face of biological invasions are likely to be novel and will require long-term resource commitment, as any letup in invasive species management will result in the loss of the conservation gains achieved. PMID- 19644110 TI - Pollination and restoration. AB - Pollination services underpin sustainability of restored ecosystems. Yet, outside of agri-environments, effective restoration of pollinator services in ecological restoration has received little attention. This deficiency in the knowledge needed to restore pollinator capability represents a major liability in restoration programs, particularly in regions where specialist invertebrate and vertebrate pollinators exist, such as global biodiversity hotspots. When compounded with the likely negative impacts of climate change on pollination services, the need to understand and manage pollinator services in restoration becomes paramount. PMID- 19644111 TI - Soil microbial communities and restoration ecology: facilitators or followers? AB - Microorganisms have critical roles in the functioning of soil in nutrient cycling, structural formation, and plant interactions, both positive and negative. These roles are important in reestablishing function and biodiversity in ecosystem restoration. Measurement of the community indicates the status of the system in relation to restoration targets and the effectiveness of management interventions, and manipulation of the community shows promise in the enhancement of the rate of recovery of degraded systems. PMID- 19644112 TI - Restoration of ecosystem services for environmental markets. AB - Ecological restoration is an activity that ideally results in the return of an ecosystem to an undisturbed state. Ecosystem services are the benefits humans derive from ecosystems. The two have been joined to support growing environmental markets with the goal of creating restoration-based credits that can be bought and sold. However, the allure of these markets may be overshadowing shortcomings in the science and practice of ecological restoration. Before making risky investments, we must understand why and when restoration efforts fall short of recovering the full suite of ecosystem services, what can be done to improve restoration success, and why direct measurement of the biophysical processes that support ecosystem services is the only way to guarantee the future success of these markets. Without new science and an oversight framework to protect the ecosystem service assets which people depend, markets could actually accelerate environmental degradation. PMID- 19644113 TI - The map of Altinum, ancestor of Venice. AB - Processing and interpretation of July 2007 digital visible and near-infrared aerial photographs, coupled by a digital terrain model, has allowed for detailed reconstruction of the topography and the paleoenvironmental setting of the Roman city of Altinum, shedding new light on the far origins of Venice. Images were taken during severe dry conditions, which stressed the maize and soy crops. The city walls and doors, the street network, dwellings, theaters, amphitheater, forum, emporia, basilica, and a complex network of rivers and canals have been mapped. PMID- 19644115 TI - Grain boundary defect elimination in a zeolite membrane by rapid thermal processing. AB - Microporous molecular sieve catalysts and adsorbents discriminate molecules on the basis of size and shape. Interest in molecular sieve films stems from their potential for energy-efficient membrane separations. However, grain boundary defects, formed in response to stresses induced by heat treatment, compromise their selectivity by creating nonselective transport pathways for permeating molecules. We show that rapid thermal processing can improve the separation performance of thick columnar films of a certain zeolite (silicalite-1) by eliminating grain boundary defects, possibly by strengthening grain bonding at the grain boundaries. This methodology enables the preparation of silicalite-1 membranes with high separation performance for aromatic and linear versus branched hydrocarbon isomers and holds promise for realizing high-throughput and scalable production of these zeolite membranes with improved energy efficiency. PMID- 19644114 TI - Rebuilding global fisheries. AB - After a long history of overexploitation, increasing efforts to restore marine ecosystems and rebuild fisheries are under way. Here, we analyze current trends from a fisheries and conservation perspective. In 5 of 10 well-studied ecosystems, the average exploitation rate has recently declined and is now at or below the rate predicted to achieve maximum sustainable yield for seven systems. Yet 63% of assessed fish stocks worldwide still require rebuilding, and even lower exploitation rates are needed to reverse the collapse of vulnerable species. Combined fisheries and conservation objectives can be achieved by merging diverse management actions, including catch restrictions, gear modification, and closed areas, depending on local context. Impacts of international fleets and the lack of alternatives to fishing complicate prospects for rebuilding fisheries in many poorer regions, highlighting the need for a global perspective on rebuilding marine resources. PMID- 19644116 TI - Ultrasmooth patterned metals for plasmonics and metamaterials. AB - Surface plasmons are electromagnetic waves that can exist at metal interfaces because of coupling between light and free electrons. Restricted to travel along the interface, these waves can be channeled, concentrated, or otherwise manipulated by surface patterning. However, because surface roughness and other inhomogeneities have so far limited surface-plasmon propagation in real plasmonic devices, simple high-throughput methods are needed to fabricate high-quality patterned metals. We combined template stripping with precisely patterned silicon substrates to obtain ultrasmooth pure metal films with grooves, bumps, pyramids, ridges, and holes. Measured surface-plasmon-propagation lengths on the resulting surfaces approach theoretical values for perfectly flat films. With the use of our method, we demonstrated structures that exhibit Raman scattering enhancements above 10(7) for sensing applications and multilayer films for optical metamaterials. PMID- 19644117 TI - Probing spin-charge separation in a Tomonaga-Luttinger liquid. AB - In a one-dimensional (1D) system of interacting electrons, excitations of spin and charge travel at different speeds, according to the theory of a Tomonaga Luttinger liquid (TLL) at low energies. However, the clear observation of this spin-charge separation is an ongoing challenge experimentally. We have fabricated an electrostatically gated 1D system in which we observe spin-charge separation and also the predicted power-law suppression of tunneling into the 1D system. The spin-charge separation persists even beyond the low-energy regime where the TLL approximation should hold. TLL effects should therefore also be important in similar, but shorter, electrostatically gated wires, where interaction effects are being studied extensively worldwide. PMID- 19644118 TI - Water and the oxidation state of subduction zone magmas. AB - Mantle oxygen fugacity exerts a primary control on mass exchange between Earth's surface and interior at subduction zones, but the major factors controlling mantle oxygen fugacity (such as volatiles and phase assemblages) and how tectonic cycles drive its secular evolution are still debated. We present integrated measurements of redox-sensitive ratios of oxidized iron to total iron (Fe3+/SigmaFe), determined with Fe K-edge micro-x-ray absorption near-edge structure spectroscopy, and pre-eruptive magmatic H2O contents of a global sampling of primitive undegassed basaltic glasses and melt inclusions covering a range of plate tectonic settings. Magmatic Fe3+/SigmaFe ratios increase toward subduction zones (at ridges, 0.13 to 0.17; at back arcs, 0.15 to 0.19; and at arcs, 0.18 to 0.32) and correlate linearly with H2O content and element tracers of slab-derived fluids. These observations indicate a direct link between mass transfer from the subducted plate and oxidation of the mantle wedge. PMID- 19644119 TI - The cAMP sensor Epac2 is a direct target of antidiabetic sulfonylurea drugs. AB - Epac2, a guanine nucleotide exchange factor for the small guanosine triphosphatase Rap1, is activated by adenosine 3',5'-monophosphate. Fluorescence resonance energy transfer and binding experiments revealed that sulfonylureas, widely used antidiabetic drugs, interact directly with Epac2. Sulfonylureas activated Rap1 specifically through Epac2. Sulfonylurea-stimulated insulin secretion was reduced both in vitro and in vivo in mice lacking Epac2, and the glucose-lowering effect of the sulfonylurea tolbutamide was decreased in these mice. Epac2 thus contributes to the effect of sulfonylureas to promote insulin secretion. Because Epac2 is also required for the action of incretins, gut hormones crucial for potentiating insulin secretion, it may be a promising target for antidiabetic drug development. PMID- 19644120 TI - Identification of splenic reservoir monocytes and their deployment to inflammatory sites. AB - A current paradigm states that monocytes circulate freely and patrol blood vessels but differentiate irreversibly into dendritic cells (DCs) or macrophages upon tissue entry. Here we show that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation. The reservoir monocytes assemble in clusters in the cords of the subcapsular red pulp and are distinct from macrophages and DCs. In response to ischemic myocardial injury, splenic monocytes increase their motility, exit the spleen en masse, accumulate in injured tissue, and participate in wound healing. These observations uncover a role for the spleen as a site for storage and rapid deployment of monocytes and identify splenic monocytes as a resource that the body exploits to regulate inflammation. PMID- 19644121 TI - Innate and adaptive immunity cooperate flexibly to maintain host-microbiota mutualism. AB - Commensal bacteria in the lower intestine of mammals are 10 times as numerous as the body's cells. We investigated the relative importance of different immune mechanisms in limiting the spread of the intestinal microbiota. Here, we reveal a flexible continuum between innate and adaptive immune function in containing commensal microbes. Mice deficient in critical innate immune functions such as Toll-like receptor signaling or oxidative burst production spontaneously produce high-titer serum antibodies against their commensal microbiota. These antibody responses are functionally essential to maintain host-commensal mutualism in vivo in the face of innate immune deficiency. Spontaneous hyper-activation of adaptive immunity against the intestinal microbiota, secondary to innate immune deficiency, may clarify the underlying mechanisms of inflammatory diseases where immune dysfunction is implicated. PMID- 19644122 TI - Chronic stress causes frontostriatal reorganization and affects decision-making. AB - The ability to shift between different behavioral strategies is necessary for appropriate decision-making. Here, we show that chronic stress biases decision making strategies, affecting the ability of stressed animals to perform actions on the basis of their consequences. Using two different operant tasks, we revealed that, in making choices, rats subjected to chronic stress became insensitive to changes in outcome value and resistant to changes in action outcome contingency. Furthermore, chronic stress caused opposing structural changes in the associative and sensorimotor corticostriatal circuits underlying these different behavioral strategies, with atrophy of medial prefrontal cortex and the associative striatum and hypertrophy of the sensorimotor striatum. These data suggest that the relative advantage of circuits coursing through sensorimotor striatum observed after chronic stress leads to a bias in behavioral strategies toward habit. PMID- 19644125 TI - Clinical implications of dynamic systems theory for phonological development. AB - PURPOSE: To examine treatment outcomes in relation to the complexity of treatment goals for children with speech sound disorders. METHOD: The clinical implications of dynamic systems theory in contrast with learnability theory are discussed, especially in the context of target selection decisions for children with speech sound disorders. Detailed phonological analyses of pre-and posttreatment speech samples are provided for 6 children who received treatment in a previously published randomized controlled trial of contrasting approaches to target selection (Rvachew & Nowak, 2001). Three children received treatment for simple target phonemes that did not introduce any new feature contrasts into the children's phonological systems. Three children received treatment for complex targets that represented feature contrasts that were absent from the children's phonological systems. RESULTS: Children who received treatment for simple targets made more progress toward the acquisition of the target sounds and demonstrated emergence of complex untreated segments and feature contrasts. Children who received treatment for complex targets made little measurable gain in phonological development. CONCLUSIONS: Treatment outcomes will be enhanced if the clinician selects treatment targets at the segmental and prosodic levels of the phonological system in such a way as to stabilize the child's knowledge of subcomponents that form the foundation for the emergence of more complex phoneme contrasts. PMID- 19644123 TI - Nucleosomal fluctuations govern the transcription dynamics of RNA polymerase II. AB - RNA polymerase II (Pol II) must overcome the barriers imposed by nucleosomes during transcription elongation. We have developed an optical tweezers assay to follow individual Pol II complexes as they transcribe nucleosomal DNA. Our results indicate that the nucleosome behaves as a fluctuating barrier that locally increases pause density, slows pause recovery, and reduces the apparent pause-free velocity of Pol II. The polymerase, rather than actively separating DNA from histones, functions instead as a ratchet that rectifies nucleosomal fluctuations. We also obtained direct evidence that transcription through a nucleosome involves transfer of the core histones behind the transcribing polymerase via a transient DNA loop. The interplay between polymerase dynamics and nucleosome fluctuations provides a physical basis for the regulation of eukaryotic transcription. PMID- 19644126 TI - Should we use telegraphic or grammatical input in the early stages of language development with children who have language impairments? A meta-analysis of the research and expert opinion. AB - PURPOSE: In working with children with language impairments, some clinical scholars and clinicians advocate using input that is simplified to the point of being ungrammatical (telegraphic input), while others advocate simplified but grammatical input. This article considers 2 types of external evidence on this topic. METHOD: First, a meta-analysis of relevant research, including intervention studies and processing studies, is reported. Next, 4 experts present their opinions. RESULTS: Children in the majority of the intervention studies showed no difference in language comprehension based on type of input, although 1 study with very few children favored telegraphic input for language production. In the processing studies, which measured immediate comprehension, children from clinical populations responded inconsistently when listening to the 2 types of input. Children who had typical language, however, favored grammatical input in their responses. Regarding the experts' opinions, 2 suggest that telegraphic input is sometimes warranted; 1, who previously indirectly promoted its occasional use, no longer believes it should be used; and 1 provides reasons why telegraphic input should not be used and may even be harmful. CONCLUSIONS: Empirical findings and expert views are summarized as ways of informing parents of the weak evidence base regarding the best type of input. PMID- 19644127 TI - Early-, middle-, and late-developing sounds in monolingual and bilingual children: an exploratory investigation. AB - PURPOSE: To examine the accuracy of early-, middle-, and late-developing (EML) sounds in Spanish-English bilingual children and their monolingual peers. METHOD: Twenty-four typically developing children, age 3-4 years, were included in this study: 8 bilingual Spanish-English-speaking children, 8 monolingual Spanish speakers, and 8 monolingual English speakers. Single-word speech samples were obtained to examine (a) differences on the accuracy of EML sounds between Spanish English bilingual children and monolingual Spanish and monolingual English children and (b) the developmental trend on the accuracy of EML sounds within languages for Spanish-English bilingual children and monolingual Spanish and monolingual English children. RESULTS: Findings support those of Shriberg (1993) for English-speaking children and suggest possible EML categories for monolingual Spanish-speaking children and bilingual Spanish-English-speaking children. CONCLUSIONS: These exploratory findings indicate the need for longitudinal examination of EML categories with a larger cohort of children to observe similarities and differences between monolingual and bilingual development. PMID- 19644128 TI - Twenty-year follow-up of children with and without speech-language impairments: family, educational, occupational, and quality of life outcomes. AB - PURPOSE: Parents, professionals, and policy makers need information on the long term prognosis for children with communication disorders. Our primary purpose in this report was to help fill this gap by profiling the family, educational, occupational, and quality of life outcomes of young adults at 25 years of age (N = 244) from the Ottawa Language Study, a 20-year, prospective, longitudinal study of a community sample of individuals with (n = 112) and without (n = 132) a history of early speech and/or language impairments. A secondary purpose of this report was to use data from earlier phases of the study to predict important, real-life outcomes at age 25. METHOD: Participants were initially identified at age 5 and subsequently followed at 12, 19, and 25 years of age. Direct assessments were conducted at all 4 time periods in multiple domains (demographic, communicative, cognitive, academic, behavioral, and psychosocial). RESULTS: At age 25, young adults with a history of language impairments showed poorer outcomes in multiple objective domains (communication, cognitive/academic, educational attainment, and occupational status) than their peers without early communication impairments and those with early speech-only impairments. However, those with language impairments did not differ in subjective perceptions of their quality of life from those in the other 2 groups. Objective outcomes at age 25 were predicted differentially by various combinations of multiple, interrelated risk factors, including poor language and reading skills, low family socioeconomic status, low performance IQ, and child behavior problems. Subjective well-being, however, was primarily associated with strong social networks of family, friends, and others. CONCLUSION: This information on the natural history of communication disorders may be useful in answering parents' questions, anticipating challenges that children with language disorders might encounter, and planning services to address those issues. PMID- 19644129 TI - Rapid, point-of-care extraction of human immunodeficiency virus type 1 proviral DNA from whole blood for detection by real-time PCR. AB - PCR detection of human immunodeficiency virus type 1 (HIV-1) proviral DNA is the method recommended for use for the diagnosis of HIV-1 infection in infants in limited-resource settings. Currently, testing must be performed in central laboratories, which are usually located some distance from health care facilities. While the collection and transportation of samples, such as dried blood spots, has improved test accessibility, the results are often not returned for several weeks. To enable PCR to be performed at the point of care while the mothers wait, we have developed a vertical filtration method that uses a separation membrane and an absorbent pad to extract cellular DNA from whole blood in less than 2 min. Cells are trapped in the separation membrane as the specimen is collected, and then a lysis buffer is added. The membrane retains the DNA, while the buffer washes away PCR inhibitors, which get wicked into the absorbent blotter pad. The membrane containing the entrapped DNA is then added to the PCR mixture without further purification. The method demonstrates a high degree of reproducibility and analytical sensitivity and allows the quantification of as few as 20 copies of HIV-1 proviral DNA from 100 microl of blood. In a blinded study with 182 longitudinal samples from infants (ages, 0 to 72 weeks) obtained from the Women and Infants Transmission Study, our assay demonstrated a sensitivity of 99% and a specificity of 100%. PMID- 19644130 TI - Spread of epidemic keratoconjunctivitis due to a novel serotype of human adenovirus in Japan. PMID- 19644132 TI - Riboflavin status in acutely ill patients and response to dietary supplements. AB - BACKGROUND: Although a number of studies have reported riboflavin deficiency in free-living older people, no data are available on riboflavin intake and status in older people during acute illness. METHODS: To determine the riboflavin response to dietary supplements during acute illness, 297 hospitalized, acutely ill older patients are randomly assigned to receive a daily oral nutritional supplement containing 1.3 mg of riboflavin or a placebo for 6 weeks. Outcome measures are riboflavin intake and riboflavin biochemical status at baseline, 6 weeks, and 6 months using the erythrocyte glutathione reductase activation coefficient (EGRAC), a measure of riboflavin tissue saturation. EGRAC values are inversely proportional to riboflavin status. RESULTS: Fifty-six percent of patients (167/297) have suboptimal riboflavin status (EGRAC > 1.30). No significant correlation is found between EGRAC and either total energy or riboflavin intakes. Significant correlations are found between total energy intake and riboflavin intakes both in hospital and at home (r = 0.67, P < .0001 and r = 0.57, P < .0001, respectively). Smokers and patients with chronic obstructive pulmonary disease (COPD) have lower riboflavin status (high EGRAC values) compared with nonsmokers and those without COPD. Riboflavin status improves significantly in the supplement group at 6 weeks compared with the placebo group, but status declines between 6 weeks and 6 months, after patients stop taking the supplements. CONCLUSIONS: A high proportion of acutely ill patients have suboptimal riboflavin status. Supplementation with a physiological amount of riboflavin in a mixed-nutrient supplement significantly improves riboflavin status, but the effect is transient and status deteriorates again after patients stop taking the supplements. PMID- 19644131 TI - Colonic GLP-2 is not sufficient to promote jejunal adaptation in a PN-dependent rat model of human short bowel syndrome. AB - BACKGROUND: Bowel resection may lead to short bowel syndrome (SBS), which often requires parenteral nutrition (PN) due to inadequate intestinal adaptation. The objective of this study was to determine the time course of adaptation and proglucagon system responses after bowel resection in a PN-dependent rat model of SBS. METHODS: Rats underwent jugular catheter placement and a 60% jejunoileal resection + cecectomy with jejunoileal anastomosis or transection control surgery. Rats were maintained exclusively with PN and killed at 4 hours to 12 days. A nonsurgical group served as baseline. Bowel growth and digestive capacity were assessed by mucosal mass, protein, DNA, histology, and sucrase activity. Plasma insulin-like growth factor I (IGF-I) and bioactive glucagon-like peptide 2 (GLP-2) were measured by radioimmunoassay. RESULTS: Jejunum cellularity changed significantly over time with resection but not transection, peaking at days 3-4 and declining by day 12. Jejunum sucrase-specific activity decreased significantly with time after resection and transection. Colon crypt depth increased over time with resection but not transection, peaking at days 7-12. Plasma bioactive GLP-2 and colon proglucagon levels peaked from days 4-7 after resection and then approached baseline. Plasma IGF-I increased with resection through day 12. Jejunum and colon GLP-2 receptor RNAs peaked by day 1 and then declined below baseline. CONCLUSIONS: After bowel resection resulting in SBS in the rat, peak proglucagon, plasma GLP-2, and GLP-2 receptor levels are insufficient to promote jejunal adaptation. The colon adapts with resection, expresses proglucagon, and should be preserved when possible in massive intestinal resection. PMID- 19644133 TI - When race matters: racially stigmatized others and perceiving race as a biological construction affect biracial people's daily well-being. AB - Stigmatized group members experience greater well-being in the presence of similar others, which may be driven by the perception that similar others value their shared stigmatized identities (i.e., high public regard). Using experience sampling methodology, this hypothesis is tested with biracial people (29 Asian/White, 23 Black/ White, and 26 Latino/White biracial participants). This study proposes that the greater percentage of stigmatized similar others in one's daily context would predict greater daily well-being for biracial people through higher public regard, but only if biracial people believe that race has biological meaning. These findings add to a growing, but limited, literature on biracial individuals. These findings are situated within the broader literature on stigma and similar others, as well as new theories regarding the consequences of believing race has biological meaning. PMID- 19644134 TI - The hereditary stomatocytoses. PMID- 19644135 TI - Flow cytometry immunophenotyping for diagnosis of myelodysplastic syndrome. PMID- 19644136 TI - Current treatment of AL amyloidosis. PMID- 19644137 TI - A novel erythroid anion exchange variant (Gly796Arg) of hereditary stomatocytosis associated with dyserythropoiesis. AB - BACKGROUND: Stomatocytoses are a group of inherited autosomal dominant hemolytic anemias and include overhydrated hereditary stomatocytosis, dehydrated hereditary stomatocytosis, hereditary cryohydrocytosis and familial pseudohyperkalemia. DESIGN AND METHODS: We report a novel variant of hereditary stomatocytosis due to a de novo band 3 mutation (p. G796R-band3 CEINGE) associated with a dyserythropoietic phenotype. Band 3 genomic analysis, measurement at of hematologic parameters and red cell indices and morphological analysis of bone marrow were carried out. We then evaluated the red cell membrane permeability and ion transport systems by functional studies of the patient's erythrocytes and Xenopus oocytes transfected with mutated band 3. We analyzed the red cell membrane tyrosine phosphorylation profile and the membrane association of the tyrosine kinases Syk and Lyn from the Src-family-kinase group, since the activity of the membrane cation transport pathways is related to cyclic phosphorylation dephosphorylation events. RESULTS: The patient showed mild hemolytic anemia with circulating stomatocytes together with signs of dyserythropoiesis. Her red cells displayed increased Na(+) content with decreased K(+)content and abnormal membrane cation transport activities. Functional characterization of band 3 CEINGE in Xenopus oocytes showed that the mutated band 3 is converted from being an anion exchanger (Cl(-), HCO(3)(-)) to being a cation pathway for Na(+) and K(+). Increased tyrosine phosphorylation of some red cell membrane proteins was observed in diseased erythrocytes. Syk and Lyn membrane association was increased in the patient's red cells compared to in normal controls, indicating perturbation of phospho-signaling pathways involved in cell volume regulation events. CONCLUSIONS: Band 3 CEINGE alters function from that of anion exchange to cation transport, affects the membrane tyrosine phosphorylation profile, in particular of band 3 and stomatin, and its presence during red cell development likely contributes to dyserythropiesis. PMID- 19644138 TI - Red blood cell aggregation, aggregate strength and oxygen transport potential of blood are abnormal in both homozygous sickle cell anemia and sickle-hemoglobin C disease. AB - BACKGROUND: Recent evidence suggests that red blood cell aggregation and the ratio of hematocrit to blood viscosity (HVR), an index of the oxygen transport potential of blood, might considerably modulate blood flow dynamics in the microcirculation. It thus seems likely that these factors could play a role in sickle cell disease. DESIGN AND METHODS: We compared red blood cell aggregation characteristics, blood viscosity and HVR at different shear rates between sickle cell anemia and sickle cell hemoglobin C disease (SCC) patients, sickle cell trait carriers (AS) and control individuals (AA). RESULTS: Blood viscosity determined at high shear rate was lower in sickle cell anemia (n=21) than in AA (n=52), AS (n=33) or SCC (n=21), and was markedly increased in both SCC and AS. Despite differences in blood viscosity, both sickle cell anemia and SCC had similar low HVR values compared to both AA and AS. Sickle cell anemia (n=21) and SCC (n=19) subjects had a lower red blood cell aggregation index and longer time for red blood cell aggregates formation than AA (n=16) and AS (n=15), and a 2 to 3 fold greater shear rate required to disperse red blood cell aggregates. CONCLUSIONS: The low HVR levels found in sickle cell anemia and SCC indicates a comparable low oxygen transport potential of blood in both genotypes. Red blood cell aggregation properties are likely to be involved in the pathophysiology of sickle cell disease: the increased shear forces needed to disperse red blood cell aggregates may disturb blood flow, especially at the microcirculatory level, since red blood cell are only able to pass through narrow capillaries as single cells rather than as aggregates. PMID- 19644139 TI - Ectopic expression of C/EBPalpha and ID1 is sufficient to restore defective neutrophil development in low-risk myelodysplasia. AB - BACKGROUND: In patients with myelodysplasia, a general defect in the multipotent stem-cell compartment results in disturbed proliferation and differentiation of the erythroid, megakaryocytic and myeloid lineages. Although a number of genetic defects in myelodysplastic progenitor cells have been described, the intracellular signaling pathways underlying aberrant regulation of myelopoiesis remain relatively undefined. DESIGN AND METHODS: Here, an ex vivo differentiation system was used to selectively screen for molecules improving defective hematopoiesis in myelodysplastic CD34(+) progenitor cells. RESULTS: Bone marrow derived CD34(+) cells isolated from patients with low-risk myelodysplastic syndrome showed impaired capacity to proliferate and differentiate as well as increased levels of apoptosis. In an attempt to improve the expansion and differentiation of the myelodysplastic CD34(+) progenitors, cells were treated with the p38MAPK pharmacological inhibitor SB203580, or retrovirally transduced to ectopically express active protein kinase B (PKB/c-akt), or the transcriptional regulators STAT5, C/EBPalpha or ID1. Whereas treatment of progenitors with SB203580, PKB or STAT5 did not enhance neutrophil development, ID1- and C/EBPalpha-transduced cells exhibited increased granulocyte/macrophage colony formation. Furthermore, ectopic expression of C/EBPalpha resulted in improved neutrophil maturation. CONCLUSIONS: These data suggest that targeting the ID1 and C/EBPalpha transcriptional regulators may be of benefit in the design of novel therapies for low-risk myelodysplasia. PMID- 19644141 TI - Histological regression of amyloid in AL amyloidosis is exclusively seen after normalization of serum free light chain. AB - BACKGROUND: Histological regression of amyloid has not been studied systematically but is assessed by clinical parameters. We analyzed the change of amyloid deposition in fat tissue in patients with AL amyloidosis following chemotherapy and studied the relation with type of hematologic response. DESIGN AND METHODS: Between January 1994 and July 2007 all consecutive patients with AL amyloidosis were evaluated in whom fat tissue aspirate was obtained before and following chemotherapy. Patients were divided into three groups depending on response of serum free light chain: complete, partial or non-responders. Fat tissue was assessed using a validated semi-quantitative test (grading 0-4). A change of 2 grades of amyloid deposition in fat tissue was considered significant and used as event to construct Kaplan-Meier curves of the patients who were able to reflect such a change. RESULTS: One hundred and twenty consecutive patients were studied. Fifty-one patients fulfilled inclusion criteria. Thirty patients had a complete response of the amyloidogenic free light chain a median 0.5 year (range 0.3-2.9 years) following chemotherapy. Reduction of 2 grades of amyloid deposition in fat tissue was seen in 50% of these patients after 2.4 years and in 80% after 3.2 years. In contrast to complete responders, none of the patients with partial (n=9) and non-response (n=12) showed reduction of 2 grades (p=0.02) with median follow-up of fat tissue analysis of 1.3 and 0.8 years, respectively. CONCLUSIONS: This study in a selected group of patients with AL amyloidosis shows significant histological regression of amyloid deposition in fat tissue exclusively after normalization of serum free light chain. PMID- 19644140 TI - The fusion proteins TEL-PDGFRbeta and FIP1L1-PDGFRalpha escape ubiquitination and degradation. AB - BACKGROUND: Chimeric oncogenes encoding constitutively active protein tyrosine kinases are associated with chronic myeloid neoplasms. TEL-PDGFRbeta (TPbeta, also called ETV6-PDGFRB) is a hybrid protein produced by the t(5;12) translocation, FIP1L1-PDGFRalpha (FPalpha) results from a deletion on chromosome 4q12 and ZNF198-FGFR1 is created by the t(8;13) translocation. These fusion proteins are found in patients with myeloid neoplasms associated with eosinophilia. Wild-type receptor tyrosine kinases are efficiently targeted for degradation upon activation, in a process that requires Cbl-mediated monoubiquitination of receptor lysines. Since protein degradation pathways have been identified as useful targets for cancer therapy, the aim of this study was to compare the degradation of hybrid and wild-type receptor tyrosine kinases. DESIGN AND METHODS: We used Ba/F3 as a model cell line, as well as leukocytes from two patients, to analyze hybrid protein degradation. RESULTS: In contrast to the corresponding wild-type receptors, which are quickly degraded upon activation, we observed that TPbeta, FPalpha and the ZNF198-FGFR1 hybrids escaped down-regulation in Ba/F3 cells. The high stability of TPbeta and FPalpha hybrid proteins was confirmed in leukocytes from leukemia patients. Ubiquitination of TPbeta and FPalpha was much reduced compared to that of wild-type receptors, despite marked Cbl phosphorylation in cells expressing hybrid receptors. The fusion of a destabilizing domain to TPbeta induced protein degradation. Instability was reverted by adding the destabilizing domain ligand, Shield1. The destabilization of this modified TPbeta reduced cell transformation and STAT5 activation. CONCLUSIONS: We have shown that chimeric receptor tyrosine kinases escape ubiquitination and down-regulation and that their stabilization is critical to efficient stimulation of cell proliferation. PMID- 19644142 TI - Timing and severity of community acquired respiratory virus infections after myeloablative versus non-myeloablative hematopoietic stem cell transplantation. AB - BACKGROUND: Respiratory virus infections are important causes of morbidity and mortality after hematopoietic cell transplantation. Their clinical course can be severe with progression to lower respiratory tract infection, co-infection with serious pulmonary co-pathogens, and high mortality. Non-myeloablative conditioning regimens achieve engraftment without eradication of host hematopoietic cells, which potentially allows for protection against infections commonly seen in hematopoietic cell transplantation patients treated with standard intensity conditioning regimens. DESIGN AND METHODS: We performed a retrospective cohort study to measure the incidence and severity of parainfluenza types 1-4, influenza (A and B), respiratory syncitial virus and human rhinovirus disease in myeloablative versus non-myeloablative versus autologous hematopoietic cell transplantation patients. RESULTS: The incidences of all respiratory virus infections were similar in the non-myeloablative and myeloablative cohorts but less in the autologous cohort (33/420 [7.9%], 150/1593 [9.4%], and 37/751 [4.9%], respectively, p<0.0001). However, respiratory virus lower tract infections were significantly less common during the first 100 days after transplantation in non myeloablative patients compared to myeloablative and autologous patients (1/420 [0.2%], 34/1593 [2.1%] and 16/751 [2.1%], respectively, p=0.005. Respiratory virus lower tract infection had high co-infection and attributable mortality rates. CONCLUSIONS: Respiratory virus lower tract infection during the first 100 days after hematopoietic cell transplantation was less common in persons receiving non-myeloablative conditioning regimens compared to myeloablative conditioning, despite a similar overall rate of acquisition. PMID- 19644143 TI - Reduced CD38 expression on CD34+ cells as a diagnostic test in myelodysplastic syndromes. AB - Diagnosis of myelodysplastic syndrome can be difficult especially in cases with a low blast count and a normal karyotype. Flow cytometry has been used to distinguish myelodysplastic syndrome from non-clonal cytopenias. No one single simple flow cytometric parameter has been proposed to be diagnostic of myelodysplastic syndrome. We have studied samples from 100 myelodysplastic syndrome patients and as control samples; 70 non-clonal cytopenias, 5 subjects with normal hematology, 31 patients with acute myeloid leukemia and 11 with chronic myelomonocytic leukemia or myeloproliferative disorder. We show that reduced relative mean fluorescence of CD38 below a threshold value on CD34(+) cells diagnosed low-grade myelodysplastic syndrome with 95% sensitivity (95% confidence interval, 87-99%) and 92% specificity (95% confidence interval, 82 97%). This simple flow cytometric test may be of value in the routine clinical diagnosis of myelodysplastic syndrome, especially in cases with a low blast count and normal karyotype. PMID- 19644144 TI - Respiratory distress and sudden death of a patient with GSDIb chronic neutropenia: possible role of pegfilgrastim. PMID- 19644149 TI - [TLR function in autoimmunological processes]. AB - TLRs (Toll-like receptors) are found in many different vertebrate and invertebrate species. TLRs have important functions in cell activation of the nonspecific immune response as well as in the indirect specific immune response. These receptors recognize a broad range of exogenous and endogenous ligands. The biological importance of TLRs depends on their potential to recognize a great number of different agonists and antagonists, among them antigens of bacterial and viral origin as well as vertebrate and invertebrate autoantigens. The responsiveness of TLRs to endogenous ligands may contribute to the development of autoimmune diseases. Increasing interest is therefore directed towards understanding the effector mechanisms and signaling pathways associated with TLR activation. This leads to the discovery of new proteins associated with TLR signaling pathways. Furthermore, efforts are underway to modify the activity of TLRs by synthetic ligands. Among the factors used to modify TLR activity are short DNA fragments known as oligo-DNA. Oligo-DNA fragments are being evaluated in clinical trials as potential drugs to treat systemic lupus erythematosus. PMID- 19644145 TI - Cautions and caveats to the treatment of acquired hemophilia A. PMID- 19644150 TI - [Oxidative stress in prostate hypertrophy and carcinogenesis]. AB - Aging, significant impairment of the oxidation/reduction balance, infection, and inflammation are recognized risk factors of benign hyperplasia and prostate cancer. Chronic symptomatic and asymptomatic prostate inflammatory processes generate significantly elevated levels of reactive oxygen and nitrogen species, and halogenated compounds. Prostate cancer patients showed significantly higher lipid peroxidation and lower antioxidant levels in peripheral blood than healthy controls, whereas patients with prostate hyperplasia did not show such symptoms. Oxidative/nitrosative/halogenative stress causes DNA modifications leading to genome instability that may initiate carcinogenesis; however, it was shown that oxidative damage alone is not sufficient to initiate this process. Peroxidation products induced by reactive oxygen and nitrogen species seem to take part in epigenetic mechanisms regulating genome activity. One of the most common changes occurring in more than 90% of all analyzed prostate cancers is the silencing of GSTP1 gene activity. The gene encodes glutathione transferase, an enzyme participating in detoxification processes. Prostate hyperplasia is often accompanied by chronic inflammation and such a relationship was not observed in prostate cancer. The participation of infection and inflammation in the development of hyperplasia is unquestionable and these factors probably also take part in initiating the early stages of prostate carcinogenesis. Thus it seems that therapeutic strategies that prevent genome oxidative damage in situations involving oxidative/nitrosative/halogenative stress, i.e. use of antioxidants, plant steroids, antibiotics, and non-steroidal anti-inflammatory drugs, could help prevent carcinogenesis. PMID- 19644151 TI - [Toll-like receptors in viral hepatitis]. AB - Toll-like receptors (TLRs) are part of the innate immune system. They recognize some protein, lipid, and nucleic structures that are common in microorganisms such as bacteria and viruses but not present in the human body. The stimulation of TLRs initiates the activation of an intracellular signaling network which results in the secretion of proinflammatory cytokines, mainly type I interferons, TNF-alpha, and IL-6. TLR2, TLR3, TLR4, TLR8, and TLR9 take part in the recognition of viral infections, four of them by discerning nucleic acids, with TLR3 recognizing dsRNA, TLR7 and TLR8-ssRNA, and TLR9-DNA. The role of TLRs in the development of infections and other inflammatory states, neoplasms, and autoimmune disorders is under investigation. The importance of TLRs in the natural course of hepatitis B and C and in the treatment of these diseases are the subject of particular interest. Attempts to apply TLR7 and TLR9 agonists in the treatment of chronic hepatitis type C are underway. A better understanding of the role of TLRs in the complex immunological phenomena accompanying viral hepatitis might put the therapeutic possibilities in these infections into a new perspective. PMID- 19644152 TI - Increased percentage of CD8+CD28- suppressor lymphocytes in peripheral blood and skin infiltrates correlates with advanced disease in patients with cutaneous T cell lymphomas. AB - INTRODUCTION: T cells with the CD8+CD28- phenotype are CD8+ lymphocytes with regulatory function. Their increased numbers were observed in infections, autoimmune and neoplastic diseases, and in elderly healthy individuals. CD8+CD28- lymphocyte levels in patients with cutaneous T-cell lymphoma (CTCL) has not yet been described. The aim of the study was to determine their levels in these patients' peripheral blood and cutaneous infiltrates and their relation to the clinical stage of disease. MATERIAL/METHODS: Forty-one untreated patients, 26 males and 15 females, with CTCL were enrolled in the study. CD8+CD28- lymphocyte levels were determined by flow cytometry in peripheral blood and by immunochemistry in skin infiltrates. RESULTS: The percentage of CD8+CD28- lymphocytes in the peripheral blood of the patients was significantly higher than in the controls. Patients with advanced disease displayed a higher percentage of CD8+CD28- lymphocytes in the peripheral blood and skin than did the individuals with early stages of the disease. Moreover, positive correlations between CD8+CD28- lymphocyte level in peripheral blood and age, clinical stage, and the levels in the skin infiltrates was revealed. Additionally, the percentage of CD8+CD28- T cells in the skin infiltrates correlated positively with age and clinical stage of the disease. CONCLUSIONS: These data suggest that CD8+CD28- lymphocytes play an important role in the development of immunotolerance in the progression of cutaneous T-cell lymphoma. PMID- 19644153 TI - [Peptides: a new class of anticancer drugs]. AB - Peptides are a novel class of anticancer agents embracing two distinct categories: natural antibacterial peptides, which are preferentially bound by cancer cells, and chemically synthesized peptides, which bind specifically to precise molecular targets located on the surface of tumor cells. Antibacterial peptides bind to both cell and mitochondrial membranes. Some of these peptides attach to the cell membrane, resulting in its disorganization. Other antibacterial peptides penetrate cancer cells without causing cell membrane damage, but they disrupt mitochondrial membranes. Thanks to phage and aptamer libraries, it has become possible to obtain synthetic peptides blocking or activating some target proteins found in cancer cells as well as in cells forming the tumor environment. These synthetic peptides can feature anti-angiogenic properties, block enzymes indispensable for sustained tumor growth, and reduce tumor ability to metastasize. In this review the properties of peptides belonging to both categories are discussed and attempts of their application for therapeutic purposes are outlined. PMID- 19644154 TI - Improved long-term survival after intra-operative single high-dose ATG-Fresenius induction in renal transplantation: a single centre experience. AB - BACKGROUND: In organ grafts donor-specific sensitization is initiated immediately after revascularization. Therefore, in 1990 we introduced the intra-operative single high-dose ATG-Fresenius (ATG-F) induction in addition to standard triple drug therapy (TDT) consisting of steroids, azathioprine and cyclosporin. A total of 778 first renal transplantations from deceased donors, performed between 1987 and 1998, were included in this evaluation. MATERIAL/METHODS: This retrospective analysis of clinic records and electronic databases presents data of all recipients of first kidney grafts who received two different ATG-F inductions (1(st) group: 9 mg/kg body weight as single high-dose intra-operatively, n=484; 2(nd) group: 3 mg/kg body weight on 7 or 8 consecutive days as multiple-dose starting also intra-operatively, n=78) and standard TDT alone (3(rd) group: TDT alone, n=216). RESULTS: The 10-year patient survival rates were 72.6+/-2.6% (TDT + ATG-F single high-dose), 79.5+/-5.1% (TDT + ATG-F multiple-dose) and 67.2+/ 3.7%% (TDT alone; Kaplan-Meier estimates with standard errors; ATG-F vs TDT alone, p=0.001). The 10-year graft survival rates with censoring of patients that died with a functioning graft were 73.8+/-2.4%, 57.7+/-5.8% and 58.4+/-3.6% (Kaplan-Meier estimates with standard errors; 1(st) vs 2(nd )and 3(rd) group, respectively, p<0.001) and the 10-year graft survival rates with patient death counted as graft failure were 58.3+/-2.7%, 55.7+/-5.8% and 48.2+/-3.5% (Kaplan Meier estimates with standard errors; ATG-F single high-dose vs TDT, p=0.023). In pre-sensitized recipients there were also significant differences in favour of ATG-F, more notably in the single high-dose ATG-F induction. A total of 69% of the patients in the two cohorts receiving ATG-F did not experience any transplant rejections compared to 56% in patients undergoing TDT alone (p=0.018). The incidence of infectious complications was comparable across all groups. CONCLUSIONS: According to evidence obtained from the routine documentation of 778 renal transplantations, ATG-F induction therapy administered as a part of immunosuppressive therapy significantly improves patient survival and reduces the risk of graft failure and transplant rejections. PMID- 19644155 TI - Evaluation of the genetic background of standard-immunosuppressant-related toxicity in a cohort of 200 paediatric renal allograft recipients--a retrospective study. AB - BACKGROUND: Immunosuppressant toxicity is a limiting factor for the efficacy and safety of long-term therapy. Whether it stems solely from drug exposure, remains unclear. MATERIAL/METHODS: Overall, 207 children and adolescents at the mean age of 11+/-4.4, with primary renal allograft were analyzed. Immunosuppression regimens included CsA or TAC, combined with AZA or MMF and steroids. Drug specific toxicities were diagnosed by renal biopsy and/or clinical criteria. Genotyping for MDR1, CYP3A5, IL1B, IL1RN, IL-6, IL-10, MCP-1, TGFB1, CCR5, VEGF and TNF-alpha gene polymorphisms was performed with the use of PCR and PCR-RFLP techniques. RESULTS: Nephrotoxicity was seen in 38.5% of patients treated with CsA and 29.5% - with TAC, while gingival hypertrophy was observed in 28% of CsA patients. Myelotoxicity was found in 3% of AZA-treated and 6.4% of MMF-treated patients. No significant correlation was seen between the patient's age, gender, type of pre-transplantation dialysis, donor age, graft origin or cold ischemia time, and the occurrence of drug-related toxicity. For CNIs, the drug exposure and the duration of treatment did not prove of significance either. TAC associated nephrotoxicity correlated with the CCR5 gene polymorphism, as the wt/32 genotype was found in 21% of patients with no detected toxicity (p<0.041) and in none of the nephrotoxicity cases. The presence of this genotype was also associated with significantly better graft function at 1 year post-transplant (GFR 115.104+/-28.40 vs 86.434+/-29.96; p=0.022). An association was seen between the MMF-induced myelotoxicity and the TNF-alpha G(-308)A polymorphism (p<0.005), but the MMF exposure was higher in patients who developed toxicity. CONCLUSIONS: Genetic background should be regarded one of the risk factors for immunosuppressant related toxicity in renal transplantation. PMID- 19644156 TI - Cytometric analysis of TH1/TH2 cytokines in the urine of patients undergoing kidney transplantation. AB - BACKGROUND: Crucial inflammatory mediators involved in development of alloimmune response leading to AR are cytokines. Our project was aimed to investigate the relation between the urine cytokine profile and the development of acute rejection (AR) episodes in patients after kidney transplantation. MATERIAL/METHODS: The project included 44 patients undergoing kidney transplantation. During the six-month period following the transplantation AR was diagnosed in 11 patients. Urine samples were collected 2, 4, 14 and 30 days posttransplantation and cytometrically tested for concentrations of IL-2, IL-4, IL-5, IL-10, IFN-gamma and TNF-alpha. RESULTS: We found the elevated posttransplant concentrations of IFN-gamma, IL-10 and TNF-alpha in the urine of patients with diagnosed AR vs. NONAR (P<.05). No significant differences in the urine concentrations of IL-2, IL-4, IL-5 between the two groups were observed (P>.05). Elevated concentrations of urine IFN-gamma and TNF-alpha in AR patients, not accompanied by higher concentrations of IL-2, may suggest an ongoing undetected nonspecific Th1 immune response, capable of amplifying the alloimmune response in the early phase postsurgery, leading to AR. Higher concentrations of IL-10 found in the urine of AR patients, in turn, can partially result from peripheral regulatory mechanisms controlling the ongoing immune reaction, and partially from activation of monocytes/macrophages. CONCLUSIONS: The results of our study suggest that higher concentrations of IFN-gamma, TNF-alpha and IL-10 in the urine of patients shortly after the kidney transplantation can be considered as risk factors increasing the probability of AR episodes. PMID- 19644157 TI - Plasma complement 3d levels in the early phase after pancreas transplantation. AB - BACKGROUND: Rejection and graft thrombosis are the main reasons leading to early graft loss after pancreas transplantation. Identifying parameters that forecast these complications would be helpful. Complement activation might occur during rejection and thrombosis leading to elevated complement split products. This prospective study analyses the plasma complement 3d (C3d) levels in the early post-pancreas transplant (PTx) period to test its predictive value to determine rejection and thrombosis. MATERIAL/METHODS: Plasma C3d levels were measured after isolated PTx (n=2), simultaneous pancreas and kidney transplantation (SPKT, n=20) and pancreas re-transplantation (n=3). RESULTS: Pancreas rejection was observed in 3, pancreas thrombosis in 4, and kidney rejection in 7 patients. Patients after isolated kidney transplantation (IKT) served as controls. Within 40 days after PTx and IKT C3d levels were significantly elevated compared to volunteers and long-term kidney transplant recipients (p<0.001). C3d levels increased during 40 days after PTx, but dropped after IKT. During pancreas rejection episodes mean C3d levels were elevated (14.0+/-3.5 mg/l) compared to those obtained during graft thrombosis (9.1+/-1.6 mg/l; p=0.012) or periods of normal graft function (10.6+/-1.9 mg/l; p=0.046). A slight elevation of C3d was observed during kidney rejection episodes in SPKT (12.7+/-2.0 mg/l; p=0.074) but not during kidney rejection after IKT. CONCLUSIONS: C3d plasma levels increase during episodes of pancreas rejection and decrease in pancreas transplant thrombosis. However, single C3d values have no predictive diagnostic value after SPKT. PMID- 19644158 TI - Chemokine receptor 5Delta32 mutation reduces the risk of acute rejection in liver transplantation. AB - BACKGROUND: Chemokine receptor 5 (CCR-5) plays a central role in allograft rejection. CCR-5Delta32 mutation results in a non-functioning receptor. Homozygous CCR-5Delta32 patients show a significantly improved kidney graft survival rate compared to CCR-5 wild-type patients. Similar correlations between the CCR-5Delta32 genotype and acute rejection or graft survival rate were shown for heart, lung and islet cell transplantation. MATERIAL/METHODS: The aim of this study was to examine CCR-5Delta32 and acute rejection after liver transplantation (OLT). 158 OLT patients were genotyped. Data of grafts and patients were collected prospectively into a transplant database. RESULTS: There were no significant differences between groups regarding patient, donor or graft variables. CCR-5 wild-type patients had explicitly more acute rejection episodes (p=0.086) than patients with the heterozygous or homozygous Delta32-mutation. Homozygous Delta32 patients had no acute rejection episodes. 12.5% of heterozygous patients had one acute rejection episode as opposed to 30.6% of wild type patients. Only wild-type patients experienced more than one rejection episode. CONCLUSIONS: Patients with the Delta32-mutation might be candidates for a minimized immunosuppressive therapy. CCR-5 could be relevant as a target for a new therapeutic approach. PMID- 19644159 TI - Risk factors and dynamics of weight gain in patients after liver transplantation. AB - BACKGROUND: Weight gain is commonly observed after OLTx. It is still debatable whether increasing weight is due to the regain of weight lost before transplantation or it is a complex metabolic disorder. MATERIAL/METHODS: Body mass index and weight gain were sought at 6 months, one, two and four years after liver transplantation (OLTx) in relation to sex, weight at the time of transplantation, aetiology of liver disease, type of immunosuppression, glucose metabolism and lipid parameters as well as cardiovascular episodes. A group of 75 patients has been studied. RESULTS: Mean weight gain and BMI change were the highest within the first six months after OLTx (6.1 kg and 2.0 kg/m(2), respectively); since than gaining weight decreased. Men gained more weight than women, especially in the first half-year after OLTx. The only clear predictive factor of overweight and obesity was the baseline weight (the higher the baseline weight the most dynamic the weight gain after OLTx). CONCLUSIONS: Dietary mistakes and lack of physical activity may play a major role in the weight increase after OLTx. Despite striking proportion of overweight and obese patients in the studied group, the number of cardiovascular episodes seem to match the general population. PMID- 19644160 TI - Serum electrolyte changes at engraftment time in patients undergoing allogeneichematopoietic stem cell transplantation. AB - BACKGROUND: Metabolic abnormalities have been reported in patients undergoing hematopoietic stem cell transplantation (HSCT). Potential causes, risk factors and outcomes of electrolyte imbalances have thoroughly been investigated. On HSCT recipients, multiple pathophysiologic contributors are inflicting electrolyte abnormalities, with special attention being paid to engraftment per se as an important contributor. Engraftment contribution to electrolyte imbalances has been reported for hypophosphatemia and for other electrolyte abnormalities in autologous setting. However in the allogeneic setting serum electrolyte level changes and the timing of any probable abnormality are unknown. MATERIAL AND METHODS: We performed a retrospective study in order to evaluate the pattern of phosphorous, magnesium, potassium and uric acid serum changes, timing of any probable abnormality and their possible association with WBC and platelet engraftment in 65 allogeneic HCT recipients from day -9 to +32 after transplantation. Besides we assessed frequency and severity of the abnormalities. RESULTS: We observed a declining pattern of electrolyte concentrations with nadirs antedating WBC and platelet engrafments. Phosphorous and potassium serum changes were correlated with natural logarithm of WBC and platelet level changes. Observed overall incidence of hypophosphatemia (9.2%) and hypomagnesemia (3%) was lower than those previously reported. CONCLUSION: Abnormalities found reflect a combination of pathophysiologic mechanisms. Occurrence of electrolyte nadirs antedating engraftment confirms increased consumption by rapidly replicating cells as a contributor in allogeneic setting and specifies a susceptible period requiring intensive monitoring. Considering high risk patients and managing various organ system complications lower incidence of some electrolyte abnormalities may be observed. PMID- 19644161 TI - Domestic versus international Iranian transplantation publication: a comparative study. AB - BACKGROUND: Scientific articles are a source of information for other researchers. The aim of the current study was to compare the characteristics of the transplantation related research efforts which have been published in domestic journals and Medline indexed journals from Iran between 1993 and 2003. MATERIAL/METHODS: Within the study period, 601 transplantation scientific papers had been published from Iran, either in 91 domestic (www.iranmedex.com) or international journals (www.ncbi.com) for all the biomedical articles published between 1993 and 2003 in 91 Iranian journals. The search was conducted using "transplantation" or "transplant" as key words. A printed copy of the papers (if available) was reviewed to identify the transplanted organ, study design, number of authors, and type of article. RESULTS: Among 601 articles, 545 (90.6%) had been published in domestic journals, and 56 (9.4%) in Medline indexed journals. Frequency of original articles was significantly higher among domestic journals (84.4% vs. 62.5%, p=0.001). The organ type was not significantly different between domestic or Medline indexed journals (61.7%, 71.4%, p=0.556). Mean author numbers was significantly less among domestic in comparison to Medline indexed journals (3.6+/-2.2 vs. 4.6+/-3.0, p=0.047). CONCLUSIONS: It seems that Iranian scientific database is a more important database, not only by means of quantity, but also by means of research characteristics, such as originality of research. So, domestic scientific databases should be regarded as a pool of valuable information, and should be introduced to researchers of other countries, such as Middle East Society for Organ Transplantation region. PMID- 19644162 TI - Development of jejunal graft damage during intestinal transplantation. AB - BACKGROUND: Intestinal transplantation (ITx) represents difficult life-saving intervention reserved for patients with irreversible intestinal failure. A serious complication of ITx is jejunal graft (JG) damage. The aim of the study was to evaluate the development of JG damage during ITx and determine the share of pathological elements (mechanical manipulation, ischemia, reperfusion) in this damage. MATERIAL/METHODS: Male Wistar rats (n=60; 30 donors and 30 recipients) were used. The harvest of JG as well as heterotopic allotransplantation was performed using a technique adapted from Balaz et al. (2003). In all transplantations, three samples of JG were obtained: immediately after harvest (Sa1), after preservation (Sa2) and 60min after transplantation (Sa3). The samples were stained using the Hematoxylin&Eosin method and histopathological injury index (HII) was assessed using Park/Chiu classification. For detection and quantification of neuroendocrine cells (NECs) Singh's modification of the Masson Hamperl argentaffin technique was used. RESULTS: The lowest level of HII was detected in Sa1=0.25+/-0.18; higher after preservation Sa2=1.42+/-0.38 and the highest HII was observed after transplantation Sa3=3.08+/-0.38. The percentage share of mechanical manipulation with the graft in jejunal damage during ITx was 8.11% (Sa1), the share of the ischemic element represented 37.98% (Sa2) and reperfusion had 53.91% of the share in jejunal damage (Sa3). The activity of NECs had sinusoidal character (Sa1=0.5+/-0.1; Sa2=1.4+/-0.0; Sa3=0.35+/-0.05). CONCLUSIONS: The development of JG damage during ITx had progressive character. Mechanical manipulation had minimal influence on jejunal damage. One third of damage was caused by the ischemic component and the largest impact on JG damage resulted from reperfusion. PMID- 19644163 TI - Acute renal allograft failure due to thrombosis of a previously stented iliac artery: salvage using mechanical thrombectomy and restenting. AB - BACKGROUND: Renal artery stenosis is the most common surgical complication after renal transplantation. RT stenosis of the iliac artery presents in a similar way. Interventional techniques can salvage the graft in most cases. CASE REPORT: We report a renal transplant recipient who developed acute ischemic graft failure due to thrombosis of a previously stented iliac artery. He was successfully treated with mechanical thrombectomy and re-stenting. By this, we were able to salvage the graft with good long-term function. CONCLUSIONS: To the best of our knowledge this is the first case of restenting of an iliac artery in the setting of RT. Interventional radiology should be the approach in such cases. PMID- 19644165 TI - What we need to promote transplantation research in Iran. PMID- 19644164 TI - Early onset post transplantation lymphoproliferative disorders: analysis of international data from 5 studies. AB - BACKGROUND: Post-transplant lymphoproliferative disease (PTLD) is a major complication after solid organ transplantation and most frequently occurs during the first year post transplantation. We analyzed patient characteristics, outcome and prognostic factors for survival of transplant patients who developed post transplant lymphoproliferative disorders within one year after transplantation reported by 5 major studies worldwide. MATERIAL/METHODS: We made a comprehensive search for the available data by Pubmed and Google scholar search engines on post transplant lymphoproliferative disorders. A standard questionnaire was developed to collect data from different published studies. Finally, trustable data of a total of 5 publishes were included in the final analysis. For data analysis we used SPSS v. 13.0. Kaplan-Meier Method was used for survival analysis. P<0.05 was defined as significant. RESULTS: Data of 16 patients who developed PTLD during the early 12 months after transplantation (2 liver and 14 renal) were recruited from 5 studies and entered into analysis. Mean age was 41.9+/-16.2 years. Univariate survival analysis showed that localization of the PTLD in brain in PTLD patients induces a highly significant adverse effect on the outcome of PTLD patients (P=0.008) but not for other localizations. We aso found that involvement of the allograft (all kidney allograft) is associated with higher rate of remission (either partial or complete remission) of PTLDs after anti-cancer therapy. No associations were found regarding other variables. CONCLUSIONS: Because of the higher incidence rate and fatal nature, early onset PTLD is of extreme relevance. Screening all renal transplant patients in the early post transplantation period for an early detection and treatment of PTLDs is crucial, particularly in patients who are more likely to develop PTLDs. PMID- 19644166 TI - A Monte Carlo EM algorithm for de novo motif discovery in biomolecular sequences. AB - Motif discovery methods play pivotal roles in deciphering the genetic regulatory codes (i.e., motifs) in genomes as well as in locating conserved domains in protein sequences. The Expectation Maximization (EM) algorithm is one of the most popular methods used in de novo motif discovery. Based on the position weight matrix (PWM) updating technique, this paper presents a Monte Carlo version of the EM motif-finding algorithm that carries out stochastic sampling in local alignment space to overcome the conventional EM's main drawback of being trapped in a local optimum. The newly implemented algorithm is named as Monte Carlo EM Motif Discovery Algorithm (MCEMDA). MCEMDA starts from an initial model, and then it iteratively performs Monte Carlo simulation and parameter update until convergence. A log-likelihood profiling technique together with the top-k strategy is introduced to cope with the phase shifts and multiple modal issues in motif discovery problem. A novel grouping motif alignment (GMA) algorithm is designed to select motifs by clustering a population of candidate local alignments and successfully applied to subtle motif discovery. MCEMDA compares favorably to other popular PWM-based and word enumerative motif algorithms tested using simulated (l, d)-motif cases, documented prokaryotic, and eukaryotic DNA motif sequences. Finally, MCEMDA is applied to detect large blocks of conserved domains using protein benchmarks and exhibits its excellent capacity while compared with other multiple sequence alignment methods. PMID- 19644167 TI - A unified approach for reconstructing ancient gene clusters. AB - The order of genes in genomes provides extensive information. In comparative genomics, differences or similarities of gene orders are determined to predict functional relations of genes or phylogenetic relations of genomes. For this purpose, various combinatorial models can be used to identify gene clusters- groups of genes that are colocated in a set of genomes. We introduce a unified approach to model gene clusters and define the problem of labeling the inner nodes of a given phylogenetic tree with sets of gene clusters. Our optimization criterion in this context combines two properties: parsimony, i.e., the number of gains and losses of gene clusters has to be minimal, and consistency, i.e., for each ancestral node, there must exist at least one potential gene order that contains all the reconstructed clusters. We present and evaluate an exact algorithm to solve this problem. Despite its exponential worst-case time complexity, our method is suitable even for large-scale data. We show the effectiveness and efficiency on both simulated and real data. PMID- 19644168 TI - An approximation algorithm for the minimum breakpoint linearization problem. AB - In the recent years, there has been a growing interest in inferring the total order of genes or markers on a chromosome, since current genetic mapping efforts might only suffice to produce a partial order. Many interesting optimization problems were thus formulated in the framework of genome rearrangement. As an important one among them, the minimum breakpoint linearization (MBL) problem is to find the total order of a partially ordered genome that minimizes its breakpoint distance to a reference genome whose genes are already totally ordered. It was previously shown to be NP-hard, and the algorithms proposed so far are all heuristic. In this paper, we present an {m(2)+m/2}-approximation algorithm for the MBL problem, where m is the number of gene maps that are combined together to form a partial order of the genome under investigation. PMID- 19644169 TI - An extended Kalman filtering approach to modeling nonlinear dynamic gene regulatory networks via short gene expression time series. AB - In this paper, the extended Kalman filter (EKF) algorithm is applied to model the gene regulatory network from gene time series data. The gene regulatory network is considered as a nonlinear dynamic stochastic model that consists of the gene measurement equation and the gene regulation equation. After specifying the model structure, we apply the EKF algorithm for identifying both the model parameters and the actual value of gene expression levels. It is shown that the EKF algorithm is an online estimation algorithm that can identify a large number of parameters (including parameters of nonlinear functions) through iterative procedure by using a small number of observations. Four real-world gene expression data sets are employed to demonstrate the effectiveness of the EKF algorithm, and the obtained models are evaluated from the viewpoint of bioinformatics. PMID- 19644170 TI - Computing the distribution of a tree metric. AB - The Robinson-Foulds (RF) distance is by far the most widely used measure of dissimilarity between trees. Although the distribution of these distances has been investigated for 20 years, an algorithm that is explicitly polynomial time has yet to be described for computing the distribution for trees around a given tree. In this paper, we derive a polynomial-time algorithm for this distribution. We show how the distribution can be approximated by a Poisson distribution determined by the proportion of leaves that lie in "cherries" of the given tree. We also describe how our results can be used to derive normalization constants that are required in a recently proposed maximum likelihood approach to supertree construction. PMID- 19644171 TI - Evolutionary optimization of kernel weights improves protein complex comembership prediction. AB - In recent years, more and more high-throughput data sources useful for protein complex prediction have become available (e.g., gene sequence, mRNA expression, and interactions). The integration of these different data sources can be challenging. Recently, it has been recognized that kernel-based classifiers are well suited for this task. However, the different kernels (data sources) are often combined using equal weights. Although several methods have been developed to optimize kernel weights, no large-scale example of an improvement in classifier performance has been shown yet. In this work, we employ an evolutionary algorithm to determine weights for a larger set of kernels by optimizing a criterion based on the area under the ROC curve. We show that setting the right kernel weights can indeed improve performance. We compare this to the existing kernel weight optimization methods (i.e., (regularized) optimization of the SVM criterion or aligning the kernel with an ideal kernel) and find that these do not result in a significant performance improvement and can even cause a decrease in performance. Results also show that an expert approach of assigning high weights to features with high individual performance is not necessarily the best strategy. PMID- 19644172 TI - Improved approximation algorithms for reconstructing the history of tandem repeats. AB - Some genetic diseases in human beings are dominated by short sequences repeated consecutively called tandem repeats. Once a region containing tandem repeats is found, it is of great interest to study the history of creating the repeats. The computational problem of reconstructing the duplication history of tandem repeats has been studied extensively in the literature. Almost all previous studies focused on the simplest case where the size of each duplication block is 1. Only recently we succeeded in giving the first polynomial-time approximation algorithm with a guaranteed ratio for a more general case where the size of each duplication block is at most 2; the algorithm achieves a ratio of 6 and runs in O(n{11}) time. In this paper, we present two new polynomial-time approximation algorithms for this more general case. One of them achieves a ratio of 5 and runs in O(n{9}) time, while the other achieves a ratio of 2.5 + epsilon for any constant epsilon > 0 but runs slower. PMID- 19644173 TI - Metrics for phylogenetic networks II: nodal and triplets metrics. AB - The assessment of phylogenetic network reconstruction methods requires the ability to compare phylogenetic networks. This is the second in a series of papers devoted to the analysis and comparison of metrics for tree-child time consistent phylogenetic networks on the same set of taxa. In this paper, we generalize to phylogenetic networks two metrics that have already been introduced in the literature for phylogenetic trees: the nodal distance and the triplets distance. We prove that they are metrics on any class of tree-child time consistent phylogenetic networks on the same set of taxa, as well as some basic properties for them. To prove these results, we introduce a reduction/expansion procedure that can be used not only to establish properties of tree-child time consistent phylogenetic networks by induction, but also to generate all tree child time consistent phylogenetic networks with a given number of leaves. PMID- 19644174 TI - Model reduction of multiscale chemical langevin equations: a numerical case study. AB - Two very important characteristics of biological reaction networks need to be considered carefully when modeling these systems. First, models must account for the inherent probabilistic nature of systems far from the thermodynamic limit. Often, biological systems cannot be modeled with traditional continuous deterministic models. Second, models must take into consideration the disparate spectrum of time scales observed in biological phenomena, such as slow transcription events and fast dimerization reactions. In the last decade, significant efforts have been expended on the development of stochastic chemical kinetics models to capture the dynamics of biomolecular systems, and on the development of robust multiscale algorithms, able to handle stiffness. In this paper, the focus is on the dynamics of reaction sets governed by stiff chemical Langevin equations, i.e., stiff stochastic differential equations. These are particularly challenging systems to model, requiring prohibitively small integration step sizes. We describe and illustrate the application of a semianalytical reduction framework for chemical Langevin equations that results in significant gains in computational cost. PMID- 19644175 TI - On subset seeds for protein alignment. AB - We apply the concept of subset seeds to similarity search in protein sequences. The main question studied is the design of efficient seed alphabets to construct seeds with optimal sensitivity/selectivity trade-offs. We propose several different design methods and use them to construct several alphabets. We then perform a comparative analysis of seeds built over those alphabets and compare them with the standard Blastp seeding method, as well as with the family of vector seeds. While the formalism of subset seeds is less expressive (but less costly to implement) than the cumulative principle used in Blastp and vector seeds, our seeds show a similar or even better performance than Blastp on Bernoulli models of proteins compatible with the common BLOSUM62 matrix. Finally, we perform a large-scale benchmarking of our seeds against several main databases of protein alignments. Here again, the results show a comparable or better performance of our seeds versus Blastp. PMID- 19644176 TI - Parsimony score of phylogenetic networks: hardness results and a linear-time heuristic. AB - Phylogenies-the evolutionary histories of groups of organisms-play a major role in representing the interrelationships among biological entities. Many methods for reconstructing and studying such phylogenies have been proposed, almost all of which assume that the underlying history of a given set of species can be represented by a binary tree. Although many biological processes can be effectively modeled and summarized in this fashion, others cannot: recombination, hybrid speciation, and horizontal gene transfer result in networks of relationships rather than trees of relationships. In previous works, we formulated a maximum parsimony (MP) criterion for reconstructing and evaluating phylogenetic networks, and demonstrated its quality on biological as well as synthetic data sets. In this paper, we provide further theoretical results as well as a very fast heuristic algorithm for the MP criterion of phylogenetic networks. In particular, we provide a novel combinatorial definition of phylogenetic networks in terms of "forbidden cycles," and provide detailed hardness and hardness of approximation proofs for the "small" MP problem. We demonstrate the performance of our heuristic in terms of time and accuracy on both biological and synthetic data sets. Finally, we explain the difference between our model and a similar one formulated by Nguyen et al., and describe the implications of this difference on the hardness and approximation results. PMID- 19644177 TI - Protein design by sampling an undirected graphical model of residue constraints. AB - This paper develops an approach for designing protein variants by sampling sequences that satisfy residue constraints encoded in an undirected probabilistic graphical model. Due to evolutionary pressures on proteins to maintain structure and function, the sequence record of a protein family contains valuable information regarding position-specific residue conservation and coupling (or covariation) constraints. Representing these constraints with a graphical model provides two key benefits for protein design: a probabilistic semantics enabling evaluation of possible sequences for consistency with the constraints, and an explicit factorization of residue dependence and independence supporting efficient exploration of the constrained sequence space. We leverage these benefits in developing two complementary MCMC algorithms for protein design: constrained shuffling mixes wild-type sequences positionwise and evaluates graphical model likelihood, while component sampling directly generates sequences by sampling clique values and propagating to other cliques. We apply our methods to design WW domains. We demonstrate that likelihood under a model of wild-type WWs is highly predictive of foldedness of new WWs. We then show both theoretical and rapid empirical convergence of our algorithms in generating high-likelihood, diverse new sequences. We further show that these sequences capture the original sequence constraints, yielding a model as predictive of foldedness as the original one. PMID- 19644178 TI - RNA search with decision trees and partial covariance models. AB - The use of partial covariance models to search for RNA family members in genomic sequence databases is explored. The partial models are formed from contiguous subranges of the overall RNA family multiple alignment columns. A binary decision tree framework is presented for choosing the order to apply the partial models and the score thresholds on which to make the decisions. The decision trees are chosen to minimize computation time subject to the constraint that all of the training sequences are passed to the full covariance model for final evaluation. Computational intelligence methods are suggested to select the decision tree since the tree can be quite complex and there is no obvious method to build the tree in these cases. Experimental results from seven RNA families shows execution times of 0.066-0.268 relative to using the full covariance model alone. Tests on the full sets of known sequences for each family show that at least 95 percent of these sequences are found for two families and 100 percent for five others. Since the full covariance model is run on all sequences accepted by the partial model decision tree, the false alarm rate is at least as low as that of the full model alone. PMID- 19644179 TI - [Tactical and technical approaches in treatment of left-sided colonic obstruction]. AB - The authors presented the method of surgical treatment of left-sided colonic obstruction. T-shape closed anastomosis with delayed opening of its lumen was created. Decompression of the colon was achieved by means of thick tube inserted into the adducing part of the intestine. 35 patients were operated, their age was from 19 to 78 years. The after-operation period was smooth in the majority of cases the tube was removed from the colostomy on the 8th day after the operation. The anastomosis began to function from the 5th day. There was one case of complication: one patient developed a chronic fistula, which had to be closed surgically. There were no cases of lethality. PMID- 19644180 TI - Characteristics of morphological change in erythrocytes during metaststic adenocarcinoma of the prostate before and after castration. AB - The objective of our study was to establish whether there is a direct link between displayed changes in Erythrocytes and hormonal shifts talking place in organism. For the experimental research we used a blood serum and erythrocytes of 15 men with metastasized adenocarcinoma before castration and a blood serum and erythrocytes of 15 men in 6 months after castration, also a blood serum and erythrocytes of practically healthy men. Age of patients varied from 60-75 years. Structural observation of erythrocytes was conducted by means of light microscope method, and quantitative calculation of steroid hormones was performed by means of the method of imunopherment analysis. Deep morphological changes of erythrocytes were observed in peripheral blood during metastasized adenocarcinoma of prostate gland before and after castration. At the same time during this pathology we detected sharp quantitative change of steroid hormones of testicular and adrenal glands. It was established that the deep morphological changes of erythrocytes in peripheral blood should be related to the cancerous processes occurring in organism (direct way); It was established that during the noted pathology hormonal shifts taking place in organism (indirect way) influence the course of erythropoiesis and cause changes of surface architectonics of erythrocytes, as a result of which pathological erythrocytes -cells with altered form and low functional activity, are formed. PMID- 19644181 TI - [Efficiency of the capecitabine in patients with breast cancer with liver metastasis]. AB - The main purpose of the present research is to study the efficiency of capecitabine in treatment of patients with breast cancer with liver metastasis. The investigation was carried on 44 patients with breast cancer with liver metastasis. Patients were divided into 2 groups. The first group was composed of patients (n=21) cycles of chemotherapy ( DCapLv) was carried out. The second group (n=23) was composed of patients treated upon the schema of CapLv. Patients had their diagnosis morphologically verified Metastatic involvement of the liver was diagnosed on the base of data of MRI, CT and ultrasonographic research. The obtained results were compared with the results of treatment of patients (n=54), who received the "classical" schema of FAC treatment. The investigation proved high efficiency of chemotherapy treatment schema in patients with breast cancer with liver metastasis. Proposed schema of chemotherapy seems to have had few hepatotoxic effects. PMID- 19644182 TI - [The influence of the external electrical pacing on precursor cells at critical patients]. AB - The treatment of the critical patients by a combination of the external electrical pacing and traditional methods in comparison with only traditional methods of treatment within first two weeks promote to stable, besides statistically significant growth of the bone marrow and peripheral blood cells quantity, including precursor and immunocompetent cells, erythrocytes, leucocytes, especially its young forms and thrombocytes, normalizes the respiratory and metabolic components of the acid-base balance, increases surviving of the patients, reduces frequency of complications and category of the invalidity and the cost and duration of the treatment. PMID- 19644183 TI - [The mechanisms of tinnitus in patients with sensor neural deafness]. AB - The mechanism that produces tinnitus remains poorly understood. This article reviews possible mechanisms of tinnitus. The evaluation of the structure of disease in the presence of hearing reduction was studied among 2820 patients who applied for otolaryngological aid. Sensor neural deafness of different genesis was revealed in 512 cases. Apart from deafness, earlier manifesting symptom of the disease was pathological noise in the ear leading to anxiety of patients. Audiological characters and course of disease under the influence of symptomatic complex therapy has been studied. The author has detected /discovered/ present mechanism of beginning of the noise in the ear real reason of which is ischemia of cochlear apparatus in the presence of sensor neural loss of hearing, necessity of carrying out therapy as well and searching other methods of. PMID- 19644184 TI - [Case report of the middle ear cholesteatoma recidive after canal wall down operation, 2 years later]. AB - Cholesteatoma is the most controversial topic within the field of middle ear surgery. Depending on the individual, many surgeons have used the two different techniques of intact canal wall and canal-wall-down tympanomastoidectomy for approaching the middle ear. Opinions conflict as to which approach provides the best visualization of different locations in the middle ear. In this article, a clinical case of recurrence of middle ear cholesteatoma which completely destroyed temporal bone, close to the inner carotid artery 20 years after canal wall-down surgical treatment is presented. PMID- 19644185 TI - [Composite resin--clinical problems and success]. AB - Biomimetic aspects of restoration of the frontal and side teeth, on one hand, facilitated achievement of the desired esthetic effect and on the other- complicated the way of achievement of the final result. Consequently, the new products of the leading manufacturers are realized in the dental clinics with the interest and impatient, though vigilantly. Goal of this research was comparative description of the effects of filling composites Profil, Charisma and Estelite. Restoration works, using the composite materials were conducted both, in clinics and experimentally, on the extracted teeth. Research results showed: micro-hybrid components of Profil and Charisma had almost identical clinical parameters (compactness, range of colors and plasticity, in modeling). Though, colors seemed to be more saturated in case of application of Profil. Micro-matrix composite Estelite, according to our results, is characterized with more prominent transparency, requiring application of the large layers of opaque shades. Though, high saturation of Estelite (82% of inorganic fraction) is conditioned by the sensity of composite, justifying its application for both, restoration of teeth and correction of the contact occlusion points. Thus, in restoration of teeth, which are subject to high load at a time of chewing (premolars, molars), Estelite is preferable. It would be better to use Profil in filling of the cavities of small size and Charisma might be recommended for the frontal teeth groups, though, in esthetic restoration, composites without filling should be preferred. PMID- 19644186 TI - [Local homeostasis and acid-based balance in the oral cavity in patients with diabetes mellitus II]. AB - 60 patients were researched for the purpose of comparable estimation of local homeostasis' indexes and acid-based balance in the oral cavity. They were divided into three groups: patients with parodontitis and diabetes (second type), patients with parodontitis only and practically healthy patients. Their blood was analyzed for glucose and glycerinated hemoglobin, mixed saliva--for the presence of glucose with use of the new method, salivation speed, bacterial composition of lingual plaque and parodontal pockets, pH of mixed of saliva, pH of lingual plaque and gingival liquor, carbamyde pH-test index. Patients with diabetes showed an increase of glucose concentration in the saliva which correlates with similar index of blood, as well as abrupt reduction of salivation and disorder of micrbiocenosis. An increase of acidosis in oral cavity and parodontal tissues, an increase of the activity of ureazpositive micro flora in lingual plaque were discovered. For express diagnosis of disbacteriosis in oral cavity the authors recommend to use indexes of local carbamyde pH-test on the tip of tongue and the new non-invasive hyperglycemia diagnosis method. PMID- 19644187 TI - [Vestibularly displaced flap with bone augmentation]. AB - The aim of this study is to achieve esthetic gingival contours with the help of less traumatic mucogingival surgeries. 9 Patients were operated with horizontal deficiencies in 9 edentulous sites, planned to be restored with fixed partial dentures. In all cases there was lack of keratinized tissues. Temporary bridges were fabricated to all patients. Before surgery the bridges were removed and the abutment teeth were additionally cleaned with ultrasonic device. A horizontal incision was made from lingual (palatal) side between the abutment teeth, which was connected with two vertical releasing incisions to the mucogingival junction from the vestibular side. The horizontal incision was made on a distance 6-10 mm from the crest of the alveolar ridge. A partial thickness flap in the beginning 3 5 mm, then a full thickness flap up to the mucogingival junction, then a partial thickness flap was made. The flap was mobilized and displaced vestibularly. In the apical part the cortical bone was perforated, graft material was put and the flap was sutured. In all 9 cases the horizontal defect was partially or fully eliminated. The width of the keratinized tissues was also augmented in all cases. The postoperative healing was without complications, discomfort and painless. The donor sites also healed without complications. The application of Solcoseryl Dental Adhesive Paste 3 times a day for 7-10 days helped for painless healing of the donor site. The offered method of soft tissue and bone augmentation is effective in the treatment of horizontal defects of edentulous alveolar ridges of not big sizes. It makes possible to achieve esthetic results without traumatizing an additional donor-site. PMID- 19644188 TI - [Anatomo-physiologic and morpho-functional characteristics of juvenile football players in Georgia]. AB - The aim of the research was to work out and to substantiate the choice of methods of assessment of anatomo-physiologic and morpho-functional characteristics of 9 17 year-old football players in Georgia. The differentiated scale of assessments consisting of 22 tests, distributed into 5 blocks is developed: the block of physical development, the block of cardio-respiratory system, the block of activity of the central nervous system, the power supply block and the physical readiness block. The offered methods of complex assessment of physical conditions allow to estimate efficiency of influence of physical activities on juvenile football players and also to reveal the most promising football players, possessing all necessary anatomic-physiological and morpho-functional data. PMID- 19644189 TI - Evaluation of safety and efficacy of prolonged suppressive therapy of genital herpes with valacyclovir. AB - The aim of study was to determine the effectiveness, safety and side effects of suppressive therapy (valacyclovir) for relapsing genital herpes virus infections. Patients with HSV were divided into three groups: the first group was composed of 82 patients (45 males and 37 females) who received 500 mg of valacyclovir single dose daily during 6 months. The second group was composed of 52 patients (29 males and 23 females) who received 500 mg of valacyclovir single dose daily during 12 months. The third group was composed of 152 patients (87 males and 65 females), who received 500 mg of valacyclovir single dose daily during 24 months. Control group was composed of 60 patients (32 males and 28 females) who were treated with topical antiseptics. Several side effects such as headache (in 12% of patients), sickness (6%) and diarrhoea (3%) have been seen with the same frequency in patients and control group. Frequency of more serious complications, such as HBV infections, leukopenia, strong headaches was very low (0.2%). Other haematological and biochemical parameters were normal. Genital herpes reoccurrence was demonstrated only in 3% of patients. Relapse of genital herpes during suppressive therapy was seen in 9 % of patients. In control groups the same measure was 86% in patients. It is concluded, that continuous suppressive therapy of HSV infections with valacyclovir is safe and effective treatment, which strongly prevents reoccurrence or transmissions of HSV infections to sexual partners. Suppressive therapy few weeks before the expected delivery will decrease: the risk of relapse and need for cesarean section. PMID- 19644190 TI - [Some aspects of the clinical use of lercamen (lercadipine)]. AB - The paper deals with the comparative study of the effects of lercamen (lercadipine) and amlodipine, two third-generation long-acting calcium channel blocker medicine of the dihydropyridine type used in the treatment of hypertension. 80 patients of both sexes, aged from 48 to 76 were treated with lercamen (10-20 mg) or amlodipine (10 mg) for twelve weeks. Some adverse reactions of the above mentioned drugs such as headache, ankle oedema and others were observed and studied with great care. A two-week treatment with lercamen (10 mg) resulted in significant decrease of both systolic and diastolic blood pressure in 74% patients. Further decrease of blood pressure was observed during the following 10 weeks. The doze of lercamen had to be doubled for 26% of patients. After 12 weeks blood pressure in lercamen group was 126+/-4.5/80.4+/ 5.3 mmHg (p<0.01 versus baseline). Amlodipine caused similar decrease of blood pressure. Sympathetic activation occurs neither with lecramene not with amlodipine during chronic therapy. Less adverse drug reactions were observed among lercamen group, which equaled with 12% than among the amlodipine group, which was 26,3%. We believe that adverse reactions are weakly expressed in lercamen group than in amlodipine group due to high lypophility and unique membrane kinetic of lercamen. Lercamen has proved not only better efficiency but also better endurance in chronic treatment of essential hypertension in patients. PMID- 19644191 TI - The influence of coronary angioplasty of the infarct-dependent artery on systolic and diastolic function of the left ventricle. AB - The target of research is to compare the changes of systolic and diastolic functions of the left ventricle in patients with at least one month infarction after infarct-dependent artery recanalization through elective stenting. The group of 60 patients was selected, 47 men and 13 women, who underwent hospitalization in Central Hospital of Oilworkers in 2006-2007. The investigation was conducted on 30 patients (24 men and 6 women), who underwent elective stenting of LAD. The control group was composed of 30 patients (23 men and 7 women) after anterior myocardial infarction without further stenting of infarct dependent artery. The clinical diagnosis was confirmed by coronary ventriculography. The patients underwent the echocardiography the day before stenting. The "Sonoline G60 (Siemens, Germany)" machine with 2.5MHz probe has been used. The echocardiography was repeated after 7 days and 3, 6, 12 months after stent implantation. The standard parameters of systolic and diastolic function of the left ventricle were identified during investigation. The statistical processing was delivered through PC with Excel program set. All data are presented in (M+/-m), where the M--mean value, m--standard mean fault. Comparison of the data was conducted with Student criterion. The results of treatment of patients with and without further stenting of infarct-dependent artery were compared. It was found that the stenting of infarct-dependent artery with standard therapy in patients after myocardial infarction has better impact on systolic function, than traditional medical therapy without further reperfusion. The stenting of infarct-dependent artery facilitates earlier improvement of the systolic and diastolic function of the left ventricle. The diastolic relaxation grade of the left ventricle after stenting of the left coronary artery is higher, than in patients without further revascularization. PMID- 19644192 TI - [To study of etiopathogenetic peculiarities of meningitis in children]. AB - The aim of the present study was to reveal some etio-pathogenetic aspects of bacterial meningitis in children. The complex clinical and microbiological investigation of 14 year old 66 children with meningeal and infectious syndromes was conducted. Bacterial meningitis was diagnosed in 90,9% patients. The meningococcal meningitis was diagnosed in 18 (30%) patients, H.influenzae meningitis--in 9 (15%), S.pneumoniae--in 8 (13,3%). Meningitis as a monoinfection was revealed in 85% cases; mixed infection--in 15%. In 28 patients the etiologic agents of disease were gram-negative bacteria, in 16 children--gram-positive. PMID- 19644193 TI - [The model specification of the period without recurrences in rats after Pliss lymphosarcoma resection]. AB - The purpose of the present study was to make an experimental model of the period without recurrences in rats after Pliss lymphosarcoma (PLS) resection. Experiments were carried out on white low-bred male rats (n=109). For the tumor transinoculation the rats received subcutaneously 0.2 ml of the aseptic 50% suspension of PLS prepared according to the standards on saline without antibiotic addition. The injections were done in the right abdomen region. The animals were classified into three groups. Group 1 was used for control. An operation of lymphosarcoma resection was carried out on the rats from group 2 on the fifth day from the tumor inoculation. The tumor in the animals from group 3 was dissected on 12-22nd day from its inoculation. At the same time the specification of the duration of the period without recurrences was estimated in every group. According to the suggested method the Pliss lymphosarcoma resection significantly increases the life duration of operated rats that proves the efficiency of surgical interventions. The absence of intraoperative and postoperative lethality on the fifth day from the Pliss lymphosarcoma resection and 100% animal death resulting from the recurrences makes the proposed model potentially suitable for the investigation of adjuvant methods that are used in the treatment of cancer. PMID- 19644194 TI - Stress-system: corticotropin-releasing hormone and catecholamines (review). AB - The brain's stress-handling system--the limbic-hypothalamic-pituitary-adrenal axis--is one of the most thoroughly studied circuitry of the central nervous system. As a result of stress-axis activation different behavioral and physical changes develop; these changes allow the organism to adapt. For this purpose stress-system closely "works" with other elements of central nervous system, which are involved in the regulation of emotion and structures, also with axes, responsible for reproduction, growth and immunity. Dysfunction of stress-system- it's hyper- or hypoactivity--is characteristic peculiarity of many pathological states and disorders. Various molecules (corticotropin-releasing hormone, vasopressin, glucocorticoids, mineralocorticoids, ACTH, its precursor proopiomelanocortin etc.) are engaged in the regulation of stress-axis. Among these molecules corticotropin-releasing hormone is supposed to have a key role in regulating the response to stress. Besides these molecules, the end-products of the stress-axis activation: catecholamines, different hormones and cytokines - control the activity of multiple levels of this axis. According some views catecholamines play one of the essential roles in the alterations provoked by stress-axis activation. In this review we cite some classical (Crousseau et al.) and modern data concerning corticotropin-releasing hormone and catecholamine activities during stress. PMID- 19644195 TI - Als-like syndrome in the patient with chronic hepatitis C. AB - Amyotrophic lateral sclerosis (ALS) is the most common and most severe form of the motor neuron disease. The etiology of ALS is unknown. Several underlying causes are proposed, including viral infection. There is clinical evidence suggesting that ALS may be associated with Human Immunodeficiency Virus. Besides, enterovirus RNA sequences have been detected in a spinal cord of patients with ALS. We describe a patient with a 9 year history of hepatitis C, with a progressive weakness and atrophy of the right arm. Neurologic examination revealed bilateral hypotrophy and fasciculations of brachial girdle muscles more expressed on the right. No sensory or sphincter deficit was present. Nerve conduction studies and EMG were performed. Local EMG of the right deltoid muscle revealed a 4-5th stage lesion of peripheral neuromotor system, characteristic to neurogenic disease. Viruses can be one of the triggering factors of ALS. HV has never been associated with ALS. However, we found it interesting to describe this case of ALS-syndrome developed on the background of the chronic hepatitis C to draw attention of specialists on the possible role of HCV in ALS. PMID- 19644196 TI - Hyperthermia-induced morphological changes in cerebral tissue of the rat. AB - The sensitivity of cerebral tissue to hyperthermia, its immediate effect, manifested by histological changes and the role of local blood flow, blood rheological properties, and the possible role of free radicals in development of mentioned changes have been studied. Through the cranial window local area of cerebral surface was irrigated by artificial CSF heated up to 41, 43 or 45 degrees C. Serial brain coronal sections 50 microm thick were analyzed under light microscope. Local Cerebral Blood Flow was measured by thermo-clearance method. Blood rheological properties were changed by injection of Dextran T-500 and free radicals existence was controlled by DMSO injection. High sensitivity of cerebral tissue to hyperthermic exposure even at a temperature of 41 degrees C has been confirmed. We consider cerebrovascular thrombosis as one of the most significant complication of brain hyperthermia. Deteriorated blood rheological properties aggravates hyperthermia-induced cerebral lesion. Administration of free radicals scavengers can partially lessen hyperthermia induced cerebral lesion. PMID- 19644197 TI - New data on epidemiology of visceral leishmaniasis in Georgia. AB - Visceral leishmaniasis is spread as sporadic cases in eastern regions of Georgia. In Georgia as throughout the world steady increase of the disease incidence is observed. It is related to socio-economic crisis of population, increase in the number of invaded dogs and global warming processes. In west Georgia visceral leishmaniasis cases were never observed in the past. From 2004 to 2008 authors registered 10 local cases of visceral leishmaniasis in kutaisi (8 children and 2 adult patients). It should be noted that from these 10 patients eight resided in sapichkia area and two were from other areas of kutaisi. Authors consider that the detailed epidemiologic evaluation of the above mentioned cases should be carried out urgently to avoid the emergence of new endemic of visceral leishmaniasis in west Georgia. PMID- 19644198 TI - [Pharmacotherapy and prevention of osteoporosis]. AB - In the article data regarding pharmacological prevention of primary osteoporosis is reviewed. Some main aspects of the disease are underlined. The primary prevention of osteoporosis is targeted on building up and sustaining the strength of the skeleton during different periods of human life. The secondary prevention is aimed to avert the fractures in the case of developed osteoporosis. The main mechanism of fracture risk lowering is prevention of bone mineral density (BMD) reduction. The prevention is based on risk-factor modification. It is important, that success during prevention of osteoporosis may be reached, if the group with high risk of disease development will be identified in time. In the article the risk-groups for BMD determination, the WHO criteria of disease diagnostics, as well the prevention approaches--healthy life style promotion and pharmacological prevention were presented. The main group of agents acting against bone resorption: bisphosphonates (BP), calcitonin, hormone replacement therapy, selective modulators of estrogen receptors, as well as fluorides stimulating bone production and recombinant agent of parathyroid hormone--teriparatide were discussed. Bisphosphonates are most powerful inhibitors of bone resorption and are discussed as first line agents for prevention and care of osteoporosis. At present, there are a large number of antiresorptive agents, with different pharmacodynamics and pharmacokinetics and the task for physician is to define the correct treatment in each case. PMID- 19644199 TI - [Influence of Gentiana lutea L extract on blood coagulation]. AB - The dry extract from the terrestrial parts of Gentiana Lutea was received in accordance to the developed by us general technological scheme. Study of the pharmacological influence of obtained extract on the coagulating properties of blood revealed that after its per os instillation into experimental animals the time of the formation of active thromboplastin reliably increases, while the time of thrombin and fibrinous cluster formation is shortened in comparison with those indices in the animals, that did not receive phyto-preparation, at the same time morphological appearance of the peripheral blood remains unchanged. Dry extract of terrestrial parts of Gentiana Lutea prepared in accordance to the technology recommended by us, together with widely known pharmacological effects, is characterized with new activity - influence on haemostasis. Obtained preliminary data concerning influence of the extract on coagulation of the blood request further deep studies of its mechanism. Revealed new activity of the terrestrial parts of Gentiana Lutea and the studies of the mechanism of its activity will serve in future as a basis for the recommendation of its use in new nosology. Terrestrial parts of Gentiana lutea L. are proposed as an alternative of the underground parts of the plant. Alongside with that, it is expedient to continue the studies devoted to the development of the haemostatic remedies of plant origin with systemic and local action (sponges, films, skin glues) from terrestrial parts of Gentiana lutea L. PMID- 19644200 TI - Mechanisms of lead-induced poisoning. AB - Lead is a ubiquitous environmental toxin that is capable of causing numerous acute and chronic circulatory, neurological, hematological, gastrointestinal, reproductive and immunological pathologies. The mechanism of lead induced toxicity is not fully understood. The prime targets to lead toxicity are the heme synthesis enzymes, thiol-containing antioxidants and enzymes (superoxide dismutase, catalase, glutathione peroxidase, glucose 6-phosphate dehydrogenase and antioxidant molecules like GSH). The low blood lead levels are sufficient to inhibit the activity of these enzymes and induce generation of reactive oxygen species and intensification oxidative stress. Oxidative stress plays important role in pathogenesis of lead-induced toxicity and pathogenesis of coupled disease. The primary target of lead toxicity is the central nervous system. There are different cellular, intracellular and molecular mechanisms of lead neurotoxicity: such as induction of oxidative stress, intensification of apoptosis of neurocites, interfering with Ca(2+) dependent enzyme like nitric oxide synthase. Population studies have demonstrated a link between lead exposure and subsequent development of hypertension and cardiovascular disease. The vascular endothelium is now regarded as the main target organ for the toxic effect of lead. Lead affects the vasoactive function of endothelium through the increased production of reactive oxygen species, inactivation of endogenous nitric oxide and downregulation of soluble guanylate cyclase by reactive oxygen species, leading to a limiting nitric oxide availability, impairing nitric oxide signaling. This review summarizes recent findings of the mechanism of the lead induced toxicity and possibilities of its prevention. PMID- 19644201 TI - [Management problems of improving the quality and efficiency of primary health care system of Georgia]. AB - Improving the quality and efficiency of primary health care system is a key challenge. In this regard, problems that have accumulated in the system over the past decade - a weak material base of outpatient-polyclinic institutions, especially in rural areas; a surplus of medical personnel; lack of control by local, regional and central authorities--still remain as serious obstacle. The issue of financing the provided health services, is also particularly important, given the fact that a significant portion of the cost of medical services is covered by the patient directly. And as a consequence, the low level of applications for outpatient-polyclinic assistance due to declining affordability of medical services. In connection with the foregoing, the authors of the paper raise the question of implementing strict, multi-component system of quality control of medical care for patients. In particular, they propose: to base modern organization works on improving the quality of primary health care system on the principles of general management theory; Modern management of service quality should be clearly oriented towards the needs of the population in health care, its structure and dynamics; accessibility, incentives, determined by economic and technological competition characteristic to the market; Modern quality management, regardless of ownership and scale of outpatient-polyclinic establishment should optimally combine the actions, methods and tools that provide, on the one hand--the organization of diagnostic and therapeutic prophylactic processes meeting the needs of the people, and on the other--the introduction of new methods and means to ensure the modern level of medical care; Schematic diagram of quality control mechanism organically interacts with the market research and includes a block of policy development in terms of quality. PMID- 19644202 TI - [Prevalence of lung cancer in "Small Caucasia" region of Azerbaijan Republic]. AB - Different environmental and geographical factors contribute to the development of lung cancer. This article reviews the epidemiology and etiology of lung cancer in the Less Caucasus geographical Zone in the Azerbaijan Republic. The case histories of 876 patients with lung cancer were analyzed. It was revealed that most of the patients with lung cancer in this region were smokers. Lung cancer was often diagnosed in patients older than 50 but it is rare in 70 year age group patients and older. The squamous cell carcinoma was the most common histological type of lung cancer in this region. PMID- 19644203 TI - The health impact and consequences of war in Shida Kartli region. AB - The current crisis between Russia and Georgia comes after several years of deterioration of relations between the countries. Given the disintegration of the health care systems and poor water and sanitation, there is a strong need for emergency life-saving interventions. The quality and availability of public medical care in Tskhinvali region deteriorated during the war. Policy making is affected during periods of political violence: by conflicting approaches by different agencies, by parallel health systems organised during the war, and by conflicts between international funding agencies and national policy makers; Operational capabilities of the health sector are difficult to establish. In Shida Qartli, policy making capacity, health workers' morale, and mechanisms for resolving conflict seem to have been negatively affected by the conflict and its aftermath. PMID- 19644204 TI - [Statistical indicators as a basis for the assessment of the demand of human resources for health in armenia]. AB - In conditions of new economic and legal relations in the "state vs. population vs. healthcare sector" system an analysis is required not only on the performance of the health care system, its certain services and organizations but also the analysis of other statistical indicators describing demographic changes, mortality and morbidity are needed. The situational analysis of the mentioned parameters for the 2002-2007 year has been conducted in Armenia based on the official information available from different agencies and organizations. Comparative indicators are derived from the permanent population of the country. There is no strict tendency revealed in both morbidity (according to the incidence rate) and mortality rates. There is sufficient number of beds (40.6 per 10,000 population) in case of hospitalization of 8.9 patients per 100 population; the average number of visits to health care facilities is 3.0 per one citizen. Despite the compliance of the numbers of medical personnel with the European average (37.5 per 10,000 population) as well as the intensive training of the specialists by National Institute of Health there is a misbalance and significant number of vacant positions in the provinces of Armenia. This study makes a basis for developing of recommendations for the optimization of the human resources management in Armenia. PMID- 19644205 TI - [Pneumocystosis distribution among accident liquidators in the Chernobyl nuclear power plant in remote period]. AB - The goal of the present study was to discover etiological role of Pneumocystis carini/jiroveci and to determine frequency of pneumocystic infection in the structure of bronchopulmonary pathology among armenians-liquidators of accident consequences in the Chernobyl Nuclear Power Plant. For the study, 65 patients liquidators with diagnosed pneumonia, 44 liquidators with chronic bronchitis and 34 with bronchial asthma were examined. The control group was included 65 patients with pneumonia, 44 with chronic bronchitis, 34 with bronchial asthma which were unlinked with radionucleotide aggression. Mean age in main group was 46,9 and in control group- 47,6 years old. Main and control groups were randomized by sexual characteristics also. Serologic examinations were performed by the ELISA (enzyme-linked immunoSorbent assay) and method of immunofluorescent detection of P.carinii. Circulation of pneumocystosis etiologic agent among patients-liquidators of accident consequences in the Chernobyl Nuclear Power Plant with different bronchopulmonary pathology was established and high percentage of seropositivity was revealed. Overall these data revealed high probability of Pneumocystis carini/jiroveci in the etiology of bronchopulmonary pathology among liquidators of accident consequences in the the Chernobyl Nuclear Power Plant. Even among immunocompromised patients, liquidators of accident consequences, represent an exclusive group, that is in risk for activation of latent infection or new infection with P. carini/jiroveci. Therefore these findings suggest that there is a need for regular complex epidemiological monitoring of these patients. PMID- 19644206 TI - [Perspective on medical work in Georgia at the contemporary stage of the society development]. AB - At contemporary stage of social-economical development of Georgia in the sphere of ensuring of effective protection of labour and the health of employed population there is the significant moment the conduction of complex measures among which the tasks of primary significance are distinguished, the realization of which allows to achieve the considerable improvement of labour conditions, and , correspondingly, of the health of employed population, to avoid the unfavorable effect of risk factors on labour conditions and health of working human, to improve the quality of the system "labour conditions--health" that represents the basis of realization of human constitutional right--to live and work in favorable conditions. PMID- 19644207 TI - [Normal sonoanatomy and ultrasound diagnosis of achilles tendon pathology]. AB - The aim of the research was to outline the normal sonoanatomy and improve achilles tendon pathology ultrasound diagnosis (Refinement of sonosemiotics) in order to optimize the diagnostic process and improve the treatment, to avoid the possible complications. 135 patients (age ranges from 15 to 70 years) underwent the radiological study of ankle joint posterior aspect. Pathology types: traumatic injuries--45%, inflammatory pathology--30% and degenerative-dystrophic diseases--25%. Unilateral pathology was diagnosed in 85%, bilateral--in 15% of cases. The diagnostic studies include: a) ultrasound, performed on digital ultrasound system using high frequency (7.5-12.0 MHz) linear probe with Doppler capability (all patients) b) X-Ray filming in antero-posterior and lateral projections (32 patients) and c) MRI - T1 and T2 weighted images in sagittal and transverse planes (5 patients). Ultrasound was successful in ankle joint posterior compartment pathology diagnosis in 132 cases (97.8%). It was ineffective in osseous pathology definition. Ultrasound failed defining pathology (posterior impingement-syndrome, due to the presence of triangular bone) in 3 cases (2.2%). In this cases MRI was helpful; it was also critical in differential diagnosis of massive partial tear and complete tear of the tendon. Ultrasound should be used as a Gold Standard when the patient presents with localized clinical symptoms (pain and swelling). Critical is the possibility of dynamic and Doppler studies in real-time. X-Ray should be used when the bony pathology is suspected and MRI should be considered if the pain is not localized exactly. PMID- 19644208 TI - [The influence of palladium containing new synthesized biological active substances to protein metabolism in organism]. AB - The aim of the research was to study new drugs with palladium developed and synthesized at the Azerbaijan Medical University Scientific-Research Center Two compounds of palladium-4-aminopyridin ammonium tetrachlor palladium and Bi 4 aminopyridin dichlor were studied as more perspective substances which decrease growth of tumor. Water solution of 0.5% of these compounds were administrated intraperitoneally during 6 sessions. There were noticeable changes in protein metabolism, particularly in alpha(1) and alpha(2) fraction. The drug toxicity (Nedoshvina method), maximal endurance (LD(0)), medium lethal dose (LD(50)), lethal dose (LD(100)), cytogenetic activity (Rappoport method) were studied. PMID- 19644209 TI - [The dynamics of infectious disease in Adjara Autonomous Republic in 2008]. AB - 15-16 nosologies are registered on Adjarian territory annually, among which the most frequently registered infections are - the diarrhea of infectious origin, other bacterial infection of guts, viruse hepatitis and by air-drop transmission of such diseases as flue and respiratory infections. 22681 cases of infectious diseases are registered in 2008. If we compare with the results of the last year, the number has increased by 979 cases. There are 60-65% of population of 0-14 years old in the age spectrum of the disease. Among other bacterial infections of guts, there are 170 cases of esherikhosis col proved laboratorially. This is 75% of infections registered by other bacterial infection diagnosis of the gut. In 2008 there were 508 cases of A+other cases of viruse hepatitis included in the epidemy controlling system. The index of flue and acute infectious diseases of upper inhalant has risen several times compared with the last years. 450 cases of flue were registered in 2008, from the observed the virus is identified in 22 cases, 16491 cases of acute virus infection of upper inhalant, 15 cases of hospitalization with the flue like disease. Within the 28 year dynamics of the flue and upper inhalant acute infections, the data of 2005-2008 years gets closer to the data of the 80s. PMID- 19644210 TI - Step by step analysis toward optimal MTF algorithm using an edge test device. AB - Comprehensive research focus on the use of an edge test device for accurate determination of the modulation transfer function (MTF) in x-ray imaging has resulted in the development of numerous edge processing algorithms. While the overall results of the relative algorithms have been compared, the individual steps within the algorithms have not previously been evaluated for similarities and differences that could significantly affect the resultant MTF. Therefore a step by step investigation to evaluate the alternative methods for each step separately holds the potential to provide insight into improving the overall algorithm by optimizing the method employed for each step. Thus this research study focused on comparing methods applicable for each step comprising the edge algorithm and providing a step by step guide for implementing the optimal algorithm based on given experimental conditions. In addition, new methods and combinations of methods were investigated in several of the algorithm steps, and were determined to provide comparable, if not superior, results to the existing methods. This included the use of different numbers of rows and columns in the region of interest (ROI) for determining the edge spread function (ESF), implementing a new three-step ESF filtering approach, and applying a median filter in both the ESF and line spread function (LSF) smoothing steps. PMID- 19644211 TI - NPS characterization and evaluation of a cone beam CT breast imaging system. AB - The Noise Power Spectrum (NPS) is a function that yields information about the spatial frequency composition of noise in images obtained by a system. It is evaluated by calculating the absolute value squared of the noise image and normalizing it with respect to the voxel and matrix sizes. Consequently, the NPS has been one of the physical characteristics that is commonly used to quantitatively measure the physical performance of a system. In this article, we evaluated the NPS of a Cone Beam CT Breast Imaging system by considering the following factors. First, we evaluated its symmetry around the x- and y-axis along with the influence of the cone angle and the matrix size on the NPS. Then, an analytical curve was suggested to best represent the NPS. Second, we analyzed the influence on the NPS of a set of seven parameters, namely the pixel size, exposure level, kVp value, number of projections acquired, voxel size, back projection filter, and the reconstruction algorithm employed. In addition, since the breast induced scattering in the image, we investigated the effect of the scattering-correction algorithm used in this system. Finally, we evaluated the uniformity of the NPS as a function of z with the matrix center located at {r = 0 mm}. The results demonstrate that the proposed curve is an ideal candidate that best represents the NPS. Hence, two parameters, the amplitude (A) and the width (sigma), can be used to characterize the curve. The results also demonstrate that the voxel size and the cone angle are the only two parameters investigated in this study that do not affect the NPS. On the other hand, the matrix and pixel sizes, the back-projection filter and the reconstruction algorithm, the exposure level and the scattering correction, all influence the NPS. Finally, the results of the last part of this investigation suggest that this imaging system does not have a 3D isotropic noise distribution along the z-axis; yielding less noisy images at around z = 0.00 m and z = 80 mm. PMID- 19644212 TI - Radiography simulation based on point-kernel model and dose buildup factors. AB - Three-dimensional point-kernel multiple scatter model for radiography simulation, based on dose X-ray buildup factors, is proposed and validated to Monte Carlo simulation. This model embraces nonuniform attenuation in object of imaging (patient body tissue). Photon multiple scattering is treated as in the point kernel integration gamma ray shielding problems via scatter voxels. First order Compton scattering is described by means of Klein-Nishina formula. Photon multiple scattering is accounted by using dose buildup factors. The proposed model is convenient in those situations where more exact techniques, like Monte Carlo, are not time consuming acceptable. PMID- 19644213 TI - Optimal densitometry wavelengths that maximize radiochromic film sensitivity while minimizing OD growth and temperature sensitivity artifacts. AB - It is well known that optical density (OD) of the radiochromic film (RCF) continues to grow after exposure at rates that have a complex dependence on dose, temperature, and densitometry wavelength. Dose rate and fractionation artifacts associated with variations in OD growth may limit the accuracy achievable by RCF dosimetry in brachytherapy and external beam applications, particularly at low doses (<5 Gy) and low dose rates (<10 cGy/h) where OD growth and sensitivity effects are large. To identify densitometry wavelengths that minimize OD growth artifacts and enhance RCF sensitivity at low doses, we have investigated Model MD 55-2 RCF response as a function of densitometry wavelength, irradiation-to densitometry time interval, dose and temperature. Using a Perkin Elmer spectrophotometer, the absorption spectrum in the 500-700 nm range was measured for doses ranging from 1-100 Gy, over post-irradiation times from 1 h to 60 days. An empirical model with time-independent, fast and slow growth components was used to fit single exposure data and the dependence of the resulting best-fit parameters on dose and densitometry wavelength was investigated. RCF OD variation with temperature in the range 22-40 degrees was measured. Wavelengths in the 660 690 nm range were found to minimize the dose-dependence of OD post-exposure growth. Densitometry wavelengths in the range of 670-680 nm enhance RCF sensitivity and show small variations in OD with temperature in the range from 22 40 degrees. Compared to 633 nm light, 675 nm densitometry reduces OD growth at 1 Gy from 70% to 10% over a period of nearly 1174.0 h relative to the initial OD measured at 1.7 h post-irradiation. In addition, RCF sensitivity is nearly doubled at this wavelength for all dose levels. PMID- 19644214 TI - Mass attenuation coefficient of chromium and manganese compounds around absorption edge. AB - The total mass attenuation coefficient for Potassium dichromate, Potassium chromate and Manganese acetate compounds are measured at different photon energies 5.895, 6.404, 6.490, 7.058, 8.041 and 14.390 keV using Fe-55, Co-57 and 241Am source with Copper target, radioactive sources. The photon intensity is analyzed using a high resolution HPGe detector system coupled to MCA under good geometrical arrangement. The obtained values of mass attenuation coefficient values are compared with theoretical values. This study suggests that measured mass attenuation coefficient values at and near absorption edges differ from the theoretical value by about 5-28%. PMID- 19644215 TI - Robust megavoltage x-ray spectra estimation from transmission measurements. AB - Megavoltage X-ray sources are commonly used for therapy planning, and knowledge of their spectral distribution is important for accurate dose calculations. There are many methods that could provide reasonable estimations of Megavoltage X-ray spectra, when very accurate attenuation data or at least very good set of initial guesses of the spectra are available. We present here a novel method, which can be used for accurate Megavoltage spectral reconstruction without any prior knowledge of spectral distribution; the method performs well even when the available transmission data are affected by noise. The method is based on a search for a smooth function that minimizes the differences between measured and calculated attenuation data. The algorithm is compared with well-known existing algorithms, using computer simulated data, both error-free and containing added random Gaussian noise. The reconstructed spectra are subsequently used to calculate the transmission through 50 cm of bone, muscle or fat tissue. It is shown that the relative errors in dose calculations, using the spectra reconstructed via this method, are significantly smaller than those obtained via well-established reconstruction algorithms--Truncated Singular Value Decomposition (TSVD) and Expectation Maximization (EM). These results suggest that the novel algorithm might be practical for routine Megavoltage therapy X-ray source calibration. PMID- 19644216 TI - Characteristics and outcomes of hospitalized patients with heart failure and reduced vs preserved ejection fraction. Report from the Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE-CARD). AB - BACKGROUND: Heart failure (HF) with preserved ejection fraction (EF) is common. We compared the characteristics, treatments, and outcomes in HF patients with reduced vs preserved EF by using the national registry database in Japan. METHODS AND RESULTS: The Japanese Cardiac Registry of Heart Failure in Cardiology (JCARE CARD) is a prospective observational study in a broad sample of patients hospitalized with worsening HF. The study enrolled 2,675 patients from 164 hospitals with an average of 2.4 years of follow-up. Patients with preserved EF (EF >or=50% by echocardiography; n=429) were more likely to be older, female, have hypertension and atrial fibrillation, and less likely to have ischemic etiology compared with those with reduced EF (EF <40%; n=985). Unadjusted risk of in-hospital mortality (6.5% vs 3.9%; P=0.03) and post-discharge mortality (22.7% vs 17.8%; P=0.058) was slightly higher in patients with preserved EF, which, however, were not different after multivariable adjustment. Patients with preserved EF had similar rehospitalization rates (36.2% vs 33.4%; P=0.515) compared with patients with reduced EF. CONCLUSIONS: HF patients with preserved EF had a similar mortality risk and equally high rates of rehospitalization as those with reduced EF. Effective management strategies are critically needed to be established for this type of HF. PMID- 19644217 TI - Diagonal ear-lobe crease is correlated with atherosclerotic changes in carotid arteries. AB - BACKGROUND: The diagonal ear-lobe crease (ELC) is reported to be a marker of cardiovascular disease. Very few reports have assessed the relationship of ELC with atherosclerosis. This relationship is investigated here using a Japanese population. METHODS AND RESULTS: A prospective cross-sectional study included 212 consecutive patients. Bilateral ear lobes were checked for the ELC and this was followed by carotid ultrasonography to measure the far wall common carotid artery intima-media thickness (CCA-IMT), plaque score (PS) and plaque number (PN). Patients with ELC had significantly higher carotid IMT than controls (0.90 +/ 0.24 vs 0.77 +/-0.15, respectively, P<0.001). ELC presence correlated significantly with carotid IMT, PS, and PN (r=0.306, P<0.0001; r=0.198, P<0.008 and r=0.221, P<0.0001, respectively), and also with age, male sex and hypertension. ELC presence and absence in mild or no PS and moderate or severe PS subgroups was significant, with a chi-squared value of 7.59 (P<0.006). In multivariate regression analysis, ELC presence correlated with CCA-IMT independently. The odds ratio for the presence of ELC in patients with CCA-IMT of <0.8 mm vs patients with CCA-IMT of >or=0.8 mm (the median value) was 0.41 (95% confidence interval, 0.22-0.76). CONCLUSIONS: The present study showed an association between ELC and increased CCA-IMT, PS, and PN. PMID- 19644218 TI - Factors that influence measurements and accurate evaluation of stent apposition by optical coherence tomography. Assessment using a phantom model. AB - BACKGROUND: Factors influencing measurements and accurate evaluation of stent apposition by optical coherence tomography (OCT) are not established. METHODS AND RESULTS: Phantom models of known luminal sizes and lengths were evaluated by OCT under various conditions and measurements were compared with actual values. Stents implanted into phantom models were examined by OCT to validate the measurement point on the stent strut surface for accurate evaluation of stent apposition. Strut thickness was measured at 3 points (midpoint, inner and outer surfaces of the stent shadow). The precision of OCT measurements of lumen diameter and area was satisfactory when the image wire was positioned in the center, but the error and deviation were unsatisfactory when the image wire was positioned eccentrically using a low frame acquisition rate. Longitudinal OCT measurements were close to actual values under all conditions examined. Measurements from the midpoint of the stent shadow to the adjacent vessel wall surface coincided with actual stent thickness. CONCLUSIONS: Significant measurement error can occur if the image wire is positioned eccentrically with a lower frame acquisition rate than specified by the manufacturer. To accurately evaluate stent apposition, the stent surface should be measured from the center of the stent reflection. PMID- 19644220 TI - No way of telling what lies ahead in one's life. PMID- 19644219 TI - High ratio of myeloid dendritic cells to plasmacytoid dendritic cells in blood of patients with acute coronary syndrome. AB - BACKGROUND: Dendritic cells (DCs) stimulate T-cells to participate in the inflammatory processes that promote the destruction of vulnerable plaques. The relationship between circulating levels of myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) in patients with acute coronary syndrome (ACS) was evaluated. METHODS AND RESULTS: Blood samples were obtained from 39 patients with ACS, 41 patients with stable angina pectoris (SAP) and 43 controls. The proportion of mDCs tended to be lower in the ACS group than in the SAP group and controls. Interleukin-12 levels associated with mDCs were significantly higher in the ACS group than in control group. The proportion of pDCs was significantly lower in the ACS groups than in the other two groups. Interferon-alpha levels secreted by pDCs, however, were not significantly different among the 3 groups. The ratio of mDCs to pDCs >or=4 is an important value for distinguishing ACS from SAP patients and control patients through receiver operating characteristic analysis (sensitivity; 85.0%, specificity; 83.4%). CONCLUSIONS: The ratio of mDCs to pDCs may be a useful marker for detecting ACS and the existence of vulnerable plaques. PMID- 19644222 TI - Hepatitis C virus utilizes lipid droplet for production of infectious virus. AB - Hepatitis C virus (HCV) establishes a persistent infection and causes chronic hepatitis. Chronic hepatitis patients often develop hepatic cirrhosis and progress to liver cancer. The development of this pathological condition is linked to the persistent infection of the virus. In other words, viral replication/multiplication may contribute to disease pathology. Accumulating clinical studies suggest that HCV infection alters lipid metabolism, and thus causes fatty liver. It has been reported that this abnormal metabolism exacerbates hepatic diseases. Recently, we revealed that lipid droplets play a key role in HCV replication. Understanding the molecular mechanism of HCV replication will help elucidate the pathogenic mechanism and develop preventive measures that inhibit disease manifestation by blocking persistent infection. In this review, we outline recent findings on the function of lipid droplets in the HCV replication cycle and describe the relationship between the development of liver diseases and virus replication. PMID- 19644224 TI - Recovery of cell nuclei from 15,000 years old mammoth tissues and its injection into mouse enucleated matured oocytes. AB - Here, we report the recovery of cell nuclei from 14,000-15,000 years old mammoth tissues and the injection of those nuclei into mouse enucleated matured oocytes by somatic cell nuclear transfer (SCNT). From both skin and muscle tissues, cell nucleus-like structures were successfully recovered. Those nuclei were then injected into enucleated oocytes and more than half of the oocytes were able to survive. Injected nuclei were not taken apart and remained its nuclear structure. Those oocytes did not show disappearance of nuclear membrane or premature chromosome condensation (PCC) at 1 hour after injection and did not form pronuclear-like structures at 7 hours after injection. As half of the oocytes injected with nuclei derived from frozen-thawed mouse bone marrow cells were able to form pronuclear-like structures, it might be possible to promote the cell cycle of nuclei from ancient animal tissues by suitable pre-treatment in SCNT. This is the first report of SCNT with nuclei derived from mammoth tissues. PMID- 19644223 TI - Accumulation of radium in ferruginous protein bodies formed in lung tissue: association of resulting radiation hotspots with malignant mesothelioma and other malignancies. AB - While exposure to fibers and particles has been proposed to be associated with several different lung malignancies including mesothelioma, the mechanism for the carcinogenesis is not fully understood. Along with mineralogical observation, we have analyzed forty-four major and trace elements in extracted asbestos bodies (fibers and proteins attached to them) with coexisting fiber-free ferruginous protein bodies from extirpative lungs of individuals with malignant mesothelioma. These observations together with patients' characteristics suggest that inhaled iron-rich asbestos fibers and dust particles, and excess iron deposited by continuous cigarette smoking would induce ferruginous protein body formation resulting in ferritin aggregates in lung tissue. Chemical analysis of ferruginous protein bodies extracted from lung tissues reveals anomalously high concentrations of radioactive radium, reaching millions of times higher concentration than that of seawater. Continuous and prolonged internal exposure to hotspot ionizing radiation from radium and its daughter nuclides could cause strong and frequent DNA damage in lung tissue, initiate different types of tumour cells, including malignant mesothelioma cells, and may cause cancers. PMID- 19644225 TI - The Ay allele at the agouti locus reduces the size and alters the shape of the mandible in mice. AB - To confirm my previous findings that the A(y) allele at the agouti locus reduced the mandible size and therefore altered the mandible shape in a KK mouse strain background, I further investigated the effects of the A(y) allele on mandible morphology on different strain backgrounds, DDD and B6. Principal component analysis revealed that the mandible was significantly smaller in A(y) mice (DDD A(y) and B6-A(y)) than in corresponding non-A(y) mice (DDD and B6, respectively). Discriminant and canonical discriminant analyses revealed that most mice were classified correctly in their own strains, and misclassification was not observed between DDD (-A(y)) and B6 (-A(y)). The results confirmed that the A(y) allele reduced the mandible size and altered the mandible shape regardless of the strain background. However, the difference in mandible morphology between A(y) mice and the corresponding non-A(y) mice within a strain was not as large as that which intrinsically underlay the two strains. Possible mechanisms of the A(y) action are discussed. PMID- 19644227 TI - Efficacy of reboxetine in the treatment of attention-deficit/hyperactivity disorder in boys with intolerance to methylphenidate: an open-label, 8-week, methylphenidate-controlled trial. AB - OBJECTIVE: Attention-deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral disorder of childhood. Principal treatment options for ADHD today include the psychostimulants, mainly methylphenidate (MPH). However, approximately 30% to 50% of children and adults with ADHD either do not respond to or do not tolerate treatment with stimulants. In this 8-week open-label, MPH controlled, parallel group design study, we investigate the efficacy of reboxetine, a new selective norepinephrine reuptake inhibitor, in the treatment of boys with ADHD with a history of intolerance to MPH therapy. METHOD: Twenty seven outpatient boys, aged 6 to 16 years, diagnosed with ADHD, participated in the study. Those with a history of intolerance to MPH therapy were assigned to treatment with reboxetine (2-8 mg/d), and the rest were assigned to treatment with MPH (10-20 mg/d) as the control group. The primary outcome measure for this study was the change in rating scores on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, ADHD Scale (DAS) that was assessed at baseline and at 8 weeks. RESULTS: At the end of 8 weeks, both reboxetine and MPH treatment regimens resulted in significant improvement in ADHD symptoms. The change in the reduction in the total DAS score and the DAS subscale scores between the reboxetine group and the MPH group was not statistically significant in any of the scores. CONCLUSIONS: Although preliminary, results of this study indicate that the use of reboxetine, a new selective norepinephrine reuptake inhibitor, in the treatment of ADHD could increase treatment options available for children who have shown intolerance or who are unresponsive to MPH. PMID- 19644226 TI - Regulation of succinate-ubiquinone reductase and fumarate reductase activities in human complex II by phosphorylation of its flavoprotein subunit. AB - Complex II (succinate-ubiquinone reductase; SQR) is a mitochondrial respiratory chain enzyme that is directly involved in the TCA cycle. Complex II exerts a reverse reaction, fumarate reductase (FRD) activity, in various species such as bacteria, parasitic helminths and shellfish, but the existence of FRD activity in humans has not been previously reported. Here, we describe the detection of FRD activity in human cancer cells. The activity level was low, but distinct, and it increased significantly when the cells were cultured under hypoxic and glucose deprived conditions. Treatment with phosphatase caused the dephosphorylation of flavoprotein subunit (Fp) with a concomitant increase in SQR activity, whereas FRD activity decreased. On the other hand, treatment with protein kinase caused an increase in FRD activity and a decrease in SQR activity. These data suggest that modification of the Fp subunit regulates both the SQR and FRD activities of complex II and that the phosphorylation of Fp might be important for maintaining mitochondrial energy metabolism within the tumor microenvironment. PMID- 19644228 TI - High doses of rotigotine transdermal patch: results of an open-label, dose escalation trial in patients with advanced-stage, idiopathic Parkinson disease. AB - OBJECTIVE: The objective of the study was to determine the maximal achievable dose of rotigotine by assessing the tolerability of escalating doses of rotigotine transdermal patch in patients with advanced-stage Parkinson disease. METHODS: Thirty-four patients aged 30 years or older on a stable dose of l-dopa with an off time of at least 2.5 h/d were randomized to 2-titration schemes. The patients started on a dosage of 4 mg/24 h and received an incremental dosage of 4 mg/24 h per week in the fast-titration group and 2 mg/24 h per week in the slow titration group to the maximal target dosage of 24 mg/24 h (patch size of 120 cm(2)). Thereafter, both groups entered a maintenance period of 42 days or longer for the rapid-titration group and 7 days or longer for the slow titration group followed by a 2-week safety follow-up period with stepwise dosage de-escalation of 4 mg/24 h for 4 days. RESULTS: Twenty-seven patients completed the trial, of whom 24 completed without dose reduction. Twenty-six patients (76%) were titrated to the maximum target dose and thus had a maximal achievable dosage of at least 24 mg/24 h. Adverse events, generally mild or moderate, included application site reaction (12%), nausea, dyskinesia, and visual hallucinations (9% each). The mean time spent off decreased by 2 to 3 h/d. Duration of on without dyskinesia periods increased (2 h/d). The mean total (SD) Unified Parkinson's Disease Rating Score decreased by 18.9 (14.2) in the fast-titration group and 17.8 (14.0) in the slow titration group. A shift from off to on without dyskinesias in status after waking up was observed. CONCLUSIONS: Rotigotine transdermal patch, up to 24 mg/24 h, was effective and well tolerated by patients with advanced-stage Parkinson disease. PMID- 19644229 TI - The 5-HT2 receptor profiles of antipsychotics in the pathogenesis of obsessive compulsive symptoms in schizophrenia. AB - Atypical antipsychotics have been reported to induce or exacerbate obsessive compulsive symptoms (OCS) in patients with schizophrenia. We report the development of de novo obsession induced by sequential treatment with risperidone, aripiprazole, and ziprasidone, which have an antagonist effect on serotonin 5-HT(2A) receptors in a patient with schizophrenia. The obsession was repeatedly improved after switching the atypical antipsychotics to amisulpride, a selective D(2) and D(3) receptor antagonist. To our knowledge, this is the first report about ziprasidone-induced OCS in a patient with schizophrenia. In conclusion, this case supports the hypothesis that the antagonist effect on 5 HT(2) receptors may be related to atypical antipsychotic-induced OCS. PMID- 19644230 TI - Clozapine-induced obsessive-compulsive syndromes improve in combination with aripiprazole. AB - Patients with schizophrenia often experience comorbid obsessive-compulsive syndromes (OCSs). Within these patients, a significant subgroup developed secondary OCS during treatment with antiserotonergic, atypical antipsychotic agents such as clozapine. Although cognitive behavioral therapy and antiobsessive antidepressants brought up inconsistent results, in some cases, dose reductions of clozapine in combination approaches were able to alleviate OCS. One suggestive agent for antiobsessive add-on treatment is aripiprazole, a partial agonist at dopamine and serotonin receptors.Here, we summarize the courses of 7 patients (6 men; mean age, 37 years; mean duration of psychotic illness, 17 years). They had been treated with clozapine for 9 years. The distressing and treatment-resistant comorbidity with OCS emerged approximately 4 years after the start of clozapine therapy. During combined treatment with mean doses of 22.9 mg of aripiprazole for 9.7 weeks, we assessed a small yet statistically not significant improvement of the psychotic disorder, whereas a marked reduction of obsessions and significant improvements of compulsions could be observed. The mean total Yale Brown Obsessive Compulsive Rating Scale decreased from 18.7 to 12.4 (P = 0.003).These data support the findings of 2 previous case reports and point toward an antiobsessive potency of aripiprazole. The relevant disabling comorbidities of psychosis and OCS need further investigation with multimodal neurobiological approaches. The proposed strategy should be further evaluated in prospective controlled trials with severity of comorbid OCS as a primary end point. PMID- 19644231 TI - Idiopathic hemifacial spasm responsive to zonisamide: a case report. AB - AIM: We describe a patient with idiopathic hemifacial spasm (HFS) that was responsive to zonisamide treatment. METHODS AND RESULTS: A 65-year-old woman presented with a 4-year history of left-sided HFS developing gradually, starting from the upper facial muscles. After several analyses, the diagnosis of idiopathic HFS was made, and the clonazepam treatment (0.5 mg every 8 hours) was started, without a complete remission of symptoms. Therefore, zonisamide (150 mg twice a day for a 6-week period) was added, with a complete resolution. The rechallenge with zonisamide after its dechallenge confirmed its effectiveness. During follow-up, the patient remained symptom-free, with no adverse drug reactions. CONCLUSIONS: We suggest that zonisamide could represent a useful therapeutic option in the treatment of idiopathic HFS. PMID- 19644232 TI - New onset somnambulism associated with different dosage of mirtazapine: a case report. AB - Somnambulism consists of variously complex behaviors that may result in harm to self or to others. Many different medications have been reported to induce somnambulism, and a few of them are newer antidepressants. A 40-year-old woman with history of major depression who experienced new onset somnambulism for successive 3 nights, whereas the antidepressant mirtazapine was increased from 30 to 45 mg/d. The notable and complex sleepwalking symptoms terminated dramatically on the first night after withdrawal of mirtazapine. There is clearly a cause-and effect relationship between the treatment of higher-dosage mirtazapine and development of somnambulism. It might be related to the different affinities to 5 hydroxytryptamine 2 (5-HT(2)) and H(1) receptors at different dosages of mirtazapine, which explain the patient experiencing sleepwalking episodes exclusively at higher doses of mirtazapine. Clinical physicians should be aware of this adverse effect and taper or discontinue the regimen if sleepwalking develops. PMID- 19644233 TI - Experimental conditions substantially influence botulinum toxin potency testing. PMID- 19644235 TI - Acute delirium in patients with multiple sclerosis treated with pregabalin. PMID- 19644236 TI - Dramatic effect of levetiracetam on posthypoxic myoclonus: difficult weaning from mechanical ventilation. PMID- 19644237 TI - Panic attack-like episodes possibly associated with ropinirole. PMID- 19644241 TI - Molybdenum supplies and nuclear medicine services. PMID- 19644244 TI - An anomalous muscle predisposing to the development of hypothenar hammer syndrome. PMID- 19644245 TI - Biostatistics. AB - LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Recognize the various terms used in biostatistics. 2. Describe the choices that are required in designing a particular research study. 3. Understand the different types of data that may be obtained in any given study. 4. Identify which statistical tools are appropriate for evaluating the different types of data. SUMMARY: Journals of medicine and surgery, such as Plastic and Reconstructive Surgery, are filled with statistics that readers may never have learned about or once understood but soon forgot. Unfortunately, critical review of any abstract requires a thorough understanding of the tools used to evaluate study results. It also requires an evaluation of whether the tools chosen were adequate or even proper, given the study design and the questions asked. This article was conceived to highlight the major topics in biostatistics. It includes a review of common definitions, an outline of the major tests used (correctly or not) in plastic surgery abstracts, and instruction as to their proper use in scientific studies. PMID- 19644246 TI - Development of a new patient-reported outcome measure for breast surgery: the BREAST-Q. AB - BACKGROUND: Measuring patient-reported outcomes has become increasingly important in cosmetic and reconstructive breast surgery. The objective of this study was to develop a new patient-reported outcome measure to assess the unique outcomes of breast surgery patients. METHODS: Patient interviews, focus groups, expert panels, and a literature review were used to develop a conceptual framework and a list of questionnaire items. Three procedure-specific questionnaires (augmentation, reduction, and reconstruction) were developed and cognitive debriefing interviews used to pilot each questionnaire. Revised questionnaires were field tested with 1950 women at five centers in the United States and Canada (response rate, 72 percent); 491 patients also completed a test-retest questionnaire. Rasch measurement methods were used to construct scales, and traditional psychometric analyses, following currently recommended procedures and criteria, were performed to allow for comparison with existing measures. RESULTS: The conceptual framework included six domains: satisfaction with breasts, overall outcome, and process of care, and psychosocial, physical, and sexual well-being. Independent scales were constructed for these domains. This new patient-reported outcome measure "system" (the BREAST-Q) contains three modules (augmentation, reconstruction, and reduction), each with a preoperative and postoperative version. Each scale fulfilled Rasch and traditional psychometric criteria (including person separation index 0.76 to 0.95; Cronbach's alpha 0.81 to 0.96; and test-retest reproducibility 0.73 to 0.96). CONCLUSIONS: The BREAST-Q can be used to study the impact and effectiveness of breast surgery from the patient's perspective. By quantifying satisfaction and important aspects of health-related quality of life, the BREAST-Q has the potential to support advocacy, quality metrics, and an evidence-based approach to surgical practice. PMID- 19644247 TI - Discussion. Development of a new patient-reported outcome measure for breast surgery: the BREAST-Q. PMID- 19644248 TI - Salvage of tissue expander in the setting of mastectomy flap necrosis: a 13-year experience using timed excision with continued expansion. AB - BACKGROUND: Mastectomy flap necrosis after immediate tissue expander placement can have profound implications, resulting in prosthetic infection necessitating tissue expander removal. The purpose of this investigation was to evaluate the safety and efficacy of timed, surgical excision during continued serial expansion in the setting of mastectomy flap necrosis and to identify an algorithm for surgeons faced with the management of this difficult problem. METHODS: Consecutive patients in whom documented mastectomy flap necrosis developed following immediate tissue expander placement from 1995 to 2008 were identified. Patient demographic, reconstructive, and complication data were obtained from a prospectively maintained clinical database. Medical records were then retrospectively reviewed to further characterize the extent of mastectomy flap necrosis and its management. RESULTS: Over the 13-year study period, 178 patients with documented mastectomy flap necrosis following immediate tissue expander were identified. In 58 patients (33 percent), surgical excision of the mastectomy flap necrosis was performed. Surgical excision occurred a mean 36 days (range, 8 to 153 days) after tissue expander placement. Mean surface area of eschar excised was 42.5 cm (range, 2.5 to 240 cm). In nine (15.5 percent) of the 58 patients, resection of such an extensive area of mastectomy flap necrosis necessitated explantation of the tissue expander and subsequent flap closure (local advancement flaps, n = 8; latissimus flap, n = 1). Of the remaining patients, only three (6 percent) developed a subsequent infection necessitating the premature removal of a tissue expander. CONCLUSIONS: Timed excision with continued expansion is a straightforward procedure associated with a low incidence of failure. This approach allows for salvage of a significant percentage of threatened tissue expanders and may be coordinated with adjuvant oncologic therapy without excessive delays. PMID- 19644249 TI - Mastopexy with mesh reinforcement: the mechanical characteristics of polyester mesh in the female breast. AB - BACKGROUND: Mastopexy is generally regarded as having only a temporary effect. To prevent recurrent ptosis, mesh has been inserted successfully and safely, without oncological drawbacks, for almost three decades. Recently, preshaped three dimensional knitted polyester mesh in different sizes was introduced to reinforce the breast during mastopexy. Until now, however, the physical and mechanical characteristics of mesh inserted in the female breast were unknown. METHODS: Polyester mesh removed from breasts in which it had been implanted was subjected to mechanical tests (two implants) and histological examination (five pieces of implant). RESULTS: Mesh induces only a thin layer of collagenous tissue together acting as a composite material. The collagen increases the in-plane stiffness of the mesh and enhances the overall strength. The composite is so strong that rupture or failure is extremely unlikely. The mesh composite shows high pliability, is therefore very supple and not palpable under the skin. CONCLUSION: Three-dimensional knitted polyester mesh appears to possess the proper mechanical characteristics to reinforce a ptotic breast during mastopexy. PMID- 19644250 TI - Shaping the breast in aesthetic and reconstructive breast surgery: an easy three step principle. Part IV--aesthetic breast surgery. AB - SUMMARY: This is part IV of four articles describing the three-step principle for easy shaping of the breast in reconstructive and aesthetic breast surgery. This article may seem overdue because aesthetic corrections are routinely performed, frequently written about, and easier to execute, as no prior ablative surgery or radiotherapy has damaged the gland. Nevertheless, a number of difficult aesthetic breast surgery cases can present themselves that might be more challenging to correct (e.g., tubular breast deformities or corrections after failed aesthetic breast surgery). By understanding the three main anatomical features of a breast- the footprint, the conus, and the skin envelope--and how they interact, as explained in part I, one is able not only to analyze the deformities of each individual problematic breast but also to teach others and to execute a specific surgical strategy on how to obtain reproducible aesthetically pleasing results. The three-step principle will be applied and explained for breast augmentation, reduction, mastopexy, and tubular breast deformity. PMID- 19644251 TI - Discussion. Shaping the breast in aesthetic and reconstructive breast surgery: an easy three-step principle. Part IV--aesthetic breast surgery. PMID- 19644252 TI - Discussion. Shaping the breast in aesthetic and reconstructive breast surgery: an easy three-step principle. Part IV--aesthetic breast surgery. PMID- 19644253 TI - Expander/implant reconstruction with AlloDerm: recent experience. AB - BACKGROUND: Expander/implant reconstruction with acellular dermal matrix (AlloDerm) has become an increasingly popular technique. Potential advantages include lengthening of the pectoralis major muscle, preventing "window-shading" after muscle release; precise control of the inframammary fold and lateral breast border; and complete coverage of the device without resorting to additional muscle or fascial elevation. METHODS: Patients undergoing immediate breast reconstruction with tissue expanders underwent acellular dermal matrix augmentation of the pectoralis major muscle. After inferior pectoralis muscle release and creation of a subpectoral pocket, the acellular dermal matrix was draped out to length and sutured to the inframammary fold. An integral port, low height tissue expander was placed into the pocket and the acellular dermal matrix was sewn to the cut edge of the muscle inferiorly. Subsequent placement of either a smooth-walled silicone gel implant or anatomically shaped cohesive gel device was performed secondarily. RESULTS: Twenty consecutive patients (29 breasts) undergoing immediate breast reconstruction with tissue expanders had acellular dermal matrix augmentation of the pectoralis major muscle. Follow-up averaged 21 months (range, 3 to 32 months). Infection occurred in one of 29 breasts (3.4 percent). One patient had a small area of suture line necrosis requiring revision. CONCLUSIONS: Acellular dermal matrix augmentation of the pectoralis major muscle in the setting of prosthetic breast reconstruction improves the soft tissue drapery around devices without resorting to additional muscle or fascial flaps. Total device coverage and precise control of the pocket dimensions permit more predictably superior results in these patients. PMID- 19644254 TI - Radiation therapy and breast reconstruction: a critical review of the literature. AB - BACKGROUND: The optimal timing and technique of breast reconstruction in patients who may require postmastectomy radiation therapy are controversial. To help surgeons make the best decisions, the authors reviewed the recent literature on this topic. METHODS: The authors searched the MEDLINE database for studies of radiation therapy and breast reconstruction with most patients treated after 1985 and mean follow-up of more than 1 year. Forty-nine articles were reviewed. RESULTS: Even with the latest prosthetic materials and modern radiation delivery techniques, the complication rate for implant-based breast reconstruction in patients undergoing postmastectomy radiation therapy is greater than 40 percent, and the extrusion rate is 15 percent. Modified sequencing of two-stage implant reconstruction, such that the expander is exchanged for the permanent implant before postmastectomy radiation therapy, results in higher rates of capsular contracture and is not generally feasible after neoadjuvant chemotherapy. Current evidence suggests that postmastectomy radiation therapy also adversely affects autologous tissue reconstruction. Even with modern radiation delivery techniques, immediate implant-based or autologous tissue breast reconstruction can distort the chest wall and limit the ability to treat the targeted tissues without excessive exposure of the heart and lungs. In patients for whom postmastectomy radiation therapy appears likely but may not be required, "delayed-immediate reconstruction," in which tissue expanders are placed at mastectomy, avoids the difficulties associated with radiation delivery after immediate reconstruction and preserves the opportunity for the aesthetic benefits of skin-sparing mastectomy. CONCLUSIONS: In patients who will receive or have already received postmastectomy radiation therapy, the optimal approach is delayed autologous tissue reconstruction after postmastectomy radiation therapy. If postmastectomy radiation therapy appears likely but may not be required, delayed-immediate reconstruction may be considered. PMID- 19644255 TI - Autologous fat grafting to the reconstructed breast: the management of acquired contour deformities. AB - BACKGROUND: Autologous fat grafting has become a workhorse for soft-tissue augmentation throughout the body. In the reconstructed breast, autologous fat grafting is a useful tool for managing secondary contour deformities. The authors have categorized these deformities into three types: type 1 deformities are step off deformities between the chest wall/reconstructed breast interface, type 2 deformities result from intrinsic deficiencies within a flap such as fat necrosis, and type 3 deformities are the result of extrinsic factors such as postoperative irradiation. METHODS: The authors conducted a detailed retrospective review of 110 patients who have received fat grafting to the reconstructed breast for the management of contour deformities. In addition, the authors reviewed the recent literature describing the use of autologous fat grafting to the breast. Particular attention has been placed on the concerns of oncologic surveillance in reconstructed breasts that have undergone fat grafting. RESULTS: The authors have had relative success in the treatment of patients who will require postoperative irradiation and even those who have rippling surrounding an implant. CONCLUSIONS: Autologous fat grafting represents an important tool for the management of secondary contour deformities of the reconstructed breast. Fat grafting is a simple, safe, and effective treatment option, with low morbidity. PMID- 19644256 TI - In vitro studies investigating the effect of subcutaneous phosphatidylcholine injections in the 3T3-L1 adipocyte model: lipolysis or lipid dissolution? AB - BACKGROUND: The demand for lipolytic injection therapies for aesthetic indications increases continuously. The substance most frequently discussed in this context is phosphatidylcholine solubilized in sodium deoxycholate, a composition known in Europe as Lipostabil (Artesan Pharma, Luchow, Germany). The evidence for its lipolytic effect is based mainly on clinical studies that suggest a decrease in adipose tissue volume after subcutaneous injections. However, neither the actual effect nor the effective supplemental effect of Lipostabil has been clearly identified so far. The purpose of this study was to investigate the effects caused by lipolytic formulations on adipocytes using an in vitro model. METHODS: 3T3-L1 adipocytes in 12-well plates were exposed to varying doses of isolated phosphatidylcholine, deoxycholate, and the combination of both (Lipostabil). Subsequently, changes in the cell membrane integrity were evaluated microscopically, and assays measuring the amount of glycerol as a biochemical lipolysis substrate (lipolysis assay) together with dimethyl thiazolyl diphenyl tetrazolium assays were performed to quantify the lipolytic effect and the cell viability. RESULTS: Deoxycholate reduced cell viability significantly (p < 0.05), even at low concentrations. Neither phosphatidylcholine nor deoxycholate led to a significant (p < 0.05) induction of a lipolytic pathway. Lipostabil, the combination of deoxycholate and phosphatidylcholine, led to a significant (p < 0.05) decrease in cell viability at low doses and to a highly significant (p < 0.01) reduction at high doses. The loss in cell viability is attributable to changes in the cell membrane integrity. CONCLUSIONS: These results suggest that no enzymatic lipolytic pathway is induced. The decrease in volume after Lipostabil injections is likely attributable to the detergent effect of deoxycholate. PMID- 19644257 TI - Preparation and integration of human amnion nerve conduits using a light activated technique. AB - BACKGROUND: Photochemical tissue bonding is a developing light-activated technique that facilitates watertight sealing between tissue surfaces. Previous work has shown that sealing with photochemical tissue bonding can improve regeneration following primary nerve repair. The authors evaluated sealing of nerve stumps with photochemical tissue bonding within customized human amnion conduits. The authors hypothesized that light-activated integration could enhance regeneration across the nerve gap. METHODS: Photochemical crosslinked amnion conduits were placed across 1-cm sciatic nerve gaps in Sprague-Dawley rats and either secured with sutures or sealed using photochemical tissue bonding. Reversed autologous nerve grafts were used in the control group. Functional recovery was measured by walking track analysis; histology and histomorphometry of nerves and gastrocnemius muscles were evaluated. RESULTS: Regeneration within the photochemical tissue bonding-sealed amnion conduit was significantly better than that observed in the amnion conduit secured with sutures and did not differ significantly from that in the autologous nerve graft. CONCLUSIONS: Photochemical crosslinked amnion appears suitable as a nerve conduit. Sealing of compatible conduits with photochemical tissue bonding may have the potential to maximize regeneration. PMID- 19644258 TI - Fibrosis is a key inhibitor of lymphatic regeneration. AB - BACKGROUND: Lymphedema is a common debilitating sequela of lymph node dissection. Although numerous clinical studies suggest that factors that lead to fibrosis are associated with the development of lymphedema, this relationship has not been proven. The purpose of these experiments was therefore to evaluate lymphatic regeneration in the setting of variable soft-tissue fibrosis. METHODS: A section of mouse tail skin including the capillary and collecting lymphatics was excised. Experimental animals (n = 20) were treated with topical collagen type I gel and a moist dressing, whereas control animals (n = 20) underwent excision followed by moist dressing alone. Fibrosis, acute lymphedema, lymphatic function, gene expression, lymphatic endothelial cell proliferation, and lymphatic fibrosis were evaluated at various time points. RESULTS: Collagen gel treatment significantly decreased fibrosis, with an attendant decrease in acute lymphedema and improved lymphatic function. Tails treated with collagen gel demonstrated greater numbers of lymphatic vessels, more normal lymphatic architecture, and more proliferating lymphatic endothelial cells. These findings appeared to be independent of vascular endothelial growth factor C expression. Decreased fibrosis was associated with a significant decrease in the expression of extracellular matrix components. Finally, decreased soft-tissue fibrosis was associated with a significant decrease in lymphatic fibrosis as evidenced by the number of lymphatic endothelial cells that coexpressed lymphatic and fibroblast markers. CONCLUSIONS: Soft-tissue fibrosis is associated with impairment in lymphatic regeneration and lymphatic function. These defects occur as a consequence of impaired lymphatic endothelial cell proliferation, abnormal lymphatic microarchitecture, and lymphatic fibrosis. Inhibition of fibrosis using a simple topical dressing can markedly accelerate lymphatic repair and promote regeneration of normal capillary lymphatics. PMID- 19644259 TI - Quantitative assessment of perfusion and vascular compromise in perforator flaps using a near-infrared fluorescence-guided imaging system. AB - BACKGROUND: Techniques currently used to determine flap perfusion are mainly subjective, with the majority of reconstructive surgeons still relying on clinical examination. In this study, the authors demonstrate the use of near infrared fluorescence angiography to directly quantify normal and abnormal perfusion in perforator flaps. METHODS: Indocyanine green was injected intravenously into anesthetized adult pigs (n = 38). A custom near-infrared fluorescence imaging system was used for image acquisition and quantitation. Thirty-nine flaps were designed based on identified perforators, and postoperative imaging was performed for comparison. In select flaps, isolated occlusion of the arterial and venous pedicle was performed. In select flaps, vascular spasm was induced by local irrigation of the vessels with epinephrine. The fluorescence intensities of select regions of interest were quantified. From these data, the authors defined two indices for abnormal perfusion: the Tmax ratio and the drainage ratio. RESULTS: The authors identified a normal pattern of perfusion before flap elevation, composed of a distinct fluorescence intensity peak at maximal arterial inflow followed by a smooth drop representing venous drainage. Delay of this peak after flap elevation, as indicated by the Tmax ratio, identified vascular spasm and arterial occlusion (p < 0.0001). Abnormal fall of fluorescence intensities after this peak, as indicated by the drainage ratio, identified venous occlusion (p < 0.0001). CONCLUSIONS: Quantitation of fluorescence intensities by near-infrared angiography accurately characterizes arterial and venous compromise. The authors' technique can assess perfusion characteristics during the intraoperative and postoperative periods and therefore complements clinically based subjective criteria now used for flap assessment. PMID- 19644260 TI - A placebo-controlled surgical trial of the treatment of migraine headaches. AB - BACKGROUND: Many of the nearly 30 million Americans suffering with migraine headaches are not helped by standard therapies, a proportion of which can harbor undesirable side effects. The present study demonstrates the efficacy of independent surgical deactivation of three common migraine headache trigger sites through a double-blind, sham surgery, controlled clinical trial. METHODS: Seventy five patients with moderate to severe migraine headache who met International Classification of Headache Disorders II criteria were studied. Trigger sites were identified (frontal, temporal, and occipital), and patients were randomly assigned to receive either actual or sham surgery in their predominant trigger site. Patients completed the Migraine Disability Assessment, Migraine-Specific Quality of Life, and Medical Outcomes Study 36-Item Short Form Health Survey health questionnaires before treatment and at 1-year follow-up. RESULTS: Of the total group of 75 patients, 15 of 26 in the sham surgery group (57.7 percent) and 41 of 49 in the actual surgery group (83.7 percent) experienced at least 50 percent reduction in migraine headache (p < 0.05). Furthermore, 28 of 49 patients in the actual surgery group (57.1 percent) reported complete elimination of migraine headache, compared with only one of 26 patients in the sham surgery group (3.8 percent) (p < 0.001). Compared with the control group, the actual surgery group demonstrated statistically significant improvements in all validated migraine headache measurements at 1 year. These improvements were not dependent on the trigger site. The most common surgical complication was slight hollowing of the temple in the group with temporal migraine headache. CONCLUSION: This study confirms that surgical deactivation of peripheral migraine headache trigger sites is an effective alternative treatment for patients who suffer from frequent moderate to severe migraine headaches that are difficult to manage with standard protocols. PMID- 19644261 TI - Discussion. A placebo-controlled surgical trial of the treatment of migraine headaches. PMID- 19644262 TI - Influence of the recipient site on the outcomes of fat grafting in facial reconstructive surgery. AB - BACKGROUND: The purpose of this study was to analyze the role of fat grafting for restoration of facial contour deformities (volumes) in traumatic and malformation cases. Outcomes were evaluated for each facial aesthetic subunit to demonstrate the role of the recipient site. An algorithm for the treatment of facial malformations and traumatic sequelae by subunits, in relation to the results obtained in this study, is proposed. METHODS: This retrospective study involved 100 patients treated by structural fat grafting of the facial region. Results were evaluated by a subjective self-evaluation survey (i.e., a questionnaire answered by patients) and an objective assessment by a five-member jury. Each subunit of the face was studied separately. Results were presented separately and compared. RESULTS: The average follow-up period was 23 months. The overall satisfaction rate of patients was 74 percent. The average score for subjective evaluation was 14.5 of 20. The objective score was 13.9 of 20. The results were significantly different depending on the aesthetic subunit of the face. The best results were achieved in the malar (89 percent good results) and lateral cheek areas (84 percent good results). The poorest results were registered for the lower and upper lip areas (34 percent and 31 percent good results, respectively). Minor complications were observed in 3 percent of the cases. CONCLUSIONS: Fat tissue grafting is a simple, efficient, and reproducible technique for restoration of facial volumes. In the absence of functional disorders, it is the authors' first choice in the decision-making process for the treatment of facial soft-tissue deficiencies. PMID- 19644263 TI - Tissue expander infections in pediatric patients: management and outcomes. AB - BACKGROUND: Tissue expansion has become a well-established method for soft-tissue reconstruction in the pediatric population; however, the complication rate is still high, with infection being the most common complication. This study looks at a segment of the authors' cases over a 4-year period to document the incidence of infection, impact on completing the planned expansion, and how the treatment impacted the completion of goals. METHODS: A database of 215 children who underwent reconstruction with tissue expanders from August of 2004 to August of 2008 at Children's Memorial Hospital in Chicago, Illinois, was reviewed with respect to tissue expander infection cases. All patients were operated on by the senior author (B.S.B). All of the patients with tissue expander infection were analyzed, with emphasis on management and outcome. RESULTS: Fifteen children, one of them with infection during two different stages of the reconstruction [total of 16 cases (7.4 percent)], had tissue expander infection (5 percent of the total number of expanders). Expansion was continued after diagnosis of infection in all but three cases (two of them had simultaneous extrusion), with a median of six total expansions per child (range, four to 11 expansions) and two additional expansions from the time of infection (range, zero to eight additional expansions). In only one case did the early removal of the expander affect the successful reconstruction. CONCLUSION: Tissue expander infection in children does not seem to preclude further expansion and successful reconstruction. PMID- 19644264 TI - Microvascular free flap failure caused by unrecognized hypercoagulability. AB - BACKGROUND: Microvascular free flap techniques have improved over the past two decades such that flap failure rates have dropped to under 3 percent in most large series of high-volume centers. However, despite technical and patient selection advances, some components of free flap failure might be attributable to undiagnosed patient factors. METHODS: In this clinicopathologic conference article, the authors present four patients with major free flap microvascular complications who were later diagnosed with multiple risk factors for hypercoagulability and biochemical abnormalities, and present the characteristic associated findings. RESULTS: Previously undiagnosed hypercoagulability was present in four patients with major free flap microvascular complications. Hematologic consultation and laboratory investigation revealed the biochemical abnormalities. CONCLUSIONS: In certain patients undergoing microvascular free flap reconstruction, undiagnosed hypercoagulability risk factors can be a source of free flap failure that is independent of patient selection or technical factors. Diagnosis, management, patient counseling, and initiation of deep venous thromboembolism prophylaxis measures are critical clinical components of care of these patients. PMID- 19644265 TI - Discussion. Microvascular free flap failure caused by unrecognized hypercoagulability. PMID- 19644266 TI - Reconstruction of complex abdominal wall defects with free flaps: indications and clinical outcome. AB - BACKGROUND: Free flaps have a distinct role in a select group of patients with large abdominal wall defects. They offer a completely autologous reconstructive solution in a single stage for difficult abdominal wounds for which pedicled flaps would be inadequate. METHODS: From 1996 to 2005, five patients with complex abdominal wall defects underwent reconstruction using free flaps. All patients had multiple comorbidities, making the use of alloplastic materials relatively contraindicated. Flaps used included a free radial forearm flap in one patient, a tensor fasciae latae myocutaneous flap in two patients, a free anterolateral thigh myocutaneous flap in one patient, and free conjoined tensor fasciae latae and anterolateral thigh myocutaneous flaps in the last patient. RESULTS: The mean defect size was 470 cm (range, 136 to 875 cm). The femoral artery and long saphenous vein reliably provided recipient vessels in cases for which suitable vessels could not be located within the abdomen. A temporary arteriovenous shunt of the long saphenous vein to the femoral artery could be created. This was later divided to provide a recipient artery and vein. Flap complications were wound edge necrosis, hematoma, infection, and venous thrombosis. All were successfully managed and there were no flap failures. The average length of hospitalization was 64 days (range, 41 to 128 days). Lateral thigh flaps based on the lateral circumflex femoral system are our preferred donor site. A large amount of soft tissue, strong fascia, and innervated muscle are available, enabling single-stage autologous reconstruction of the entire anterior abdominal wall. CONCLUSIONS: Free flaps offer a reliable single-stage solution to complex abdominal wall defects. With these techniques, even the most challenging defects can be reconstructed with completely autologous tissue. PMID- 19644267 TI - Penile reconstruction: is the radial forearm flap really the standard technique? AB - BACKGROUND: The ideal goals in penile reconstruction are well described, but the multitude of flaps used for phalloplasty only demonstrates that none of these techniques is considered ideal. Still, the radial forearm flap is the most frequently used flap and universally considered as the standard technique. METHODS: In this article, the authors describe the largest series to date of 287 radial forearm phalloplasties performed by the same surgical team. Many different outcome parameters have been described separately in previously published articles, but the main purpose of this review is to critically evaluate to what degree this supposed standard technique has been able to meet the ideal goals in penile reconstruction. RESULTS: Outcome parameters such as number of procedures, complications, aesthetic outcome, tactile and erogenous sensation, voiding, donor site morbidity, scrotoplasty, and sexual intercourse are assessed. CONCLUSIONS: In the absence of prospective randomized studies, it is not possible to prove whether the radial forearm flap truly is the standard technique in penile reconstruction. However, this large study demonstrates that the radial forearm phalloplasty is a very reliable technique for the creation, mostly in two stages, of a normal-appearing penis and scrotum, always allowing the patient to void while standing and in most cases also to experience sexual satisfaction. The relative disadvantages of this technique are the rather high number of initial fistulas, the residual scar on the forearm, and the potential long-term urologic complications. Despite the lack of actual data to support this statement, the authors feel strongly that a multidisciplinary approach with close cooperation between the reconstructive/plastic surgeon and the urologist is an absolute requisite for obtaining the best possible results. PMID- 19644268 TI - Avoiding denervation of the rectus abdominis muscle in DIEP flap harvest III: a functional study of the nerves to the rectus using anesthetic blockade. PMID- 19644270 TI - Discussion. Free tissue transfer for lower extremity reconstruction: a study of the role of computed angiography in the planning of free tissue transfer in the posttraumatic setting. PMID- 19644269 TI - Free tissue transfer for lower extremity reconstruction: a study of the role of computed angiography in the planning of free tissue transfer in the posttraumatic setting. AB - BACKGROUND: Computed tomographic angiography can be used as a means of assessing lower leg vasculature before performing free tissue transfer, but its reliability within a trauma setting has not been evaluated. The aim of this study was to examine the findings of preoperative computed tomographic angiography and correlate these findings to flap survival and limb salvage. METHODS: Seventy-six consecutive lower extremity trauma patients underwent preoperative computed tomographic angiography before free flap reconstruction. Arterial inflow, venous outflow, and the incidence of traumatic occlusion were recorded. Flap survival rates, limb salvage, and postoperative complications were noted. RESULTS: There were no complications associated with the computed tomographic angiography procedure. Computed tomographic angiography demonstrated normal vascular anatomy in 40 patients (52.6 percent), anatomical variants in seven patients, and atherosclerotic occlusive disease in six patients. Traumatic arterial occlusion was identified in 22 patients (28.9 percent). Flap failure was seen in five patients and the limb salvage rate was 94.7 percent. All four of the limbs amputated had at least a single artery occluded on preoperative computed tomographic angiography; preoperative arterial occlusion was found to be a significant predictor of limb loss (p < 0.05). CONCLUSIONS: The incidence of single-vessel traumatic arterial occlusion within traumatized lower limbs undergoing free tissue transfer may be as high as 29 percent. Computed tomographic angiography provided excellent visualization of lower extremity vasculature, and its routine use for trauma patients is safe. Flap failure rates were low when using this technique for preoperative planning. Flap failure occurred only in patients with evidence of arterial injury. Evidence of arterial occlusion on computed tomographic angiography may be a risk factor for limb loss. PMID- 19644271 TI - Infrapopliteal lower extremity replantation. AB - BACKGROUND: Replantation surgery in lower extremity amputations continues to be controversial. Overall results have been considered poor and the procedure is usually discouraged. It is the opinion of the authors that infrapopliteal replantation may be indicated. METHODS: A series of 12 patients with 13 amputations through the tibia or below were treated with replantation of the parts. The main indication was an intact sole and amenability of direct tibial nerve repair. Extensive bone loss or soft-tissue damage was not a contraindication. All replantations were orthotopic, and in one case a temporary ectopic replantation was performed. All transtibial replantations underwent subsequent bone lengthening (8 to 13 cm). RESULTS: The survival rate of the replanted segments was 100 percent. There was one death caused by pulmonary thromboembolism. The number of additional operations was 3.1 (range, one to five). Soft-tissue necrosis occurred in 83 percent of cases, requiring flap coverage. A free flap was used in 90 percent of these cases, with a 100 percent success rate. Chen functional grade was I or II (good or excellent) in all but one case. Treatment time averaged 11.3 months (range, 8 to 16 months). No delayed amputations or plantar ulcers occurred. CONCLUSIONS: Although the complication rate has been high, in dedicated teams and with proper selection of patients, replantation of infrapopliteal lower limb amputations can yield satisfactory results. PMID- 19644272 TI - Ultrasound assessment of deep tissue injury in pressure ulcers: possible prediction of pressure ulcer progression. AB - BACKGROUND: The concept of deep tissue injury under intact skin helps us understand the pathogenesis of pressure ulcers, but the best method for detecting and evaluating deep tissue injury remains to be established. METHODS: Intermediate-frequency (10-MHz) ultrasonography was performed to evaluate deep tissue injury. The authors analyzed 12 patients (nine male patients and three female patients aged 16 to 92 years) who showed deep tissue injury-related abnormal findings on ultrasonography at the first examination and were followed up until the pressure ulcer reached a final stage. RESULTS: The stage of ulcer worsened in six of 12 cases compared with baseline, and healed in the remaining six patients. The authors recognized four types of abnormal signs unique to deep tissue damage in ultrasonography: unclear layered structure, hypoechoic lesion, discontinuous fascia, and heterogeneous hypoechoic area. Unclear layered structure, hypoechoic lesion, discontinuous fascia, and heterogeneous hypoechoic area were detected at the first examination in 12, 10, seven, and five patients, respectively. Unclear layered structure and hypoechoic lesion were more commonly seen in pressure ulcers in deep tissue injury than the other features, but the follow-up study suggested that discontinuous fascia and heterogeneous hypoechoic area are more reliable predictors of future progression of pressure ulcers. CONCLUSIONS: The use of intermediate-frequency ultrasound reliably identified deep tissue injury and was believed to contribute to prevention and treatment of pressure-related ulcers. The results suggest that specific ultrasonographic characteristics may predict which pressure ulcers will progress. PMID- 19644273 TI - Pediatric dog bite injuries: a 5-year review of the experience at the Children's Hospital of Philadelphia. AB - BACKGROUND: The objective of this study was to characterize the nature of dog bite injuries treated over a 5-year period at a large tertiary pediatric hospital and to identify relevant parameters for public education and injury prevention. METHODS: Investigators performed a retrospective review of emergency room records of a single tertiary pediatric hospital. Records of all patients who were evaluated for dog bite injuries between April of 2001 and December of 2005 were reviewed. All demographic, patient, and injury details were recorded. RESULTS: Five hundred fifty-one patients aged 5 months to 18 years were treated in the emergency department after suffering dog bite injuries during the study period. The majority of injuries (62.8 percent) were sustained by male children. Dog bite injuries were most prevalent during the months of June and July (24.1 percent). Grade school-aged children (6 to 12 years) constituted the majority of victims (51 percent), followed by preschoolers (2 to 5 years; 24.0 percent), teenagers (13 to 18 years; 20.5 percent), and infants (birth to 1 year; 4.5 percent). Injuries sustained by infants and preschoolers often involved the face (53.5 percent), whereas older children sustained injuries to the extremities (60.7 percent). More than 30 different offending breeds were documented in the medical records. The most common breeds included pit bull terriers (50.9 percent), Rottweilers (8.9 percent), and mixed breeds of the two aforementioned breeds (6 percent). CONCLUSIONS: Pediatric dog bites are preventable injuries, yet they persist as a prevalent public health problem. Evaluation of data from high-volume tertiary pediatric health care institutions identifies predictable patterns of injury with respect to patient age and gender, animal breed, provocation, and seasonality. PMID- 19644274 TI - Discussion. Pediatric dog bite injuries: a 5-year review of the experience at the Children's Hospital of Philadelphia. PMID- 19644275 TI - Isolated capitate shortening osteotomy for the early stage of Kienbock disease with neutral ulnar variance. AB - BACKGROUND: Kienbock disease is an aseptic necrosis of the lunate for which the treatment is still debated, particularly in the rare cases with neutral ulnar variance. One option is to perform a capitate shortening osteotomy associated with a capitate-hamatum arthrodesis. The aim of this study was to evaluate a simple capitate osteotomy without arthrodesis. METHODS: This is a retrospective study of 11 cases. All patients had a mild form of Kienbock disease (stage I to IIIA according to the classification of Lichtman). A shortening capitate osteotomy was performed through a dorsal medial approach and fixed with staples. RESULTS: At the final follow-up evaluation (mean, 67.4 months), the mean visual analogue scale score was 1.7 (range, 0 to 7). Based on the Nakamura score, the authors obtained six good, two fair, and three poor results. Mean strength improvement was 25 percent compared with the healthy side, and the authors observed no change in range of motion. The radiologic follow-up showed no difference in either the Stahl or the Youm index between preoperative and postoperative measurements. No complication was observed; however, in two cases, the result was evaluated as poor and a revision procedure was performed. CONCLUSION: This technique is a simple and reliable method with which to manage the early stages of Kienbock disease with neutral ulnar variance. PMID- 19644276 TI - Biomechanical comparison of lasso, Pulvertaft weave, and side-by-side tendon repairs. AB - BACKGROUND: The authors' group has developed and used a lasso repair as a substitute to the Pulvertaft weave when joining two tendons for tendon grafts and transfers. This study compared the maximum load, weave time, tendon length required, and bulkiness of the lasso, Pulvertaft weave, and side-by-side repairs. METHODS: Sixty porcine trotter flexor tendons were used to perform 30 repairs--10 lasso, 10 Pulvertaft weave, and 10 side-by-side. The lasso and Pulvertaft repairs were standardized by initial incision locations, whereas side-by-side repair was standardized to a 2.5-cm overlap. An Instron tensiometer machine was used to test repairs to failure. Maximum load was recorded using data-acquisition software. Weave time, tendon length required, and width at the thickest point of each repair were also measured. RESULTS: The mean maximum load of lasso, Pulvertaft weave, and side-by-side repairs was 155.8, 159.7, and 88.6 N, respectively. Maximum load was equivalent between lasso and Pulvertaft weave repairs. Lasso repair was thicker by 4.9 mm at its widest point than the Pulvertaft weave but, on average, required less than half the weave time and 7 mm less tendon length. CONCLUSIONS: The strength of the lasso tendon repair compared well with the Pulvertaft weave and was more convenient to perform. Side-by-side repair was inferior because of its low maximum load. This study suggests that lasso repair may be an alternative to the Pulvertaft weave in tendon grafts and transfers. PMID- 19644277 TI - Gingivoperiosteoplasty following alveolar molding with a Latham appliance versus secondary bone grafting: the effects on bone production and midfacial growth in patients with bilateral clefts. AB - BACKGROUND: The role of gingivoperiosteoplasty in closure of bilateral alveolar clefts remains unclear. The purpose of this study was to evaluate bone production and midfacial growth in patients with bilateral clefts treated with gingivoperiosteoplasty following alveolar molding with a pin-retained Latham appliance versus secondary bone grafting. METHODS: Patients with complete bilateral clefts past permanent canine eruption were included. Ethics approval and informed consent were obtained. Periapical films and lateral cephalograms were analyzed by one blinded rater based on three radiographic grading scales- Bergland, Witherow et al., and Long et al.--and standard cephalometric landmarks, respectively. Repeated measurements were recorded to assess intrarater reliability. Measurements were grouped according to gingivoperiosteoplasty versus secondary bone grafting and compared using parametric and nonparametric tests. RESULTS: Fifty-three patients (gingivoperiosteoplasty, n = 43; secondary bone grafting, 10) met inclusion criteria. Average age was 15 years and 66 percent were male patients. Thirty-five patients had adequate radiographs for evaluation (gingivoperiosteoplasty, n = 25; secondary bone grafting, n = 10). Gingivoperiosteoplasty was clinically less successful than secondary bone grafting, 58 percent versus 90 percent, respectively. The quantitative radiographic success rate of gingivoperiosteoplasty, however, was 28 percent. Secondary bone grafting demonstrated higher Bergland, eight-point, and location grading (p < 0.002), and less alveolar notching (p = 0.008). Anteroposterior maxillary and mandibular dimensions were significantly decreased for the gingivoperiosteoplasty group versus the secondary bone grafting group. CONCLUSIONS: Bone quantity and location were inferior following bilateral gingivoperiosteoplasty versus secondary bone grafting, and the majority of patients required subsequent bone grafting. The gingivoperiosteoplasty group had decreased maxillary growth with mandibular compensation. Secondary bone grafting therefore remains our first choice for repair of bilateral alveolar clefts. PMID- 19644278 TI - Tongue dysmorphology in craniofacial microsomia. AB - BACKGROUND: Craniofacial microsomia is one of the most common and well characterized craniofacial anomalies. Tongue dysmorphism, however, has been neither thoroughly investigated nor reported in the context of this disease. This review focuses on the true prevalence of tongue dysmorphology in craniofacial microsomia and its relation to the deformities seen in this condition. METHODS: A 20-year retrospective study was performed to determine the number of patients who had a documented tongue anomaly and any relation to the development of abnormal speech. In recognition of the limitations of this approach, a 1-year prospective study was also performed to see the true prevalence of tongue dysmorphology in these patients. RESULTS: Eight of 167 patients (4.8 percent) in the retrospective study were found to have tongue dysmorphologies, as opposed to 24 of 55 (43.6 percent) in the prospective study. The majority of tongue anomalies were mild. Of the eight retrospective patients, seven currently have intelligible speech with a combination of intensive speech therapy and/or surgical correction. The eighth patient is without intelligible speech. Tongue dysmorphology was positively correlated with the degree of hard- and soft-tissue deformity. CONCLUSIONS: Tongue dysmorphologies in craniofacial microsomia, although usually mild, are frequently overlooked. The correlation of the tongue, soft tissue, and mandible anomalies may point to a common error early in gestation or an interdependence of adjacent growth centers. PMID- 19644279 TI - Airway changes following Le Fort III distraction osteogenesis for syndromic craniosynostosis: a clinical and cephalometric study. AB - BACKGROUND: Le Fort III distraction osteogenesis improves midface form and dental relationships in patients with syndromic craniosynostosis, but its effect on the upper airway is not well documented. METHODS: A retrospective review was conducted of patients with syndromic craniosynostosis undergoing Le Fort III distraction osteogenesis from 2000 to 2006 (n = 20). Changes in velar angle and nasopharyngeal, velopharyngeal, oropharyngeal, and hypopharyngeal spaces were measured cephalometrically. Three-dimensional airway casts were created from computed tomographic data to ascertain circumferential airspace changes. Patients with the preoperative diagnosis of severe obstructive sleep apnea or a tracheostomy were designated as having significant airway compromise. Cephalometric differences in the preoperative superior airspace were compared between patients with and without significant airway compromise. Improvement in the symptoms of obstructive sleep apnea was studied. RESULTS: Cephalometric analysis revealed an increase in the velar angle (121 degrees to 148 degrees; p < 0.001) and an increase in the nasopharyngeal (3.9 mm to 13.0 mm; p < 0.001) and velopharyngeal airspaces (2.0 mm to 5.9 mm; p < 0.01). Three-dimensional computed tomographic analysis confirmed these findings. Comparison between preoperative cephalograms of patients with (n = 10) and without significant airway compromise (n = 10) revealed smaller nasopharyngeal (2.2 mm versus 5.7 mm; p < 0.05) and velopharyngeal airspaces (0.9 mm versus 3.0 mm; p = 0.05). Nine of 10 patients with significant airway compromise experienced improvement in their symptoms of obstructive sleep apnea or had their tracheostomy removed. CONCLUSIONS: Le Fort III distraction osteogenesis significantly increases nasopharyngeal and velopharyngeal airspaces in patients with syndromic craniosynostosis. Midface distraction improves but does not resolve all causes of obstructive sleep apnea in this patient population. PMID- 19644280 TI - A consecutive case review of orbital blowout fractures and recommendations for comprehensive management. AB - BACKGROUND: The orbital blowout fracture is a common facial injury, but full consensus has not been reached regarding its optimal management. The authors retrospectively explored consecutive cases of blowout fractures and proposed new recommendations for treatment. METHODS: Two hundred eight newly registered patients were selected from the database of Nagasaki University Hospital over the past 5 years. One hundred nine patients in the authors' department were then reviewed regarding computed tomographic classification of fracture types, preoperative complaints, and outcomes. RESULTS: Of the 208 patients reviewed, 43 underwent surgical repair: 37 for diplopia and 14 for enophthalmos, including eight patients who were treated for both conditions. Regarding floor fractures, the punched-out type fracture was the most common, but the burst type was associated with the highest likelihood of undergoing surgery. For medial wall fractures, the punched-out type dominated, but the overall operative incidence was lower than that observed for the floor fractures. For diplopia, more than half of the operations were performed within 2 weeks, but only two cases were performed within 3 days. For enophthalmos, over 60 percent of operations were carried out after 1 month. Two cases, later discovered to involve muscle strangulation, continued to demonstrate residual diplopia in ordinary use, and two patients continued to show enophthalmos. However, overall outcomes were considered satisfactory. CONCLUSIONS: If computed tomographic findings disclose a linear fracture with muscular strangulation, urgent surgery must be performed. However, for linear fractures without impaction of the muscle, or punched-out or burst type fractures, close observation for days may be appropriate. In addition, surgical intervention can be performed electively when diplopia persists for several days of observation. PMID- 19644281 TI - Refinements of the unilateral Millard technique: the Texas Children's Hospital Approach. PMID- 19644282 TI - Eyebrow and eyelid dimensions: an anthropometric analysis of African Americans and Caucasians. AB - BACKGROUND: Knowledge of the average dimensions of periocular features based on age, gender, and race is critical for surgeons so that complications can be avoided and ideal outcomes can be achieved. In this study, the authors sought to determine whether significant differences exist for certain eyelid and eyebrow dimensions between African American and white adults. METHODS: Both eyes of 89 African American and 75 white subjects, aged 20 to 80 years, were evaluated. Subjects were divided by gender into three, 20-year age cohorts. Measurements of palpebral fissure height, palpebral fissure width, palpebral fissure inclination, pretarsal skin height, crease height, eyebrow height, eyebrow apex angle, and distance of the brow apex from the lateral corneal limbus were taken from standardized photographs. Mean values by race, age, and gender were compared using linear mixed modeling. Double-lid crease prevalence was also evaluated. RESULTS: A significant difference was found between races for palpebral fissure width, pretarsal skin height, and crease height in men, and for eyebrow height in both men and women. A significant difference between genders was found for palpebral fissure height, palpebral fissure width, pretarsal skin height, and crease height in whites; for palpebral fissure inclination, eyebrow height, and distance of the brow apex from the lateral corneal limbus in both whites and blacks; and for eyebrow apex angle in blacks. Significant differences were also found between age cohorts for palpebral fissure height in black women and for eyebrow height in black men. Thirty-seven percent of African Americans had a double-lid crease versus 15 percent of whites. CONCLUSIONS: Race, gender, and age differences exist for certain eyelid and eyebrow positions. These factors can impact surgical decision-making and thus highlight the need for an individualized approach to patients. PMID- 19644283 TI - The aging lip: a comparative histological analysis of age-related changes in the upper lip complex. AB - BACKGROUND: Upper lip rejuvenation is achieved by a large variety of different treatment approaches that clearly lack a unified theoretical background of the aging processes of the upper lip complex. In this study, the histological changes that occur in the aging upper lip were systematically evaluated for the first time. METHODS: Histological cross-cuts of the upper lip complex of 20 individuals in two age groups, young (<40 years, n = 10) and old (>80 years, n = 10), were analyzed. The specimens were collected during the autopsies of individuals with no facial injuries. Hematoxylin-eosin and elastica van Gieson staining was performed, and the relevant anatomical structures were measured and compared using Student's t test. RESULTS: Histomorphometric analysis revealed statistically significant thinning of the cutis, thinning of the orbicularis oris muscle, and an increase of the orbicularis oris muscle angle defining the vermilion border in the old lip group. Elastic and collagen fibers in the cutis undergo degeneration processes during aging. The orbicularis oris muscle is not subject to fatty or fibroblastic degeneration, but shows signs of atrophy. CONCLUSIONS: The histomorphometric and histomorphological analyses shed light on the, so far, only unsystematically and episodically described process of upper lip aging on a histological level. The distinct changes add further evidence to the theory that the aged look is due to a loss of elasticity and resultant ptosis of the upper lip rather than to often-postulated but unproven total volume loss. PMID- 19644284 TI - Protective effect of topical antibiotics in breast augmentation. AB - BACKGROUND: Previous studies indicate that antibacterial lavage and/or use of topical antibiotics may reduce infection in breast implant surgery and perhaps also reduce occurrence of capsular contracture. A retrospective analysis was performed to evaluate this effect. METHODS: The study participants included all women (n = 436) who underwent breast augmentation during two different time periods: 2000 to 2002 (n = 218) and 2005 to 2007 (n = 218). During the first period (2000 to 2002), cephalothin (Keflin), was added to the saline/epinephrine solution, which was used to irrigate the implant pocket and filled into the outer lumen of the saline/gel implants. In the second period (2005 to 2007), only saline/epinephrine was used. All women were operated on at the same clinic and by the same surgeon. Recorded postoperative complications included occurrence of infection, seroma, and capsular contracture. RESULTS: Medical records were identified for 414 women (94.9 percent): 2000 to 2002 (n = 203) and 2005 to 2007 (n = 211); 99.8 percent of all implants were placed in the submuscular position and 99.8 percent of all incisions were periareolar. Frequency of infection in the 2005 to 2007 cohort (12.8 percent) exceeded substantially the frequency among the 2000 to 2002 cohort (6.7 percent; p = 0.044), as did the frequency of seroma (7.6 percent versus 2.9 percent, respectively; p = 0.036). There was no significant difference in development of capsular contraction between the two groups (8.1 percent versus 5.9 percent; p = 0.393). CONCLUSION: The authors' data support the use of topical antibiotics in cosmetic breast surgery, because significant increases of both infections and seroma were seen in patients not treated with topical antibiotics compared with a cohort of similar patients where topical antibiotics were used. PMID- 19644285 TI - Outpatient abdominoplasty facilitated by rib blocks. AB - BACKGROUND: Striving to increase patient comfort and feasibility of performing abdominoplasties as outpatient procedures, investigators have been exploring alternative methods of anesthesia to safely avoid general anesthesia. These techniques may result in decreased narcotic administration, and decreased postoperative nausea and vomiting. The authors have added the use of preoperative local anesthesia rib blocks with sedation to replace general anesthesia in abdominoplasties. METHODS: All cases of abdominoplasty performed by the senior author (B.M.M.) were reviewed from 1999 to 2006 and divided into two groups. Group 1 was composed of 39 operations performed using general anesthesia. Group 2 was composed of 29 operations performed using rib blocks placed by the surgeon and supplemented by intravenous sedation. Chart review collected data on time in the operating and recovery rooms, use of narcotics and antiemetics, frequency of postoperative nausea and vomiting, and patient-reported pain. Possible confounding factors, additional procedures, anesthetic and surgical complications, and the need for hospitalization were also recorded. Statistical analysis with two-tailed Mann-Whitney and chi-square testing was used to reject the null hypothesis when comparing the two groups. RESULTS: Statistically significant decreases in recovery room time, postoperative narcotics, postoperative nausea and vomiting, and pain were achieved using rib blocks. All other measures were similar for both groups. There were no hospitalizations, pneumothoraxes, major complications or deaths. CONCLUSION: Rib blocks placed before the start of surgery result in decreased recovery room times, pain, and postoperative nausea and vomiting, achieving increased patient comfort and feasibility of performing abdominoplasties in the outpatient setting. PMID- 19644287 TI - Obstructive sleep apnea: implications for the plastic surgeon and ambulatory surgery centers. PMID- 19644286 TI - Analysis of the body mass index and leg profiles of Asian women after total leg sculpture. AB - BACKGROUND: In addition to the conventional methods used to improve leg contours, total leg sculpture, including liposuction, selective neurectomy, and transilluminated powered phlebectomy, provides a one-time solution of leg contour problems, which is a major aesthetic concern among Asian women. The authors present the postoperative results of total leg sculpture and determine any significance and correlation between the leg variables and body mass index by statistical analysis. METHODS: Thirty female patients who underwent total leg sculpture between 2005 and 2008 were included in the study, and prospective analysis of the patients' data was performed during a follow-up period of 1 year. Local measurement variables and body mass index were recorded, and the correlation between them was determined by Pearson's correlation and regression analysis. A paired t test was used to compare the postoperative outcomes. RESULTS: Subjectively, all patient results were satisfactory. There were significant differences between preoperative and postoperative measurements for all variables for total leg sculpture. Body mass index was strongly correlated with all leg indexes, and there was a significant positive correlation between the index and variables related to the buttocks and upper thigh. The satisfactory postoperative leg variables were buttocks circumference (87.85 cm), thigh circumference (T60, 44.20 cm), maximal calf circumference (32.24 cm), and calf ratio (0.78). Each preoperative body mass index increment represents a 0.3 percent circumference improvement around the buttocks after surgery. No obvious morbidities or long-term hospital stays were noted. CONCLUSIONS: Total leg sculpture provides a combined aesthetic solution for improving limb contours with minimal morbidity. Patients with larger body mass index values exhibit better aesthetic improvement than those with smaller values. PMID- 19644288 TI - Creativity, innovation, and knowledge should defeat financial crisis in plastic surgery. PMID- 19644292 TI - Correction of frontonasoethmoidal encephalocele: the HULA procedure. PMID- 19644291 TI - Regarding "Application-specific selection of biomaterials for pediatric craniofacial reconstruction: developing a rational approach to guide clinical use". PMID- 19644296 TI - An algorithmic approach to reconstructive surgery and prosthetic rehabilitation after orbital exenteration. PMID- 19644297 TI - Alar augmentation in the management of Binder syndrome. PMID- 19644299 TI - The cross-lip flap from 1756 to 1898. Reply to "The Sabattini-Abbe flap: a historical note". PMID- 19644300 TI - Diced cartilage grafts in rhinoplasty surgery: current techniques and applications. PMID- 19644303 TI - Use of the buccal fat pad flap for congenital cleft palate repair. PMID- 19644304 TI - The use of suction drains in abdominal dermolipectomy: a randomized clinical trial. Are "significant" findings always so? PMID- 19644305 TI - Use of 2-octyl-cyanoacrylate skin adhesive (Dermabond) for wound closure following reduction mammaplasty: a prospective, randomized intervention study. "tips and tricks" to improve statistical analysis and significance of results. PMID- 19644306 TI - The error of omission: a simple checklist approach for improving operating room safety. PMID- 19644307 TI - Teach the leech the site to bite: another technical tip to tame Hirudo medicinalis. PMID- 19644317 TI - The efficacy of the synthetic interbody cage and Grafton for anterior cervical fusion. AB - STUDY DESIGN: Prospective study of 31 patients who underwent anterior cervical fusion. OBJECTIVE: To investigate the efficacy of polyetheretherketone (PEEK) cages and demineralized bone matrix (DBM) for anterior cervical discectomy and fusion (ACDF). SUMMARY OF BACKGROUND DATA: Although high fusion rates can be achieved with autogenous bone grafts, donor-site morbidity affects the patient's satisfaction with the surgical outcome. METHODS: Thirty-one consecutive patients treated with ACDF using the PEEK cage with DBM (Grafton, Osteotech, Inc., Shrewsbury, NJ) at 42 levels were prospectively evaluated with a minimum of 12 month follow-up (mean: 16 months). Twenty-one patients underwent a single-level ACDF, 9 patients underwent a 2-level ACDF, and 1 patient had a 3-level ACDF. The affected level was C3-C4 in 7 patients; C4-C5 in 9, C5-C6 in 16, and C6-C7 in 10. The neurologic outcomes were evaluated using the VAS score for neck and arm pain and the Japanese Orthopedic Association scoring system for myelopathy at 3, 6, and 12 months. The cervical lordosis and fusion status were assessed on radiographs including flexion/extension radiographs. RESULTS: At 12 months, the radiographs demonstrated grades I, II, and III new bone formation at 1, 13, and 28 levels, respectively. There was a significant improvement in both the neck and arm pain and a significant improvement in the Japanese Orthopedic Association scores at the last follow-up. There was no case with implant-related complications such as cage failure or migration, and no complications associated with the use of Grafton. CONCLUSION: ACDF using the Solis cage packed with Grafton demonstrated good clinical and radiologic outcomes. The fusion rate was comparable with the published results of the traditional ACDF using tricortical iliac crest grafts. Therefore, the results of this study suggest that the ongoing use of the PEEK cage packed with DBM and autologous bone chips in ACDF is a safe and effective alternative to the gold standard of autologous iliac bone grafts. PMID- 19644318 TI - Age-related changes in the orientation of lumbar facet joints. AB - STUDY DESIGN: A measurement and analysis of the orientation of the lumbar facet joints at the L4-L5 level of different age groups. OBJECTIVE: To explore the correlation between age and orientation of the lumbar facet joints. SUMMARY OF BACKGROUND DATA: Previous studies have shown an association between sagittal orientation of the lumbar facet joints and degenerative spondylolisthesis, however, there is no information available on the association between orientation of the lumbar facet joints and age. This article studied the association between orientation of the lumbar facet joints and age. METHODS: Three hundred spinal disease-free people coming for periodic physical examination during May 2007 and 2008 in our hospital accepted lumbar computed tomography (CT) scanning and were randomly selected. All the subjects were divided into 6 groups based on age (group I: <30 years of age, group II: 31-40 years, group III: 41-50 years, group IV: 51-60 years, group V: 61-70 years, and group VI: >70 years of age). CT scans of the lumbar spine were stored in digitized form for measurement and analysis. The orientation of the lumbar facet joints at the L4-L5 was measured on axial CT scans, and the intersection angle of the midsagittal line of vertebra to the facet line represent the orientation of the facet joint. RESULTS: The angles of the L4-L5 facet joints to the vertebral sagittal plane of group I to VI are 50.61 degrees +/- 6.55 degrees, 47.05 degrees +/- 7.53 degrees, 46.56 degrees +/- 7.38 degrees, 43.39 degrees +/- 6.19 degrees, 40.95 degrees +/- 7.27 degrees, and 39.89 degrees +/- 9.05 degrees, respectively (P = 0.000). CONCLUSION: The coronal orientation of the L4-L5 facet joints was negatively correlated to age (r = 0.456, P = 0.000), which could be one of the explanations that the aging people are prone to degenerative spondylolisthesis. PMID- 19644319 TI - Pelvic tilt and truncal inclination: two key radiographic parameters in the setting of adults with spinal deformity. AB - STUDY DESIGN: Prospective radiographic and clinical analysis. OBJECTIVE: Investigate the relationship between spino-pelvic parameters and patient self reported outcomes on adult subjects with spinal deformities. SUMMARY OF BACKGROUND DATA: It is becoming increasingly recognized that the study of spinal alignment should include pelvic position. While pelvic incidence determines lumbar lordosis, pelvic tilt (PT) is a positional parameter reflecting compensation to spinal deformity. Correlation between plumbline offset (sagittal vertical axis [SVA]) and Health Related Quality of Life (HRQOL) measures has been demonstrated, but such a study is lacking for PT. METHODS: This prospective study was carried out on 125 adult patients suffering from spinal deformity (mean age: 57 years). Full-length free-standing radiographs including the spine and pelvis were available for all patients. HRQOL instruments included: Oswestry Disability Index, Short Form-12, Scoliosis Research Society. Correlation analysis between radiographic spinopelvic parameters and HRQOL measures was pursued. RESULTS: Correlation analysis revealed no significance pertaining to coronal plane parameters. Significant sagittal plane correlations were identified. SVA and truncal inclination measured by T1 spinopelvic inclination (T1-SPI) (angle between T1-hip axis and vertical) correlated with: Scoliosis Research Society (appearance, activity, total score), Oswestry Disability Index, and Short Form-12 (physical component score). Correlation coefficients ranged from 0.42 < r < 0.55 (P < 0.0001). T1-SPI revealed greater correlation with HRQOL compared to SVA. PT showed correlation with HRQOL (0.28 < r < 0.42) and with SVA (r = 0.64, P < 0.0001). CONCLUSION: This study confirms that pelvic position measured via PT correlates with HRQOL in the setting of adult deformity. High values of PT express compensatory pelvic retroversion for sagittal spinal malalignment. This study also demonstrates significant T1-SPI correlation with HRQOL measures and outperforms SVA. This parameter carries the advantage of being an angular measurement which avoids the error inherent in measuring offsets in noncalibrated radiographs. PMID- 19644320 TI - Guidelines for management of scoliosis in Rett syndrome patients based on expert consensus and clinical evidence. AB - STUDY DESIGN: Modified Delphi technique. OBJECTIVE: To develop guidelines for the clinical management of scoliosis in Rett syndrome through evidence review and consensus expert panel opinion. SUMMARY OF BACKGROUND DATA: Rett syndrome is a rare disorder and clinical expertise is thus with small case series. Scoliosis is a frequent association and the evidence base dealing with scoliosis management in this syndrome is limited. Parents of affected girls and women have expressed needs for more information about scoliosis and Rett syndrome. METHODS: An initial draft of scoliosis guidelines was created based on literature review and open ended questions where the literature was lacking. Perspectives of four parents of Rett syndrome patients informed this initial draft. Access to an online and a Microsoft Word formatted version of the draft were then sent to an international, multidisciplinary panel of clinicians via e-mail with input sought using a 2 stage modified Delphi process to reach consensus agreement. Items included clinical monitoring and intervention before the diagnosis of scoliosis; monitoring after the diagnosis of scoliosis; imaging; therapy and conservative management; bracing; and preoperative, surgical, and postoperative considerations. RESULTS: The first draft contained 71 statements, 65 questions. The second draft comprised 88 items with agreement to strong agreement achieved on 85, to form the final guideline document. A comprehensive, life-span approach to the management of scoliosis in Rett syndrome is recommended that takes into account factors such as physical activity, posture, nutritional and bone health needs. Surgery should be considered when the Cobb angle is approximately 40 degrees to 50 degrees and must be supported by specialist management of anesthesia, pain control, seizures, and early mobilization. CONCLUSION: Evidence- and consensus-based guidelines were successfully created and have the potential to improve care of a complex comorbidity in a rare condition and stimulate research to improve the current limited evidence base. PMID- 19644321 TI - A meta-analysis of circumferential fusion versus instrumented posterolateral fusion in the lumbar spine. AB - STUDY DESIGN: A meta-analysis of circumferential fusion versus instrumented posterolateral fusion (PLF) in the lumbar spine. OBJECTIVE: To compare the clinical efficacy of circumferential fusion and instrumented PLF and to collate the scientific evidence to find a useful fusion method. SUMMARY OF BACKGROUND DATA: Clinical results, advantages, and postoperative complications of circumferential fusion and instrumented PLF were shown in many studies. However, there are different opinions among surgeons concerning the preferred method for the 2 fusion methods. METHODS: A highly sensitive search strategy was used to identify all published randomized controlled trials up to December 2007. A criteria list taken from Koes et al was used to evaluate the risk of bias of the included studies. The 5 questions that were recommended by the Cochrane Back Review Group were used to evaluate the clinical relevance. Cochrane methodology was used for the results of this meta-analysis. RESULTS: Four randomized controlled trials of surgery for lumbar degenerative disease were identified. No significant difference was found in the primary beneficial clinical outcome (odds ratios[OR]: 0.96, 95% confidence limits[95% CI]: [0.59, 1.55], [P = 0.87]). Significant difference was found in the complication rate (OR: 1.89, 95% CI: [1.14, 3.14], [P = 0.01]), which reflects the primary harm outcome. In the secondary outcomes, significant differences were found between circumferential fusion and instrumented PLF in the fusion rate (OR: 2.11, 95% CI: [1.06, 4.19], [P = 0.03]), the reoperation rate (OR: 0.44, 95% CI: [0.25, 0.77], [P = 0.004]), and the amount of blood loss (WMD = 349.95, 95% CI: [138.26, 561.64], [P = 0.001]). No significant difference was found the operating time (WMD = 90.24, 95% CI: [-9.71, 190.20], [P = 0.08]). CONCLUSION: Compared with instrumented PLF, circumferential fusion can increase the fusion rate and reduce the reoperation rate, but it can also increase the complication rate and the amount of blood loss. No significant difference was found in the global assessment of clinical outcome about the 2 fusion procedures. PMID- 19644322 TI - Multimodal therapy for vertebral involvement of systemic mastocytosis. AB - STUDY DESIGN: Case report and clinical discussion. OBJECTIVE: To describe a rare case of vertebral involvement of systemic mastocytosis and its multimodal therapy. SUMMARY OF BACKGROUND DATA: Vertebral fractures in young men are rare events. A thorough diagnostic work-up that unravels the underlying cause of osteoporosis and appropriate therapy are crucial to prevent further fractures. METHODS: A 36-year-old man was evaluated for severe back pain and was found to suffer from progressive osteoporosis and multiple vertebral fractures. Bone biopsy analysis revealed tryptase-positive mast cells that were positive for c KIT, thus confirming the diagnosis of systemic mastocytosis. RESULTS: In addition to zoledronic acid (4 mg per month) and prednisolone (50 mg per day) treatment, the patient underwent kyphoplasty. The procedure was associated with arterial hypotension which was most likely because of pressure-induced mast cell degranulation. Follow-up visits demonstrated stable bone mineral density and tolerable back pain while on zoledronic acid. CONCLUSION: Systemic mastocytosis is a rare cause of vertebral fractures in young men. Because of the potential risk of pressure-induced release of the allergy mediator histamine, kyphoplasty for vertebral involvement of systemic mastocytosis should be conducted with appropriate precautions. PMID- 19644323 TI - Traumatic posterior lumbosacral spondyloptosis in a six-year-old: a case report and review of the literature. AB - STUDY DESIGN: Report of a traumatic posterior lumbosacral spondyloptosis in a 6 year-old. OBJECTIVES: To describe this type of fracture-dislocation in children. To evaluate a possible trauma mechanism. To evaluate specific characteristics of this type of lesion in children. SUMMARY OF BACKGROUND DATA: Fractures of the lumbar spine in children are rare. They are without exception caused by high energy trauma. Fracture-dislocations mostly occur in the anterior direction. There are several reports of traumatic retrolisthesis in adults. To our knowledge, this is the first report of a retrolisthesis at the lumbosacral junction in a child. METHODS: While sitting, a 6-year-old boy was hit by a truck. He presented with a flaccid paraparesis below L3. Radiologic investigations showed a posterior spondyloptosis at L5-S1. He was treated by open reduction with a pediatric posterior spinal instrumentation and posterolateral grafting. RESULTS: After 1 year, the patient showed good radiologic fracture reduction and graft incorporation. There was no pain in the lumbar area. There was still a complete neurologic deficit beneath the L3 level, with loss of bladder and anal sphincter function. The patient was entered into a children's rehabilitation program 5 weeks after surgery and is continuously improving his overall functional level. CONCLUSION: Traumatic retrolisthesis of the lumbosacral spine is extremely rare, especially in children. We believe shear force while sitting is the key traumatic factor. We believe a simple posterior fusion with posterolateral grafting is sufficient to stabilize the spine in children. Extensive soft tissue damage causes an elevated risk of infection. Because of root avulsion, the level of paralysis can be several levels higher than the level of dislocation. PMID- 19644325 TI - Introduction to the congenital spine deformity focus issue. PMID- 19644326 TI - The natural history of congenital scoliosis and kyphosis. AB - STUDY DESIGN: Review article. OBJECTIVE: To discuss natural history of congenital scoliosis and kyphosis. SUMMARY OF BACKGROUND DATA: Review of previously published literature on natural history of congenital spine deformities. METHODS: Medline and google search for congenital scoliosis, kyphosis, and kyphoscoliosis, congenital spine anomalies, deformities, and pathologies, and congenital vertebral anomalies, deformities, and pathologies was performed. RESULTS: Congenital vertebral anomalies have potential to progress and careful assessment and monitoring is essential and early intervention may be desirable. CONCLUSION: Congenital vertebral anomalies invariably result from disturbed asymmetric growth and can have serious consequences. PMID- 19644327 TI - Classification of congenital scoliosis and kyphosis: a new approach to the three dimensional classification for progressive vertebral anomalies requiring operative treatment. AB - STUDY DESIGN: We reviewed three-dimensional (3D) computed tomography (CT) images of congenital spinal deformities and proposed a new classification based on the information obtained. OBJECTIVES: The purposes of this article were to clearly illustrate the limitations of two-dimensional classification, to summarize the clinical significance of 3D analysis of congenital vertebral anomalies, and to propose a new 3D classification of congenital vertebral anomalies. SUMMARY OF BACKGROUND DATA: The classification of congenital scoliosis or kyphosis were based on radiographic findings of plain radiograph images of congenital vertebral anomalies, it is sometimes difficult in classifying the large variety of anomalous vertebrae or severely twisted 3D curves. METHODS: Three-dimensional CT images of more than 150 patients with congenital spinal deformities were analyzed and compared with plain radiograph images. By developing the algorithm for the evaluation of malformed vertebrae in terms of numbers of abnormal vertebrae, type of formation failure, and type of segmentation failure in separate steps, we attempted to revise the classification of congenital spinal deformities. RESULTS: The images of plain radiograph cannot demonstrate the spatial relationship of each structure of the vertebrae. Three-dimensional findings in congenital deformed vertebrae included several types of laminae and clearer definitions of each type of anomalous vertebrae. By developing an algorithm for the evaluation of congenital spinal deformity, congenital spinal deformity could be mainly classified into 4 types of congenital vertebral abnormalities: Type 1: solitary simple, Type 2: multiple simple, Type 3: complex, Type 4: segmentation failure. CONCLUSION: The large volume of information that can be obtained by evaluating 3D CT images of congenitally deformed vertebrae can be a great help in developing a strategy for surgical treatment. We need to develop a new classification of congenital scoliosis based on the perspective of 3D imaging to understand the etiology and embryology, as well as to determine an operative strategy. PMID- 19644328 TI - Update on congenital spinal deformities: preoperative evaluation. AB - STUDY DESIGN: Review. OBJECTIVE: To review and outline the preoperative evaluation and approach in assessing children with congenital vertebral malformation. SUMMARY OF BACKGROUND DATA: Congenital vertebral malformations encompass a broad spectrum of conditions. A high association of renal, cardiac, and intraspinal anomalies with congenital vertebral malformation has been well documented in the literature. Vertebral malformation with involvement of the thoracic cage may lead to the development of thoracic insufficiency. The natural history, the character, and location of the deformity ultimately influence the propensity for progression and the necessity for treatment. Multiple factors should be considered before treatment with the goal of treatment aimed at providing the best possible care to be able to optimize the child's overall function and potential for growth. METHODS: Narrative and review of literature. CONCLUSION: Congenital scoliosis is a multifaceted condition. The presentation of the condition can be quite varied from those presenting with an isolated hemivertebrae to those with severe malformations, complicated by multiple medical conditions. A thorough preoperative evaluation is necessary before the institution of any treatment protocol. The presence of any medical condition must be addressed; the treatment should be tailor-made for each patient putting into consideration the patients' age and the effects of treatment on pulmonary function at maturity. PMID- 19644329 TI - Instrumentation and fusion for congenital spine deformities. AB - STUDY DESIGN: A retrospective clinical review. OBJECTIVE: To review the use of modern instrumentation of the spine for congenital spinal deformities. SUMMARY OF BACKGROUND DATA: Spinal instrumentation has evolved since the advent of the Harrington rod. There is a paucity of literature, which discusses the use of modern spinal instrumentation in congenital spine deformity cases. This review focuses on modern instrumentation techniques for congenital scoliosis and kyphosis. METHODS: A systematic review was performed of the literature to discuss spinal implant use for congenital deformities. RESULTS: Spinal instrumentation may be safely and effectively used in cases of congenital spinal deformity. CONCLUSION: Spinal surgeons taking care of children with congenital spine deformities need to be trained in all aspects of modern spinal instrumentation. PMID- 19644330 TI - Hemivertebra resection and osteotomies in congenital spine deformity. AB - STUDY DESIGN: Retrospective study of posterior hemivertebra resection and osteotomies with transpedicular instrumentation in very young children. OBJECTIVE: Assessment of early intervention in congenital scoliosis with almost complete correction of the main deformity. SUMMARY OF BACKGROUND DATA: There is a trend to early correction of congenital deformities, however, there is a lack of long-term follow-up. METHODS: Forty-one children aged 1 to 6 years with congenital scoliosis were operated on by hemivertebra resection by a posterior only approach with transpedicular instrumentation. Mean age at time of surgery was 3 years 5 months. They were retrospectively studied with a mean follow-up of 6 years 2 months. RESULTS: In group 1 (patients without bar formation), the average Cobb angle of the main curve was 36 degrees before surgery and 7 degrees after surgery. Compensatory cranial curve improved spontaneously from 15 degrees to 3 degrees, compensatory caudal curve from 17 degrees to 4 degrees. The angle of kyphosis was 22 degrees before surgery and 8 degrees after surgery. In group 2 (patients with bar formation) the main curve improved from 69 degrees to 23 degrees, cranial curve from 27 degrees to 11 degrees, caudal curve from 34 degrees to 14 degrees, and kyphosis from 24 degrees to 9 degrees. CONCLUSION: Posterior hemivertebra resection, in case of bar formation with osteotomy of the bar, allows for excellent correction in both the frontal and sagittal planes, with a short segment of fusion. Early surgery in young children prevents the development of severe local deformities and secondary structural curves, thus allowing for normal growth in the unaffected parts of the spine. PMID- 19644331 TI - Fusionless instrumentation systems for congenital scoliosis: expandable spinal rods and vertical expandable prosthetic titanium rib in the management of congenital spine deformities in the growing child. AB - STUDY DESIGN: Review of relevant literature including personal opinions. OBJECTIVE: To review the current researches investigating the efficacy of growing rod and thoracic expansion techniques in the treatment of congenital spine deformity of young children, and to highlight the contrasting advantages and limitations in the fusionless treatment of progressive congenital scoliosis. SUMMARY OF BACKGROUND DATA: Congenital scoliosis has the potential for severe spinal deformity and thoracic insufficiency syndrome (TIS). Conventional fusion treatments in children tend to shorten the spine further exacerbating trunk shortening and TIS. In the surgical treatment of congenital spinal deformities in young children, while reconstructing the spinal deformity, one should simultaneously pursue preserving the growth potential of the vertebrae, improving the volume, symmetry, and functions of the thorax, and protecting this improvement during the growth. Today, employed in the treatment of spinal deformities of young children, there are 2 deformity reconstruction methods serving these targets: Growing rod technique and vertical expandable prosthetic titanium rib (VEPTR) with or without expansion thoracostomy. METHODS: Peer reviewed research articles and major international meeting presentations were reviewed. Methods were compared in terms of advantages and limitations. RESULTS: The growing rod technique is a safe and reliable method in the treatment of congenital spine deformity of young children who present some flexibility in the anomalous segment, or when the congenital anomaly involves a vertebral segment too long for resection, or with compensating curve with structural pattern concomitant to the congenital deformity. Expansion thoracostomy and VEPTR are the appropriate choice for severe congenital spine deformity when a large amount of growth remains. Although ventilator dependence is significantly decreasing, thoracic volume and space available for the lung are increased after expansion thoracostomy and VEPTR. CONCLUSION: Growing rod technique should be used in patients where the primary problem is at the vertebral column. If the patient has rib fusions and/or TIS has developed, in other words, if the primary problem involves the thoracic cage, expansion thoracostomy and VEPTR should be an appropriate option. PMID- 19644332 TI - The surgical treatment of congenital kyphosis. AB - STUDY DESIGN: Retrospective study with clinical and radiologic evaluation of 15 patients with congenital kyphosis or kyphoscoliosis who underwent anterior instrumented spinal fusion for posterolateral or posterior hemivertebra (HV). The management of congenital kyphosis has been described in the literature using a variety of techniques. The presentation of patients at diagnosis is discussed. The question of when to begin treatment is reviewed. The pitfalls in the management and how to avoid these are discussed. The different published techniques are reviewed. We present our own techniques and our results of treatment of congenital kyphosis in very young children. OBJECTIVE: To evaluate the safety and efficacy of early surgical anterior instrumented fusion with partial preservation of the HV in the treatment of progressive congenital kyphosis in children below the age of 3. We discuss the management of patients presenting with neurologic compromise. We aim to systematically review the literature and to present our own experience in the management of these deformities, so that the issues common to treating physicians may be explored. SUMMARY OF BACKGROUND DATA: A variety of treatments have been described in the literature for the treatment of congenital kyphosis due to HV. We report the results of our technique. METHODS: Between 1997 and 2005 we have treated 15 consecutive patients with progressive congenital kyphosis with anterior instrumented fusion and strut grafting. Thirteen patients had a single posterolateral HV and 2 patients had a single posterior HV. Of the 15 patients in the study, 5 were girls and 10 boys. Mean age at surgery was 22 months (range, 8 33). Mean follow-up period was 6.8 years. Thirteen HV were located in the thoracolumbar junction (T10-L2) and 2 in the thoracic spine. RESULTS: The average operating time of procedure was 150 minutes (range, 130-210 minutes). The average blood loss was 180 mL (range, 100-330 mL), equivalent to a mean external blood volume loss of 15% (range, 11%-24%).Preoperative segmental Cobb angle averaging 34 degrees at last follow-up. Compensatory coronal cranial and caudal curves were corrected by 50%. The angle of segmental kyphosis averaged 39 degrees (range, 20 degrees-80 degrees) before surgery and 21 degrees (range, 11 degrees-40 degrees) at last follow-up. This represents a 43% of improvement of the segmental kyphosis, and a 64% of improvement of the segmental scoliosis at last follow-up. One case with initial kyphosis of 80 degrees continued to progress and required revision anterior and posterior surgery. There were no neurologic complications. PMID- 19644333 TI - Spine deformities in rare congenital syndromes: clinical issues. AB - STUDY DESIGN: A focused review of the literature with regard to the important system abnormalities of patients with spinal deformities associated with exotic congenital syndromes with additional data from the author's own experience in assessment of patients with rare syndromes treated for thoracic insufficiency syndrome. OBJECTIVES: The objectives of this study are to emphasize important medical considerations that influence the choice of surgical treatment of spinal deformity in patients with exotic congenital syndromes and point out preoperative strategies that reduce treatment morbidity and mortality of these patients. SUMMARY OF BACKGROUND DATA: Individual experience is limited in the treatment of spine abnormality in rare exotic syndromes and the medical aspects of these syndromes that may impact spinal treatment are seldom discussed in detail in the orthopedic literature. For a successful outcome in the treatment of spinal deformity in these unique patients, a working knowledge of the unique pitfalls in their medical care is necessary in order to avoid morbidity and mortality during their treatment. METHODS: The literature was reviewed for 6 exotic congenital syndromes with known or unreported spinal abnormalities and the author's personal 22-years experience of the treatment of thoracic insufficiency syndrome in the relevant congenital syndromes was summarized. RESULTS: Children with Marfan syndrome and spinal deformity may have serious cardiac abnormalities. Spontaneous dissection of the aortic root is a clear danger and patients should be monitored by serial echocardiograms. Prophylactic cardiac surgery may be necessary before spinal surgery is to be performed. Patients with Jeune syndrome have a high rate of proximal cervical stenosis and should undergo screening with cervical spine films at birth. Significant stenosis or instability may require decompression and cervical-occipital fusion. Arthrogryposis may be associated with a severe scoliosis and jaw contracture may make intubation difficult. Larsen syndrome may have early onset scoliosis that is very rigid and requires early intervention. Cervical kyphosis and subluxation may be lethal in these patients and screening radiographs are important. Upper airway abnormalities are an anesthesia concern. Jarcho-Levin syndrome is a thoracic volume depletion deformity due to shortness of the thorax, either a spondylocostal dysostosis variant or spondylothoracic dysplasia. The former has a chaotic congenital scoliosis with varied combination of missing and fused ribs. Although spondylocostal dysostosis has a benign reputation in the literature for respiratory complications, respiratory insufficiency is nevertheless common and 1 death is known from respiratory failure. Spondylothoracic dysplasia seldom has significant scoliosis, but has a mortality rate approaching 50% from respiratory complications due to thoracic insufficiency syndrome. In spite of severe restrictive respiratory disease, adult survivors of spondylothoracic dysplasia appear to do well clinically for unknown reasons. Cerebrocostomandibular syndrome has scoliosis, micrognathia, and thoracic insufficiency syndrome, due to an "implosion" deformity of the thorax from congenital pseudarthrosis of the posterior ribs. CONCLUSION: For optimal patient care, it is necessary to have a clear understanding of exotic congenital syndromes and how they may impact on both the presentation of spinal deformity and the response to treatment, as well as how they may introduce additional morbidity into standard treatment plans. It is clear that with this understanding that preoperative strategies can be employed to enhance the safety of spinal treatment for these unique children. PMID- 19644334 TI - Sagittal plane considerations and the pelvis in the adult patient. AB - STUDY DESIGN: Research update, focused review. OBJECTIVE: Identify the role of the pelvis in the setting of adults with spinal deformity. SUMMARY OF BACKGROUND DATA: Sagittal plane alignment is increasingly recognized as a critical parameter in the setting of adult spinal deformity. Additionally, pelvic parameters reveal to be a key component in the regulation of sagittal alignment. METHODS: Analysis of the pelvis in the sagittal plane is commonly assessed by 3 angular measurements: the pelvic incidence (morphologic parameter directly linked to sagittal morphotypes), the pelvic tilt (or pelvis retroversion used to maintain an upright posture in the setting of spinal deformity), and the sacral slope. Recent work using force plate technology has revealed that in the setting of anterior trunk inclination ("spinal imbalance"), the pelvis shifted posteriorly (toward the heels) in order to maintain a balanced mass distribution. The complex relationship between pelvic and spinal parameter were investigated in order to construct predictive formulas of postoperative spinopelvic alignment. It has emerged that pelvic tilt is highly correlated with patient self reported function (ODI, SF-12, and SRS). CONCLUSION: It has become evident that good clinical outcome in the treatment of spinal deformity requires proper alignment. Pelvis parameters play an essential role not only in terms of spine morphotypes but also in regulating standing balance and postoperative alignment. Thus, optimal treatment of a patient with spinal deformity requires integration of the pelvis in the preoperative evaluation and treatment plan. PMID- 19644335 TI - Zonal responsiveness of the human intervertebral disc to bone morphogenetic protein-2. AB - STUDY DESIGN: In vitro experiment using bone morphogenetic protein-2 (BMP-2) and cells from the nucleus pulposus (NP), transitional zone (TZ), and anulus fibrosus (AF) of the human intervertebral disc (IVD). OBJECTIVE: To demonstrate the differential effect of BMP-2 on DNA synthesis, proteoglycan synthesis, and osteocalcin mRNA expression in human IVD cells from the NP, TZ, and AF, respectively. SUMMARY OF BACKGROUND DATA: BMP-2 has been proven to be effective in stimulating proteoglycan synthesis in articular chondrocytes and IVD cells from the NP. Nevertheless, the effect of BMP-2 on cells from different regions of the IVD has not yet been thoroughly elucidated. METHODS: Human IVDs were harvested from surgical disc procedures and tissue from the NP, TZ, and AF was obtained. Disc tissue was enzymatically digested, and IVD cells were cultured three-dimensionally in alginate beads. Then IVD cell cultures from the NP, TZ, and AF were exposed to BMP-2. DNA synthesis and newly synthesized proteoglycan were measured. Reverse transcription-polymerase chain reaction for mRNA expression of bone sialoprotein, DLX5, osteocalcin, and collagen type I, was performed. RESULTS: Cells from the AF responded to BMP-2 with mitogenesis. There was no significant increase in DNA synthesis in cultures from the NP and TZ treated with BMP-2. Only cells from the NP showed a significant increase in newly synthesized proteoglycan in response to BMP-2. IVD cells from all zones demonstrated no significant expression of bone sialoprotein, DLX5, osteocalcin mRNA after treatment with BMP-2. CONCLUSION: BMP-2 clearly exerted a mitogenic effect on AF cells, and stimulated proteoglycan synthesis in NP cells. However, BMP-2 did not have an osteogenic effect in any IVD region. Taken together, these results confirm that BMP-2 can be used as an anabolic agent for mitogenesis in AF cells and NP cell matrix regeneration without the possibility of osteogenesis. PMID- 19644336 TI - Correlation of Risser sign, radiographs of hand and wrist with the histological grade of iliac crest apophysis in girls with adolescent idiopathic scoliosis. AB - STUDY DESIGN: A correlation analysis between histologic grade (HG) of iliac crest apophysis and skeletal age assessments. OBJECTIVE: To study the correlation between HGs of iliac crest apophysis and the skeletal age of hand and wrist, digital skeletal age (DSA), and Risser sign in the girls with adolescent idiopathic scoliosis (AIS). SUMMARY OF BACKGROUND DATA: The evaluation of the remaining growth of the patients clinically and radiologically is highly significant in predicting the curve progression and thus influencing the treatment strategy in AIS. METHODS: Fifty-three AIS girls with a mean age of 14.0 years undergoing corrective posterior spinal surgery and instrumentation with autogenous bone graft were recruited. Menarche status was recorded while the skeletal age of hand and wrist, DSA, and Risser grade were evaluated radiologically. Using a standardized HG of proliferative chondrocyte zone of the iliac crest apophysis, correlation between the HGs and the radiologic and clinical skeletal maturity parameters was analyzed. RESULTS: The HGs were negatively correlated with the radiologic parameters with the highest correlation coefficient between HGs and skeletal age of hand and wrist. The negative correlation between HGs and the 2 clinical parameters was significant and could be enhanced by combining with the radiologic parameters. No proliferative chondrocyte zone of the apophysis was detected when patients were either over 16 years of skeletal age or Risser grade 5, as well as 2-year postmenarche or over 15 years of chronological age in patients with DSA stage III and Risser grade 4. CONCLUSION: Radiologic skeletal age of the wrist and digits can provide important information for maturity assessment in girls with AIS. It can also enhance the sensitivity of clinical parameters in determining the remaining growth potential. PMID- 19644337 TI - Grading apical vertebral rotation without a computed tomography scan: a clinically relevant system based on the radiographic appearance of bilateral pedicle screws. AB - STUDY DESIGN: Bench-top and retrospective analysis to assess vertebral rotation based on the appearance of bilateral pedicle screws in patients with adolescent idiopathic scoliosis (AIS). OBJECTIVE: To develop a clinically relevant radiographic grading system for evaluating postoperative thoracic apical vertebral rotation that would correlate with computed tomography (CT) measures of rotation. SUMMARY OF BACKGROUND DATA: The 3-column vertebral body control provided by bilateral pedicle screws has enabled scoliosis surgeons to develop advanced techniques of direct vertebral derotation. Our ability to accurately quantify spinal deformity in the axial plane, however, continues to be limited. METHODS: Trigonometry was used to define the relationship between the position of bilateral pedicle screws and vertebral rotation. This relationship was validated using digital photographs of a bench-top model. The mathematical relationships were then used to calculate vertebral rotation from standing postoperative, posteroanterior radiographs in AIS patients and correlated with postoperative CT measures of rotation. RESULTS: Fourteen digital photographs of the bench-top model were independently analyzed twice by 3 coauthors. The mathematically calculated degree of rotation was found to correlate significantly with the actual degree of rotation (r = 0.99; P < 0.001) and the intra- and interobserver reliability for these measurements were both excellent (kappa = 0.98 and kappa = 0.97, respectively). In the retrospective analysis of 17 AIS patients, the average absolute difference between the radiographic measurement of rotation and the CT measure was only 1.9 degrees +/- 2.0 degrees (r = 0.92; P < 0.001). Based on these correlations a simple radiographic grading system for postoperative apical vertebral rotation was developed. CONCLUSION: An accurate assessment of vertebral rotation can be performed radiographically, using screw lengths and screw tip-to-rod distances of bilateral segmental pedicle screws and a trigonometric calculation. These data support the use of a simple radiographic grading system to approximate apical vertebral rotation in AIS patients treated with bilateral apical pedicle screws. PMID- 19644338 TI - Prevalence of self-reported neck-shoulder-arm pain and concurrent low back pain or psychological distress: time-trends in a general population, 1990-2006. AB - STUDY DESIGN: Analysis of repeated cross-sectional surveys. OBJECTIVE: To investigate the prevalence of neck-shoulder-arm pain and concurrent low back pain and psychological distress in a geographical area over a 16-year period. SUMMARY OF BACKGROUND DATA: A large number of studies have shown that nonspecific neck, shoulder, and arm pain is a very common symptom in the general population. However, few studies have followed the prevalence of neck-shoulder-arm pain within a geographical area, in order to investigate time-trends. METHODS: This study provides an analysis of questionnaire data collected every 4 years between 1990 and 2006 on the prevalence of neck-shoulder-arm pain and concurrent low back pain or psychological distress in the County of Stockholm, Sweden (response rate: 61%-69%). All individuals aged 21 to 64 years (n = 1976-26,611) were included in the study. RESULTS: Over the 16-year period, the prevalence of self-reported neck shoulder-arm pain rose slightly, from 22.8% to 25.0% among females (prevalence rate ratio [PRR]: 1.10) and from 12.8% to 15.4% among males (PRR: 1.21). The prevalence of neck-shoulder-arm pain with concurrent low back pain also rose slightly, from 8.4% to 10.8% among females (PRR: 1.28) and from 5.3% to 6.6% among males (PRR: 1.24). In contrast, the prevalence of neck-shoulder-arm pain with concurrent psychological distress rose more substantially, from 4.4% to 8.5% among females (PRR: 1.91) and from 2.0% to 4.3% among males (PRR: 2.18). All prevalence rates rose between 1990 and 2002, and decreased in 2006 compared to 2002. The gender gap in prevalence did not change over time. CONCLUSION: Although the prevalence of neck-shoulder-arm pain and concurrent symptoms decreased in 2006 compared to 2002, it is still too early to conclude that we have reached and passed the peak of the "epidemic" of neck-shoulder-arm pain. PMID- 19644339 TI - Risk factors for postoperative spinal wound infections after spinal decompression and fusion surgeries. AB - STUDY DESIGN: This is a multivariate analysis of a prospectively collected database. OBJECTIVE: To determine preoperative, intraoperative, and patient characteristics that contribute to an increased risk of postoperative wound infection in patients undergoing spinal surgery. SUMMARY OF BACKGROUND DATA: Current literature sites a postoperative infection rate of approximately 4%; however, few have completed multivariate analysis to determine factors which contribute to risk of infection. METHODS: Our study identified patients who underwent a spinal decompression and fusion between 1997 and 2006 from the Veterans Affairs' National Surgical Quality Improvement Program database. Multivariate logistic regression analysis was used to determine the effect of various preoperative variables on postoperative infection. RESULTS: Data on 24,774 patients were analyzed. Wound infection was present in 752 (3.04%) patients, 287 (1.16%) deep, and 468 (1.89%) superficial. Postoperative infection was associated with longer hospital stay (7.12 vs. 4.20 days), higher 30-day mortality (1.06% vs. 0.5%), higher complication rates (1.24% vs. 0.05%), and higher return to the operating room rates (37% vs. 2.45%). Multivariate logistic regression identified insulin dependent diabetes (odds ratios [OR] = 1.50), current smoking (OR = 1.19) ASA class of 3 (OR = 1.45) or 4 to 5 (OR = 1.66), weight loss (OR = 2.14), dependent functional status (1.36) preoperative HCT <36 (1.37), disseminated cancer (1.83), fusion (OR = 1.24) and an operative duration of 3 to 6 hours (OR = 1.33) or >6 hours (OR = 1.40) as statistically significant predictors of postoperative infection. CONCLUSION: Using multivariate analysis of a large prospectively collected data from the National Surgical Quality Improvement Program database, we identified the most important risk factors for increased postoperative spinal wound infection. We have demonstrated the high mortality, morbidity, and hospitalization costs associated with postoperative spinal wound infections. The information provided should help alert clinicians to presence of these risks factors and the likelihood of higher postoperative infections and morbidity in spinal surgery patients. PMID- 19644340 TI - Creep and fatigue development in the low back in static flexion. AB - STUDY DESIGN: In vivo measurements of low back flexion posture and muscle activity before, during, and after static flexion. OBJECTIVE: To identify the occurrence of creep and muscle fatigue development in the low back during static upper body deep flexion that resembled an above ground work posture. SUMMARY OF BACKGROUND DATA: Static lumbar flexion has been related to the development of low back disorders, and its injury mechanism has been focused on the changes in passive spinal tissues. Potential influences of muscle fatigue of extensor muscles have not been explored. METHODS: A total of 20 asymptomatic subjects performed submaximal isometric trunk extension exertions and an isokinetic trunk flexion before and immediately after 5-minute static flexion while the trunk sagittal flexion angle and the myoelectric activities (electromyography [EMG]) of back extensor muscles were recorded simultaneously. Changes in the flexion relaxation onset angle, maximum flexion angle, muscle activity level, and the median power frequency of EMG associated with the static flexion were evaluated. RESULTS: Flexion-relaxation onset angle in isokinetic flexion and EMG amplitude of isometric extension were significantly greater after static flexion, indicating creep of spinal tissues in static flexion. Median power frequency of lumbar erector spinae EMG during isometric extension was significantly lower after static flexion, suggesting the development of muscle fatigue. Consistent but low level of EMG was observed together with sporadic muscle spasms during the static flexion period. CONCLUSION: Fatigue of low back extensor muscles may occur in static flexion due to prolonged passive stretching of the muscles. Low back extensor muscles are required to generate more active forces in weight holding or lifting after static flexion to compensate for the reduced contribution of creep deformed passive tissues in maintaining spinal stability and the posture. The degraded force generating capacity of the fatigued muscles can be a significant risk factor for low back pain. PMID- 19644342 TI - Re: Chi JH, Gokaslan Z, Chi JH, Gokaslan Z, et al. Selecting treatment for patients with malignant epidural spinal cord compression--does age matter? Results from a randomized clinical trial. Spine 2009;34:431-5. PMID- 19644341 TI - Anterior approach to disc herniation with modified anterior microforaminotomy at C7-T2: technical note. AB - STUDY DESIGN: An easy surgical method to reach C7-Th and T1-T2 foraminal disc herniation is described. OBJECTIVE: To describe a surgical technique that involves an anterior approach to disc herniation with inverted cone-shaped partial minicorpectomy. SUMMARY OF BACKGROUND DATA: Anterior approaches to the cervicothoracic junction are difficult in spinal surgery because the operative area is narrow. The manubrium, the clavicles, and the slope of the vertebral bodies obstruct the view of the surgeon. The vascular and neural structures of the superior mediastinum limit the surgical approach. The thoracic duct and recurrent laryngeal nerve present risks for injury, especially with approaches from the right side. Disc herniations at the C7-T2 level are very rare. Posterior approaches at these levels are advocated because radicular symptoms occur more often than myelopathic symptoms, but anterior discectomy and fusion are generally preferred by many spinal surgeons, as these are approaches that are more intuitive. METHODS: We review the case histories of all of our patients that underwent inverted cone-shaped partial minicorpectomy and fusion at the C7-T2 disc levels between 2000 and 2008. We applied the surgical techniques described in this manuscript. RESULTS: The mean follow-up duration was 50 months postoperation. Physical examinations were performed and radiographs were taken at the end of the first 6 months postoperative and every 12 months thereafter. No meaningful changes were recorded on either the Visual Analog Scale or the Neck Disability Index. Cervical alignment was unchanged before and after surgery. CONCLUSION: Minicorpectomy technique of C7 or T1 vertebra is an easy and appropriate method for treating foraminal disc herniation between the C7-T1 and T1-T2 levels. PMID- 19644343 TI - Re: Usul H, Arslan E, Cansever T, et al. Effects of clotrimazole on experimental spinal cord ischemia/reperfusion injury in rats. Spine 2008;33:2863-7. PMID- 19644344 TI - Re: Matsumoto M, Watanabe K, Tsuji T, et al. Nocturnal leg cramps: a common complaint in patients with lumbar spinal canal stenosis. Spine 2009;34:E189-94. PMID- 19644346 TI - Spatial phylodynamics of HIV-1 epidemic emergence in east Africa. AB - DESIGN: We sought to investigate the evolutionary and historical reasons for the different epidemiological patterns of HIV-1 in the early epidemic. In order to characterize the demographic history of HIV-1 subtypes A and D in east Africa, we examined molecular epidemiology, geographical and historical data. METHODOLOGY: We employed high-resolution phylodynamics to investigate the introduction of HIV 1A and D into east Africa, the geographic trends of viral spread, and the demographic growth of each subtype. We also used geographic information system data to investigate human migration trends, population growth, and human mobility. RESULTS: HIV-1A and D were introduced into east Africa after 1950 and spread exponentially during the 1970s, concurrent with eastward expansion. Spatiotemporal data failed to explain the establishment and spread of HIV based on urban population growth and migration. The low prevalence of the virus in the Democratic Republic of Congo before and after the emergence of the pandemic was, however, consistent with regional accessibility data, highlighting the difficulty in travel between major population centers in central Africa. In contrast, the strong interconnectivity between population centers across the east African region since colonial times has likely fostered the rapid growth of the epidemic in this locale. CONCLUSION: This study illustrates how phylodynamic analysis of pathogens informed by geospatial data can provide a more holistic and evidence based interpretation of past epidemics. We advocate that this 'landscape phylodynamics' approach has the potential to provide a framework both to understand epidemics' spread and to design optimal intervention strategies. PMID- 19644347 TI - Design of a HIV-1-derived HLA-B07.02-restricted polyepitope construct. AB - OBJECTIVE: To design a vaccine construct containing various but conserved HIV-1 derived epitopes and generating broad CD8 T cell responses. METHODS: HLA-B7 transgenic H-2KD KO transgenic mice were used to identify potential new HLA B07.02-restricted HIV-1-derived epitopes. Immunological recognition of these epitopes was confirmed by IFN-gamma ELISpot assays with PBMCs from HLA-B*0702 HIV 1-infected individuals. For these peptides as well as others previously identified, the capacity to induce cross-reactive responses against their frequent allelic variants was evaluated in the mouse model. A set of epitopes inducing strong T cell responses against various and conserved regions of HIV-1 was selected. A DNA vaccine was designed to express them as a unique antigen with or without a three amino acid ARY extension flanking each epitope. The spectrum of CD8 T responses generated by polyepitope constructs was tested in HLA-B7 transgenic mice. RESULTS: Five new epitopes were identified in accessory and regulatory HIV-1 proteins. Twelve HLA-B07.02-restricted epitopes were selected on the basis of their structural conservation and cross-reactive immunogenicity. The ARY N-terminal extension flanking each epitope markedly increases their affinity for TAP and the use of this flanking extension in polyepitope vaccine has a sizable advantage to induce CD8 T cell cytotoxic responses in mice following DNA immunization. CONCLUSION: The HLA-B7 mouse model allows to rapidly identify various HIV-1-derived epitopes of vaccine interest. Grouped in a polyepitope construct designed to increase their processing, this vaccine may be suitable for inducing multiple and relevant HIV-1-specific CTL responses in humans. PMID- 19644349 TI - Endograft repair of traumatic aortic injury-a technique in evolution: a single institution's experience. AB - OBJECTIVE: We evaluated a large single center experience of endograft repair of blunt traumatic injury of the thoracic aorta. SUMMARY BACKGROUND DATA: Traumatic aortic transection is a devastating injury with high morbidity and mortality. Endograft repair of these injuries has reduced the rates of death and paraplegia seen with open surgical treatment in the past. However, endograft repair has been associated with a higher incidence of device related failure. METHODS: The records of 43 consecutive cases of endograft treatment of traumatic aortic injury from December 2004 to November 2008 were reviewed. Patient demographics, procedure details, and outcomes were recorded. Aortic morphology was analyzed for predictors of device failure. RESULTS: Forty-three patients (32 men) with a mean age of 44 years (range: 17-88) were treated. Primary technical success was 86%. Six proximal endoleaks (14.3%) occurred. Two were repaired with a more proximal cuff, but 3 required explantation and open repair (7%). Mortality in this series was 11.6%, but no death was aorta related. No patient having endograft treatment suffered postoperative paraplegia. Early device failure is associated with sharp angulation of the aorta and shortened distance between the left subclavian artery and the site of injury. Follow-up ranged from 1 to 38 months (mean: 7.4 months). There were no late device failures or complications. CONCLUSIONS: Endovascular repair of blunt traumatic aortic injury can be performed with a low morbidity and mortality. Anatomic patterns in the aortic arch appear to be predictive of early device failure. Midterm durability is excellent, but reliable follow-up remains challenging in this group of patients. PMID- 19644350 TI - Does surgical quality improve in the American College of Surgeons National Surgical Quality Improvement Program: an evaluation of all participating hospitals. AB - BACKGROUND/OBJECTIVE: The National Surgical Quality Improvement Program (NSQIP) has demonstrated quality improvement in the VA and pilot study of 14 academic institutions. The objective was to show that American College of Surgeons (ACS) NSQIP helps all enrolled hospitals. METHODS: ACS-NSQIP data was used to evaluate improvement in hospitals longitudinally over 3 years (2005-2007). Improvement was defined as reduction in risk-adjusted "Observed/Expected" (O/E) ratios between periods with risk adjustment held constant. Multivariable logistic regression based adjustment was performed and included indicators for procedure groups. Additionally, morbidity counts were modeled using a negative binomial model, to estimate the number of avoided complications. RESULTS: Multiple perspectives reflected improvement over time. In the analysis of 118 hospitals (2006-2007), 66% of hospitals improved risk-adjusted mortality (mean O/E improvement: 0.174; P < 0.05) and 82% improved risk adjusted complication rates (mean improvement: 0.114; P < 0.05). Correlations between starting O/E and improvement (0.834 for mortality, 0.652 for morbidity), as well as relative risk, revealed that initially worse-performing hospitals had more likelihood of improvement. Nonetheless, well-performing hospitals also improved. Modeling morbidity counts, 183 hospitals (2007), avoided ~9598 potential complications: ~52/hospital. Due to sampling this may represent only 1 of 5 to 1of 10 of the true total. Improvement reflected aggregate performance across all types of hospitals (academic/community, urban/rural). Changes in patient risk over time had important contributions to the effect. CONCLUSIONS: ACS-NSQIP indicates that surgical outcomes improve across all participating hospitals in the private sector. Improvement is reflected for both poor- and well-performing facilities. NSQIP hospitals appear to be avoiding substantial numbers of complications- improving care, and reducing costs. Changes in risk over time merit further study. PMID- 19644353 TI - The pediatric surgeons' contribution to in utero treatment of twin-to-twin transfusion syndrome. AB - OBJECTIVE: To evaluate the outcome of twin-to-twin transfusion syndrome (TTTS) treated using a combination of endoscopic fetal surgery-specific techniques and surgical restraint. SUMMARY BACKGROUND DATA: TTTS is a condition of identical twins that, if progressive and left untreated, leads to 100% mortality. The best treatment option is obliteration of the intertwin placental anastomoses, but fetal surgery carries significant maternal and fetal risks. Even if successful, percutaneous endoscopic laser ablation of placental vessels (LASER) causes premature rupture of membranes (PROM) in 10% to 20% of pregnancies. Patient selection is particularly critical because the progression of the disease is unpredictable. This has prompted many to intervene early, yielding survival rates of >=1 twin of 75% to 80%. METHODS: We developed a minimally invasive approach to fetal surgery, a unique membrane sealing technique and a conservative algorithm that reserves intervention for severe TTTS. Pregnancies with TTTS (stages I-IV) managed in the last 8 years were reviewed. LASER was offered in stage III/IV only. RESULTS: Ninety-eight cases of TTTS were managed in a pediatric surgery/maternal-fetal medicine collaborative Fetal Treatment Program-39 were observed (40%) and 59 underwent LASER (60%). Survival of >= twin was seen in 82.7%, and overall survival was 69.4%. These survival rates are similar to, or better than, other comparable series with similar stage distribution (low:high stage ratio 1:1) in which all patients underwent LASER. PROM rate was 4%. CONCLUSIONS: Reserving LASER treatment for severe TTTS results in outcomes similar to, or better than, LASER for all stages. Applying fetal surgery-specific endoscopic techniques, including port-site sealing, reduces postoperative complications. PMID- 19644348 TI - Impact of HAART and CNS-penetrating antiretroviral regimens on HIV encephalopathy among perinatally infected children and adolescents. AB - OBJECTIVES: Prior to antiretroviral treatment, HIV-infected children frequently developed encephalopathy, resulting in debilitating morbidity and mortality. This is the first large study to evaluate the impact of HAART and central nervous system (CNS)-penetrating antiretroviral regimens on the incidence of HIV encephalopathy and survival after diagnosis of HIV encephalopathy among perinatally infected children. DESIGN: A total of 2398 perinatally HIV-infected children with at least one neurological examination were followed in a US-based prospective cohort study conducted from 1993 to 2007. METHODS: Trends in incidence rates over calendar time were described and Cox regression models were used to estimate the effects of time-varying HAART and CNS-penetrating antiretroviral regimens on HIV encephalopathy and on survival after diagnosis of HIV encephalopathy. RESULTS: During a median of 6.4 years of follow-up, 77 incident cases of HIV encephalopathy occurred [incidence rate 5.1 cases per 1000 person-years, 95% confidence interval (CI) 4.0-6.3]. A 10-fold decline in incidence was observed beginning in 1996, followed by a stable incidence rate after 2002. HAART regimens were associated with a 50% decrease (95% CI 14-71%) in the incidence of HIV encephalopathy compared with non-HAART regimens. High CNS penetrating regimens were associated with a substantial survival benefit (74% reduction in the risk of death, 95% CI 39-89%) after HIV encephalopathy diagnosis compared with low CNS-penetrating regimens. CONCLUSION: A dramatic decrease in the incidence of HIV encephalopathy occurred after the introduction of HAART. The use of HAART was highly effective in reducing the incidence of HIV encephalopathy among perinatally infected children and adolescents. Effective CNS-penetrating antiretroviral regimens are important in affecting survival after diagnosis of HIV encephalopathy. PMID- 19644351 TI - Predictors of survival after resection of retroperitoneal sarcoma: a population based analysis and critical appraisal of the AJCC staging system. AB - OBJECTIVE: To identify predictors of survival after resection of retroperitoneal sarcoma (RPS) and to evaluate the performance of the American Joint Committee on Cancer (AJCC) staging system for RPS. SUMMARY BACKGROUND DATA: Previous studies of survival after RPS resection are restricted to at most several institutions, yet the current AJCC staging system for RPS is based entirely on these relatively small studies. METHODS: Patients undergoing resection of primary RPS from 1988 to 2005 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazards models were used to analyze survival and evaluate AJCC staging. RESULTS: In 1365 patient undergoing resection of primary RPS, the most prevalent histologies were liposarcoma (50%), leiomyosarcoma (26%), and malignant fibrous histiocytoma (11%). Median, 5-year, and 10-year survival after resection were 55 months, 47%, and 27%. Histological subtype (P < 0.001), histological grade (grade 3-4 vs. grade 1; HR, 2.42; P < 0.001), and tumor invasion of adjacent structures (HR, 1.37; P < 0.001) were associated with survival on multivariable analysis. However, tumor size had no prognostic value. Consequently, the AJCC T classification system demonstrated poor discriminatory ability (c = 0.50). The AJCC stage grouping system demonstrated moderate discriminatory ability (c = 0.66) but performed no better than a much simpler system that omits information on tumor size and lymph node metastasis (c = 0.67). CONCLUSIONS: Indicators of tumor aggressiveness (histological grade and invasion of adjacent structures) as well as histological subtype predict survival after RPS resection. Tumor size, however, does not impact survival. The AJCC staging system for RPS is in need of revision. PMID- 19644354 TI - Small-incision mitral valve repair: safe, durable, and approaching perfection. AB - OBJECTIVE: To critically evaluate an initial experience with small-incision mitral valve operation with respect to safety, durability, and effectiveness. SUMMARY BACKGROUND DATA: Mitral valve (MV) surgery is dominated by a sternotomy approach, with MV repair rates which average 60%. Advantages of valvular repair compared with replacement include lower operative and long-term mortality, decreased stroke and infection risks, and superior freedom from reoperation and complications of anticoagulation. METHODS: Right chest small-incision MV surgery was performed on 187 consecutive patients. Outcomes including operative mortality and major morbidity were recorded. All patients underwent predismissal echocardiography in a core laboratory. RESULTS: Between 2003 and 2008, 57% (187/327) of isolated MV operations were performed using an anterolateral 6 cm 4th intercostal space small-incision. Operative techniques included femoral arterial and venous plus internal jugular cannulation and direct aortic cross clamping. Pathology of the anterior leaflet was present in 22%, and PTFE neochordal repairs were used in 36% of cases. The rate of MV repair was 96.3% (180/187) and was 100% for patients with degenerative disease. Median cardiopulmonary bypass and aortic cross-clamp times were 108 and 82 minutes, respectively. There were no deaths, strokes, renal failure, or wound infections. Two patients (1.1%) were re-explored for bleeding, and 27% received blood transfusions. The median hospital stay was 4 days. Clinical core laboratory assessed freedom from significant (MR > mild) at hospital discharge was 99%. Survival at a median follow-up of 2.5 years was 99%. CONCLUSIONS: Direct visualization of the mitral valve through a right chest small-incision enables safe and effective performance of complex MV repair, with repair rates in excess of 95%. PMID- 19644356 TI - Successful sunitinib treatment of metastatic renal cell carcinoma in a patient with end stage renal disease on hemodialysis. AB - Sunitinib is a tyrosine kinase inhibitor with a low toxicity profile and proven activity against metastatic renal cell carcinoma (mRCC). However, there is very limited data on the effect of sunitinib on end stage renal disease owing to mRCC. We report our experience with the use of sunitinib in a patient with mRCC and end stage renal disease undergoing hemodialysis. PMID- 19644355 TI - A novel histone deacetylase inhibitor, CG0006, induces cell death through both extrinsic and intrinsic apoptotic pathways. AB - Histone deacetylase inhibitors (HDACIs) are potent anticancer drugs, and suberoylanilide hydroxamic acid is used for the treatment of cutaneous T-cell lymphoma patients. We synthesized a novel hydroxamate-based HDACI, CG0006, and assessed its antiproliferative effects on the NCI-60 cancer cell panel and cell lines from liver and stomach cancers that are common in Korea. Micromolar levels of CG0006 induced cell death in several breast, central nervous system, colon, hematopoietic, lung, melanoma, ovarian, prostatic, renal, and stomach cancer cell lines. We further analyzed cell death mechanisms activated by CG0006 in HCT116 (colon cancer) and K562 (leukemia) cells. First, to test the activity of CG0006, we analyzed acetylation of substrates of HDACs and effect on gene expression. CG0006 increased acetylation of histone 3, histone 4, and tubulin in a time dependent and dose-dependent manner in both HCT116 and K562 cells. Moreover, CG0006 increased the mRNA level of p21 and decreased that of Bcl-xl efficiently in HCT116 cells. Cell cycle analysis showed G2-M arrest, and increased apoptosis in populations of HCT116 and K562 cells treated with CG0006. Western blot analysis showed that CG0006 increased levels of p21 in HCT116 cells and of p21 and p27 in K562 cells. In addition, CG0006 activated caspase-9, caspase-3, and caspase-8. These results indicate that CG0006 induces death in HCT116 and K562 cells through both intrinsic and extrinsic apoptotic pathways. The HDACI CG0006 may be a potent anticancer drug for solid tumors and leukemia. PMID- 19644358 TI - Phlegmonous gastritis in a patient with myeloid sarcoma: a case report. AB - Phlegmonous gastritis is a rare acute bacterial infection of the gastric wall with an extremely high mortality rate. Early diagnosis is crucial for immediate treatment that could improve the outcomes. Here we report a case in which a patient with underlying chronic myelomonocytic leukemia was diagnosed with phlegmonous gastritis on biopsy. This 57-year-old man presented with shortness of breath and intermittent upper quadrant abdominal pain for 4 days. Laboratory tests showed markedly increased white blood cell. A diagnosis of chronic myelomonocytic leukemia was made based on a peripheral blood smear and flow cytometry. Gastric biopsy showed suppurative inflammation in the submucosal region, prompting the diagnosis of phlegmonous gastritis. The patient was given empirical antibiotic treatment, and the white blood cell decreased dramatically. Surgical intervention was discussed but deferred. Despite continued antibiotics treatment, the patient died. The limited autopsy confirmed the diagnosis of phlegmonous gastritis. Immunohistochemical studies further revealed the occurrence of myeloid sarcoma that involved the gastrointestinal tract. PMID- 19644357 TI - Immunohistochemical detection of hepatitis C virus (genotype 4) in B-cell NHL in an Egyptian population: correlation with serum HCV-RNA. AB - BACKGROUND AND AIM: Retrospective evaluation of hepatitis C virus (HCV) prevalence in lymphoma tissues has important applications in clarifying the contribution of viral factors to the pathogenesis. Trials for detection of HCV at the cellular level in lymphoma tissues are, so far, minimal with unsatisfactory results. We aimed to study the detection and localization of HCV in the tissues of B-cell non-Hodgkin lymphoma (NHL) patients. DESIGN: We performed immunohistochemistry to detect the HCV nonstructural 3 protein in paraffin embedded tissue specimens of B-cell NHL patients, in 39 serum HCV-RNA positive samples and 35 serum HCV-RNA negative samples as controls. The serum analysis was carried out for HCV antibodies using enzyme-linked immunoassay and for HCV-RNA using reverse transcription-polymerase chain reaction. Reverse transcription polymerase chain reaction was used to detect the HCV-RNA in tissues in immunohistochemically positive cases. We correlated the results with the clinicopathologic characteristics of the patients. RESULTS: A diffuse cytoplasmic immunohistochemical staining for HCV in the lymphoid cells was detected in 8 of 39 serum positive cases (20.5%), all of which were genotype 4, which is the most prevalent HCV genotype in Egypt. Only 2 out of 35 serum negative control samples showed positive staining and in 1 of them HCV-RNA was detected in tissue. No significant correlation was detected between HCV positive cases and the clinicopathologic features of the patients. CONCLUSIONS: Immunohistochemical detection of HCV proteins in lymphoma tissues supports a potential role of viral replication in lymphomagenesis. The low number of cases showing expression of viral proteins may represent a low viral load in lymphoid tissue and/or restriction of HCV protein expression to certain subtypes of B-cell NHL. Immunohistochemistry can be used as a complementary tool for specific HCV detection in the paraffin-embedded material of lymphoma tissues not suitable for RNA analysis. PMID- 19644360 TI - The prognosis and treatment of acquired hemophilia: a systematic review and meta analysis. AB - The inhibition of factor VIII by autoantibody development, or acquired hemophilia, occurs in approximately one person per million each year and can cause life-threatening bleeding. Due to the disease rarity, there are no randomized studies addressing prognostic features and treatment. The goal of this study is to identify prognostic indictors in acquired hemophilia to guide treatment choices. MEDLINE and EMBASE search from 1985-2008 retrieved 32 studies with detailed clinical information on five or more patients with acquired hemophilia. Univariate and multivariate analysis of the effects of age, sex, underlying condition, inhibitor titer, and treatment regimen were evaluated with regards to complete remission and death. A total of 32 studies containing 359 patients with acquired hemophilia were included in the analysis. The all-cause mortality rate in this cohort was 21%. Multivariate analyses revealed that patients more likely to die are the elderly [odds ratio (OR) 2.4, 95% confidence interval (CI) 1.32-4.36] and those with underlying malignancy (OR 2.76, CI 1.38 5.50). Early achievement of complete remission resulted in improved survival. Complete remission occurred in 94% of patients receiving combination chemotherapy, 82% receiving dual therapy, and 68% receiving steroids alone. Patients receiving immunosuppression had reduced odds of persistent hemophilia, with combination chemotherapy being the most efficacious (OR 0.04, CI 0.01-0.23) and steroid therapy alone being the least (OR 0.38, CI 0.14-0.94). In acquired hemophilia, increased age, underlying malignancy, and lack of complete remission are risk factors for death. Although the included studies were not randomized, patients treated with combination chemotherapy had the greatest odds of remission and the lowest odds of death. PMID- 19644359 TI - Fibrin formation and lysis studies in dengue virus infection. AB - Dengue virus is a mosquito-borne human viral pathogen that has recently become a major public health concern particularly in tropical and subtropical countries, predominantly in urban and periurban areas. Plasma from five patients infected by the virus was selected since they have in different degrees prolonged thrombin times: +2.1, +3.4, +5.7, +7.1 and +18.5 s, like a transitory acquired dysfibrinogenemia. The serotype could be determined in only two patients, being DEN-1 and DEN-3. The fibrinogen concentration was normal ranging from 2.5 to 3.2 g/l. In general, the fibrin degradation products of the patients were high, reaching values of 6000 ng/ml. The polymerization process was quite similar to that of the control, except in two cases where the final turbidity was almost half the control value. In one of these patients, the fibrinogen was purified and mixed with normal fibrinogen (v: v); the patients' fibrinogen impaired normal fibrin polymerization. Studies of the fibrinolytic process revealed that clots from dengue patients started to lyze before they have reached the maximum turbidity, although this was not reflected in the time needed for complete clot dissolution, which was similar to that of the control for all the patients. Fibrinolysis of clots made by mixing normal and patient purified fibrinogen (2.5: 1) was impaired. Clot images obtained by scanning electron microscopy showed that the patients' fibrin network had some degree of degradation and the fibers were thicker than those of the control (P < 0.05). This preliminary study seems to indicate that the dengue virus infection modifies the balance of coagulation fibrinolysis toward hyperfibrinolysis and could modify the normal fibrinogen molecule. PMID- 19644361 TI - Efficacy and safety of botulinum neurotoxin NT 201 in poststroke upper limb spasticity. AB - OBJECTIVE: To assess the impact of the new botulinum neurotoxin type A preparation NT 201 (Xeomin; Merz Pharmaceuticals GmbH, Frankfurt, Germany) on muscle tone, functional disability, and caregiver burden in patients with poststroke upper limb spasticity in a randomized, placebo-controlled, double blind study. METHODS: One hundred forty-eight patients with an Ashworth Scale score of 2 or higher for wrist and finger flexors and at least moderate disability in their principal therapeutic target of the Disability Assessment Scale were treated either with NT 201 (median, 320 U) or placebo and followed up for up to 20 weeks. Treatment of the wrist and finger muscles was mandatory. RESULTS: A significantly higher proportion of patients treated with NT 201 were responders (improvement of > or =1 point in the Ashworth Scale score), as observed in comparison to placebo 4 weeks after treatment in wrist flexors (odds ratio, 3.97; 95% confidence interval, 1.9-8.3; P < 0.001, intent to treat). For all treated flexor muscle groups, statistically significant odds ratios in favor of NT 201 were observed at week 4 (P < or = 0.009). Statistically significant results in favor of NT 201 were observed at all postinjection visits until week 12 in the principal therapeutic target (P < or = 0.005), in the global assessment of efficacy (P < 0.001), and in some tasks of the Carer Burden Scale (P < 0.05). Similar numbers of patients in each group experienced at least 1 adverse event (NT 201, n = 21; placebo, n = 20). Importantly, none of the patients developed neutralizing antibodies. CONCLUSIONS: NT 201 led to statistically significant improvements in muscle tone and disability and was well tolerated in patients with poststroke upper limb spasticity. PMID- 19644362 TI - Genetics and epidemiology: asthma and infection. AB - PURPOSE OF REVIEW: This review will consider how recent epidemiological studies have helped reveal the role of respiratory infection in asthma inception early in life. We will also review the importance of respiratory infections and exacerbations of asthma and will discuss genetic factors controlling host immune responses to respiratory infection and the influence these may exert on asthma pathogenesis. RECENT FINDINGS: Birth cohort studies have demonstrated bidirectional relationships between early life severe respiratory infections and asthma development; however, whether there is a clear causal role for severe respiratory infection early in life leading directly to asthma development remains unknown. The role of rhinovirus infection in asthma exacerbations has been investigated experimentally, with asthmatic patients exhibiting greater clinical illness severity, which was related to increased virus load and lower airways inflammation. Polymorphisms in genes involved in innate, antiviral and Th1 and Th2 immune responses have been linked to asthma as well as to early life severe respiratory infections, suggesting that host factors are likely to play an important role in their association. SUMMARY: Early in life, such genetic factors contribute to the risk of severe lower respiratory tract viral infection as well as later development of wheezing illness and asthma. Respiratory viruses are also the most frequent cause of asthma exacerbations at all ages. PMID- 19644364 TI - Obstructive sleep apnea and cardiovascular disease. AB - PURPOSE OF REVIEW: To update the reader on the most recent developments linking obstructive sleep apnea to cardiovascular disease. RECENT FINDINGS: Significant progress has been made in defining the relationship between obstructive sleep apnea and cardiovascular disease. However, much work remains to be done to clarify the pathophysiologic mechanisms and the potential role of treatment of sleep apnea in the prevention of cardiovascular morbidity and mortality. SUMMARY: At present there is only limited evidence to recommend the routine treatment of obstructive sleep apnea specifically for the prevention of cardiovascular disease. PMID- 19644363 TI - The chitinase and chitinase-like proteins: a review of genetic and functional studies in asthma and immune-mediated diseases. AB - PURPOSE OF REVIEW: The present review provides an overview of the chitinase and chitinase-like proteins, chitotriosidase (CHIT1), YKL-40, and acid mammalian chitinase, and summarizes the genetic studies of asthma and immune-mediated diseases with polymorphisms in the genes encoding these proteins, CHIT1, CHI3L1, and CHIA, respectively. RECENT FINDINGS: Polymorphisms in the CHIT1, CHIA, and CHI3L1 genes influence chitotriosidase enzyme activity, acid mammalian chitinase activity, and YKL-40 levels, respectively. Regulatory SNPs in CHI3L1 were also associated with asthma, atopy, and immune-mediated diseases, and nonsynonymous SNPs in CHIA were associated with asthma. No CHIT1 polymorphisms, including a common nonfunctional 24-bp duplication allele, have been associated with asthma. SUMMARY: These genes represent novel asthma susceptibility genes. Variations in CHI3L1 and CHIA have been associated with asthma risk. Polymorphisms in CHIT1 have not yet been associated with asthma, but few studies have been reported. Given that chitotriosidase is the major chitinase in the airways and a common nonfunctional allele is present in many populations, additional studies of this gene are warranted. Lastly, studies of all three genes need to be conducted in populations of diverse ancestries. PMID- 19644365 TI - Pleiotropic role of growth arrest-specific gene 6 in atherosclerosis. AB - PURPOSE OF REVIEW: Growth arrest-specific gene 6 (Gas6) belongs to the family of vitamin K-dependent coagulation proteins, but in contrast to its other members, has only a limited role in hemostasis. Instead, Gas6 plays a prominent role in conditions of injury, inflammation and repair. Gas6 amplifies the activation of various cell types including endothelial cells and platelets in different models of thrombosis and inflammation, processes also important in atherosclerosis. RECENT FINDINGS: Recently, we showed that in human and murine atherosclerotic plaques, Gas6 is expressed by endothelial cells, smooth muscle cells and most abundantly by macrophages, and that its expression increases with atherosclerosis severity. Moreover, genetic loss of Gas6 in ApoE mice reduced the influx of inflammatory cells in the plaque and induced plaque fibrosis, hence creating a stable plaque phenotype. Consistent herewith, Gas6 plasma levels are increased in patients with unstable angina pectoris, which is a common consequence of atherosclerotic plaque rupture. SUMMARY: Inhibition of Gas6 would be an attractive therapeutic target for stabilizing atherosclerotic plaques and for the prevention of vascular thrombotic occlusion after plaque rupture. Here we will critically review the existing literature on the potential roles of Gas6 and its receptors in the different stages of atherosclerosis. PMID- 19644366 TI - The role of hypoxia in atherosclerosis. AB - PURPOSE OF REVIEW: It is important to address the factors involved in the progression of atherosclerosis because advanced atherosclerotic lesions are prone to rupture, leading to disability or death. Hypoxic areas are known to be present in human atherosclerotic lesions, and lesion progression is associated with the formation of lipid-loaded macrophages and increased local inflammation. Here we summarize the role of hypoxia in the development of advanced atherosclerotic lesions by promoting lipid accumulation, inflammation, ATP depletion, and angiogenesis. RECENT FINDINGS: A recent study clearly demonstrated the presence of hypoxia in macrophage-rich regions of advanced human carotid atherosclerotic lesions. We showed that hypoxia increases the formation of lipid droplets in macrophages and promotes increased secretion of inflammatory mediators, and recent evidence indicates that lipid droplets may play a role in mediating the inflammatory response. Hypoxia also promotes lesion progression by exacerbating ATP depletion and lactate accumulation, and the presence of hypoxia in human carotid atherosclerotic lesions correlates with angiogenesis. SUMMARY: Recent studies indicate that hypoxia may play a key role in the progression to advanced lesions by promoting lipid accumulation, increased inflammation, ATP depletion, and angiogenesis. Further understanding of the effects of hypoxia in atherosclerotic lesions could indicate potential therapeutic targets. PMID- 19644367 TI - Update on posterior uveal melanoma: treatment of the eye and emerging strategies in the prognosis and treatment of metastatic disease. AB - PURPOSE OF REVIEW: The current treatment options for posterior uveal melanoma and its metastases are reviewed in this paper. Recent developments in understanding genetic and molecular features of these tumors are discussed with emphasis on clinical application. RECENT FINDINGS: The management of uveal melanomas has shifted to more eye-sparing approaches without significant improvement in patient survival. There has been an increased understanding of the genetic and molecular abnormalities that lead to melanomas that are more likely to metastasize. Treatments of metastatic disease remain inadequate. SUMMARY: Uveal melanoma appears to be a systemic disease at presentation. Treatment of the primary disease may be curative in some patients. However, up to 50% of patients will ultimately succumb to the metastatic disease. The accuracy of patient prognostication can be enhanced by tumor cytogenetics. Even with this knowledge, no effective adjuvant treatments exist. Further research and innovation will allow tailored therapies for patients with high-risk tumor features. PMID- 19644369 TI - Editorial comment: life after transplantation. PMID- 19644368 TI - Changing paradigms in the treatment of diabetic retinopathy. AB - PURPOSE OF REVIEW: To review current treatment approaches in diabetic retinopathy. RECENT FINDINGS: Diabetic retinopathy remains one of the leading causes of blindness worldwide. Strict metabolic control, tight blood pressure control, laser photocoagulation, and vitrectomy remain the standard care for diabetic retinopathy. Focal/grid photocoagulation is a better treatment than intravitreal triamcinolone acetonide in eyes with diabetic macular edema. The current evidence suggests that intravitreal triamcinolone acetonide or antivascular endothelial growth factor agents are effective adjunctive treatment to laser photocoagulation or vitrectomy. However, triamcinolone is associated with risks of elevated intraocular pressure and cataract. Vitrectomy with removal of the posterior hyaloid without internal limiting membrane peeling seems to be effective in eyes with persistent diffuse diabetic macular edema, particularly in eyes with associated vitreomacular traction. Emerging therapies include islet cell transplantation, fenofibrate, ruboxistaurin, and intravitreal hyaluronidase. SUMMARY: A variety of promising new medical and surgical therapies are emerging, but more randomized controlled clinical trials are required to clarify their role alone or in combination. PMID- 19644371 TI - Youth suicide prevention: does access to care matter? AB - PURPOSE OF REVIEW: Recent increases in adolescent suicide rates after a decade of decline highlight the relevance of pediatric suicide prevention. Existing strategies to intervene with youth at risk for suicide are largely based on the premise that access to effective services is of critical importance. This review aims to examine the relationship between youth suicide and access to care. RECENT FINDINGS: Promising reductions in suicidal thinking and behavior have been associated with the application of manualized psychotherapies, collaborative interventions in primary care, lithium for mood-disordered adults, and clozapine in schizophrenia. Suicide rates correlate inversely with indices of care access across the lifespan, including antidepressant prescription rates. SUMMARY: Suicide is a preventable cause of death, and any public health relevant effort to prevent youth suicide must include improving access to effective care for at-risk youth as a strategy. Education and training of professionals and consumers, the integration of mental health services in primary care, and the use of novel technologies to track and maintain contact with at-risk youth are worthy of study. Additional research on the relationship between specific treatments, especially antidepressants, and youth suicide risk reduction is desperately needed. PMID- 19644370 TI - Deconvoluting the 'omics' for organ transplantation. AB - PURPOSE OF REVIEW: The desire for biomarkers for diagnosis and prognosis of diseases has never been greater. With the availability of genome data and an increased availability of proteome data, the discovery of biomarkers has become increasingly feasible. This article reviews some recent applications of the many evolving 'omic technologies to organ transplantation. RECENT FINDINGS: With the advancement of many high-throughput 'omic techniques such as genomics, metabolomics, antibiomics, peptidomics, and proteomics, efforts have been made to understand potential mechanisms of specific graft injuries and develop novel biomarkers for acute rejection, chronic rejection, and operational tolerance. SUMMARY: The translation of potential biomarkers from the laboratory bench to the clinical bedside is not an easy task and will require the concerted effort of the immunologists, molecular biologists, transplantation specialists, geneticists, and experts in bioinformatics. Rigorous prospective validation studies will be needed using large sets of independent patient samples. The appropriate and timely exploitation of evolving 'omic technologies will lay the cornerstone for a new age of translational research for organ transplant monitoring. PMID- 19644373 TI - History of psychiatry and the psychiatric profession. AB - PURPOSE OF REVIEW: The present article reviews the English language literature on the history of psychiatry published within the previous year. RECENT FINDINGS: Research has been conducted in the history of clinical syndromes, famous people and psychiatrists, psychiatric institutions, treatments and legislations. The importance of the sociocultural contexts has been shown, particularly in research emanating from Europe and North America, which addresses late 18th to late 20th century issues. SUMMARY: Much varied and important research on the history of psychiatry is being performed around the world. This scholarship provides insight into the cultural context and ways in which psychiatry was practised in the past and can help shed light on the way in which psychiatry is conducted today. PMID- 19644372 TI - Epidemiology of youth suicide and suicidal behavior. AB - PURPOSE OF REVIEW: Suicide is the third leading cause of death among young people in the U.S. and represents a significant public health problem worldwide. This review focuses on recent developments in our understanding of the epidemiology and risk factors for adolescent suicide and suicidal behavior. RECENT FINDINGS: The suicide rate among children and adolescents in the U.S. has increased dramatically in recent years and has been accompanied by substantial changes in the leading methods of youth suicide, especially among young girls. Much work is currently underway to elucidate the relationships between psychopathology, substance use, child abuse, bullying, internet use, and youth suicidal behavior. Recent evidence also suggests sex-specific and moderating roles of sex in influencing risk for suicide and suicidal behavior. SUMMARY: Empirical research into the causal mechanisms underlying youth suicide and suicidal behavior is needed to inform early identification and prevention efforts. PMID- 19644374 TI - Neurobiology of cognitive disorders. AB - PURPOSE OF REVIEW: Neurodegenerative brain diseases, including Alzheimer's disease, frontotemporal degeneration and Lewy body disease, are the most frequent pathologies underlying cognitive disorders in old age. This review outlines recent advances in the understanding of key molecular mechanisms involved in these neurodegenerations, particularly with regard to the abnormal processing of proteins. The consequences of these novel insights for therapeutic interventions are also explained. RECENT FINDINGS: Aberrant processing, misfolding, and subsequent deposition of amyloid beta protein, TAU, alpha-synuclein, and TDP-43 are key events in the pathological cascades of neurodegenerations leading to cognitive impairment and dementia. The nonpolymerized, oligomeric forms of these proteins have neurotoxic properties including the disruption of synaptic function and the induction of oxidative stress. The aggregation and deposition of these proteins may represent a neuronal repair mechanism which ultimately worsens the deleterious effects of the preaggregated forms. Novel disease-modifying treatment strategies aim at down-regulating protein production, inhibiting polymerization, or removing preaggregated forms of the proteins from the brain. SUMMARY: Recent research has elucidated important molecular events in neurodegenerative diseases upstream of the aggregation and deposition of proteins which forms their histopathological hallmarks. These insights translate into novel therapeutic strategies which are currently evaluated in clinical trials. PMID- 19644375 TI - Infection control in cystic fibrosis: barriers to implementation and ideas for improvement. AB - PURPOSE OF REVIEW: This review will focus on recent research documenting baseline adherence to infection control recommendations and barriers to their implementation as experienced by multidisciplinary cystic fibrosis (CF) care providers. In addition, controversies regarding optimal infection control will be discussed. Finally, suggestions to improve infection control in CF will be proposed. RECENT FINDINGS: Compliance with recent guidelines was assessed for clinical microbiology laboratories and for infection control policies at CF care centers in the United States. Unlike earlier reports, the vast majority of laboratories used selective media for Burkholderia cepacia complex and identified all species of nonlactose fermenting Gram-negative bacilli. Fewer used selective media for Staphylococcus aureus or used agar-based susceptibility testing assays for Pseudomonas aeruginosa. Only 103 (65%) of 158 CF care centers provided written infection control policies for review and these were more likely to address inpatient than outpatient settings. Surveys of healthcare professionals showed that access to a copy of the CF infection control guidelines reduced barriers to adherence to selected infection control practices. SUMMARY: These data suggest that access to national infection control guidelines and written local policies are critically important to improving infection control for CF. PMID- 19644376 TI - Palliative and end-of-life care in cystic fibrosis: what we know and what we need to know. AB - PURPOSE OF REVIEW: This review will examine what is now known about palliative and end-of-life care for cystic fibrosis (CF) patients, including the changing demographics and context of such care, and then outline a brief research agenda to guide further work in this area. RECENT FINDINGS: We have now entered an era of more invasive end-of-life care in CF, due in part to changes in the demographics of death in CF and in part to the wider pursuit of lung transplantation. Recent single-center studies suggest that lung transplant listing changes the location and intensity of end-of-life care and complicates end-of-life care decision-making for the patient, family, and clinician. Further studies have demonstrated a high burden of daily symptoms in CF, especially pain and depression. In addition, there is evidence of an increasing burden related to the expanding daily treatment regimen for CF. SUMMARY: The time has come for national, multicenter studies of palliative and end-of-life care practices in CF, followed by systematic evaluation of the efficacy of existing interventions. Studies of the symptoms and treatment burdens in CF should continue with an emphasis on interventions to improve health-related quality of life throughout the lifespan of children and adults with CF. PMID- 19644377 TI - Theoretical and practical basis for early aggressive therapy in paediatric autoimmune disorders. AB - PURPOSE OF REVIEW: The clinical practice of introducing anti-inflammatory therapies in paediatric autoimmune disorders has changed substantially in the last two decades. This is partly due to the fact that we are able to put disease into remission with potent drugs, and so the issue of when to introduce these drugs is important. This review will seek to highlight the consequences of chronic inflammation and the change to outcomes if adequate or 'aggressive' treatment is given early to induce remission. RECENT FINDINGS: The review not only highlights publications on this topic over the past 12-18 months but also refers to key publications before when appropriate. The disorders reviewed are juvenile idiopathic arthritis, systemic lupus erythematosis, Wegener's granulomatosis, juvenile dermatomyositis, juvenile scleroderma and autoinflammatory syndromes. SUMMARY: Outcomes can be influenced by potent anti inflammatory therapies. Their use early in the evolution of the disorder in question can limit damage and allow the possibility of normal life and function in the child. PMID- 19644378 TI - B cell depletion in lupus and Sjogren's syndrome: an update. AB - PURPOSE OF REVIEW: The critical role of B cells in the pathogenesis of systemic lupus erythematosus and Sjogren's syndrome has provided a strong rationale to specifically target B cells. This review summarizes recent advances in the field of B cell depletion in systemic lupus erythematosus and Sjogren's syndrome. RECENT FINDINGS: Reports of successful B cell depletion therapy in refractory SLE have continued to surface over the last year. The accumulation of positive results therefore stands in stark contrast to the recent reports that two phase III randomized placebo controlled trials employing B cell depletion with rituximab in nonlupus and lupus nephritis (Explorer and Lunar, respectively) did not achieve. Multiple reasons, including trial design, limitations of outcome instruments and sort follow-up have been invoked to explain these disconcerting results. In the representative studies addressing B cell depletion in lupus in the last year, complete and partial remission in lupus nephritis has been achieved in 60-89% of cases. Improvements in the British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores were associated with decrease in anti-dsDNA and increase in complement levels. B cell depletion seemed quite efficacious also in pediatric SLE. While more definitive studies are still lacking for primary Sjogren's syndrome, incidental reports indicating potential efficacy have also been recently published. SUMMARY: Despite the disappointing results of Explorer and Lunar trials, other evidence continues to be published in support of the notion that B cell depletion could be useful for patients with refractory disease, including lupus nephritis, and antibody-mediated cytopenias, possibly in combination with other immunosuppressant medication. PMID- 19644379 TI - Six percent hydroxyethyl starch 130/0.4 impacts differently on blood glucose than 4% gelatine in a swine model of mixed acidaemia. AB - BACKGROUND: Tris-hydroxymethyl aminomethane can be used as a buffer in case of restricted ventilation, but hypoglycaemia is one adverse effect. The influence of a starch-based colloid [6% hydroxyethyl starch 130 kDa/0.4 (HES130)] vs. a gelatine-based colloid (4% polysuccinated gelatine) on blood glucose was investigated in a swine model of mixed acidaemia. METHODS: Continuous colloid infusion was done in anaesthetized pigs with exogenously induced mixed acidaemia, which was maintained for 3 h. Pigs (approximately 40 kg, n = 6 in each group) were randomized to HES130 or 4% gelatine infusion (4 ml kg h(-1)). Infusion of an acid solution and low tidal volume ventilation induced mixed acidaemia. Treatment of mixed acidaemia with tris-hydroxymethyl aminomethane buffer, which is known to induce hypoglycaemia, prolonged anaesthesia, and volume support challenged the control of blood glucose. Hypoglycaemia was treated by individually dosed infusion of 5% glucose in sterile water. RESULTS: Bolus infusion of HES130 led to a moderate peak in blood glucose in four pigs. Four pigs in the 4% gelatine group and three in the HES130 group needed glucose infusion to prevent a drop in blood glucose levels below the set threshold (4 mmol l(-1)). The total amount of the glucose infusion was significantly lower in the HES130 group compared with the 4% gelatine group (100 vs. 295 ml per pig, median, P < 0.05). Generally, the HES130 pigs required glucose at later time points during anaesthesia. The first HES130 pig needed 5% glucose 2 h later than the first 4% gelatine pig to prevent a drop of blood glucose below 4 mmol l(-1). CONCLUSION: Volume support impacted specifically on blood glucose in this porcine model. Thus, an additional control of blood glucose seems recommendable whenever a change in the volume support occurs. PMID- 19644380 TI - Drugs mediating myocardial protection. AB - The occurrence of myocardial ischaemia will result in either reversible or irreversible myocardial dysfunction. Even when revascularization is successful, some reperfusion injury may occur that transiently impairs myocardial function. Therefore, treatment should not only be directed towards prompt restoration of myocardial blood flow but measures should also be taken to prevent or alleviate the consequences of myocardial reperfusion injury. Over the years, various strategies have been developed. The present contribution reviews a number of these strategies focusing on pharmacological treatments that have been developed to address myocardial reperfusion injury. PMID- 19644381 TI - Characteristics and health outcomes of internally displaced population in unofficial rural self-settled camps after the 2005 Kashmir, Pakistan earthquake. AB - OBJECTIVES: No published study, to date, has examined the characteristics and health outcomes of natural disaster-affected populations in unofficial rural self settled internally displaced camps. By examining resident profiles in various unofficial rural displaced settlements after the 2005 Kashmir, Pakistan earthquake, this study aims to (i) describe the demographic and epidemiological characteristics of residents, (ii) compare their health outcomes with those of residents in official displaced camps, and (iii) highlight health needs and discuss implications for future disaster health relief operations. METHODS: A cross-sectional, cluster-sampling, face-to-face household survey was conducted in 167 households in various forms of internally displaced camps within a 185 km radius around Muzafarabad city 4 months after the 2005 Kashmir, Pakistan earthquake. Demographic characteristics, earthquake damage, and self-reported health outcomes were collected from these camps, and descriptive statistics were determined and chi significance comparison conducted. RESULTS: Significant differences in demographic characteristics and health outcomes were found according to the size of the unofficial internally displaced camps. Although residents of larger unofficial self-settled camps seemed to have similar characteristics and health outcomes to residents of official camps, those living in smaller unofficial camps had the largest average family size; received the least assistance and resources to sustain livelihood; had less access to information, medical service, and chronic disease medication for underlying medical problems; and worse self-reported health outcomes. CONCLUSION: The study results indicate that future post-earthquake medical relief operations should evaluate health needs and consider delivery of direct medical assistance to small unofficial self-settled camps in affected rural communities. PMID- 19644382 TI - Susceptibility to Simian immunodeficiency virus ex vivo predicts outcome of a prime-boost vaccine after SIVmac239 challenge. AB - BACKGROUND: Efficacy assessment of AIDS vaccines relies both on preclinically challenging immunized monkeys with simian immunodeficiency virus (SIV) or monitoring infection rates in large human trials. Although conventional parameters of vaccine-induced immune responses do not completely predict outcome, existing methods for testing cellular immunity are sophisticated and difficult to establish in resource-limited settings. METHODS: We have used virus replication kinetics (VVR) on ConA-stimulated peripheral blood mononuclear cells from rhesus monkeys immunized with DNA replication-defective adenovirus vector expressing various SIV genes, as an ex vivo model, to mimic the effects of different immune effector functions on viral infection. RESULTS: VVR was attenuated by the immunization and correlated 2 weeks after first boost, with the number of interferon gamma-secreting cells and T-cell noncytotoxic antiviral responses. Importantly, VVR on the day of challenge but not interferon gamma responses correlated with viremia and with memory CD4+ T-cell measurements after SIVmac239 challenge. Similarly, T-cell noncytotoxic antiviral responses on the day of challenge correlated directly with memory CD4 T cell and inversely with plasma viremia after challenge. CONCLUSIONS: VVR thus served as a better predictor of protective capacity of the vaccine regimen in these monkeys. We suggest that VVR be considered in the evaluation of candidate AIDS vaccines in humans. PMID- 19644384 TI - Development of HIV-1 drug resistance through 144 weeks in antiretroviral-naive subjects on emtricitabine, tenofovir disoproxil fumarate, and efavirenz compared with lamivudine/zidovudine and efavirenz in study GS-01-934. AB - Study 934 was an open-label, randomized Phase III study of emtricitabine + tenofovir DF + efavirenz (FTC + TDF + EFV) compared with lamivudine + zidovudine + efavirenz (3TC + ZDV + EFV) in antiretroviral therapy-naive HIV-1 infected subjects. Baseline genotyping revealed the presence of primary nonnucleoside reverse transcriptase inhibitor resistance (NNRTI-R) in 22 of 509 enrolled patients (4.3%, 11 subjects in each group). The 487 subjects without baseline NNRTI-R formed the primary efficacy population (modified intent-to-treat population). Through 144 weeks, 50 of 487 modified intent-to-treat subjects (FTC + TDF + EFV, n = 19; 3TC + ZDV + EFV, n = 31) were analyzed for resistance development after virologic failure. NNRTI-R, primarily the K103N mutation, was the most common form of resistance that developed in both groups. No subject on FTC + TDF + EFV developed the K65R mutation. Significantly fewer subjects on FTC + TDF + EFV compared with 3TC + ZDV + EFV developed the M184V/I mutation (two versus 10, respectively, P = 0.021). Thymidine analog mutations developed in two subjects on 3TC + ZDV + EFV. Subjects with baseline NRTI genotypic resistance (TAMs, n = 13) or non-B HIV-1 subtypes (n = 28) showed no evidence of reduced treatment responses in either group. Nine of 22 patients with baseline NNRTI-R experienced virologic failure (FTC + TDF + EFV, n = 4; 3TC + ZDV + EFV, n = 5); seven of nine developed M184V/I and/or additional NNRTI-R, but none developed K65R. Baseline NNRTI-R was significantly associated with virologic failure in both groups (P < 0.001). PMID- 19644385 TI - Tirofiban administration and percutaneous coronary intervention with stenting of saphenous vein graft thrombosis. AB - Distal embolization during percutaneous coronary intervention (PCI) of saphenous vein graft (SVG) lesions is associated with a high risk of myonecrosis and myocardial infarction. PCI guidelines advocate the use of distal embolic protection devices, when technically feasible, in patients undergoing PCI for SVG disease. To date, alternative management strategies are not fully investigated. We report a case of an 84-year-old male patient with acute coronary syndrome who underwent PCI for a quite occlusive stenosis of an SVG on the first diagonal branch of the left anterior descending artery complicated by wide endoluminal thrombosis with poor antegrade coronary blood flow and absent opacity of the distal first diagonal vessel. A strategy of delayed PCI after upstream, 48 h long tirofiban administration in order to obtain a thrombus burden reduction was decided. After tirofiban administration, a high-level thrombus resolution was obtained, with a significant improvement in coronary flow, and a successful PCI with stenting was performed. There was neither clinical nor instrumental periprocedural sign of ischemia, and the patient remained asymptomatic throughout his hospital stay. Preprocedural tirofiban administration followed by PCI with stenting of an SVG thrombotic lesion without a distal protection device might be a well-tolerated and feasible option for patients with degenerated SVG disease. Further studies are needed to further expand our findings. PMID- 19644386 TI - Unintended stent removal during fractured-guidewire removal in emergency angioplasty. AB - We report a case of removal of fractured guidewire and stent during an emergency angioplasty for an acute coronary syndrome. PMID- 19644383 TI - Clinical and genotypic findings in HIV-infected patients with the K65R mutation failing first-line antiretroviral therapy in Nigeria. AB - INTRODUCTION: The HIV-1 epidemic in African countries is largely due to non-B HIV 1 subtypes. Patterns and frequency of antiretroviral drug resistance mutations observed in these countries may differ from those in the developed world, where HIV-1 subtype B predominates. METHODS: HIV-1 subtype and drug resistance mutations were assayed among Nigerian patients with treatment failure on first line therapy (plasma HIV RNA >1000 copies/mL). Sequence analysis of the reverse transcriptase and protease gene revealed drug resistance mutations and HIV-1 viral subtype. Specific patterns of mutations and clinical characteristics are described in patients with the K65R mutation. RESULTS: Since 2005, 338 patients were evaluated. The most prevalent subtypes were CRF02_AG [152 of 338 (44.9%)] and G [128 of 338 (37.9%)]. Three hundred seven of 338 (90.8%) patients had previously received stavudine and/or zidovudine + lamivudine + efavirenz or nevirapine; 41 of 338 (12.1%) had received tenofovir (TDF). The most common nucleoside reverse transcriptase inhibitor mutations observed were M184V (301, 89.1%) and K70R (91, 26.9%). The K65R mutation was present in 37 of 338 patients (10.9%). The Q151M (P < 0.05), K219R, and T69del (P < 0.01) mutations were more common in patients with K65R who had not received TDF. CONCLUSIONS: The K65R mutation is increasingly recognized and is a challenging finding among patients with non-B HIV subtypes, whether or not they have been exposed to TDF. PMID- 19644388 TI - Time rate of blood pressure variation is associated with impaired renal function in hypertensive patients. AB - OBJECTIVES: The rate of blood pressure (BP) variation has been positively associated with intima-media thickness of common carotid arteries and left ventricular mass. We evaluated the association between the rate of BP variation derived from ambulatory blood pressure monitoring (ABPM) data analysis and impaired renal function. METHODS: Twenty-four-hour ABPM was performed in 803 untreated hypertensive patients. The estimated glomerular filtration rate (eGFR) was assessed using the abbreviated equation of the Modification Diet for Renal Disease study. Patients were divided into two groups: those with an eGFR less than 60 ml/min per 1.73 m(2) (group A) and those with an eGFR 60 ml/min per 1.73 m(2) or more (group B). RESULTS: The 24-h rate of systolic BP variation was significantly (P = 0.004) higher in group A [0.616 mmHg/min; 95% confidence interval (CI) 0.596-0.636] than in group B patients (0.585 mmHg/min; 95% CI 0.578 0.591), even after adjusting for baseline characteristics and ABPM parameters. In the entire study population, the multiple logistic regression models revealed the following variables as independent determinants of impaired renal function: age, male sex, office systolic BP and 24-h rate of systolic BP variation. In this model, the odds ratio for impaired renal function associated with each 0.1 mmHg/min increase in 24-h rate of systolic BP variation was 1.49 (95% CI 1.18 1.88, P = 0.001). CONCLUSION: The 24-h rate of SBP variation is independently associated with impaired renal function. Target-organ damage in hypertensive patients, in addition to BP levels, dipping status and BP variability, may also be related to a steeper rate of BP fluctuations. PMID- 19644387 TI - Autoregulation after ischaemic stroke. AB - OBJECTIVES: Absent outcome data from randomized clinical trials, management of hypertension in acute ischaemic stroke remains controversial. Data from human participants have failed to resolve the question whether cerebral blood flow (CBF) in the peri-infarct region will decrease due to impaired autoregulation when systemic mean arterial pressure (MAP) is rapidly reduced. METHODS: Nine participants, 1-11 days after hemispheric ischaemic stroke, with systolic blood pressure more than 145 mmHg, underwent baseline PET measurements of regional CBF. Intravenous nicardipine infusion was then used to rapidly reduce mean arterial pressure 16 +/- 7 mmHg and CBF measurement was repeated. RESULTS: Compared with the contralateral hemisphere, there were no significant differences in the percent change in CBF in the infarct (P = 0.43), peri-infarct region (P = 1.00) or remainder of the ipsilateral hemisphere (P = 0.50). Two participants showed CBF reductions of greater than 19% in both hemispheres. CONCLUSION: In this study, selective regional impairment of CBF autoregulation in the infarcted hemisphere to reduced systemic blood pressure was not a characteristic of acute cerebral infarction. Reductions in CBF did occur in some individuals, but it was bihemispheric phenomenon that likely was due to an upward shift of the autoregulatory curve as a consequence of chronic hypertension. These results indicate individual monitoring of changes in global CBF, such as with bedside transcranial Doppler, may be useful to determine individual safe limits when MAP is lowered in the setting of acute ischaemic stroke. The benefit of such an approach can only be demonstrated by clinical trials demonstrating improved patient outcome. PMID- 19644389 TI - Hydrogen sulfide derived from periadventitial adipose tissue is a vasodilator. AB - BACKGROUND: Recently, periadventitial adipose tissue (PAT) was found to secrete bioactive factors playing an important role in the regulation of vascular tension. Hydrogen sulfide (H(2)S), a novel cardiovascular gasotransmitter, relaxes vessels through the K(ATP) channel in a calcium-dependent and endothelial independent manner. METHODS: We first identified the endogenous H(2)S-generated key enzyme cystathionase (CSE) expressed in adipocytes of PAT and H(2)S released from PAT in rats. RESULTS: The CSE inhibitors DL-propargylglycine and/or beta cyano-L-alanine largely blocked the vasorelaxing effects on aorta rings (removed adventitia), induced by PAT, the culture medium of PAT or isolated adipocytes from PAT. Phenylephrine, serotonin and angiotensin II inhibited endogenous H(2)S production from the aortic medium but increased its release from PAT. Endogenous H(2)S generated in the aorta and PAT was decreased but the level of CSE protein was increased with the aging of rats. In rats with hypertension induced by abdominal aortic banding, H(2)S generation and CSE protein expression were significantly increased in PAT but not aortic tissues. Transplanting PAT into periadventitia of stenotic aortas ameliorated the elevated arterial blood pressure and decreased angiotensin II level in aorta. CONCLUSION: These results suggested PAT could endogenously generate H(2)S, which might act as an adipocyte derived relaxing factor and contribute to the pathogenesis of hypertension. PMID- 19644390 TI - The value of certification in infusion nursing. PMID- 19644392 TI - Gallbladder dysfunction in cholesterol ester storage disease. PMID- 19644391 TI - Ethnic and sex differences in the association between metabolic syndrome and suspected nonalcoholic fatty liver disease in a nationally representative sample of US adolescents. AB - OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized among overweight adolescents. Metabolic syndrome often coexists with NAFLD in adults. This study aimed to determine whether, in US adolescents, metabolic syndrome increases the odds of alanine aminotransferase (ALT)>40 U/L, a surrogate for NAFLD. MATERIALS AND METHODS: A cross-sectional study of the association between metabolic syndrome and ALT>40 U/L was undertaken in a sample of 12- to 19 year-olds from the National Health and Nutrition Examination Survey, 1999 to 2002, representative of the US adolescent population. Subjects were excluded for incomplete data, pregnancy, steroid or hepatotoxic drug use, cholestasis or viral hepatitis, and alcohol intake. The metabolic syndrome was defined by adult criteria adapted for pediatric body size and blood pressure. The association of metabolic syndrome with ALT>40 U/L, effect modifiers, and confounders were analyzed using National Health and Nutrition Examination Survey sampling weights. RESULTS: Of 4902 adolescents, the 1323 included were similar to the excluded ones, except for the important variable sex (55% vs 49% male, P=0.03, respectively). The metabolic syndrome was associated with ALT>40 U/L (odds ratio [OR] 16.7, confidence interval [CI] 6.2-45.1, P<0.001) with significant interaction by sex: OR 20.4 (CI 6.2-66.7, P<0.001) for males versus 3.1 (CI 0.4 25.1, P=0.3) for females. Further stratification of males suggested interaction by ethnicity: OR 5.0 (CI 1.3-19.0, P=0.02) for Hispanics versus 34.3 (CI 7.61 55.4, P<0.001) for non-Hispanics. Among Hispanic males, adjustment for body mass index z score explained the association (OR 0.6; CI 0.1-2.9, P=0.5), whereas among non-Hispanic males, the association remained after adjustment for BMIz (OR 11.1; CI 3.2-38.0, P<0.001). CONCLUSIONS: Metabolic syndrome is strongly associated with ALT>40 U/L in US male adolescents. Body mass index z score explained this association among Hispanics, but not among non-Hispanic males. Significant sex and ethnic differences exist in the association of pediatric metabolic syndrome with elevated ALT. PMID- 19644393 TI - VP7 and VP4 sequence analyses of rotavirus strains from Italian children with viraemia and acute diarrhoea. AB - Information on genotypes or variants associated with systemic rotavirus infection is lacking. Seven viraemic children with acute rotavirus diarrhoea were evaluated. All faecal strains were genotyped (5 G1P[8] type, 1 G9P[8], 1 G1 G4P[8]). Only 3 of 7 blood strains were typeable (G1P[8], G4P8, and G1P[ND]). A discrepancy between faecal and blood VP7 amino acid sequences (Ser-->Asp at position 94) was found in the first child. Two amino acid substitutions (Ile- >Val and Asn-->Ser at position 106 and 113) in the VP4 sequences were demonstrated in the second child. Complete correspondence was found in the third child. All of the observed amino acid substitutions may be involved in rotavirus neutralisation. We speculate that during co-infection by multiple strains, a preferential extraintestinal dissemination of some variants may occur, possibly because of differential viral characteristics. PMID- 19644394 TI - Impact of anxiety in the puerperium on breast-feeding outcomes: role of parity. AB - OBJECTIVE: : Studies in animals indicate that stress and anxiety can depress lactation, but there is much less information available concerning humans. We aimed to determine whether maternal anxiety in puerperium, potentially exacerbated by the primiparity inexperience, has a negative impact on breast feeding outcomes. SUBJECTS AND METHODS: : The state-trait anxiety inventory Y form (Spielberger, 1983) was administered to a total of 204 mothers, 101 primiparae, and 103 pluriparae on the third to fourth day postpartum. RESULTS: : We found that primiparae had state anxiety (T) scores significantly higher than pluriparae (44.57 +/- 5.85 vs 43.28 +/- 7.10, P = 0.03). Increased state anxiety levels impaired breast-feeding success. In addition, in the logistic regression analysis model used to assess factors predictive of breast-feeding longer than 3 months, maternal state anxiety was the most significant risk factor (odds ratio 0.99; 0.88-0.98, P < 0.01). CONCLUSIONS: : In the puerperium, anxiety, potentially exacerbated by primiparae inexperience, is associated with impaired lactation. Alleviating maternal anxiety could be beneficial for stimulating breast-feeding in more vulnerable women. PMID- 19644395 TI - Comparison of clinical associations and laboratory abnormalities in children with moderate and severe dehydration. AB - OBJECTIVES: To search for possible early clinical associations and laboratory abnormalities in children with severe dehydration in northern Jordan. PATIENTS AND METHODS: We prospectively evaluated 251 children with acute gastroenteritis. Dehydration assessment was done following a known clinical scheme. Probable clinical associations and laboratory abnormalities were examined against the preassigned dehydration status. RESULTS: Children with severe dehydration had significantly more hypernatremia and hyperkalemia, less isonatremia, and higher mean levels of urea, creatinine, and glucose (P < 0.005). Receiver operating characteristic curves showed statistically significant area under the curve values for laboratory variables. These area under the curve values were 0.991 (95% confidence interval [CI] 0.980-1.001) for serum urea, 0.862 (95% CI 0.746 0.978) for sodium, 0.850 (95% CI 0.751-0.949) for creatinine, 0.69 (95% CI 0.555 0.824) for potassium, and 0.684 (95% CI 0.574-0.795) for glucose (P < 0.05 for all). Certain independent serum cutoff levels of urea, creatinine, sodium, glucose, and potassium had high negative predictive value (100%), whereas other cutoff values for each, except potassium, had high positive predictive value (100%) for severe dehydration. Historic clinical characteristics of patients did not correlate to dehydration degree. CONCLUSIONS: Serum urea, creatinine, sodium, potassium, and glucose were useful independently in augmenting clinical examination to diagnose the degree of dehydration status among children presenting with gastroenteritis. Serum urea performed the best among all. On the contrary, none of the examined historical clinical patterns could be correlated to the dehydration status. Larger and multicenter studies are needed to validate our results and to examine their impact on final outcomes. PMID- 19644396 TI - Pro- and prebiotic supplementation induces a transient reduction in hemoglobin concentration in infants. AB - OBJECTIVES: : Regarding safety, we investigated the effect of prenatal probiotic and 6 months of pro- and prebiotic supplementation of infants on their hematologic values at 6 months and 2 years and factors affecting these values. PATIENTS AND METHODS: : In a prospective randomized controlled probiotic intervention trial in infants at high risk for allergy, we obtained blood samples consecutively from 98 infants at 6 months and from 658 children at 2 years to measure hematologic values. We collected fecal samples at 3 and 6 months to measure immunologic development by calprotectin, alpha-1-antitrypsin, tumor necrosis factor-alpha, and immunoglobulin A. RESULTS: : At 6 months, infants in the probiotic group had significantly lower hemoglobin (Hb) values than did the placebo group, mean (SD): 119.8 g/L (6.3) versus 123.3 g/L (8.4), P = 0.025. Adjustment for factors that might affect Hb values (breast-feeding duration, solid-food introduction, and sex), revealed no need for adjustment. A significant negative correlation emerged between Hb values at 6 months and fecal calprotectin at age 3 months r = -0.301, P = 0.009, which was affected neither by breast feeding, sex, nor study group. At 2 years, hematologic values in both groups became similar. CONCLUSIONS: : Probiotics cause a gut mucosal inflammation with decreased Hb values during intervention, corrected after halting the supplementation. PMID- 19644397 TI - Celiac disease: predictors of compliance with a gluten-free diet in adolescents and young adults. AB - AIMS: To identify risk as well as protective factors related to compliance with the gluten-free diet in a cohort of teenagers with celiac disease (CD). PATIENTS AND METHODS: Two hundred four patients with CD (European Society for Pediatric Gastroenterology, Hepatology, and Nutrition criteria) older than or equal to 13 years and residents of Campania (southern Italy) were enrolled in the study. Patients underwent clinical examination and blood sampling, and were interviewed about school performance, social relationships, family integration, smoking habit, and compliance with a gluten-free diet. Anti-tissue transglutaminase antibodies were assayed with an enzyme-linked immunosorbent assay. RESULTS: One hundred fifty of 204 (73.5%) reported no dietary transgressions, and 54 of 204 (26.5%) reported occasional or frequent transgressions. During the previous month 29 of 54 (53.7%) poor compliers ate from 0.001 to 1 g of gluten per day, 14 (25.9%) from 1 to 5 g, and 11 (20.4%) more than 5 g. The daily intake of gluten was significantly related to anti-tissue transglutaminase antibodies (chi2 = 38.872, P = 0.000). Height was below the third percentile in 19 of 204 (9.3%), and weight was above the 97th percentile in 20 of 204 (9.8%). Diet compliance did not seem to influence the weight and height. One hundred eleven of 150 good compliers (74%) and 31 of 54 (57.4%) poor compliers were asymptomatic. Most patients reported good family relationships (88.7%), social relationships (91.2%), and school integration (88.2%). Alternatively, 54% of patients reported some limitation in their social life. Compliance was good in patients who reported excellent school integration (83%) and social relationships (81%). CONCLUSION: Optimal school integration significantly contributes to the likelihood of good compliance. A better understanding within the school environment about CD-related issues could improve motivation to adhere to a gluten-free diet. PMID- 19644398 TI - Parenteral lipid emulsions based on olive oil compared with soybean oil in preterm (<28 weeks' gestation) neonates: a randomised controlled trial. AB - BACKGROUND: : New olive oil-based (OL) lipid emulsions (olive:soy oil = 4:1) have lower polyunsaturated fatty acid (PUFA) (20% vs 60%) and higher vitamin E content (an antioxidant) compared with traditional soybean oil (SO) emulsions. OBJECTIVE: : Compare efficacy and safety of OL with SO emulsions in preterm neonates (<28 weeks) at high risk for oxidative stress. PATIENTS AND METHODS: : Preterm neonates (gestation 23-<28 weeks) were randomised to receive OL or SO emulsion for 5 days using a standard protocol in a tertiary perinatal centre (King Edward Memorial Hospital for Women, Perth, Western Australia). Investigators and outcome assessors were masked to allocation. Plasma F2-isoprostanes (lipid peroxidation marker), plasma, and red blood cell fatty acids were measured before and after the study. Safety was monitored by liver function tests. RESULTS: : Forty-four of 50 participants (OL-23, SO-21) completed the study. Both emulsions were well tolerated with no significant adverse events. F2-isoprostane levels were comparable at baseline and study end. Oleic and linoleic acid levels were significantly high on day 6 in OL and SO groups, respectively. Long-chain PUFA levels were similar between groups despite the lower PUFA content of OL. The olive oil-based group had significantly higher levels of C18:4n-3, suggesting Delta6-desaturase enzyme inhibition in the SO group. CONCLUSIONS: : Olive oil based emulsion was safe and well tolerated by preterm neonates. Similar long chain PUFA levels were achieved in the OL group despite significantly lower amount of PUFA content; however, there was no difference in lipid peroxidation (F2-isoprostane levels). Large trials are needed to confirm these benefits. PMID- 19644399 TI - Teaching and tomorrow: a novel recruitment program for a pediatric subspecialty. AB - OBJECTIVES: : In 2001, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition created Teaching and Tomorrow, a novel pediatric subspecialty recruitment program to provide prospective fellows the opportunity to participate in the society's annual meeting and to interact with current trainees and members. The aims of this report are to describe participant survey data from the first 4 years of the program and to explore potential influences of participation on outcomes and proposed career choices. MATERIALS AND METHODS: : Pre- and postprogram surveys were administered during opening and closing breakfast meetings, respectively, to ascertain demographics, certainty of career intent, factors influencing choice of specialty, and anticipated benefits from participation. RESULTS: : Among 189 applications, 107 (57%) participated and 107 (57%) matriculated into gastroenterology(GI) fellowship. The matriculation rate was similar between participants and nonparticipants. Among applicants who became GI fellows, there was a 42% lower odds of being female than male (OR 0.42; chi = 8.48, P < 0.01). Among participants who completed both pre- and postprogram surveys (n = 91) and who reported certainty about entering GI both before and after, 79% entered GI fellowship. Among participants who reported uncertainty about entering GI both before and after, 8% entered GI. More participants were interested in jobs as clinician-investigators and funded clinical or translational investigators. CONCLUSIONS: : In a selected population of pediatric residents with high interest in pediatric gastroenterology, there was no difference in the matriculation rate into pediatric GI fellowship training among those who participated compared with those who did not. However, those who eventually matriculated had a higher odds of being male than female. There was a high retention rate of participants who were initially certain and a modest conversion rate of those who were initially uncertain about pursuing a career in pediatric GI. PMID- 19644400 TI - Prevalence of metabolic bone disease in children with celiac disease is independent of symptoms at diagnosis. AB - OBJECTIVES: : Given dietary gluten exposure, growing children with celiac disease may experience malabsorption of nutrients, negatively affecting bone health. The purpose of this study was to determine the prevalence of low bone mass in children with celiac disease, according to the presence of symptoms at diagnosis. MATERIALS AND METHODS: : A retrospective chart review of the Stollery Children's Hospital Celiac Clinic charts (April 1989-September 2007) was conducted. Bone mineral density (BMD) of the spine was measured using dual energy x-ray absorptiometry. Demographics, symptoms at presentation, and anthropometric and biochemical data relevant to bone health were recorded. RESULTS: : Seventy-four children (9.6 +/- 3.7 years; range 3.3-16.0 years) were included. Lumbar BMD z scores more than or equal to -1 were observed in 58 cases (65%), z scores below 1 but above -2 were observed in 14 cases (19%) and z scores less than or equal to -2 were observed in 12 cases (16%). There was no significant difference in mean lumbar BMD z scores between symptomatic and asymptomatic children (P = 0.34). When adjusted for bone age and bone surface area, BMD lumbar z score was inversely correlated with age at diagnosis (P < 0.05). CONCLUSIONS: : An equivalent reduction in spine bone mass was observed in children with celiac disease at diagnosis regardless of the presence of symptoms. Delayed diagnosis of children with celiac disease may increase the risk of adult osteoporosis. Appropriate screening of children at risk of celiac disease for the purpose of early diagnosis, as well as routine evaluation of bone mineral density in such children, are important to prevent long-term complications associated with poor bone health. PMID- 19644401 TI - No association between protein C levels and bacteremia in children with febrile neutropenia. AB - BACKGROUND: Little is known about protein C levels and outcomes of pediatric febrile neutropenia. The primary aim was to evaluate the relationship between markers of activated coagulation including protein C levels and bacteremia in pediatric oncology patients with febrile neutropenia. METHODS: In this prospective cohort study, we collected a blood specimen from pediatric oncology patients who were admitted to a tertiary care hospital between October 2, 2002 and February 3, 2006 with febrile neutropenia. Levels of protein C, soluble thrombomodulin, soluble endothelial protein C receptor, thrombin-antithrombin complex, fibrinogen degradation products and activated protein C were measured. Associations between markers of activated coagulation and bacteremia were examined using univariate logistic regression. RESULTS: Of the 73 evaluable patients, 10 had bacteremia. None of the above measured markers of activated coagulation were associated with bacteremia. More specifically, the median level of protein C in those with bacteremia was 0.64 U/mL (interquartile range: 0.58 to 0.72) in comparison with the median level in those without bacteremia of 0.73 U/mL (interquartile range: 0.61 to 0.92), odds ratio 0.18 (95% confidence interval 0.00 to 8.33); P=0.38. CONCLUSIONS: Protein C levels do not differ between pediatric febrile neutropenic patients with and without bacteremia. PMID- 19644402 TI - Risk factors for typhlitis in pediatric patients with cancer. AB - Data on the risk factors for typhlitis in children with cancer are limited. The aim of the study was to define the epidemiologic and clinical features of typhlitis and to elucidate predisposing factors for its development. The medical records of pediatric patients with cancer who were diagnosed with typhlitis from 1995 to 2005 were reviewed for clinical, laboratory, and imaging findings. The results were compared with a group of patients with cancer but without typhlitis who were hospitalized during the same period. Of the 843 cancer patients, 42 (5%) had episodes of typhlitis; 32 of them (76%) were being treated for hematologic malignancies. The incidence was highest in patients with Burkitt's lymphoma (15%) and acute myeloblastic leukemia (12%). Work-up included abdominal x-ray in all patients; abdominal ultrasonography and computed tomography were performed in 23% and 11% of patients, respectively. No cases were missed by plain x-ray when compared with computed tomography and ultrasonography. The typhlitis was treated without surgery and survival was 100%. On multivariate analysis, mucositis [odds ratio (OR) = 30.7], stem cell transplantation (OR = 58.9), and receipt of chemotherapy in the previous 2 weeks (OR = 12.9) were significantly associated with the occurrence of typhlitis. We conclude that most children with typhlitis may be treated without surgery in most cases with favorable outcome. A high index of suspicion may be warranted in patients after stem cell transplantation or chemotherapy and patients with mucositis. PMID- 19644406 TI - The effects of coenzyme Q10 supplementation on performance during repeated bouts of supramaximal exercise in sedentary men. AB - The objective of this study was to determine the effects of oral coenzyme Q10 (CoQ10) supplementation on performance during repeated bouts of supramaximal exercise. This randomized, double-blind, crossover study was composed of two 8 week periods of supplementation with either 100 mg.d(-1) CoQ10 or placebo. Fifteen healthy and sedentary men participated in the study. Five Wingate tests (WTs) with 75 g.kg(-1) body weight load with 2-minute intervals between tests were performed 3 times at baseline, after CoQ10, or placebo supplementation during the study period. Peak power (PP), mean power (MP), and fatigue index were calculated. During the 5 WTs, PP and MP tended to decrease and fatigue index tended to increase in all groups (p < 0.05). Peak power decreased with CoQ10 and placebo supplementation during the WT1, WT2, and WT2 (p < 0.05). Mean power increased only with CoQ10 supplementation during the WT5. Fatigue indexes decreased with CoQ10 supplementation, but these decreases did not differ from that seen with placebo supplementation. According to these results, CoQ10 may show performance-enhancing effects during the repeated bouts of supramaximal exercises and CoQ10 might be used as ergogenic aid. PMID- 19644407 TI - Variability of competitive performance assessment of elite surfboard riders. AB - No previous study has examined the reliability of competitive performance in a subjective (i.e., externally judged) sport such as surfboard riding (i.e., surfing). This reliability is important for the athletes' competitive success prospects and for their support crew interested in strategies or factors that might influence performance. We have therefore determined the typical variation in competitive performance of elite surfers. We obtained official scores (points) for the 11 competitions of the World Championship Tour (WCT). We analyzed 46 male surfers who entered 6 or more such events held in 1 competitive season. To further explore the variability of competitive performance, a separate analysis was performed on official performance points for 182 male surfers who competed on 3 consecutive events within the World Qualifying Series (WQS). Our measure of variability was the typical error (i.e., within-subject variation) expressed as a Cohen effect size (ES) of log-transformed final scores obtained for the surfers after finishing each event. Performance scores in surfing competition showed moderate to large variability. For the 11 WCT events and the 3 WQS events, the ES ranged from 0.72 to 1.01 (n = 46) and from 0.61 to 1.04 (n = 182), respectively. In conclusion, surfers showed much larger variability in performance than previously reported for sports such as running, swimming, or weightlifting. Thus, competition outcomes are largely unpredictable. Considering this large variability in competitive performance, a practitioner monitoring an individual athlete will have little chances of noticing small to moderate changes in competitive performance between consecutive events. Several competitions in a row appear to be needed for tracking the smallest worthwhile performance changes in competition scores as a result of training or other interventions. PMID- 19644403 TI - Etiology and clinical course of febrile neutropenia in children with cancer. AB - BACKGROUND: The etiology, clinical course, and outcome of fever and neutropenia (FN) in children with cancer using the current FN guidelines and diagnostic resources in the United States have not been well described. PATIENTS AND METHODS: Medical records of a randomly selected FN episode per patient during 2004-2005 at a pediatric oncology center were reviewed. Patients were managed as per institutional FN guidelines and blood cultures collected in continuously read BACTEC bottles. RESULTS: Of 337 FN episodes, infection was proven in 86 (25%) and probable in 75 (22%). In all, 177 episodes (53%) were judged fever of unknown origin (FUO). Bacteremia accounted for most (41) of the proven bacterial episodes, with viridans streptococci (13), Pseudomonas spp. (6) and Escherichia coli (6) the most frequently isolated organisms. The median time to positivity of blood cultures was 12 hours (range, 5.4-143.7) with 93% positive within 24 hours of incubation. Viral pathogens were identified in 29 (34%) episodes. Compared with other patients, those with FUO had shorter median duration of fever (0.5 vs. 2.0 d; P<0.0001) and hospitalization (3 vs. 6 d; P<0.0001), longer median duration since last chemotherapy (6.0 vs. 4.0 d; P=0.01), and were less likely to have a diagnosis of acute myelogenous leukemia (11% vs. 22%; P=0.009) or develop a clinical complication (5.1% vs. 24.4%; P<0.0001). CONCLUSIONS: Despite currently available diagnostic resources, the majority of patients with FN have FUO marked by a low rate of clinical complications and no infection-related mortality. Emergence of viridans streptococci as the most common blood isolate has affected FN treatment recommendations. Study findings will help further development of strategies for risk stratified management of fever with neutropenia in pediatric patients. PMID- 19644408 TI - Permissive hypercapnia, instituted via reduction of pressure amplitude on pulmonary tissue protection during high frequency oscillatory ventilation, is not protective in a rat model of acid-induced lung injury. AB - BACKGROUND: Assuming that HFOV (high frequency oscillatory ventilation) with hypercapnia could be more protective than normocapnia, in a rat model of lung injury, we evaluated the effect of hypercapnic acidosis during HFOV. MATERIAL/METHODS: After inducing lung injury by intratracheal instillation of hydrochloric acid (HCl), we randomly assigned the animals to two groups: in the hypercapnia group (n=9), airway pressure amplitude (Pamp) was titrated to achieve PaCO2 greater than 80 mmHg; in the normocapnia group (n=9), Pamp was titrated to achieve PaCO2 less than 50 mmHg. Hemodynamics, histology, wet-to-dry ratio and inflammatory cytokines were evaluated after all the animals had received HFOV for 5 h. RESULTS: While the right-lung wet-to-dry ratio in the hypercapnia group was statistically significantly lower than in the normocapnia group (7.70+/-1.31 vs. 8.59+/-0.66, p<0.05), no statistically significant intergroup differences were found for blood pressure, heart rate, alveolar-arterial oxygen gradient, levels of cytokines (TNF-alpha, IL-6 and CINC-1) in bronchoalveolar lavage fluid and serum, and lung histological injury scores. CONCLUSIONS: Although edema formation was less pronounced in the hypercapnia group, we found no increased numbers of inflammatory cytokines or general histological evidence to suggest that permissive hypercapnia during HFOV was protective. PMID- 19644409 TI - Combining "open-lung" ventilation and arteriovenous extracorporeal lung assist: influence of different tidal volumes on gas exchange in experimental lung failure. AB - BACKGROUND: Although low-tidal ventilation may reduce mortality in acute respiratory distress syndrome (ARDS), it can also result in severe respiratory acidosis and lung derecruitment. This study tested the hypothesis that combining "open-lung" ventilation and arteriovenous extracorporeal lung assist (av-ECLA) allows for maximal tidal volume (VT) reduction without the development of decompensated respiratory acidosis and impairment of oxygenation. MATERIAL/METHODS: After induction of ARDS in eight female pigs (56.1+/-3.2 kg), lung recruitment was performed and positive end-expiratory pressure was set 3 cmH2O above the lower inflection point of the pressure-volume curve. All animals were ventilated in the pressure-controlled ventilation mode (PCV) with VTs ranging from 0-8 ml/kg. At each VT, gas exchange and hemodynamic measurements were obtained with the av-ECLA circuit clamped and declamped. With each declamping, the gas flow through the membrane lung was set to 10 l of oxygen/min. The respiratory rate was adjusted to maintain normocapnia, but limited to 40/min. RESULTS: After lung recruitment, oxygenation remained significantly improved although VTs were minimized to 0 ml/kg (p<0.05). PaO2 was significantly improved during PCV and av-ECLA compared with PCV alone at VTs <4 ml/kg (p<0.05). With VT <6 ml/kg, severe acidosis could only be avoided if PCV was combined with av-ECLA. CONCLUSIONS: Due to sufficient CO2 elimination during av-ECLA, the VTs could be reduced to 0-2 ml/kg without the risk of decompensated respiratory acidosis. It was also shown that the "open-lung" strategy chosen was associated with sustained improvements in oxygenation, even though VTs were minimized. PMID- 19644410 TI - Focal adhesion kinase (FAK) immunocytochemical expression in breast ductal invasive carcinoma (DIC): correlation with clinicopathological parameters and tumor proliferative capacity. AB - BACKGROUND: Focal adhesion kinase (FAK) is an enzyme of the tyrosine kinase group linked to signaling pathways between cells and the extracellular matrix. In tumor cells in vitro, FAK expression correlated with their ability for invasion and metastasis. Additionally, in vivo FAK has been implicated in malignant transformation and disease progression. The aim of the present study was to evaluate the clinical significance of FAK expression in breast ductal invasive carcinoma (DIC). MATERIAL/METHODS: Immunocytochemical techniques were used to assess FAK expression on cytological material obtained from 73 patients with breast DIC. FAK expression status (positivity, overexpression, and intensity of immunostaining) was compared with clinicopathological parameters and the tumor cells' proliferative capacity. RESULTS: Sixty-four of the 73 DIC cases (88%) were FAK positive and FAK protein overexpression was noted in 15 of the 73 (21%). In the DIC cases examined, FAK positivity correlated with tumor size (p=0.016) and FAK protein overexpression with tumor histological grade (p=0.034) and the tumor cells' proliferative capacity (p=0.003). The intensity of FAK protein staining did not significantly correlate with any of the examined clinicopathological parameters. CONCLUSIONS: In breast DIC it becomes evident that FAK protein positivity and overexpression correlate with important clinicopathological parameters. Further molecular and clinical studies are required to delineate the significance of FAK as a factor for better prognosis and management of breast cancer patients. PMID- 19644411 TI - Antiproliferative effects of preservative-free triamcinolone acetonide on cultured human retinal pigment epithelial cells. AB - BACKGROUND: The control of retinal pigment epithelial cell proliferation is an essential factor in the clinical management of proliferative vitreoretinopathy (PVR). Factors inhibiting PVR without toxic potential are of special interest in ophthalmology. The aim of the study was to investigate the antiproliferative and cytotoxic effects of a preservative-free triamcinolone acetonide (PFTA) suspension on a human retinal pigment epithelial (ARPE19) cell line in vitro. MATERIAL/METHODS: ARPE19 cells (immortal non-transformed cells from a human donor) were seeded and incubated in vitro with increasing concentrations of PFTA (0.01-1 mg/ml). After 1, 3, and 7 days, cellular proliferative activity was assessed by 5'-bromo-2'-deoxyuridine (BrdU) incorporation into cellular DNA and cell proliferation was determined using the 3-(4,5-dimethylthiazol-2yl)-2,5 diphenyltetrazolium bromide (MTT) assay. To determine cytotoxicity, ARPE19 cells were grown to confluence and subsequently cultured in serum-deficient medium to ensure a static milieu and the MTT test was performed after 24 hours of incubation with PFTA. Cell recovery after transient PFTA exposure was also compared with continuous exposure after 7 days. RESULTS: PFTA inhibits ARPE19 cell proliferation in a dose-dependent manner. Significant inhibition of cell proliferation was observed on the first day of the study at 1, 0.1, and 0.01 mg/ml PFTA and significant reductions in ARPE19 cells were noted for 1 and 0.1 mg/ml PFTA. Proliferation was resumed in all ARPE19 cultures and was dependent on the initial PFTA concentration. PFTA did not cause a cytotoxic effect. CONCLUSIONS: PFTA influences the proliferation of vital ARPE19 cells in a reversible manner without cytotoxic effect. PMID- 19644413 TI - Coronary flow velocity reserve in patients with ischemic stroke. AB - BACKGROUND: The usefulness and safety of coronary flow velocity reserve (CFVR) in patients with acute ischemic stroke were examined. MATERIAL/METHODS: We studied 36 patients with acute ischemic stroke. Transthoracic Doppler recording of diastolic coronary flow velocity was performed at baseline and after maximal vasodilation by adenosine triphosphate infusion. CFVR was defined as the ratio of hyperemic to basal averaged peak coronary flow velocity. Patients with CFVR <2.1 were assigned in Positive group. RESULTS: Fourteen patients had impaired CFVR. Age over 70 years and arterial stenosis were more frequent in the Positive group. In the Positive group, 11 underwent coronary angiography; 9 of them had some abnormal findings. The positive predictive value of impaired CFVR for detecting coronary artery disease was 82%. CONCLUSIONS: CFVR is useful for detecting coronary heart disease in stroke patients, and may be indicated in patients over 70 years or in those with arterial stenosis. PMID- 19644412 TI - Polymorphisms in the vitamin D receptor gene and risk of lung cancer. AB - BACKGROUND: Differences between the individual variations in DNA may modulate lung cancer process. Many studies reported that Vitamin D Receptor (VDR) gene polymorphisms may influence the cancer risk due to their antiproliferative, antiangiogenic, antimetastatic and apoptotic effects. MATERIAL/METHODS: The genotype and haplotype frequencies of three polymorphisms of VDR, i.e. TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232), were studied using PCR-RFLP in 137 patients with lung cancer and 156 controls. RESULTS: Differences were observed in genotype (P=0.024) and allele (P=0.011) frequencies of TaqI polymorphism due to the "T" allele. Furthermore, compared with the "tt" genotype, the odds ratio for the "TT" genotype increased 2.24 times (95%CI=1.05-4.77, P=0.037). Comparing cases and controls, smoking habit (P=0.012) and gender distribution (P=0.005) were found to increase the risk of lung cancer in patients with "TT" homozygotes, demonstrating the role of gene-environment interaction in lung cancer. In addition, when age and gender within the case group only were evaluated in relation to genotype, the adjusted odds ratios for the "TT" genotype increased 2.20 times (95%CI=1.01-4.78, P=0.047) for age and 2.24 times (95%CI=1.05-4.80, P=0.037) for gender. However, no differences were observed for the distribution of variant genotypes of the BsmI and ApaI polymorphisms (P>0.05). To evaluate the joint effects of these polymorphisms, haplotype analysis was performed which showed that the haplotype baT was associated with higher lung cancer risk compared with the most common haplotype BAt (P=0.026). CONCLUSIONS: This is perhaps the first study suggesting that TaqI polymorphism of the VDR gene might be a risk factor for lung cancer and that age, gender, and smoking habit could have an impact on lung cancer risk. PMID- 19644414 TI - Relationship between haplotypes of KCNN4 gene and susceptibility to human vascular diseases in Japanese. AB - BACKGROUND: Human vascular diseases such as myocardial infarction (MI) and cerebral infarction (CI) are thought to be affected by several environmental factors and genetic variants. It has been suggested that the expression of the KCNN4 calcium-activated potassium channel is associated with the developing vascular smooth-muscle cells of human neointimal hyperplasia. The aim of this study was to investigate the relationship between single-nucleotide polymorphisms (SNPs) in the human KCNN4 gene or haplotypes and the incidence of MI or CI in Japanese. MATERIAL/METHODS: Three hundred thirteen MI and 176 CI patients with 290 controls were enrolled in two independent case-control studies that examined the use of a haplotype-based case-control study involving five SNPs of the human KCNN4 gene (rs670950, rs2306801, rs2306799, rs347519, and rs3786954). RESULTS: There were significant differences between the MI and control groups in the overall distribution of genotypes and dominant or recessive models of rs670950, rs2306799, and rs3786954. Multiple logistic regression analyses revealed that even after adjusting for confounding factors (odds ratio: 1.96), the frequency of the G/G genotype of rs2306799 in the MI group was significantly higher than in the control group (p=0.005). Furthermore, the G-T-A haplotype of rs2306799 rs347519-rs3786954 was significantly more frequent in the MI (88.8%) than in the control group (83.6%). CONCLUSIONS: The specific SNPs and haplotypes in the KCNN4 gene showed significant differences between MI and control patients. These results indicate that these polymorphisms and haplotypes could be genetic markers for MI. PMID- 19644415 TI - Ultrasonographic assessment of the prevalence of cholelithiasis and biliary sludge in beta-thalassemia patients in Iran. AB - BACKGROUND: Thalassemia is a hereditary disease related to hemoglobin synthesis. The aim of this study was to determine the prevalence of gallbladder sludge and stones in beta-thalassemic children. MATERIAL/METHODS: One hundred fifty-three beta-thalassemia patients on a long-term transfusion/chelation program were selected by a cluster randomized method and were evaluated ultrasonographically for the presence of sludge and biliary lithiasis. Relationships between the prevalence of gallbladder sludge and stones with age, sex, age at the start and the frequency of transfusion, mean pretransfusion Hb and ferritin levels, age at start of deferoxamine injection, splenectomy, and degree of splenomegaly were evaluated statistically. RESULTS: Gallstones and biliary sludge were detected in 12.4% and 13.1% of the patients, respectively. There was a significant increase in the prevalence of gallstones with increasing age, transfusion periods of <21 days, severe splenomegaly, splenectomy, and deferoxamine injection started after 5 years of age. Such a relationship was not detected for hemoglobin and ferritin levels. Multiple logistic regression analysis revealed that the frequency of transfusions and age at the start of deferoxamine injections were the only positive factors that predicted the subsequent development of gallstones. CONCLUSIONS: Longer survival of beta-thalassemic patients leads to a higher prevalence gallbladder sludge and stones. Therefore a proper follow-up of patients with abdominal ultrasonography and improving the transfusion/chelation program should be mandatory. PMID- 19644416 TI - New clinical insights for transiently evoked otoacoustic emission protocols. AB - BACKGROUND: The objective of the study was to optimize the area of a time frequency analysis and then investigate any stable patterns in the time-frequency structure of otoacoustic emissions in a population of 152 healthy adults sampled over one year. MATERIAL/METHODS: TEOAE recordings were collected from 302 ears in subjects presenting normal hearing and normal impedance values. The responses were analyzed by the Wigner-Ville distribution (WVD). The TF region of analysis was optimized by examining the energy content of various rectangular and triangular TF regions. The TEOAE components from the initial and recordings 12 months later were compared in the optimized TF region. RESULTS: The best region for TF analysis was identified with base point 1 at 2.24 ms and 2466 Hz, base point 2 at 6.72 ms and 2466 Hz, and the top point at 2.24 ms and 5250 Hz. Correlation indices from the TF optimized region were higher, and were statistically significant, than the traditional indices in the selected time window. CONCLUSIONS: An analysis of the TF data within a 12-month period indicated a 85% TEOAE component similarity in 90% of the tested subjects. PMID- 19644417 TI - Down's syndrome and the pattern of congenital heart disease in a community with high parental consanguinity. AB - BACKGROUND: It is speculated that parents' consanguinity status effects the pattern of congenital heart defects (CHDs). In this study the CHD pattern in children with Down's syndrome (DS) was determined in a Saudi population with a high consanguineous marriage rate and compared with historical cohorts from populations with low prevalence of parental consanguinity. MATERIAL/METHODS: The prospective study was conducted in an open-access pediatric echocardiography clinic in Riyadh, Saudi Arabia. The subjects were all children with DS proven by clinical and cytogenetic study and referred to the pediatric cardiology service from 2001-2004. Parents' consanguinity was documented and 2D echocardiography and Doppler studies were performed after physical examination, ECG, and chest X-ray for each patient. RESULTS: CHDs were detected in 54/110 (49%) children. These included ventricular septal defect (VSD: 23/54), patent ductus arteriosus (PDA: 4/54), secundum atrial septal defect (ASD: 14/54), atrioventricular septal defect (AVSD: 8/54), tetralogy of Fallot (2/54), bicuspid aortic valve (1/54), supra pulmonary stenosis (1/54), and double outlet right ventricle (1/54). Consanguinity was found in 25% of all parents. Aortic stenosis, coarctation of the aorta, transposition of great arteries, and complex heart diseases were not detected. CONCLUSIONS: A slightly higher frequency of CHD was documented in DS children from this population with a high consanguineous marriage rate. The frequencies of specific lesions were similar to those reported locally and internationally; VSD was the most frequently detected in this study. Interesting was the predominance of left-right shunt lesions and the relative rarity of cyanotic and complex CHD in this DS population. PMID- 19644418 TI - Catabolism of salivary glycoconjugates in acute ethanol intoxication. AB - BACKGROUND: The aim was to study the effects of a single large dose of ethanol (approximately 2.0 g/kg of body weight, as 40% vodka) on the specific activities of alpha-mannosidase, alpha-fucosidase, beta-glucuronidase, and beta galactosidase as well as on the total protein concentration in saliva in eight healthy young volunteers. MATERIAL/METHODS: Resting whole saliva samples were collected 12 hours prior to and 36 and 108 hours after alcohol consumption. Exoglycosidase activities were assayed in the supernatants by the colorimetric method. Protein content was determined by the Lowry method. RESULTS: Thirty-six hours after alcohol consumption the specific activities of alpha-fucosidase and beta-glucuronidase were significantly higher than before drinking. The specific activity of beta-galactosidase showed a greater tendency to increase than alpha mannosidase after the drinking session. The total protein concentration was significantly lower after alcohol consumption than at baseline, even at 108 hr. Significant inverse correlations between total protein content and the specific activities of the exoglycosidases in saliva were found after the drinking session. CONCLUSIONS: Acute ingestion of a large dose of ethanol increased the activity of salivary exoglycosidases, which might be followed by subsequent degradation of proteins in saliva. The observed changes might contribute to salivary defense system malfunction as well as to oral malodor production. PMID- 19644419 TI - Performance of manual hyperinflation: a skills lab study among trained intensive care unit nurses. AB - BACKGROUND: The aim of manual hyperinflation (MH) is to mobilize airway secretions and prevent sputum plugging in intubated and mechanically ventilated patients. With MH, the nurse applies a larger than normal breath with a slow inspiratory flow and, after an inspiratory pause, a high expiratory flow is created by completely releasing the resuscitation bag. MATERIAL/METHODS: This was a prospective observational study in a skills lab of a university hospital. Intensive care unit nurses performed MH procedures for an imaginary patient in three different compliance settings. Data were collected via direct video recordings and an air-flow analyzer. RESULTS: One hundred nurses participated. Video recordings demonstrated inappropriate performance of MH, reflected by the appearance of inspirations which were too rapid (53% of cases), absence of holds (60%), and absence of complete release of the resuscitation bag (78%). In the majority of cases the applied volumes were too large according to what was advised in the local guideline (80%). Peak inspiratory flow was 70 (range: 55-89) l/min for all compliance settings and peak expiratory flows were low: for over compliant (46, range: 42-51), normal (51, range: 45-57), and noncompliant lungs (58, range: 52-64 l/min). CONCLUSIONS: Performance of MH by certified ICU nurses is far from appropriate. These results emphasize the necessity for clearer guidelines with explicit directions for this frequently applied procedure, if it is decided to practice it in the daily care of intubated and mechanically ventilated patients. PMID- 19644420 TI - Physical activities among other types of health-related behaviour in people losing weight. AB - BACKGROUND: The role of physical activity in a health-seeking life style is increasingly and frequently about the improvement of one's silhouette. This constitutes the problem that we are trying to resolve in this article--are physical activities a part of actions aimed at the reduction of weight in people trying to lose it? MATERIAL/METHODS: We studied a group of adults trying to lose weight (N=398) aged 24-35. The Inventory of Healthy Behaviour (IHB) by Juczynski was applied, together with a questionnaire on physical activity and slimming. The IHB test results are analysed in four aspects: proper nutritional habits, prophylactic behaviour, positive mental attitude, and health-related practice. RESULTS: The more the studied people weigh, the more they would like to lose; this correlation is significantly stronger in women. Women desire a lower weight and height norm; men--a higher. Men are more realistic in their expectations. Both women and men spent 5 hours a week exercising, participating in four different forms of activity. Only a relatively small percentage do not exercise. CONCLUSIONS: Women exercise not for health, but in order to have a better silhouette. A slim beautiful body and, in effect, sexual attractiveness are the most emphasised element in their promotion of health, for which physical activity is paramount. PMID- 19644421 TI - Esophageal pressure method and impulse oscillometry to assess mechanical properties of the respiratory system in healthy men. AB - BACKGROUND: Lung elasticity can be assessed by pulmonary compliance using the esophageal pressure method, but this technique is invasive and time-consuming. Impulse oscillometry has been established as a non-invasive method to describe mechanical properties of the respiratory system and preliminary data suggest that it may be used as a marker of lung elasticity. Therefore we compared impulse oscillometry and pulmonary compliance in healthy subjects. MATERIAL/METHODS: In 31 healthy male volunteers aged 20 to 25 years we performed pulmonary function tests including spirometry, bodyplethysmography and pulmonary compliance by the esophageal pressure method. Impulse oscillometry (IOS) was used to determine capacitance (X 5 Hz) and resistance (R 5 Hz and R 20 Hz). RESULTS: Mean dynamic pulmonary compliance was 2.53+/-0.58 l/kPa and mean static pulmonary compliance was 2.82+/-0.85 l/kPa. R 5 Hz and R 20 Hz were between 0.14 and 0.49 kPa/(l/s), while mean X 5 Hz was -0.08+/-0.02 kPa/(l/s). There was demonstrated a highly significant correlation between impulse oscillometric capacitance X 5 Hz and pulmonary compliance parameters. CONCLUSIONS: The results of the present study suggest that impulse oscillometry may be used as an alternative for the invasive esophageal pressure method in determining pulmonary elasticity. PMID- 19644422 TI - Age related decline of microvascular regulation measured in healthy individuals by retinal dynamic vessel analysis. AB - BACKGROUND: The present study investigates the regulative retinal vascular answer to flicker as measured by Dynamic Vessel Analysis (DVA) in relation to age. MATERIAL/METHODS: 52 clinically healthy volunteers (age 20-78 years) free of cardiovascular risk factors according to an extensive medical history, lab values and blood pressure (BP) were examined by retinal DVA. The regulative arterial and venous responses to flicker were recorded with a Retinal Vessel Analyzer (Imedos, Jena/Germany). RESULTS: The retinal arterial regulative amplitude, consisting of a dilation and constriction component, diminished by 45% with age, mainly due to the constricting component diminishing by 75%. The venous response to flicker was unaltered. CONCLUSIONS: The vascular regulative amplitude as well as its constriction part are observable in retinal arteries. They undergo major reduction in healthy individuals during adult lifetime. The results can be explained by the change of biomechanical properties of the vessel wall as well as physiological changes of the vascular endothelial function with age. Hereby the DVA technique shows good potential for investigating cardiovascular aspects in preventive medicine. Whenever doing functional DVA testing these results should be taken in account. The data obtained are first normative age related DVA data. PMID- 19644423 TI - Prognostic value of immunohistochemistry in the Ewing's sarcoma family of tumors. AB - BACKGROUND: The expressions of different markers have been immunohistochemically studied in various types of the Ewing's sarcoma family of tumors, especially for diagnostic purposes. However, little is known about their prognostic value in combination with the clinicopathological data of such patients. MATERIAL/METHODS: This retrospective study investigated the immunohistochemical expressions of NSE, TdT, EMA, S-100, CK MNF116, p53, bcl-2, CD99, and CD117 on formalin-fixed paraffin-embedded material of 72 patients (age range: 2-59 years) with various types of Ewing's sarcoma family of tumors using the tissue microarray method. The immunohistochemical results were compared with clinicopathological features using survival analysis (Cox regression). RESULTS: CD99 expression was detected in 90%, CD117 in 75.8%, bcl-2 in 70.1%, NSE in 66.6%, p53 in 66.6%, EMA in 26%, S-100 in 25.4%, TdT in 22.1%, and CK MNF116 in 10.2% of the cases. No immunoreactivity was observed in the normal tissue around the tumors. CONCLUSIONS: The expressions of EMA (p=0.107), NSE (p=0.126), CD99 (p=0.14), TdT (p=0.198), bcl-2 (p=0.382), p53 (p=0.54), CD117 (p=0.612), S-100 (p=0.867), and CK MNF116 (p=0.934) had no statistically significant impact on survival. Patient age at the time of diagnosis (p=0.008) and the presence of tumor necrosis (p=0.033) were the only significant prognostic factors in this study. Tumor location was an insignificant prognostic factor (p=0.38). PMID- 19644424 TI - Catatonia recognition and treatment. AB - BACKGROUND: Catatonic syndrome is no longer considered a subtype of schizophrenia but is more frequently associated with mood disorders (mania, melancholia, and psychotic depression) as well as general medical conditions (neurological disorders, drug-induced and toxic-induced conditions, metabolic conditions). A case of catatonia is reported which occurred after alcohol withdrawal. CASE REPORT: Catatonia occurred 48 hours after alcohol withdrawal in a 54-year-old woman who had stopped all her treatment (in the context of a type II bipolar disorder). A dramatic improvement of symptoms was observed after oral administration of zolpidem. CONCLUSIONS: This case seems to confirm that catatonia can represents a nonspecific response to stress factors. The withdrawal of multiple medications was already described as a basis for catatonia. Alcohol withdrawal could constitute an additional risk factor for catatonia. The zolpidem test is a useful diagnostic and therapeutic test. PMID- 19644425 TI - Nephrotic-range proteinuria with small glomerular fibrillary deposits in a patient on diphenylhydantoin treatment. AB - BACKGROUND: Although the exact role of the diphenylhydantoin treatment on the immune system is still unclear, prolonged administration of diphenylhydantoin has been suggested to be associated with immune-based disorders and syndromes. CASE REPORT: A case of fibrillary glomerulonephritis associated with DPH treatment is reported. This is the first reported case of fibrillary glomerulonephritis associated with this commonly used common anticonvulsive drug. CONCLUSIONS: A more routine surveillance for proteinuria in patients receiving DPH is recommended. PMID- 19644427 TI - Doppler sonography measurements of renal vascular resistance in autosomal dominant polycystic kidney disease. AB - BACKGROUND: The aim of this study was to assess the clinical usefulness of duplex Doppler sonography in ADPKD patients by measuring the resistive indices (RIs) and pulsatility indices (PIs) of renal and interlobar arteries and investigating the correlation between these parameters and relevant clinical data. MATERIAL/METHODS: RI and PI in renal and interlobar arteries of 61 patients with ADPKD and 27 healthy subjects were calculated and correlated with age, serum creatinine, age at diagnosis, and duration of disease. RESULTS: In the control subjects the median RI was 0.61 (interquartile range: 0.075) in the renal arteries and 0.58 (0.06) in the interlobar arteries vs. 0.72 (0.1) and 0.69 (0.1), respectively, in the ADPKD patients. Median PI was 1.07 (0.1425) in the renal arteries and 0.94 (0.1525) in the interlobar arteries vs. 1.41 (0.655) and 1.25 (0.395), respectively, in the ADPKD patients. Doppler indices were significantly higher in the ADPKD patients (p<0.0001). Almost all Doppler indices correlated positively and significantly with age, serum creatinine, age at diagnosis, and duration of disease. No significant correlation was observed between the indices and blood pressure. CONCLUSIONS: Because of the strong correlation between Doppler measurements of renovascular resistance and renal function tests together and duration of the disease observed in this study, this method, despite its pitfalls such as the influence of high blood pressure, compression by renal cysts, vascular calcification, and age, could be useful in the evaluation of disease progression in patients with ADPKD. PMID- 19644426 TI - Orbital tumor as an initial manifestation of Wegener's granulomatosis in children: a series of four cases. AB - BACKGROUND: Wegener's granulomatosis (WG) is a rare idiopathic disease in which small and medium-sized arteries are affected by necrotizing granulomatous inflammation. It is associated with a triad of pulmonary (cavitating granulomatous lesions with hemoptysis, cough, and dyspnea), renal (glomerulonephritis with hematuria, proteinuria), and head (otitis media, recurrent sinusitis, eye or orbital involvement) manifestations. CASE REPORT: Four children aged 7-11 years diagnosed with WG between 1995-2008 initially presented with unilateral proptosis and ptosis due to orbital tumor. CT or MRI, orbital lesion biopsy, and laboratory tests (ERS, CRP, ANCA) were part of the diagnostic workup. The diagnoses were based on correlation between clinical presentation and diagnostic findings. All four patients had orbital lesions on contrast-enhanced CT and MRI. Two had lesions of the temporal pyramid. Orbital tumor biopsies showed granulomatous lesions in two patients, necrotizing vasculitis with leukocytoclasia in three, and an orbital pseudotumor in one. ESR and CRP were positive in all. ANCA positivity was variable (c-ANCA did not allow WG diagnosis or there were atypical ANCAs). All had blood and protein in the urine, but only one had advanced renal involvement. All were treated with oral steroid and immunosuppression; remission was successful. CONCLUSIONS: WG is often more difficult to diagnose in children than in adults due to frequent absence of its signature features. The absence of the classic triad and atypical laboratory or biopsy findings do not exclude a diagnosis of WG. Orbital demonstration helps achieve early diagnosis and treatment of this potentially fatal rheumatologic disease. PMID- 19644428 TI - Risk-tendency graph (RTG): a new gait-analysis technique for monitoring FES assisted paraplegic walking stability. AB - BACKGROUND: Gait analysis techniques guide the use and design of functional electrical stimulation (FES) systems for paraplegic walking. However, published studies on dynamic gait stability for the effective use of FES are limited. This paper introduces a new risk-tendency graph (RTG) technique to analyze and process gait stability in FES-assisted paraplegic walking. MATERIAL/METHODS: The main instrument was a specialized walker dynamometer system based on a multi-channel strain-gauge bridge network affixed to the frame of the walker. This system collects force information for the handle reaction vector (HRV) between the patient's upper extremities and the walker during walking. The information is then converted into a walker tipping index (WTI), which is an indicator of the patient's walking stability. Dynamic gait stability is then combined with spatio temporal locating methods for WTI and visually described as morphological curves in the temporal and spatial domains, namely RTGs. RESULTS: To demonstrate the potential usefulness of RTG in gait analysis, a preliminary clinical trial was conducted with one male paraplegic patient who was undergoing FES walking training. The gait stability levels for the patient under different stimulation patterns were quantified using the results of temporal and 3-D spatial RTG. Relevant instable phases in the gait cycle and dangerous inclinations of the patient's body while walking were also clearly identified. CONCLUSIONS: The new RTG technique is a practical method for distinguishing useful gait information from the viewpoint of stability and may be further applied in FES-assisted paraplegic walking rehabilitation. PMID- 19644429 TI - Implementation of a virtual laryngoscope system using efficient reconstruction algorithms. AB - BACKGROUND: Conventional fiberoptic laryngoscope may cause discomfort to the patient and in some cases it can lead to side effects that include perforation, infection and hemorrhage. Virtual laryngoscopy (VL) can overcome this problem and further it may lower the risk of operation failures. Very few virtual endoscope (VE) based investigations of the larynx have been described in the literature. MATERIAL/METHODS: CT data sets from a healthy subject were used for the VL studies. An algorithm of preprocessing and region-growing for 3-D image segmentation is developed. An octree based approach is applied in our VL system which facilitates a rapid construction of iso-surfaces. Some locating techniques are used for fast rendering and navigation (fly-through). RESULTS: Our VL visualization system provides for real time and efficient 'fly-through' navigation. The virtual camera can be arranged so that it moves along the airway in either direction. Snap shots were taken during fly-throughs. The system can automatically adjust the direction of the virtual camera and prevent collisions of the camera and the wall of the airway. CONCLUSIONS: A virtual laryngoscope (VL) system using OpenGL (Open Graphics Library) platform for interactive rendering and 3D visualization of the laryngeal framework and upper airway is established. OpenGL is supported on major operating systems and works with every major windowing system. The VL system runs on regular PC workstations and was successfully tested and evaluated using CT data from a normal subject. PMID- 19644430 TI - Psychological distress in Brazilian Crohn's disease patients: screening, prevalence, and risk factors. AB - BACKGROUND: Psychological disturbances are frequent in Crohn's disease (CD) patients. However, epidemiological studies of non-western CD populations are limited and may be confounded by genetic and disease-related influences. The aim of this study was to assess the prevalence and risk factors for depression and symptoms of anxiety in Brazilian patients with CD. MATERIAL/METHODS: In this cross-sectional study, 110 CD patients and 110 control subjects with erosive esophagitis were assessed for depression and anxiety symptoms using the Beck Depression Inventory and the Hospital Anxiety and Depression Scale. RESULTS: The Crohn's and control groups were similar with regard to socio-demographic data. Compared with the controls, the CD patients had a significantly higher prevalence of depressed mood (25.4% vs. 8.2%, P=0.003). There was no significant difference in the prevalence of anxiety between CD subjects (33.6%) and controls (22.7%). Depressed mood rates were higher among those who had active disease and greater CDAI scores (OR: 3.4, 95%CI 1.1-10.8). Family history of depression (OR: 5.3, 95%CI: 2.7-15.1) was related to the co-occurrence of anxiety symptoms. CONCLUSIONS: In CD patients, depression and anxiety are highly concurrent conditions. Disease activity was strongly associated with depressed mood, while a family history of depression was related to anxiety. Screening for depression and anxiety should be carried out routinely as part of quality of care improvement in CD individuals. PMID- 19644431 TI - Genetic disorders and periodontal health: a literature review. AB - Periodontal diseases include a group of inflammatory diseases characterized by progressive destruction of the periodontium. Dental plaque is the initiator of periodontal disease, but disease severity and response to treatment are determined predominantly by host-based risk factors. Genetic disorders can modify the host defense mechanisms or influence the homeostasis of the periodontium during childhood, thus increasing patients' susceptibility to periodontal disease. The periodontal manifestations of these disorders may persist into adulthood. When dealing with periodontal problems, particularly in children and adolescents, it is advisable to establish a differential diagnosis of periodontal disease due to systemic conditions. This paper reviews the current literature concerning the effect on periodontal health of genetic disorders such as connective tissue metabolism disorders, metabolic disorders, skin disorders, leukocyte defects, and chromosome abnormalities. Treatment strategies of patients with genetic disorders affected by periodontal diseases are also suggested according to the evidence available. In patients affected by genetic disorders, the response to treatment is not always as expected, and sometimes the progression of periodontal disease is inevitable despite adequate maintenance treatment. PMID- 19644432 TI - Autoinflammatory syndromes behind the scenes of recurrent fevers in children. AB - Many children experience recurrent fevers with no easily identifiable source and only a careful follow-up helps in the early identification of other presenting symptoms of other defined conditions which require medical intervention. Autoinflammatory syndromes are rare childhood-onset disorders of the innate immunity in which recurrent flares of fever and inflammation affecting skin, joints, the gastrointestinal tube, or serous membranes are the most striking signs, without any evidence of autoantibody production or underlying infections. Among the pediatric conditions belonging to this group we can consider hereditary recurrent fevers (familial Mediterranean fever, mevalonate kinase deficiency syndrome, tumor necrosis factor receptor-associated periodic syndrome, cryopyrin associated periodic syndromes), pyogenic disorders (PAPA syndrome, CRMO syndrome, Majeed syndrome), immune-mediated granulomatous diseases (Blau syndrome, Crohn's disease), and idiopathic febrile syndromes (systemic-onset juvenile idiopathic arthritis, PFAPA syndrome, Behcet syndrome). Their genetic background has only been partially elucidated and advances in their molecular pathogenesis are shedding new light on the innate immune system, whilst more and more diseases are being reconsidered at a pathogenetic level and included in this new chapter of postgenomic medicine. The diagnosis of most autoinflammatory syndromes relies on clinical history, demonstration of an increased acute-phase response during inflammatory attacks, and, possibly, genetic confirmation, which is still elusive especially for idiopathic febrile syndromes. This astonishing progress in the awareness and knowledge of autoinflammatory syndromes has anticipated the actual possibilities of medical intervention and rationalized treatment with targeted biologic agents. PMID- 19644435 TI - Bedside lung ultrasound in critical care practice. AB - Ultrasonographic scanning of the lung is gaining ever-growing recognition as a diagnostic and monitoring imaging technique. Its role in trauma assessment has already been established as an extension of the focused assessment of trauma with sonography for the diagnosis of pneumothorax. As more centers are discovering the advantages of ultrasound and conducting experimental and comparative studies, its use for diagnosing many other lung pathologies is becoming even more important. In-depth studies and innovative ideas are needed to explore the possibilities of this technology. We believe that, ultimately, the advantages for the patient will far outweigh the disadvantages of ultrasonography. Here, we review all possible applications of lung ultrasonography used thus far in Intensive Care Units, where a readily available and biologically non-invasive imaging technique may make the difference in diagnosis. In addition, we describe how the non-invasive nature of ultrasonography allows it to be used as a monitoring device of disease progression vs the healing process. We also provide a detailed explanation of the methods and materials necessary and a few indications towards unanswered questions in this field of research. PMID- 19644434 TI - Expression of monocyte human leukocyte antigen-DR in relation with sepsis severity and plasma mediators. AB - AIM: After an initial septic hit, the immune response to a new antigen changes as time progresses, with an unpredictable efficiency. The aim of this study was to characterize the monocyte functional phenotype by HLA-DR expression in septic patients at the onset of sepsis and during recovery in relation to organ failure and plasma mediators. METHODS: Twenty-six patients were analyzed as either single organ failure at worst (SOF) or multiple organ failure (MOF) over 14 days. Twelve patients received immunosuppressive (IS) drugs before sepsis. We measured: 1) monocyte HLA-DR expression (mHLA-DR); 2) plasma pro-inflammatory mediators (IL 12p40, macrophage Migration Inhibitory Factor [MIF]); 3) plasma anti-inflammatory mediators (IL-10, cortisol); and 4) in vitro lipopolysaccharide (LPS) stimulated mHLA-DR in 6-hour whole blood culture or after plasma replacement with standard milieu. RESULTS: mHLA-DR expression was equally decreased in patients who were treated with IS drugs as those who were not. Despite the difference in severity, SOF patients showed a similar profound mHLA-DR downregulation as MOF patients at day 0, but tended to recover earlier. MOF patients presented higher plasma IL-10 and cortisol levels than SOF patients but similar plasma IL-12p40 and MIF levels. In vitro LPS stimulation showed an impaired mHLA-DR response in both groups. Plasma replacement by milieu elicited a slight improvement in the response to LPS in SOF but not MOF patients. CONCLUSIONS: At the onset of sepsis, an initial low mHLA-DR was not related to any prior IS drug regimen, the severity of the sepsis or the outcome. The duration of mHLA-DR downregulation could be related to plasma factors in SOF, while other mechanisms may be implicated in MOF evolution. PMID- 19644436 TI - Epidural analgesia in a parturient with essential thrombocythemia. PMID- 19644437 TI - Perioperative antibiotic prophylaxis in adults: the 2008 update of the Italian Guidelines. How can we as anesthetists contribute to the reduction of surgical site infections? PMID- 19644438 TI - Perioperative antibiotic prophylaxis in adults. Outline of the principal recommendations. National reference guidelines. PMID- 19644439 TI - Laboratory-acquired vaccinia virus infection--Virginia, 2008. AB - Vaccinia virus (VACV) is the live viral component of smallpox vaccine. Inadvertent exposure to VACV can result in infection, and severe complications can occur in persons with underlying risk factors (e.g., pregnancy, immunodeficiencies, or dermatologic conditions). The Advisory Committee on Immunization Practices (ACIP) recommends smallpox vaccination for laboratory workers who handle nonhighly attenuated VACV strains or other orthopoxviruses (e.g., monkeypox, cowpox, or variola). On July 8, 2008, CDC was notified by a Virginia physician of a suspected case of inadvertent autoinoculation and VACV infection in an unvaccinated laboratory worker. This report describes the subsequent investigations conducted by the Virginia Department of Health and CDC to identify the source of infection and any cases of contact transmission. Of the patient's 102 possible contacts, seven had underlying risk factors for developing serious vaccinia infection. Investigators found no evidence of contact transmission and, based on the results of molecular typing, further concluded that the patient had been exposed to a VACV strain that had contaminated the seed stock from the laboratory where the patient worked. This case underscores the importance of adherence to ACIP vaccination recommendations for laboratory workers and use of safety precautions when working with nonhighly attenuated VACV. PMID- 19644440 TI - Fatalities caused by cattle--four States, 2003-2008. AB - During 2003-2007, deaths occurring in the production of crops and animals in the United States totaled 2,334; of these, 108 (5%) involved cattle as either the primary or secondary cause. During the same period, Iowa, Kansas, Missouri, and Nebraska accounted for 16% of the nation's approximately 985,000 cattle operations and 21% of the nation's cattle and calf herd. To better characterize cattle-caused deaths in these four states, investigators reviewed all such deaths occurring during the period 2003-2008 that were detected by two surveillance programs, the Iowa Fatality Assessment and Control Evaluation (IA FACE) and the Great Plains Center for Agricultural Health (GPCAH). This report summarizes that investigation, which identified 21 cattle-related deaths. These deaths occurred throughout the year, and decedents tended to be older (aged =60 years) (67%) and male (95%). Except in one case, the cause of death was blunt force trauma to the head or chest. Circumstances associated with these deaths included working with cattle in enclosed areas (33%), moving or herding cattle (24%), loading (14%), and feeding (14%). One third of the deaths were caused by animals that had previously exhibited aggressive behavior. To reduce the risk for death from cattle-caused injuries, farmers and ranchers should be aware of and follow recommended practices for safe livestock-handling facilities and proper precautions for working with cattle, especially cattle that have exhibited aggressiveness. PMID- 19644441 TI - Status of state electronic disease surveillance systems--United States, 2007. AB - The National Electronic Disease Surveillance System (NEDSS) is a web-based system that uses standard health information technology (IT) codes to integrate disease surveillance systems, enabling them to transfer public health, laboratory, and clinical data securely from health-care providers to public health departments. Each jurisdictions' system consists of a base system and modules that can be used for specific surveillance purposes. States also use NEDSS-like or other electronic systems to conduct surveillance on specific diseases or conditions. Until recently, no assessment had been done to describe the status and characteristics of state electronic disease surveillance systems. The Council of State and Territorial Epidemiologists (CSTE) conducted such an assessment in August 2007 in all 50 states. This report presents the results of that assessment, which indicated that, in 2007, state electronic disease surveillance systems varied widely and were in various stages of implementation. Each state had either custom-built systems or purchased systems that were customizable, with associated disease modules to meet its own surveillance needs. As interoperability becomes the standard for electronic data sharing, more states will face customization costs and the need to hire more technical specialists who can manage health information and exchange. Further collaboration and support from surveillance and health-care IT stakeholders with public health will be needed to improve the efficacy and quality of electronic disease surveillance systems. PMID- 19644442 TI - Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices (ACIP), 2009. AB - This report updates the 2008 recommendations by CDC's Advisory Committee on Immunization Practices (ACIP) regarding the use of influenza vaccine for the prevention and control of seasonal influenza (CDC. Prevention and control of influenza: recommendations of the Advisory Committee on Immunization Practices [ACIP]. MMWR 2008;57[No. RR-7]). Information on vaccination issues related to the recently identified novel influenza A H1N1 virus will be published later in 2009. The 2009 seasonal influenza recommendations include new and updated information. Highlights of the 2009 recommendations include 1) a recommendation that annual vaccination be administered to all children aged 6 months-18 years for the 2009 10 influenza season; 2) a recommendation that vaccines containing the 2009-10 trivalent vaccine virus strains A/Brisbane/59/2007 (H1N1)-like, A/Brisbane/10/2007 (H3N2)-like, and B/Brisbane/60/2008-like antigens be used; and 3) a notice that recommendations for influenza diagnosis and antiviral use will be published before the start of the 2009-10 influenza season. Vaccination efforts should begin as soon as vaccine is available and continue through the influenza season. Approximately 83% of the United States population is specifically recommended for annual vaccination against seasonal influenza; however, <40% of the U.S. population received the 2008-09 influenza vaccine. These recommendations also include a summary of safety data for U.S. licensed influenza vaccines. These recommendations and other information are available at CDC's influenza website (http://www.cdc.gov/flu); any updates or supplements that might be required during the 2009-10 influenza season also can be found at this website. Vaccination and health-care providers should be alert to announcements of recommendation updates and should check the CDC influenza website periodically for additional information. PMID- 19644443 TI - 36 degrees step size of proton-driven c-ring rotation in FoF1-ATP synthase. AB - Synthesis of adenosine triphosphate ATP, the 'biological energy currency', is accomplished by F(o)F(1)-ATP synthase. In the plasma membrane of Escherichia coli, proton-driven rotation of a ring of 10 c subunits in the F(o) motor powers catalysis in the F(1) motor. Although F(1) uses 120 degrees stepping during ATP synthesis, models of F(o) predict either an incremental rotation of c subunits in 36 degrees steps or larger step sizes comprising several fast substeps. Using single-molecule fluorescence resonance energy transfer, we provide the first experimental determination of a 36 degrees sequential stepping mode of the c-ring during ATP synthesis. PMID- 19644444 TI - Distinct histone modifications define initiation and repair of meiotic recombination in the mouse. AB - Little is known about the factors determining the location and activity of the rapidly evolving meiotic crossover hotspots that shape genome diversity. Here, we show that several histone modifications are enriched at the active mouse Psmb9 hotspot, and we distinguish those marks that precede from those that follow hotspot recombinational activity. H3K4Me3, H3K4Me2 and H3K9Ac are specifically enriched in the chromatids that carry an active initiation site, and in the absence of DNA double-strand breaks (DSBs) in Spo11(-/-) mice. We thus propose that these marks are part of the substrate for recombination initiation at the Psmb9 hotspot. In contrast, hyperacetylation of H4 is increased as a consequence of DSB formation, as shown by its dependency on Spo11 and by the enrichment detected on both recombining chromatids. In addition, the comparison with another hotspot, Hlx1, strongly suggests that H3K4Me3 and H4 hyperacetylation are common features of DSB formation and repair, respectively. Altogether, the chromatin signatures of the Psmb9 and Hlx1 hotspots provide a basis for understanding the distribution of meiotic recombination. PMID- 19644445 TI - ZIP: a novel transcription repressor, represses EGFR oncogene and suppresses breast carcinogenesis. AB - Despite the importance of epidermal growth factor receptor (EGFR) in animal development and malignant transformation, surprisingly little is known about the regulation of its expression. Here, we report a novel zinc finger and G-patch domain-containing protein, ZIP. We demonstrated that ZIP acts as a transcription repressor through the recruitment of the nucleosome remodelling and deacetylase complex. Transcriptional target analysis revealed that ZIP regulates several cellular signalling pathways including EGFR pathways that are critically involved in cell proliferation, survival, and migration. We showed that ZIP inhibits cell proliferation and suppresses breast carcinogenesis, and that ZIP depletion leads to a drastic tumour growth in vivo. We found that ZIP is downregulated in breast carcinomas and that its level of expression is negatively correlated with that of EGFR. Our data indicate that ZIP is a novel transcription repressor and a potential tumour suppressor. These findings may shed new light on the EGFR related breast carcinogenesis and might offer a potential new target for breast cancer therapy. PMID- 19644446 TI - Bipartite functions of the CREB co-activators selectively direct alternative splicing or transcriptional activation. AB - The CREB regulated transcription co-activators (CRTCs) regulate many biological processes by integrating and converting environmental inputs into transcriptional responses. Although the mechanisms by which CRTCs sense cellular signals are characterized, little is known regarding how CRTCs contribute to the regulation of cAMP inducible genes. Here we show that these dynamic regulators, unlike other co-activators, independently direct either pre-mRNA splice-site selection or transcriptional activation depending on the cell type or promoter context. Moreover, in other scenarios, the CRTC co-activators coordinately regulate transcription and splicing. Mutational analyses showed that CRTCs possess distinct functional domains responsible for regulating either pre-mRNA splicing or transcriptional activation. Interestingly, the CRTC1-MAML2 oncoprotein lacks the splicing domain and is incapable of altering splice-site selection despite robustly activating transcription. The differential usage of these distinct domains allows CRTCs to selectively mediate multiple facets of gene regulation, indicating that co-activators are not solely restricted to coordinating alternative splicing with increase in transcriptional activity. PMID- 19644448 TI - Identification of a perinuclear positioning element in human subtelomeres that requires A-type lamins and CTCF. AB - The localization of genes within the nuclear space is of paramount importance for proper genome functions. However, very little is known on the cis-acting elements determining subnuclear positioning of chromosome segments. We show here that the D4Z4 human subtelomeric repeat localizes a telomere at the nuclear periphery. This perinuclear activity lies within an 80 bp sequence included within a region known to interact with CTCF and A-type Lamins. We further show that a reduced level of either CTCF or A-type Lamins suppresses the perinuclear activities of D4Z4 and that an array of multimerized D4Z4 sequence, which has lost its ability to bind CTCF and A-type Lamins, is not localized at the periphery. Overall, these findings reveal the existence of an 80 bp D4Z4 sequence that is sufficient to position an adjacent telomere to the nuclear periphery in a CTCF and A-type lamins-dependent manner. Strikingly, this sequence includes a 30 bp GA-rich motif, which binds CTCF and is present at several locations in the human genome. PMID- 19644447 TI - Endo-siRNAs depend on a new isoform of loquacious and target artificially introduced, high-copy sequences. AB - Colonization of genomes by a new selfish genetic element is detrimental to the host species and must lead to an efficient, repressive response. In vertebrates as well as in Drosophila, piRNAs repress transposons in the germ line, whereas endogenous siRNAs take on this role in somatic cells. We show that their biogenesis depends on a new isoform of the Drosophila TRBP homologue loquacious, which arises by alternative polyadenylation and is distinct from the one that functions during the biogenesis of miRNAs. For endo-siRNAs and piRNAs, it is unclear how an efficient response can be initiated de novo. Our experiments establish that the endo-siRNA pathway will target artificially introduced sequences without the need for a pre-existing template in the genome. This response is also triggered in transiently transfected cells, thus genomic integration is not essential. Deep sequencing showed that corresponding endo siRNAs are generated throughout the sequence, but preferentially from transcribed regions. One strand of the dsRNA precursor can come from spliced mRNA, whereas the opposite strand derives from independent transcripts in antisense orientation. PMID- 19644450 TI - The structural basis of Arf effector specificity: the crystal structure of ARF6 in a complex with JIP4. AB - The JNK-interacting proteins, JIP3 and JIP4, are specific effectors of the small GTP-binding protein ARF6. The interaction of ARF6-GTP with the second leucine zipper (LZII) domains of JIP3/JIP4 regulates the binding of JIPs to kinesin-1 and dynactin. Here, we report the crystal structure of ARF6-GTP bound to the JIP4 LZII at 1.9 A resolution. The complex is a heterotetramer with dyad symmetry arranged in an ARF6-(JIP4)(2)-ARF6 configuration. Comparison of the ARF6-JIP4 interface with the equivalent region of ARF1 shows the structural basis of JIP4's specificity for ARF6. Using site-directed mutagenesis and surface plasmon resonance, we further show that non-conserved residues at the switch region borders are the key structural determinants of JIP4 specificity. A structure derived model of the association of the ARF6-JIP3/JIP4 complex with membranes shows that the JIP4-LZII coiled-coil should lie along the membrane to prevent steric hindrances, resulting in only one ARF6 molecule bound. Such a heterotrimeric complex gives insights to better understand the ARF6-mediated motor switch regulatory function. PMID- 19644449 TI - The structure of myostatin:follistatin 288: insights into receptor utilization and heparin binding. AB - Myostatin is a member of the transforming growth factor-beta (TGF-beta) family and a strong negative regulator of muscle growth. Here, we present the crystal structure of myostatin in complex with the antagonist follistatin 288 (Fst288). We find that the prehelix region of myostatin very closely resembles that of TGF beta class members and that this region alone can be swapped into activin A to confer signalling through the non-canonical type I receptor Alk5. Furthermore, the N-terminal domain of Fst288 undergoes conformational rearrangements to bind myostatin and likely acts as a site of specificity for the antagonist. In addition, a unique continuous electropositive surface is created when myostatin binds Fst288, which significantly increases the affinity for heparin. This translates into stronger interactions with the cell surface and enhanced myostatin degradation in the presence of either Fst288 or Fst315. Overall, we have identified several characteristics unique to myostatin that will be paramount to the rational design of myostatin inhibitors that could be used in the treatment of muscle-wasting disorders. PMID- 19644451 TI - Leptin and the control of body weight: a review of its diverse central targets, signaling mechanisms, and role in the pathogenesis of obesity. PMID- 19644452 TI - Expression and regulation of soluble epoxide hydrolase in adipose tissue. AB - Obesity is an increasingly important public health issue reaching epidemic proportions. Visceral obesity has been defined as an important element of the metabolic syndrome and expansion of the visceral fat mass has been shown to contribute to the development of insulin resistance and cardiovascular disease. To identify novel contributors to cardiovascular and metabolic abnormalities in obesity, we analyzed the adipose proteome and identified soluble epoxide hydrolase (sEH) in the epididymal fat pad from C57BL/6J mice that received either a regular diet or a "western diet." sEH was synthesized in adipocytes and expression levels increased upon differentiation of 3T3-L1 preadipocytes. Although normalized sEH mRNA and protein levels did not differ in the fat pads from mice receiving a regular or a "western diet," total adipose sEH activity was higher in the obese mice, even after normalization for body weight. Furthermore, peroxisome proliferator-activated receptor gamma (PPARgamma) agonists increased the expression of sEH in mature 3T3-L1 adipocytes in vitro and in adipose tissue in vivo. Considering the established role for sEH in inflammation, cardiovascular diseases, and lipid metabolism, and the suggested involvement of sEH in the development of type 2 diabetes, our study has identified adipose sEH as a potential novel therapeutic target that might affect the development of metabolic and cardiovascular abnormalities in obesity. PMID- 19644454 TI - SHOREmap: simultaneous mapping and mutation identification by deep sequencing. PMID- 19644453 TI - The CB1 antagonist rimonabant decreases insulin hypersecretion in rat pancreatic islets. AB - Type 2 diabetes and obesity are characterized by elevated nocturnal circulating free fatty acids, elevated basal insulin secretion, and blunted glucose stimulated insulin secretion (GSIS). The CB1 receptor antagonist, Rimonabant, has been shown to improve glucose tolerance and insulin sensitivity in vivo but its direct effect on islets has been unclear. Islets from lean littermates and obese Zucker (ZF) and Zucker Diabetic Fatty (ZDF) rats were incubated for 24 h in vitro and exposed to 11 mmol/l glucose and 0.3 mmol/l palmitate (GL) with or without Rimonabant. Insulin secretion was determined at basal (3 mmol/l) or stimulatory (15 mmol/l) glucose concentrations. As expected, basal secretion was significantly elevated in islets from obese or GL-treated lean rats whereas the fold increase in GSIS was diminished. Rimonabant decreased basal hypersecretion in islets from obese rats and GL-treated lean rats without decreasing the fold increase in GSIS. However, it decreased GSIS in islets from lean rats without affecting basal secretion. These findings indicate that Rimonabant has direct effects on islets to reduce insulin secretion when secretion is elevated above normal levels by diet or in obesity. In contrast, it appears to decrease stimulated secretion in islets from lean animals but not in obese or GL-exposed islets. PMID- 19644455 TI - Sub-angstrom accuracy in protein loop reconstruction by robotics-inspired conformational sampling. PMID- 19644456 TI - Probing the basis for genotype-phenotype relationships. AB - Transposon mutagenesis coupled with microarray analysis helps to rapidly generate information about changing genotype-phenotype relationships in laboratory-evolved bacteria. PMID- 19644457 TI - New genetic tools for cell lineage analysis in Drosophila. AB - Real-time lineage tracing in flies gets a boost with three techniques to specifically label a progenitor's daughter cells. PMID- 19644458 TI - Statistical methods for analysis of high-throughput RNA interference screens. AB - RNA interference (RNAi) has become a powerful technique for reverse genetics and drug discovery, and in both of these areas large-scale high-throughput RNAi screens are commonly performed. The statistical techniques used to analyze these screens are frequently borrowed directly from small-molecule screening; however, small-molecule and RNAi data characteristics differ in meaningful ways. We examine the similarities and differences between RNAi and small-molecule screens, highlighting particular characteristics of RNAi screen data that must be addressed during analysis. Additionally, we provide guidance on selection of analysis techniques in the context of a sample workflow. PMID- 19644460 TI - Spheroid-based human endothelial cell microvessel formation in vivo. AB - The study of angiogenic endothelial cells (ECs) has in recent years greatly stimulated multiple fields of vascular biology research. A number of cellular models and numerous complex developmental, manipulatory and tumor animal models have been developed to study angiogenesis in vitro and in vivo. To connect the versatility of cellular assays with the complexity of readouts of in vivo experimentation, we have developed an endothelial transplantation assay. This assay is based on grafting ex vivo generated EC spheroids (2 d) in a suitable matrix in immunocompromised mice, to give rise to a 3D network of capillaries (20 d). This vasculature connects to the mouse vasculature, is perfused and matures by recruiting mouse mural cells. Here we describe the detailed protocol for this assay, including generation of spheroids, injection into mice, excision and processing of resulting plugs, and quantification by immunohistochemical analysis of the resulting vasculature. PMID- 19644461 TI - Studying physical chromatin interactions in plants using Chromosome Conformation Capture (3C). AB - Gene regulation in higher eukaryotes frequently involves physical interactions between genomic sequence elements tens of kilobases apart on the same chromosome but can also entail interactions between different chromosomes. Chromosome Conformation Capture (3C) is a powerful tool to identify such interactions. 3C technology is based on formaldehyde crosslinking of chromatin, followed by restriction digestion and intramolecular ligation. Quantitative detection of ligation products by PCR (qPCR; not discussed in this protocol) provides insight into the interaction frequencies between chromosomal fragments and thereby the spatial organization of a genomic region. Detailed 3C protocols have been published for yeast and mammals. However, these protocols cannot simply be transferred to plant tissues. In this paper, we provide a maize-specific 3C protocol and present a general strategy to systematically optimize the protocol for other plants. Once the technique and appropriate controls are established, the 3C procedure (including qPCR) can be completed in 5-7 d. PMID- 19644463 TI - Public-private partnership tackles TB challenges in parallel. AB - The Global Alliance for TB Drug Development and Tibotec have joined forces to develop a potential first-in-class drug for both drug-susceptible and drug resistant tuberculosis. PMID- 19644462 TI - A murine model of urinary tract infection. AB - Urinary tract infections (UTIs) inflict extreme pain and discomfort to those affected and have profound medical and socioeconomic impact. Although acute UTIs are often treatable with antibiotics, a large proportion of patients suffer from multiple recurrent infections. Here, we describe and provide a protocol for a robust murine UTI model that allows for the study of uropathogens in an ideal setting. The infections in the urinary tract can be monitored quantitatively by determining the bacterial loads at different times post-infection. In addition, the simple bladder architecture allows observation of disease progression and the uropathogenic virulence cascade using a variety of microscopic techniques. This mouse UTI model is extremely flexible, allowing the study of different bacterial strains and species of uropathogens in a broad range of mouse genetic backgrounds. We have used this protocol to identify important aspects of the host pathogen interaction that determine the outcome of infection. The time required to complete the entire procedure will depend on the number of bacterial strains and mice included in the study. Nevertheless, one should expect 4 h of hands-on time, including inoculum preparation on the day of infection, transurethral inoculation, tissue harvest and post-harvest processing for a small group of mice (e.g., 5 mice). PMID- 19644464 TI - Retuning the immune system: the future of type 1 diabetes therapy? AB - Strategies that restore immune tolerance are attracting growing interest in their potential to advance the treatment of type 1 diabetes beyond lifelong insulin therapy. PMID- 19644467 TI - Immunotherapy shows promise in Phase III neuroblastoma trial. PMID- 19644466 TI - Deal-making trends in oncology. PMID- 19644468 TI - IL-1beta-targeted antibody approved for rare autoinflammatory disorders. PMID- 19644470 TI - An audience with...Joseph Bolen. Interview by Bethan Hughes. AB - Chief Scientific Officer, Millennium: The Takeda Oncology Company,Cambridge, Massachusetts, USA. Prior to joining Millennium, Joseph Bolen, Ph.d., held positions including Vice President and Global head of Oncologic diseases at hoechst Marion Roussel, and executive director of oncology drug discovery at the Bristol-Myers Squibb Pharmaceutical Research institute. in addition to other senior academic positions, he was Section Chief of the Biochemical Oncology Department at the National Cancer Institute in Maryland, USA, and a founding member of their laboratory of tumor virus biology. PMID- 19644471 TI - Pharmaceutical R&D: the road to positive returns. PMID- 19644472 TI - Tolvaptan. AB - In May 2009, tolvaptan (Samsca; Otsuka), a selective vasopressin V(2) receptor antagonist, was approved by the US FDA for the treatment of clinically significant hypervolaemic and euvolaemic hyponatraemia. PMID- 19644473 TI - Targeting the phosphoinositide 3-kinase pathway in cancer. AB - The phosphoinositide 3-kinase (PI3K) pathway is a key signal transduction system that links oncogenes and multiple receptor classes to many essential cellular functions, and is perhaps the most commonly activated signalling pathway in human cancer. This pathway therefore presents both an opportunity and a challenge for cancer therapy. Even as inhibitors that target PI3K isoforms and other major nodes in the pathway, including AKT and mammalian target of rapamycin (mTOR), reach clinical trials, major issues remain. Here, we highlight recent progress that has been made in our understanding of the PI3K pathway and discuss the potential of and challenges for the development of therapeutic agents that target this pathway in cancer. PMID- 19644477 TI - Potential restoration of HDL function with apolipoprotein A-I mimetic peptide in end-stage renal disease. AB - High-density lipoprotein (HDL) cholesterol level is low in dialysis patients. The HDL that is present is dysfunctional, failing to protect low-density lipoprotein (LDL) from oxidation and reduce levels of oxidized LDL. Addition of the orally absorbable amphipathic peptide 4-F to LDL obtained from dialysis patients protects LDL from oxidation in vitro and reduces the capacity of oxidized LDL to induce expression of monocyte chemoattractant protein-1 (MCP-1) by vascular endothelial function in culture, potentially providing a tool to reduce cardiovascular risk in dialysis patients. PMID- 19644478 TI - It's not over till the last glomerulus forms. AB - The Brenner hypothesis postulated that low birth weight and decreased nephron number at birth are linked to chronic kidney disease and systemic hypertension in adulthood. To date, little is known about the effect of extrauterine growth retardation (EUGR) on adult kidney disease. Bacchetta et al. present novel data using inulin to show a decrease in renal function for premature children with EUGR. The role of protein nutrition and timing in nephrogenesis is discussed. PMID- 19644474 TI - Therapeutic manipulation of immune tolerance in allergic disease. AB - Immune tolerance - the adaptation of the immune system to external antigens or allergens - might be therapeutically manipulated to restore normal immunity in conditions such as allergy, asthma and autoimmune diseases. The field of allergen specific immunotherapy is experiencing exciting and novel developments for the treatment of allergic and autoimmune diseases, and recent insights into the reciprocal regulation and counter-balance between different T-cell subsets is foreseen to facilitate new strategies for immunointervention. This Review highlights current knowledge of immunomodulatory therapies for the manipulation of immune tolerance and highlights recent approaches to improve allergen-specific immunotherapy for the treatment of allergic diseases. PMID- 19644479 TI - Tissue transglutaminase inhibition as treatment for diabetic glomerular scarring: it's good to be glueless. AB - Diabetic nephropathy is characterized by enhanced glomerular and tubulointerstitial deposition of extracellular matrix proteins, which are bound together by tissue transglutaminase (TG2). Huang et al. demonstrate that infusion of a novel TG2 inhibitor in diabetic rats prevented renal scarring and albuminuria and preserved glomerular filtration rate. These studies confirm the role of TG2 in the pathogenesis of diabetic nephropathy and add to an emerging literature that demonstrates that TG2 is an attractive therapeutic target for sclerosing kidney diseases. PMID- 19644480 TI - Acute renal failure presenting as a granulomatous interstitial nephritis due to cryptococcal infection. PMID- 19644481 TI - The missing medullary sponge kidney. PMID- 19644482 TI - Clopidogrel in ESRD patients with acute coronary syndrome. PMID- 19644484 TI - It takes two to Twist. PMID- 19644486 TI - Dividing stage 3 of chronic kidney disease (CKD): 3A and 3B. PMID- 19644487 TI - Cystatin C levels are unaltered in patients with diabetes mellitus and normal renal function. PMID- 19644489 TI - The case: the eyes have it! PMID- 19644490 TI - Takotsubo cardiomyopathy in a patient undergoing hemodialysis. PMID- 19644491 TI - Gene therapy continues to mature and to face challenges. PMID- 19644494 TI - Rapid tumor cell swelling and bursting: beware of collateral damage. PMID- 19644496 TI - Genetic correction of hematopoiesis in Fanconi anemia: the case for a non-HSC autonomous defect. PMID- 19644499 TI - Stromal cell contributions to the homeostasis and functionality of the immune system. AB - A defining characteristic of the immune system is the constant movement of many of its constituent cells through the secondary lymphoid tissues, mainly the spleen and lymph nodes, where crucial interactions that underlie homeostatic regulation, peripheral tolerance and the effective development of adaptive immune responses take place. What has only recently been recognized is the role that non haematopoietic stromal elements have in many aspects of immune cell migration, activation and survival. In this Review, we summarize our current understanding of lymphoid compartment stromal cells, examine their possible heterogeneity, discuss how these cells contribute to immune homeostasis and the efficient initiation of adaptive immune responses, and highlight how targeting of these elements by some pathogens can influence the host immune response. PMID- 19644500 TI - ARF stimulates XPC to trigger nucleotide excision repair by regulating the repressor complex of E2F4. AB - The tumour suppressor ARF (alternative reading frame), which is mutated or silenced in various tumours, has a crucial role in tumour surveillance to suppress unwarranted cell growth and proliferation. ARF has also been linked to the DNA-damage-induced response of p53 because of its ability to inhibit murine double minute 2 (MDM2). Here, however, we provide genetic evidence for a role of ARF in nucleotide excision repair (NER) that is independent of p53. Cells lacking ARF are deficient in NER. Expression of ARF restores the repair activity, which coincides with increased expression of the damaged-DNA recognition protein xeroderma pigmentosum, complementation group C (XPC). We provide evidence that, by disrupting the interaction between E2F transcription factor 4 (E2F4) and DRTF polypeptide 1 (DP1), ARF reduces the interaction of the E2F4-p130 repressor complex with the promoter of XPC to ensure high-level expression of XPC. Together, our results point to an important 'care-taker'-type tumour-suppression function for ARF in NER through the increased expression of XPC. PMID- 19644501 TI - The SCAR and WASp nucleation-promoting factors act sequentially to mediate Drosophila myoblast fusion. AB - The actin nucleation-promoting factors SCAR/WAVE and WASp, together with associated elements, mediate the formation of muscle fibres through myoblast fusion during Drosophila embryogenesis. Our phenotypic analysis, following the disruption of these two pathways, suggests that they function in a sequential manner. Suppressor of cyclic AMP receptor (SCAR) activity is required before the formation of pores in the membranes of fusing cells, whereas Wiskott-Aldrich syndrome protein (WASp) promotes the expansion of nascent pores and completion of the fusion process. Genetic epistasis experiments are consistent with this step wise temporal progression. Our observations further imply a separate, Rac dependent role for the SCAR complex in promoting myoblast migration. In keeping with the sequential utilization of the two systems, we observe abnormal accumulations of filamentous actin at the fusion sites when both pathways are disrupted, resembling those present when only SCAR-complex function is impaired. This observation further suggests that actin-filament accumulation at the fusion sites might not depend on Arp2/3 activity altogether. PMID- 19644502 TI - A functional antagonism between the pgc germline repressor and torso in the development of somatic cells. AB - Segregation of the germline is a fundamental event during early development. In Drosophila, germ cells are specified at the posterior pole of the embryo by the germplasm. As zygotic expression is activated, germ cells remain transcriptionally silent owing to the polar granule component (Pgc), a small peptide present in germ cells. Somatic cells at both the embryonic ends are specified by the torso (Tor) receptor tyrosine kinase, and in tor mutants the somatic cells closer to the germ cells fail to cellularize correctly. Here, we show that extra wild-type gene copies of pgc cause a similar cellularization phenotype, and that both excessive pgc and a lack of tor are associated with an impairment of transcription in somatic cells. Moreover, a lack of pgc partly ameliorates the cellularization defect of tor mutants, thus revealing a functional antagonism between pgc and tor in the specification of germline and somatic properties. As transcriptional quiescence is a general feature of germ cells, similar mechanisms might operate in many organisms to 'protect' somatic cells that adjoin germ cells from inappropriately succumbing to such quiescence. PMID- 19644503 TI - Association between central systolic blood pressure, white matter lesions in cerebral MRI and carotid atherosclerosis. AB - White matter hyperintensities (WMHs) observed on cerebral magnetic resonance images (MRIs) are associated with age and hypertension, suggesting a vascular mechanism of pathogenesis. Central systolic blood pressure (cSBP) correlates more closely with measures of cardiovascular disease risk than brachial pressure. We sought to determine whether cSBP correlates with WMHs and if cSBP is predictive of cerebrovascular disease. Radial applanation tonometric measurements for cSBP and augmentation index (AI) were carried out in unselected individuals undergoing carotid ultrasound. WMHs were assessed retrospectively using fluid-attenuated inversion recovery (FLAIR)-MRIs as periventricular (PVH) and deep white matter hyperintensities (DWMH), and they were rated using the Fazekas scale. A total of 179 patients, 94 (53%) men and 85 (47%) women, with a mean age of 66+/-13 years were included in the study. On MRI, 17, 74, 67 and 21 patients had PVH grades 0, 1, 2 and 3, respectively. Forty-eight, 69, 49 and 13 had DWMH grades 0, 1, 2 and 3, respectively. In our study population, PVH correlated with age, brachial SBP, cSBP and AI (r=0.49, 0.28, 0.23; P<0.002 and r=0.13; P<0.05, respectively). DWMH also correlated with age, brachial SBP and cSBP (r=0.41, 0.30, 0.22; P<0.003, respectively), but not with AI. cSBP values were associated with PVH/DWMH grades 2 and 3, but brachial SBP correlated only with grade 3. Mean carotid intima-media thickness (common carotid arteries (CCA)-IMT) was 0.68+/-0.13 mm. CCA-IMT and plaque score (PS) correlated with PVH/DWMH. Multivariate regression analysis showed cSBP, age and PS to be independently associated with PVH and DWMH. Correlation of cSBP with PVH and DWMH was independent of PS. Central SBP correlated with PVH and DWMH in FLAIR-MRIs and can better predict WMHs than brachial SBP in earlier stages. PMID- 19644504 TI - Hemodynamics of dexamethasone-induced hypertension in the rat. AB - Although dexamethasone (DEX) is known to cause hypertension in humans and in animals, the hemodynamic characteristics of DEX-induced hypertension (DEX-HT) in the rat remain unclear. This study evaluated central and regional hemodynamics, and the role of total peripheral resistance (TPR) using a vasodilator minoxidil. Rats were divided into four groups, namely saline (n=20), DEX (n=21), minoxidil+saline (n=10) and minoxidil+DEX (n=10). Tail-cuff systolic blood pressure was recorded every second day. After 10-14 days of treatment, central (saline: n=9, DEX: n=10) and regional (saline: n=11, DEX: n=11) hemodynamic parameters were measured. Central hemodynamic data were also obtained from minoxidil-treated rats. DEX increased blood pressure (P<0.0005) in association with an increase in TPR (P<0.05). However, individual assessments of renal, mesenteric and hindquarter circulations did not detect any significant increase in resistance in these beds. Minoxidil increased cardiac output (P'<0.01) and cardiac index (P'<0.005) as well as decreased TPR (P'<0.05) without affecting DEX HT. DEX prevented weight gain and decreased thymus weight. The increase in TPR in DEX-HT in rats was not simply explained by isolated alterations to resistance in the renal, mesenteric or hindquarter circulations. Minoxidil effectively prevented the increase in TPR but not the increase in blood pressure, suggesting that an increase in TPR is not essential for DEX-induced blood pressure increase. PMID- 19644505 TI - The efficacy and safety of sildenafil in Chinese patients with pulmonary arterial hypertension. AB - Sildenafil has been suggested to be a cost-effective treatment for pulmonary arterial hypertension (PAH). On account of the lack of data confirming its benefit in PAH patients, sildenafil has not been adopted in China for the treatment of PAH. The purpose of this study was to evaluate the efficacy, safety and 1-year survival of Chinese patients with PAH treated with sildenafil. Sixty Chinese patients with PAH were enrolled in this preliminary study. Their 6-min walk distance, WHO functional class and hemodynamic parameters (such as right atrial pressure, pulmonary arterial pressure, cardiac index and pulmonary vascular resistance) at both baseline and 16 weeks after initiation of sildenafil treatment were recorded. In addition, 1-year overall survival was assessed in this cohort. The 6-min walk distance improved from 392.13+/-91.35 to 467.22+/ 80.38 m during the course of treatment (P<0.001). There was a significant decrease in the mean pulmonary vascular resistance (15.28+/-8.12-14.99+/-7.88 Woods units; P=0.02) and a significant increase in the mean cardiac index (2.39+/ 0.90-2.75+/-0.92 l/min/m(2), P=0.006) of the included patients at 16 weeks. The mean systemic oxygen saturation improved significantly at 16 weeks (91.44+/-7.54% 94.11+/-4.28%; P=0.002). No serious adverse reactions were reported. The Kaplan Meier analysis showed that the 1-year survival rate improved significantly in the sildenafil-treated cohort compared with predicted survival (94.7% compared with 63.3%, P=0.03). In conclusion, sildenafil may be a safe and effective treatment for Chinese PAH patients. Sildenafil, when added to conventional therapy, was associated with improvements in exercise capacity, hemodynamic parameters and overall survival in a cohort of Chinese patients with PAH. PMID- 19644506 TI - Effect of heart rate on the risk of developing metabolic syndrome. AB - High heart rate and metabolic syndrome are risk factors for cardiovascular morbidity and mortality. The relationship between heart rate and risk of developing metabolic syndrome has not been studied in a large cohort. We examined the relationship between heart rate and the risk of developing metabolic syndrome in individuals who participated in a health evaluation program from 1997 to 2002. Among the 7958 individuals who participated in the program, 1677 were excluded from our study because they were being treated for heart disease or had been diagnosed with metabolic syndrome at baseline examination. A total of 6281 individuals (3789 men and 2492 women, 20-89 years of age) were evaluated. They were categorized according to their baseline heart rate and were followed up for a mean of 47+/-16 months (range: 7-71 months). Over the 5-year period, 619 individuals (9.9%) developed metabolic syndrome. Men with elevated baseline heart rates were more likely to experience metabolic syndrome than were those with normal heart rates. This was not true for female patients. The odds ratio (95% confidence interval) of developing metabolic syndrome among men in the highest quartile for heart rate was 1.725 (1.282-2.320) compared with those in the lowest quartile. Each increase in the heart rate category led to an approximately 1.2 fold increase in the risk of developing metabolic syndrome for men only, even after adjusting for age and lifestyle. Elevated heart rate is a risk factor for developing metabolic syndrome in men. PMID- 19644507 TI - Peroxisome proliferator-activated receptor-alpha activator fenofibrate prevents high-fat diet-induced renal lipotoxicity in spontaneously hypertensive rats. AB - We investigated the effects of a high-fat (HF) diet and peroxisome proliferator activated receptor (PPAR)-alpha activation on the intrarenal lipotoxicity associated with the renin-angiotensin system (RAS) and oxidative stress using spontaneously hypertensive (SHR) rats. Male SHR and Wistar-Kyoto (WKY) rats at 8 weeks of age were fed either a normal-fat diet or an HF diet without or with fenofibrate treatment for 12 weeks. Severe intrarenal lipid accumulation was noted in the SHR rats fed an HF diet than in WYK rats fed an HF diet (P<0.05). This lipid accumulation was associated with a 70% decrease in renal PPARalpha expression in SHR rats, whereas an HF diet increased the expression of PPARalpha in WKY rats by threefold. An HF diet also activated intrarenal, not systemic, RAS and induced oxidative stress associated with reduced nitric oxide (NO) bioavailability. By contrast, fenofibrate attenuated weight gain, fat mass and insulin resistance. Fenofibrate recovered HF diet-induced decreases in intrarenal PPARalpha expression and fat accumulation, and abolished intrarenal RAS activation and oxidative stress in SHR-HF animals (P<0.01). These activities conferred protection against increased blood pressure (BP), glomerulosclerosis and renal inflammation. Intrarenal free fatty acid and triglyceride concentrations were positively correlated with angiotensin II (gamma=0.63, 0.36) and 24-h urinary 8-hydroxy-deoxyguanosine (gamma=0.36, 0.39), and negatively correlated with PPARalpha contents (gamma=-0.47, -0.44; P<0.05). An HF diet induced lipotoxicity by depletion of intrarenal PPARalpha aggravated BP and renal inflammation as a result of intrarenal RAS activation and oxidative stress. Therefore, intervention with PPARalpha activators can effectively prevent diet induced renal lipotoxicity in hypertensive rats. PMID- 19644508 TI - PICK1-mediated GluR2 endocytosis contributes to cellular injury after neuronal trauma. AB - Constitutive and activity-dependent regulation of the AMPA receptor GluR2 content is recognized as an important mediator of both neuronal plasticity and vulnerability to excitotoxic neuron death. In the latter case, inclusion of GluR2 protects against glutamate excitotoxicity in CNS disease by lowering receptor single-channel conductance and preventing deleterious calcium influx. We investigated the hypothesis that aberrations in GluR2 trafficking after in vitro and in vivo cerebral trauma contribute to excitotoxicity and associated calcium dependent cell death processes. First, in an in vitro model of traumatic brain injury (TBI), we observed PICK1 and N-methyl-D-aspartic acid (NMDA) receptor dependent phosphorylation and internalization of GluR2. The contributing cell signaling mechanisms involved enhanced binding between PKCalpha (the kinase that phosphorylates GluR2) and PICK1 (its PDZ-binding partner), and a novel protein interaction between PKCalpha and the NMDA receptor scaffolding protein PSD-95. Functionally, these phenomena enhanced single cell AMPAR mEPSCs and protracted calcium extrusion. In vivo TBI similarly promoted GluR2 phosphorylation and internalization, with enhanced expression of calcium-permeable AMPARs in the injured hippocampus. Peptide-mediated perturbation of the PKCalpha/PICK1 protein interaction after trauma preserved surface GluR2 expression, attenuated AMPAR mediated toxicity, and occluded the sensitivity of neuronal physiology to calcium permeable AMPAR antagonists. These findings suggest that experimental TBI promotes the expression of injurious GluR2-lacking AMPARs, thereby enhancing cellular vulnerability to secondary excitotoxicity. PMID- 19644509 TI - MicroRNAs as regulators of death receptors signaling. AB - Death receptors, belonging to the TNF receptor superfamily, induce apoptosis through two different pathways, one involving the effector caspases directly (type I cells or mitochondria-independent death), the other one amplifying the death signal through the mitochondrial pathway (type II cells or mitochondria dependent death). MicroRNAs (miRNAs) are a class of small noncoding RNAs that regulate the stability or translational efficiency of targeted messenger RNAs. MiRNAs are involved in many cellular processes that are altered in cancer, such as differentiation, proliferation and apoptosis. In this review we will discuss recent findings implicating miRNAs as regulators of death receptors and pro- and antiapoptotic genes involved in programmed cell death pathways. PMID- 19644510 TI - Granzyme F induces a novel death pathway characterized by Bid-independent cytochrome c release without caspase activation. AB - Granzyme F (GzmF) belongs to a unique group of granzymes in mice. Murine GzmF is highly expressed in NK3.1 cells and in lymphokine-activated killer (LAK) cells. However, the manner in which GzmF works in granule-mediated cytolysis is unknown. In this study, we first demonstrated that GzmF causes a novel cell death pathway. The death is characterized by an externalization of phosphatidylserine, by nuclear condensation, mitochondrial damage, cytochrome c (cyt c) release, caspase inactivation and single-stranded DNA nicking. GzmF-induced chromatin was incompletely condensed and segmented at the nuclear periphery. Cellular organelles were damaged and the cytoplasm showed an extensive vacuolization that is reminiscent of necroptosis. GzmF can cause rapid mitochondrial swelling, depolarization and reactive oxygen species accumulation. GzmF-induced death does not involve caspase activation, Bid cleavage or activation of DNA nickase NM23H1. GzmF-silenced LAK cells showed reduced cytotoxicity against caspase-inhibited target tumor cells. Moreover, cyt c release is independent of Bid or Bax/Bak. We further showed that GzmF impairs mitochondrial electron transport to abolish ATP generation. ATP decline may contribute to a failure of apoptosome formation, leading to caspase inactivation. PMID- 19644511 TI - IPS-1 is crucial for DAP3-mediated anoikis induction by caspase-8 activation. AB - Detachment of adherent epithelial cells from the extracellular matrix induces apoptosis, a process known as anoikis. We have shown that DAP3 is critical for anoikis induction. However, the mechanism for anoikis induction mediated by DAP3 is still unclear. Here, we show that interferon-beta promoter stimulator 1 (IPS 1) binds DAP3 and induces anoikis by caspase activation. Recently, IPS-1 has been shown to be critical for antiviral immune responses, although there has been no report of its function in apoptosis induction. We show that overexpression of IPS 1 induces apoptosis by activation of caspase-3, -8, and -9. In addition, IPS-1 knockout mouse embryonic fibroblasts were shown to be resistant to anoikis. Interestingly, IPS-1 expression, recruitment of caspase-8 to IPS-1, and caspase-8 activation were induced after cell detachment. Furthermore, DAP3-mediated anoikis induction was inhibited by knockdown of IPS-1 expression. Therefore, we elucidated a novel function of IPS-1 for anoikis induction by caspase-8 activation. PMID- 19644512 TI - The adenine nucleotide translocator 1 acts as a type 2 transglutaminase substrate: implications for mitochondrial-dependent apoptosis. AB - In this study we provide in vitro and in vivo evidence showing that the protein disulphide isomerase (PDI) activity of type 2 transglutaminase (TG2) regulates the correct assembly and function of the mitochondrial ADP/ATP transporter adenine nucleotide translocator 1 (ANT1). We demonstrate, by means of biochemical and morphological analyses, that ANT1 and TG2 physically interact in the mitochondria. Under physiological conditions, TG2's PDI activity regulates the ADP/ATP transporter function by controlling the oligomerization of ANT1. In fact, mitochondria isolated from hearts of TG2(-/-) mice exhibit increased polymerization of ANT1, paralleled by an enhanced ADP/ATP carrier activity, as compared to mitochondria belonging to TG2(+/+) mice. Interestingly, upon cell death induction, ANT1 becomes a substrate for TG2's cross-linking activity and the lack of TG2 results in a reduction of apoptosis as well as in a marked sensitivity to the ADP/ATP exchange inhibition by atractyloside. These findings suggest a complex TG2-dependent regulation of the ADP/ATP transporter and reveal new important avenues for its potential applications in the treatment of some mitochondrial-dependent diseases, including cardiovascular and neurodegenerative diseases. PMID- 19644513 TI - Japanese map of the earwax gene frequency: a nationwide collaborative study by Super Science High School Consortium. AB - Wet/dry types of earwax are determined by the c.538G>A single-nucleotide polymorphism (SNP) in the ABCC11 gene; GA and GG genotypes give the wet type and AA the dry type. The Japanese population may have a dual structure comprising descendants of mixtures between the ancient 'Jomon' and 'Yayoi' populations. We hypothesized that the dry type was introduced by the Yayoi people to the Jomon population where the wet type was predominant, and as the mixture of the two populations has not yet been complete, the allele-A frequency (f(A)) would even now be higher along a putative Yayoi man's peopling route within Japanese islands. To know the frequency, a nationwide Super Science High School (SSH) Consortium collected 1963 fingernail samples of pupils/students from at least one high school/university in every prefecture. All further procedures, DNA extraction, SNP genotyping and gene frequency estimation, were carried out by trained SSH pupils. Although the allele-A frequency varied among the 47 prefectures, the Gifu/Kyoto and Okinawa prefectures showed the highest and lowest values, respectively. Areas with high frequencies included Northeastern Kyushu, Northern Shikoku and Kinki districts, showing a belt-like zone, whereas those with low frequencies other than Okinawa were the Southwestern Kyushu, Hiroshima prefecture and Tohoku districts. The f(A) value in Kinki district was statistically higher than those in prefectures westward and east-northward from it. The result may provide another line of evidence supporting a possible route of the Yayoi-man's peopling in Japan. PMID- 19644514 TI - A survey of the population genetic variation in the human kinome. AB - Protein kinases are key regulators of various biological processes, such as control of cell growth, metabolism, differentiation and apoptosis. Therefore, protein kinases have been an important class of targets for anticancer drugs. Health-related disparities such as differential drug response have been observed between human populations. A survey of the human kinases and their ligand genes for those containing population-specific genetic variants could provide new insights into the mechanisms of these health disparities and suggest novel targets for ethnicity-specific personalized medicine. Using the International HapMap Project genotypic data on single-nucleotide polymorphisms (SNPs), the protein kinase complement of the human genome (kinome) and some experimentally verified ligand genes were scanned for the existence of population-specific SNPs (eSNPs). In general, protein kinases were found to contain a much higher proportion of eSNPs than the whole genome background, indicating a stronger pressure for adaptation in individual populations. In contrast, the proportion of ligand genes containing eSNPs was not different from that of the whole genome background. Although with some important limitations, our results suggest that human kinases are more likely to be under recent positive selection than ligands. Our findings suggest that the health-related disparities associated with kinase signaling pathways are more likely to be driven by the genetic variation in the kinase genes than their cognate ligands. Illustrating the role of molecular evolution in the genetic variation of the human kinome could provide a promising route to understand the ethnic differences in cancer and facilitate the realization of ethnicity-based individualized medicine. PMID- 19644515 TI - Structural bases of GM1 gangliosidosis and Morquio B disease. AB - Allelic mutations of the lysosomal beta-galactosidase gene cause heterogeneous clinical phenotypes, such as GM1 gangliosidosis and Morquio B disease, the former being further classified into three variants, namely infantile, juvenile and adult forms; and heterogeneous biochemical phenotypes were shown in these forms. We tried to elucidate the bases of these diseases from a structural viewpoint. We first constructed a three-dimensional structural model of human beta galactosidase by means of homology modeling. The human beta-galactosidase consists of three domains, such as, a TIM barrel fold domain, which functions as a catalytic domain, and two galactose-binding domain-like fold domains. We then constructed structural models of representative mutant beta-galactosidase proteins (G123R, R201C, I51T and Y83H) and predicted the structural change associated with each phenotype by calculating the number of affected atoms, determining the root-mean-square deviation and the solvent-accessible surface area, and by color imaging. The results show that there is a good correlation between the structural changes caused by amino-acid substitutions in the beta galactosidase molecule, as well as biochemical and clinical phenotypes in these representative cases. Protein structural study is useful for elucidating the bases of these diseases. PMID- 19644516 TI - Gombapyrones, new alpha-pyrone metabolites produced by Streptomyces griseoruber Acta 3662. AB - Gombapyrones A-D, new members of the alpha-pyrone family of secondary metabolites, were produced by Streptomyces griseoruber Acta 3662, which was isolated from bamboo tree rhizosphere. The strain was characterized by its morphological and chemotaxonomical features and by 16S rDNA sequencing as S. griseobuber. The gombapyrone structures were determined by mass spectrometry and by NMR experiments, and were found to have an inhibitory activity against protein tyrosine phosphatase 1B and glycogen synthase kinase 3beta. PMID- 19644517 TI - Nitro derivatives from the Arctic ice bacterium Salegentibacter sp. isolate T436. AB - Twenty-five aromatic nitro, dinitro and trinitro compounds were isolated in low yields of less than 1 mg l(-1) from a Salegentibacter sp. strain T436 derived from Arctic pack ice. Their structures were elucidated by MS and NMR techniques. Seven of these compounds, namely, 2-hydroxy-3-(4'-hydroxy-3'-nitrophenyl) propionic acid methyl ester (6), 2-chloro-3- (4'-hydroxy-3'-nitrophenyl)propionic acid methyl ester (7), 3-(4'-hydroxy-3',5'-dinitrophenyl)-propionic acid methyl ester (14), 4'-hydroxy-3',5'-dinitrophenylethylchloride (16), (4'-hydroxy-3',5' dinitrophenyl)-2-chloropropionic acid methyl ester (17), N-acetyl-3',5' dinitrotyramine (18) and 2,6-dinitro-4-(2'-nitroethenyl)phenol (19) are new, and five are reported in this study from a natural source for the first time. PMID- 19644518 TI - Haplofungins, novel inositol phosphorylceramide synthase inhibitors, from Lauriomyces bellulus SANK 26899 I. Taxonomy, fermentation, isolation and biological activities. AB - In the course of screening for antifungal agents, we have discovered eight novel compounds, haplofungin A, B, C, D, E, F, G and H, from a culture broth of the fungus strain Lauriomyces bellulus SANK 26899. Haplofungins are composed of an arabinonic acid moiety linked through an ester to a modified long alkyl chain and show potent inhibitory activities against fungal inositol phosphorylceramide (IPC) synthase. Haplofungin A inhibited the activity of IPC synthase from Saccharomyces cerevisiae with an IC(50) value of 0.0015 microg ml(-1). This inhibitor also suppressed the growth of Candida glabrata at the MIC value of 0.5 microg ml(-1). PMID- 19644519 TI - Haplofungins, new inositol phosphorylceramide synthase inhibitors, from Lauriomyces bellulus SANK 26899 II. Structure elucidation. AB - Eight new inositol phosphorylceramide synthase inhibitors: haplofungin A, B, C, D, E, F, G and H, were discovered in a culture broth of the fungus Lauriomyces bellulus SANK 26899. The planar structures for these haplofungins were elucidated by various spectroscopic analyses and a GC/MS analysis of their degradation products. All eight compounds were found to comprise an arabinonic acid moiety linked through an ester bond to a modified long alkyl chain. PMID- 19644520 TI - Biosynthetic genes for aminoglycoside antibiotics. AB - Biosynthetic studies of aminoglycoside antibiotics have progressed remarkably during the last decade. Many biosynthetic gene clusters for aminoglycoside antibiotics including streptomycin, kanamycin, butirosin, neomycin and gentamicin have been identified to date. In addition, most butirosin and neomycin biosynthetic enzymes have been functionally characterized using recombinant proteins. Herein, we reanalyze biosynthetic genes for structurally related 2 deoxystreptamine (2DOS)-containing aminoglycosides, such as kanamycin, gentamicin and istamycin, based on genetic information including characterized biosynthetic enzymes in neomycin and butirosin biosynthetic pathways. These proposed enzymatic functions for uncharacterized enzymes are expected to support investigation of the complex biosynthetic pathways for this important class of antibiotics. PMID- 19644521 TI - KDIGO clinical practice guideline for the diagnosis, evaluation, prevention, and treatment of Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD). AB - The 2009 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline on the management of chronic kidney disease-mineral and bone disorder (CKD-MBD) is intended to assist the practitioner caring for adults and children with CKD stages 3-5, on chronic dialysis therapy, or with a kidney transplant. The guideline contains recommendations on evaluation and treatment for abnormalities of CKD-MBD. This disease concept of CKD-MBD is based on a prior KDIGO consensus conference. Tests considered are those that relate to the detection and monitoring of laboratory, bone, and cardiovascular abnormalities. Treatments considered are interventions to treat hyperphosphatemia, hyperparathyroidism, and bone disease in patients with CKD stages 3-5D and 1-5T. The guideline development process followed an evidence based approach and treatment recommendations are based on systematic reviews of relevant treatment trials. Recommendations for testing used evidence based on diagnostic accuracy or risk prediction and linked it indirectly with how this would be expected to achieve better outcomes for patients through better detection, evaluation or treatment of disease. Critical appraisal of the quality of the evidence and the strength of recommendations followed the GRADE approach. An ungraded statement was provided when a question did not lend itself to systematic literature review. Limitations of the evidence, especially the lack of definitive clinical outcome trials, are discussed and suggestions are provided for future research. PMID- 19644531 TI - Viruses, gene therapy and stem cells for the treatment of human glioma. AB - Cancer gene therapy is based on the transfer of genetic material to cancer cells to modify a normal or abnormal cellular function, or to induce cell death. Modified viruses or stem cells have been used as carriers to transfer the genetic material to cancer cells avoiding trafficking through normal cells. However, although the current vectors have been successful in delivering genes in vitro and in vivo, little has been achieved with human cerebral gliomas. Poor transduction efficiency of viruses in human glioma cells and limited spread and distribution to the tumor limits our current expectations for successful gene therapy of central nervous system cancer until and if effective transfer vehicles are available. Nevertheless, continuing research in better vector development may overcome these limitations and offer a therapeutic advantage over the standard therapies for glioma. PMID- 19644532 TI - Surgery: are we performing enough tonsillectomies? PMID- 19644534 TI - Targeted therapies: GIST adjuvant therapy-some answers and more questions. PMID- 19644533 TI - Pediatric oncology: methotrexate-exploring dosing and administration in ALCL. PMID- 19644535 TI - Radiotherapy: prophylactic cranial irradiation for small-cell lung cancer. PMID- 19644536 TI - Eleven years disease-free: role of chemotherapy in metastatic BRCA2-related breast cancer. AB - BACKGROUND: Infiltrating ductal carcinoma of the breast, staged as pT1N3, was diagnosed in a 41-year-old premenopausal French-Canadian woman. Rapid nodal recurrence progressed to diffuse bone metastases, despite tamoxifen and megestrol. Following enrollment in an in-house study protocol, she received high dose anthracycline-based induction chemotherapy followed by tandem autologous bone marrow transplantation with high-dose alkylator and platinum-based conditioning regimens. Upon full remission, protocol-mandated locoregional breast and prophylactic cranial radiation was delivered. Complete clinical and radiologic remission has been maintained in the 11 years since study enrolment, which prompted further investigation. INVESTIGATIONS: Pedigree construction and BRCA1/2 mutation analysis. DIAGNOSIS: A BRCA2 8765delAG mutation was identified, in the context of unusual and sustained complete remission from widely metastatic breast cancer. MANAGEMENT: The patient is now followed at a multidisciplinary high-risk prevention clinic because BRCA2 mutations are associated with increased risk of ovarian and breast cancers. This case supports the possibility of differential treatment response in BRCA2-positive breast cancer, although this remains to be conclusively demonstrated. PMID- 19644537 TI - Comprehensive evidence-based guidelines for interventional techniques in the management of chronic spinal pain. AB - BACKGROUND: Comprehensive, evidence-based guidelines for interventional techniques in the management of chronic spinal pain are described here to provide recommendations for clinicians. OBJECTIVE: To develop evidence-based clinical practice guidelines for interventional techniques in the diagnosis and treatment of chronic spinal pain. DESIGN: Systematic assessment of the literature. METHODS: Strength of evidence was assessed by the U.S. Preventive Services Task Force (USPSTF) criteria utilizing 5 levels of evidence ranging from Level I to III with 3 subcategories in Level II. OUTCOMES: Short-term pain relief was defined as relief lasting at least 6 months and long-term relief was defined as longer than 6 months, except for intradiscal therapies, mechanical disc decompression, spinal cord stimulation and intrathecal infusion systems, wherein up to one year relief was considered as short-term. RESULTS: The indicated evidence for accuracy of diagnostic facet joint nerve blocks is Level I or II-1 in the diagnosis of lumbar, thoracic, and cervical facet joint pain. The evidence for lumbar and cervical provocation discography and sacroiliac joint injections is Level II-2, whereas it is Level II-3 for thoracic provocation discography. The indicated evidence for therapeutic interventions is Level I for caudal epidural steroid injections in managing disc herniation or radiculitis, and discogenic pain without disc herniation or radiculitis. The evidence is Level I or II-1 for percutaneous adhesiolysis in management of pain secondary to post-lumbar surgery syndrome. The evidence is Level II-1 or II-2 for therapeutic cervical, thoracic, and lumbar facet joint nerve blocks; for caudal epidural injections in managing pain of post-lumbar surgery syndrome, and lumbar spinal stenosis, for cervical interlaminar epidural injections in managing cervical pain (Level II-1); for lumbar transforaminal epidural injections; and spinal cord stimulation for post lumbar surgery syndrome. The indicated evidence for intradiscal electrothermal therapy (IDET), mechanical disc decompression with automated percutaneous lumbar discectomy (APLD), and percutaneous lumbar laser discectomy (PLDD) is Level II-2. LIMITATIONS: The limitations of these guidelines include a continued paucity of the literature, lack of updates, and conflicts in preparation of systematic reviews and guidelines by various organizations. CONCLUSION: The indicated evidence for diagnostic and therapeutic interventions is variable from Level I to III. These guidelines include the evaluation of evidence for diagnostic and therapeutic procedures in managing chronic spinal pain and recommendations for managing spinal pain. However, these guidelines do not constitute inflexible treatment recommendations. Further, these guidelines also do not represent "standard of care." PMID- 19644539 TI - Glandular odontogenic cyst: report of two cases and review of literature. AB - Glandular odontogenic cyst (GOC) is an uncommon jaw bone cyst of odontogenic origin described in 1987 by Gardner et al. It is a cyst having an unpredictable and potentially aggressive behaviour. It also has the propensity to grow to a large size and tendency to recur with only 111 cases having been reported thus far. The first case occurred in a 42-year-old female and presented as a localized swelling extending from 19 to 29 regions. There was a history of traumatic injury at the site. There was evidence of bicortical expansion and radiographs revealed a multilocular radiolucency. The second case occurred in a 21-year-old male, as a large swelling in the mandible and radiograph revealed radiolucency in the region. On histopathological examination, these lesions were diagnosed as GOC. It was concluded that, two cases submitted by us correlate with the existing literature that GOC's affect more commonly in the middle age group, having predilection for mandible and that trauma could be a precipitating factor for its occurrence. The increased recurrence rates can be due to its intrinsic biological behavior, multilocularity of the cyst, and incomplete removal of the lining following conservative treatment. PMID- 19644538 TI - A case of recurrent multifocal central giant cell granulomas. AB - One case of recurrent multifocal central giant cell granulomas (CGCG) is presented. Initially, the lesions presented concurrently in the maxilla and mandible with subsequent recurrence in the mandible. Now, two recurrences are seen in the maxillary sinus and ethmoid region. The literature regarding multifocal CGCG is reviewed. PMID- 19644540 TI - Primary extracranial meningiomas: an analysis of 146 cases. AB - Primary extracranial meningiomas are rare neoplasms, frequently misdiagnosed, resulting in inappropriate clinical management. To date, a large clinicopathologic study has not been reported. One hundred and forty-six cases diagnosed between 1970 and 1999 were retrieved from the files of the Armed Forces Institute of Pathology. Histologic features were reviewed, immunohistochemistry analysis was performed (n = 85), and patient follow-up was obtained (n = 110). The patients included 74 (50.7%) females and 72 (49.3%) males. Tumors of the skin were much more common in males than females (1.7:1). There was an overall mean age at presentation of 42.4 years, with a range of 0.3-88 years. The overall mean age at presentation was significantly younger for skin primaries (36.2 years) than for ear (50.1 years) and nasal cavity (47.1 years) primaries. Symptoms were in general non-specific and reflected the anatomic site of involvement, affecting the following areas in order of frequency: scalp skin (40.4%), ear and temporal bone (26%), and sinonasal tract (24%). The tumors ranged in size from 0.5 up to 8 cm, with a mean size of 2.3 cm. Histologically, the majority of tumors were meningothelial (77.4%), followed by atypical (7.5%), psammomatous (4.1%) and anaplastic (2.7%). Psammoma bodies were present in 45 tumors (30.8%), and bone invasion in 31 (21.2%) of tumors. The vast majority were WHO Grade I tumors (87.7%), followed by Grade II (9.6%) and Grade III (2.7%) tumors. Immunohistochemically, the tumor cells labeled for EMA (76%; 61/80), S-100 protein (19%; 15/78), CK 7 (22%; 12/55), and while there was ki-67 labeling in 27% (21/78), <3% of cells were positive. The differential diagnosis included a number of mesenchymal and epithelial tumors (paraganglioma, schwannoma, carcinoma, melanoma, neuroendocrine adenoma of the middle ear), depending on the anatomic site of involvement. Treatment and follow-up was available in 110 patients: Biopsy, local excision, or wide excision was employed. Follow-up time ranged from 1 month to 32 years, with an average of 14.5 years. Recurrences were noted in 26 (23.6%) patients, who were further managed by additional surgery. At last follow-up, recurrent disease was persistent in 15 patients (mean, 7.7 years): 13 patients were dead (died with disease) and two were alive; the remaining patients were disease free (alive 60, mean 19.0 years, dead 35, mean 9.6 years). There is no statistically significant difference in 5-year survival rates by site: ear and temporal bone: 83.3%; nasal cavity: 81.8%; scalp skin: 78.5%; other sites: 65.5% (P = 0.155). Meningiomas can present in a wide variety of sites, especially within the head and neck region. They behave as slow-growing neoplasms with a good prognosis, with longest survival associated with younger age, and complete resection. Awareness of this diagnosis in an unexpected location will help to avoid potential difficulties associated with the diagnosis and management of these tumors. PMID- 19644542 TI - Sialadenosis in patients with advanced liver disease. AB - Sialadenosis (sialosis) has been associated most often with alcoholic liver disease and alcoholic cirrhosis, but a number of nutritional deficiencies, diabetes, and bulimia have also been reported to result in sialadenosis. The aim of this study was to determine the prevalence of sialadenosis in patients with advanced liver disease. Patients in the study group consisted of 300 candidates for liver transplantation. Types of liver disease in subjects with clinical evidence of sialadenosis were compared with diagnoses in cases who had no manifestations of sialadenosis. The data were analyzed for significant association. Sialadenosis was found in 28 of the 300 subjects (9.3%). Among these 28 cases, 11 (39.3%) had alcoholic cirrhosis. The remaining 17 (60.7%) had eight other types of liver disease. There was no significant association between sialadenosis and alcoholic cirrhosis (P = 0.389). These findings suggest that both alcoholic and non-alcoholic cirrhosis may lead to the development of sialadenosis. Advanced liver disease is accompanied by multiple nutritional deficiencies which may be exacerbated by alcohol. Similar metabolic abnormalities may occur in patients with diabetes or bulimia. Malnutrition has been associated with autonomic neuropathy, the pathogenic mechanism that has been proposed for sialadenosis. PMID- 19644541 TI - Solitary fibrous tumor of the oral cavity: clinicopathologic and immunohistochemical study of 21 cases. AB - We describe clinical, morphologic, and immunohistochemical features of 21 cases of solitary fibrous tumor presenting in the oral cavity. There were 9 male and 12 female patients with a median age of 51 years (range 37-83). The most common locations included the buccal mucosa (the most common site), lip, maxillary or mandibular vestibule and tongue. Histopathologic examination showed well circumscribed tumors with two well-defined patterns: the classic pattern with densely cellular areas alternating with hypocellular areas in a variably collagenous, vascular stroma and a more uniformly sclerotic pattern with only subtle classic areas. The spindle-shaped neoplastic cells consistently showed immunoreactivity for antibodies directed against CD34. Five of nineteen cases (26%) were reactive for CD99 and 19 of 19 for Bcl-2. Follow-up information was available in 17 cases and averaged 54 months, with no evidence of recurrence or metastasis in any of these patients. Awareness that solitary fibrous tumor may present in the oral cavity is important so that confusion with other spindle cell neoplasms can be avoided. We also briefly describe the differential diagnosis and compare this series, the largest single series of intraoral SFT, to cases previously reported in the literature. PMID- 19644543 TI - Orthokeratinized odontogenic cyst of the mandible with heterotopic cartilage. AB - Cartilaginous metaplasia is a rare but well-documented phenomenon occurring in the wall of odontogenic keratocyst. The mural cartilage not associated with odontogenic keratocyst has been reported only once in a maxillary teratoid cyst of congenital origin to our knowledge. A case presented is a 38-year-old man with intraosseous keratinizing epidermoid cyst in the mandible, the wall of which contained a nodule of mature hyaline cartilage. The present lesion likely represents a previously undescribed, histologic hybrid consisting of orthokeratinized odontogenic cyst and cartilaginous heterotopia. PMID- 19644544 TI - Acinic cell carcinoma with extensive neuroendocrine differentiation: a diagnostic challenge. AB - Primary salivary gland carcinoma with neuroendocrine differentiation is of rare occurrence, especially so in the parotid gland. Amongst the various reported primary tumors with neuroendocrine differentiation, acinic cell carcinoma (ACC) one such tumor. A 48 year old lady presented with a gradually increasing right infra-auricular swelling for a period of 1 year which enlarged suddenly in a short period. Contrast Enhanced Computed Tomography (CECT) suggested diagnosis of Pleomorphic Adenoma. Fine Needle Aspiration Cytology (FANC) yielded a cystic fluid suggesting a possibility of Warthin's tumor or Oncocytic lesion. Intraoperative findings were suggestive of a Warthin's tumor. Initial histopathological examination of the tumor was suggestive of neuroendocrine carcinoma. However, extensive sectioning revealed peripheral islands of ACC. Immunoexpression of S-100, Neuron specific Enolase (NSE), Chromogranin A and Synaptophysin confirmed the diagnosis. The possibility of neuroendocrine differentiation in a primary salivary gland tumor should be kept in mind whenever a salivary gland tumor shows only neuroendocrine histology. PMID- 19644545 TI - Multinucleated giant cells' incidence, immune markers, and significance: a study of 172 cases of papillary thyroid carcinoma. AB - Multinucleated giant cells (MGCs) are often detected in cases of papillary thyroid carcinoma (PTC). Their origin and significance, however, has not been established. One possibility is that they form in response to injury induced by fine needle aspiration biopsy (FNAB). Other hypotheses are that the chemically altered colloid produced by PTC induces MGCs to act as colloidophages, or else MGCs are a non-specific immune response ingesting neoplastic follicle cells. We assigned 172 cases of PTC a semi-quantitative score for MGCs. Cases with "many" MGCs were immunohistochemically stained for AEI/AEIII, CD68, and CD163 to assess for epithelial vs histiocytic differentiation, and for thyroglobulin and TTF-1 to assess for MGC ingestion of colloid or thyroid follicle cells respectively. Overall, we identified MGCs in 100/172 (58.1%) PTC specimens; in 45 (26.2%), "many" MGCs were found, while in 55 (31.9%) MGCs were "few." The mean sizes of PTC in cases with many as opposed to rare/no MGCs was 2.50 cm vs 1.8 [P = 0.003]. The cases of PTC with many MGCs had higher multifocality (26/45 vs 51/127 [P = 0.06]), extrathyroidal extension (21/45 vs 36/127 [P = 0.03]), and recurrence (8/45 vs 9/127 [P = 0.08]), than did cases with rare or no MGCs. The majority of patients both with and without numerous MGCs had previous histories of FNA or hemilobectomy: 40/45 and 99/127 respectively (P = 0.062). The majority of MGCs were positive for CD68 (45/45), CD163 (44/45), thyroglobulin (34/45) and negative for AEI/AEIII (44/45) and TTF-1 (44/45). These results indicate that MGCs in PTC are of histiocytic origin. Cases of PTC with many MGCs have a significantly greater likelihood of extrathyroidal extension and greater tumor size than cases with few/no MGCs. MGCs appear to be functioning largely as colloidophages. PMID- 19644547 TI - Cellular angiofibroma of oral mucosa: report of two cases. AB - Cellular angiofibroma is a benign vascular neoplasm that typically arises in the vulva, perineal, and paratesticular region. Microscopically the lesions exhibit multiple small, non-dilated capillary channels, many of which contain erythrocytes. The endothelial lining cells are prominent, with monomorphic oval nuclei. Interposed among the vessels are both delicate and mature collagen fibers with fibroblastic hypercellularity that is variable in older lesions where sclerosis is prominent. The lesions usually do not recur following simple excision. Recent evidence indicates that cellular angiofibromas may be cytogenetically related to spindle cell lipoma. This represents the first reported instances of cellular angiofibroma in the oral cavity. PMID- 19644546 TI - Non-functional parathyroid carcinoma: a review of the literature and report of a case requiring extensive surgery. AB - Parathyroid carcinoma is a rare malignancy, and only accounts for 0.5-2% of cases of primary hyperparathyroidism. Less than 10% of parathyroid carcinomas are non functional, and as such, they have been rarely reported in the literature. Importantly, margin status at resection is related to prognosis, and only a handful of case reports of non-functional carcinoma note this important parameter. Here we report the first case of non-functional parathyroid carcinoma with negative margins, and review the literature on this rare entity. Whether functional or non-functional, parathyroid carcinoma can often be difficult to differentiate from benign parathyroid adenoma. While diagnosis has been based on clinical and histological criteria, recent data concerning the molecular underpinnings of parathyroid carcinoma may allow for improved accuracy in distinguishing benign and malignant parathyroid tumors. PMID- 19644548 TI - Cementoblastoma. PMID- 19644549 TI - Chondromyxoid fibroma of sphenoid sinus with unusual calcifications: case report with literature review. AB - Chondromyxoid fibroma (CMF) is a rare benign primary tumor which usually affects the metaphyses of the long bone of the lower extremities in childhood and young adults. Rarely, CMF occurs in the skull base and parasinuses, which may be difficult to distinguish from chondrosarcoma or chordoma and other tumors in the head. It is composed of chondroid, myxoid, and fibrous tissue growth in a lobular pattern, infrequently with calcifications. We report one case of CMF involving the sphenoid sinus mimicking a chondrosarcoma. The tumor mass showed calcifications on images and histology. PMID- 19644550 TI - Adenoid cystic carcinoma ex pleomorphic adenoma of the parotid gland. AB - There is a considerable variation in the histologic subtype of epithelial malignancies among carcinoma ex pleomorphic adenomas (CXPA) and virtually any known carcinoma entity can develop. To our knowledge, adenoid cystic carcinoma (AdCC) ex PA is quite rare despite the fact that de novo AdCC is the fourth most common salivary gland malignancy. We describe a new case of AdCC ex PA in the parotid gland of a 62 year-old woman. In our patient, there was a short interval of time between parotidectomy and local recurrence and rapid development of distant metastases. Although most of the reported cases are considered low-grade, evidence is presented here that AdCC can take the form of a high-grade malignancy in PA. PMID- 19644551 TI - Interfacing Sca-1(pos) mesenchymal stem cells with biocompatible scaffolds with different chemical composition and geometry. AB - An immortalized murine mesenchymal stem cell line (mTERT-MSC) enriched for Lin(neg)/Sca-1(pos) fraction has been obtained through the transfection of MSC with murine TERT and single-cell isolation. Such cell line maintained the typical MSC self-renewal capacity and continuously expressed MSC phenotype. Moreover, mTERT-MSC retained the functional features of freshly isolated MSC in culture without evidence of senescence or spontaneous differentiation events. Thus, mTERT MSC have been cultured onto PLA films, 30 and 100 microm PLA microbeads, and onto unpressed and pressed HYAFF-11 scaffolds. While the cells adhered preserving their morphology on PLA films, clusters of mTERT-MSC were detected on PLA beads and unpressed fibrous scaffolds. Finally, mTERT-MSC were not able to colonize the inner layers of pressed HYAFF-11. Nevertheless, such cell line displayed the ability to preserve Sca-1 expression and to retain multilineage potential when appropriately stimulated on all the scaffolds tested. PMID- 19644553 TI - Are Hylobates lar Extirpated from China? AB - The Nangunhe Nature Reserve in Southwest Yunnan (PRC) has long been presumed to be the last stronghold of lar (or white-handed) gibbons (Hylobates lar) in China and the likely last place of occurrence of Hylobates lar yunnanensis. We conducted a comprehensive survey to assess the status of lar gibbons at Nangunhe. We found no visual or auditory evidence of them still residing at the reserve and therefore tentatively conclude that lar gibbons have become extinct in China. It appears that large-scale destruction of primary forests in the 1960s and 1970s brought about an initial decline in their numbers, and subsequent uncontrolled hunting has resulted in their extirpation. The situation for the six Chinese ape taxa is nothing less than disastrous, with 1 taxon assumed to have become extinct during the last few years, 1 taxon not having been confirmed since the 1980s, and 2 species at the very brink of extinction with only tens of individuals remaining in China. PMID- 19644554 TI - Social Relationships in Free-Ranging Male Macaca arctoides. AB - Macaque social relationships differ greatly between species. Based on captive studies that focus mainly on females, researchers have classified stumptail macaque (Macaca arctoides) social relationships as tolerant, as indicated by a high rate of affiliation, frequent aggression, and symmetrical conflicts. To accumulate more data on male social relationships, which are relatively understudied, and to generate comparative data, we investigated male social relationships in a provisioned group of 68 free-ranging, naturally dispersing stumptail macaques in southern Thailand. We collected continuous focal animal and ad libitum data on 7 adult and 2 subadult males, recording social behavior during 283 contact hours between December 2006 and March 2007. Stumptail macaques of this population were less tolerant than predicted based on previous studies on captive groups: Rates of spatial proximity, affiliation, and aggression were low, most males directed affiliative behavior toward higher-ranking males, and conflicts were generally of low intensity and relatively asymmetrical. Thus, male stumptail macaques of the focal group appear to differ in their social style from a previous study of a captive group that mainly comprised of females. In some traits, they are even more intolerant than rhesus macaques, an intensively studied intolerant macaque species. We also compare our data on stumptail macaque males to those on other male macaques, but available data are too sparse to draw final conclusions. PMID- 19644552 TI - A plastic temporal brain code for conscious state generation. AB - Consciousness is known to be limited in processing capacity and often described in terms of a unique processing stream across a single dimension: time. In this paper, we discuss a purely temporal pattern code, functionally decoupled from spatial signals, for conscious state generation in the brain. Arguments in favour of such a code include Dehaene et al.'s long-distance reverberation postulate, Ramachandran's remapping hypothesis, evidence for a temporal coherence index and coincidence detectors, and Grossberg's Adaptive Resonance Theory. A time-bin resonance model is developed, where temporal signatures of conscious states are generated on the basis of signal reverberation across large distances in highly plastic neural circuits. The temporal signatures are delivered by neural activity patterns which, beyond a certain statistical threshold, activate, maintain, and terminate a conscious brain state like a bar code would activate, maintain, or inactivate the electronic locks of a safe. Such temporal resonance would reflect a higher level of neural processing, independent from sensorial or perceptual brain mechanisms. PMID- 19644555 TI - Effects of condylar elastic properties to temporomandibular joint stress. AB - Mandibular condyle plays an important role in the growth and reconstruction of the temporomandibular joint (TMJ). We aimed to obtain orthotropic elastic parameters of the condyle using a continuous-wave ultrasonic technique and to observe the effects of condylar elastic parameters on stress distribution of the TMJ using finite element analysis (FEA). Using the ultrasonic technique, all nine elastic parameters were obtained, which showed that the mandibular condyle was orthotropic. With the condyle defined as orthotropic, the occlusal stress was transferred fluently and uniformly from the mandible to the TMJ. The stress distribution in the isotropic model showed stepped variation among different anatomical structures with higher stress values in the cartilage and condyle than in the orthotropic model. We conclude that anisotropy has subtle yet significant effects on stress distribution of the TMJ and could improve the reality of simulations. PMID- 19644556 TI - Perspectives on adipose tissue, chagas disease and implications for the metabolic syndrome. AB - The contribution of adipose tissue an autocrine and endocrine organ in the pathogenesis of infectious disease and metabolic syndrome is gaining attention. Adipose tissue and adipocytes are one of the major targets of T. cruzi infection. Parasites are detected 300 days postinfection in adipose tissue. Infection of adipose tissue and cultured adipocytes triggered local expression of inflammatory mediators resulting in the upregulation of cytokine and chemokine levels. Adipose tissue obtained from infected mice display an increased infiltration of inflammatory cells. Adiponectin, an adipocyte specific protein, which exerts antiinflammatory effects, is reduced during the acute phase of infection. The antiinflammatory regulator peroxisome proliferator activated receptor-gamma (PPAR gamma) is downregulated in infected cultured adipocytes and adipose tissue. T. cruzi infection is associated with an upregulation of signaling pathways such as MAPKs, Notch and cyclin D, and reduced caveolin-1 expression. Adiponectin null mice have a cardiomyopathy and thus we speculate that the T. cruzi-induced reduction in adiponectin contributes to the T. cruzi-induced cardiomyopathy. While T. cruzi infection causes hypoglycemia which correlates with mortality, hyperglycemia is associated with increased parasitemia and mortality. The T. cruzi-induced increase in macrophages in adipose tissue taken together with the reduction in adiponectin and the associated cardiomyopathy is reminiscent of the metabolic syndrome. PMID- 19644557 TI - A wavelet-based multiresolution reconstruction method for fluorescent molecular tomography. AB - Image reconstruction of fluorescent molecular tomography (FMT) often involves repeatedly solving large-dimensional matrix equations, which are computationally expensive, especially for the case where there are large deviations in the optical properties between the target and the reference medium. In this paper, a wavelet-based multiresolution reconstruction approach is proposed for the FMT reconstruction in combination with a parallel forward computing strategy, in which both the forward and the inverse problems of FMT are solved in the wavelet domain. Simulation results demonstrate that the proposed approach can significantly speed up the reconstruction process and improve the image quality of FMT. PMID- 19644558 TI - MicroRNAs as New Players for Diagnosis, Prognosis, and Therapeutic Targets in Breast Cancer. AB - MicroRNAs are small nonprotein-coding RNAs that regulate the expressions of a wide variety of genes by sequence-specific base pairing on the 3'UTR of mRNA targets resulting in mRNA degradation or inhibition of translation. Aberrant expressions of miRNAs have been linked to tumor development, metastasis, diagnosis, prognosis, and therapy response in human breast cancer. Some miRNAs have been considered to have potential clinical applications as a tool for breast cancer prognosis and therapy. Here we describe and discuss lines of evidence supporting the important relationship between miRNAs and breast cancer, and its therapeutic strategies. PMID- 19644559 TI - Nevus-like appearance of primary malignant melanoma of the esophagus. AB - The primary malignant melanoma of the esophagus (PMME) is a rare malignant disease, accounting for only 0.1-0.2% of all esophageal neoplasms, and the majority of the patients are diagnosed at advanced stages with poor prognosis. We present here a case of 56-year-old woman with epigastric pain and her endoscopic finding revealed several flat and black pigmented mucosal lesions within the distal portion of the esophagus which looked like flat nevus. The histopathology and immunohistochemical profile of the tissue specimens were diagnostic of malignant melanoma. PMID- 19644560 TI - Functional expression of a DNA-topoisomerase IB from Cryptosporidium parvum. AB - Cryptosporidium parvum, one of the most important causative organisms of human diarrheas during childhood, contains a monomeric DNA-topoisomerase IB (CpTopIB) in chromosome 7. Heterologous expression of CpTopIB gene in a budding yeast strain lacking this activity proves that the cryptosporidial enzyme is functional in vivo. The enzymatic activity is comprised in a single polypeptide, which contains all the structural features defining a fully active TopIB. Relaxation activity of the yeast extracts was detected only when CpTopIB ORF was expressed in a yeast expression system showing time and protein dependence under steady state kinetic conditions. The susceptibility of CpTopIB-transformed yeast to the irreversible inhibitor camptothecin and its water-soluble derivatives (topotecan and SN-38) was assessed. PMID- 19644563 TI - Highlights of Programmatic, Interdisciplinary Research on Writing. PMID- 19644562 TI - Clinical significance of epigenetic inactivation of hMLH1 and BRCA1 in Tunisian patients with invasive breast carcinoma. AB - Aberrant hypermethylation of gene promoter regions is one of the mechanisms for inactivation of tumour suppressor genes in many human cancers including breast carcinoma. In the current study, we aimed to assess by MSP, the methylation pattern of two cancer-related genes involved in DNA repair: hMLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli) and BRCA1 (breast cancer 1, early onset) in 78 primary breast cancers from Tunisian patients. The methylation frequencies were 24.36% for hMLH1 and 46% for BRCA1. BRCA1 methylation correlated with age at diagnosis (P = .015) and 5-years disease free survival (P = .016) while hMLH1 methylation was more frequent in larger tumors (P = .002) and in presence of distant metastasis (P = .004). Furthermore, methylation of hMLH1 significantly correlated with high level of P53 expression (P = .006) and with overall survival (P = .015) suggesting that silencing of hMLH1 through aberrant promoter methylation could be used as a poor prognosis indicator in breast cancer. PMID- 19644561 TI - p,p'-DDE induces apoptosis of rat Sertoli cells via a FasL-dependent pathway. AB - One,1-dichloro-2,2 bis(p-chlorophenyl) ethylene (p,p'-DDE), the major metabolite of 2,2-bis(4-Chlorophenyl)-1,1,1-trichloroethane (DDT), is a known persistent organic pollutant and male reproductive toxicant. It has antiandrogenic effect. However, the mechanism by which p,p'-DDE exposure causes male reproductive toxicity remains unknown. In the present study, rat Sertoli cells were used to investigate the molecular mechanism involved in p,p'-DDE-induced toxicity in male reproductive system. The results indicated that p,p'-DDE exposure at over 30 muM showed the induction of apoptotic cell death. p,p'-DDE could induce increases in FasL mRNA and protein, which could be blocked by an antioxidant agent, N-acetyl-l cysteine (NAC). In addition, caspase-3 and -8 were activated by p,p'-DDE treatment in these cells. The activation of NF-kappaB was enhanced with the increase of p,p'-DDE dose. Taken together, these results suggested that exposure to p,p'-DDE might induce apoptosis of rat Sertoli cells through a FasL-dependent pathway. PMID- 19644564 TI - Recent advances in image-guided radiotherapy for head and neck carcinoma. AB - Radiotherapy has a well-established role in the management of head and neck cancers. Over the past decade, a variety of new imaging modalities have been incorporated into the radiotherapy planning and delivery process. These technologies are collectively referred to as image-guided radiotherapy and may lead to significant gains in tumor control and radiation side effect profiles. In the following review, these techniques as they are applied to head and neck cancer patients are described, and clinical studies analyzing their use in target delineation, patient positioning, and adaptive radiotherapy are highlighted. Finally, we conclude with a brief discussion of potential areas of further radiotherapy advancement. PMID- 19644565 TI - Regioselective Domino Metathesis of 7-Oxanorbornenes and Its Application to the Synthesis of Biologically Active Glutamate Analogues. AB - A highly regioselective domino metathesis reaction of 7-oxanorbornene was developed that employed an intramolecular association of an amide carbonyl group to a ruthenium metal centre. By using this reaction, twelve glutamate analogues inspired by dysiherbaine were efficiently synthesized over 12-14 steps; one of the analogues exhibited bioactivity consistent with central nervous system depression. PMID- 19644568 TI - Rejoinder: Why Do We Test Multiple Traits in Genetic Association Studies? PMID- 19644566 TI - Review: Intrarenal angiotensin II levels in normal and hypertensive states. PMID- 19644570 TI - Curcumin is not a ligand for peroxisome proliferator-activated receptor-gamma AB - Curcumin, a compound found in the spice turmeric, has been shown to possess a number of beneficial biological activities exerted through a variety of different mechanisms. Some curcumin effects have been reported to involve activation of the nuclear transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-gamma), but the concept that curcumin might be a PPAR-gamma ligand remains controversial. Results reported here demonstrate that, in contrast to the PPAR gamma ligands ciglitazone and rosiglitazone, curcumin is inactive in five different reporter or DNA-binding assays, does not displace [(3)H]rosiglitazone from the PPAR-gamma ligand-binding site, and does not induce PPAR-gamma-dependent differentiation of preadipocytes, while its ability to inhibit fibroblast-to myofibroblast differentiation is not affected by any of four PPAR-gamma antagonists. These multiple lines of evidence conclusively demonstrate that curcumin is not a PPAR-gamma ligand and indicate the need for further investigation of the mechanisms through which the compound acts. PMID- 19644569 TI - Prescribing new medications: a taxonomy of physician-patient communication. AB - Physician-patient communication about new medications can influence patient medication adherence. Little is known about the detailed content of conversations about new medications, or about how physicians and patients word information when discussing new medications. Yet nuances in communication may influence patient comprehension and affect behaviour. A comprehensive coding framework delineating the intricacies of physician-patient discussions is needed to better understand the range of communication about new prescriptions. This study used analytic induction to analyse 185 audiotaped outpatient encounters, during which 243 new medications were prescribed by family physicians, internists and cardiologists in two healthcare settings. Seventy-six codes were developed to demonstrate the range of physician counselling about information concerning new prescriptions, such as medication name, purpose, directions for use, side effects, acquisition and monitoring. The conversational content represented by the codes can be used to understand the breadth of conversations regarding new medications, identify sources of potential patient misunderstandings when medication instructions are conveyed, and inform recommendations for desired communication content. The coding system also can be used to measure the quality of new medication discussions for linkage to outcomes and can inform interventions to improve communication when prescribing new drugs. PMID- 19644572 TI - Heart, calcium and time. PMID- 19644567 TI - Innate Immunity in the Female Reproductive Tract: Role of Sex Hormones in Regulating Uterine Epithelial Cell Protection Against Pathogens. AB - The mucosal immune system in the upper female reproductive tract is uniquely prepared to maintain a balance between the presence of commensal bacteria, sexually transmitted bacterial and viral pathogens, allogeneic spermatozoa, and an immunologically distinct fetus. At the center of this dynamic system are the epithelial cells that line the Fallopian tubes, uterus, cervix and vagina. Epithelial cells provide a first line of defense that confers continuous protection, by providing a physical barrier as well as secretions containing bactericidal and virucidal agents. In addition to maintaining a state of ongoing protection, these cells have evolved to respond to pathogens, in part through Toll-like receptors (TLRs), to enhance innate immune protection and, when necessary, to contribute to the initiation of an adaptive immune response. Against this backdrop, epithelial cell innate and adaptive immune function is modulated to meet the constraints of procreation. The overall goal of this review is to focus on the dynamic role of epithelial cells in the upper reproductive tract, with special emphasis on the uterus, to define the unique properties of these cells as they maintain homeostasis in preparation for successful fertilization and pregnancy while at the same time confer protection against sexually transmitted infections, which threaten to compromise women's reproductive health and survival. By understanding the nature of this protection and the ways in which innate and adaptive immunity are regulated by sex hormones, these studies provide the opportunity to contribute to the foundation of information essential for ensuring reproductive health. PMID- 19644573 TI - Comparison between left and right heart function in the isolated biventricular working rat heart. AB - OBJECTIVE: To provide a basic characterization of the crystalline perfused isolated rat heart preparation in its biventricular working mode. ANIMALS AND METHODS: In 110 isolated biventricular heart preparations, flows and intraventricular pressures were examined by applying 24 and 28 different loading conditions to the left (LV) and right ventricle (RV), respectively. RESULTS: LV and RV flows responded analogously to changes in loading conditions and were in accordance with the Frank-Starling principle. Linearization of parameters derived from the LV and RV function curves showed that the operation of both ventricles was quantitatively similar when unloaded and increasingly dissimilar when loaded. With increasing RV preload, the characteristics of the RV pump function curves changed; however, those of the LV hardly changed. Power, contractility and relaxation data of the ventricles were compared by applying the concept of corresponding afterloads, which showed that these parameters, except for power, had an inconsistent preload and afterload dependence in the LV and RV. Even though LV and RV performances displayed coexisting analogies, quantitative similarities and qualitative dissimilarities, in the case of relaxation, a concept unifying the heterogeneous data set for both ventricles has been developed. The hypothesis may be put forward that the macroscopic relaxation process of the heart muscle runs in parallel with cellular calcium handling. CONCLUSIONS: At the level of the isolated denervated rat heart model, the common LV and RV functional parameters were only partially similar between the ventricles. However, a particular functional interdependence of relaxation data has been proposed to provide a unifying description of both LV and RV function. PMID- 19644574 TI - Effects of adrenaline pretreatment on the arrhythmias observed following ischemia and reperfusion in conscious and anesthetized rats. AB - A short episode of ischemia induced by coronary artery occlusion can precondition the myocardium against arrhythmia. The factors that have the potential to protect the myocardium from subsequent ischemia and reperfusion are controversial. In this study, the preconditioning-like effects of adrenaline were investigated in both anesthetized and conscious rats. Adrenaline 0.1 and 0.5 mg/kg or saline was administered 10 min before coronary occlusion in conscious and anesthetized rats. The 0.5 mg/kg dose of adrenaline decreased the total duration of arrhythmia in both models. The incidence of ventricular fibrillation decreased and survival rate increased only in conscious rats administered 0.5 mg/kg adrenaline. As a result, it is suggested that exogenous administration of adrenaline before coronary ligation may precondition and protect the heart against arrhythmia. PMID- 19644575 TI - Glyburide prevents isoflurane's reducing effects on hydroxyl radical formation in the postischemic reperfused rat heart. AB - BACKGROUND: The role of K(ATP) channels in isoflurane's reducing effects on oxygen free radical formation are not well known. OBJECTIVES: To investigate whether glyburide, an ATP-regulated potassium (K(ATP)) channel blocker, abolishes isoflurane-induced cardioprotective effects and whether it affects hydroxyl radical formation in the postischemic reperfused heart. ANIMALS AND METHODS: Thirty-nine male Wistar rats were divided into four groups: group C (control, n=10), group I (isoflurane, n=9), group G (glyburide, n=10) and group GI (glyburide and isoflurane, n=10). The hearts were perfused as a Neely's working heart model. Afterwards, global heart ischemia was induced for 15 min followed by reperfusion for 20 min. The formation of hydroxyl radicals in the coronary effluent and heart was measured with high performance liquid chromatography. RESULTS: Isoflurane alone and glyburide alone produced significant decreases in the duration of ventricular fibrillation during reperfusion (group C 452+/-345, group I 247+/-60, group G 261+/-135 s; P<0.05). In the presence of glyburide, isoflurane did not further decrease the duration of arrhythmia (group GI 230+/-48 s). Isoflurane reduced hydroxyl radical formation significantly in the coronary effluent during ischemia and reperfusion, but this was prevented by glyburide. CONCLUSION: The results suggest that isoflurane reduces hydroxyl radical formation, at least in part, through activation of K(ATP) channels. PMID- 19644576 TI - Poststress left ventricular function in patients with coronary artery disease measured by Tl-201 ECG-gated SPECT. AB - BACKGROUND: The phenomenon of reversible impairment in left ventricular function has been well described and is known as myocardial stunning. OBJECTIVE: To assess myocardial stunning in patients with stress-induced ischemia by the use of Tl-201 myocardial perfusion-gated single-photon emission computed tomography (SPECT). PATIENTS AND METHODS: Fifty-six patients (63+/-11 years old) with coronary artery disease participated in the study. All patients underwent exercise thallium scintigraphy. Electrocardiographically gated SPECT was obtained after stress (10 min after the injection of 111 MBq of thallium at the time of peak exercise) and at rest (after 180 min). The left ventricular ejection fraction (LVEF) and end systolic and end diastolic (EDV) volumes were determined using a quantitative gated SPECT (QGS) program. Patients were angiographically classified into three groups: one-vessel disease (n=38), two-vessel disease (n=9) and three-vessel disease (n=9). In 56 patients, resting left ventricular parameters determined by QGS were compared with those obtained by contrast left ventriculography (LVG) to investigate the feasibility of using thallium-gated SPECT to evaluate left ventricular function. RESULTS: Good correlation was obtained between LVEF measured by QGS and LVEF measured by LVG (r=0.893, P<0.01). EDV measured by QGS correlated well with EDV measured by LVG (r=0.067, P<0.001). There was a significant difference between poststress LVEF and resting LVEF in patients with three-vessel disease (P<0.05); the difference was not significant in either of the other groups. The magnitude of the depression of LVEF after stress relative to that at rest correlated with the severity of ischemia (P<0.05). CONCLUSION: Thallium-gated SPECT determines left ventricular function as well as perfusion does. Impaired poststress LVEF was detected using thallium-gated SPECT in patients with three-vessel disease. Poststress functional data would provide further diagnostic information in patients with coronary artery disease. PMID- 19644577 TI - Molecular biology of doxorubicin-induced cardiomyopathy. AB - The anthracycline doxorubicin is an antineoplastic agent, eliciting chronic cardiac toxicity. It occurs in patients after prolonged administration of doxorubicin, leading to congestive heart failure. The pathogenesis of the doxorubicin-induced car-diomyopathy is not well understood. The present article summarizes the unique effect of doxorubicin on cardiac-specific gene expression. In addition to binding to DNA, doxorubicin directly affects the function of a variety of proteins. Free radical generation, damage to mitochondria and active cell death are also critical in the development of doxorubicin-induced cardiac toxicity. Agents providing effective cardioprotection are also reviewed. PMID- 19644580 TI - Relationship between basal nitric oxide and ventricular repolarization in an intact heart. AB - Recent studies suggest that endogenous nitric oxide (NO) attenuates ischemia- or reperfusion-induced shortening in the action potential duration of ventricular myocytes. The effect of basal NO on ventricular repolarization in an intact heart remains unclear. The activation-recovery interval was measured from 32 epicardial electrocardiograms in six anesthetized, open-chest sheep. Intravenous administration of N(G)-nitro-L-arginine, a NO synthase inhibitor, increased left ventricular systolic pressure from 101+/-7 mmHg to 118+/-10 mmHg (P=0.02), and left ventricular end diastolic pressure from 6.3+/-1.5 mmHg to 8.8+/-1.8 mmHg (P<0.01) without changing the heart rate (96+/-4 beats/min versus 94+/-3 beats/min, P=0.06). The average activation-recovery interval from the 32 ventricular sites remained unchanged in each animal after the administration of N(G)-nitro-L-arginine (P>0.05). The pooled activation-recovery interval in the six animals before and 60 min after drug administration was 287+/-21 ms and 288+/ 27 ms, respectively (P>0.05). It was concluded that basal NO is important in maintaining hemodynamics but has limited impact on ventricular repolarization. PMID- 19644579 TI - Loss of cardioprotection induced by ischemic preconditioning after an initial ischemic period in isolated rat hearts. AB - BACKGROUND: The beneficial effect of ischemic preconditioning (PC) has been extensively studied in normal hearts but its effects on diseased hearts remain largely unknown. The effect of PC in the already ischemic myocardium has not been previously studied, although ischemia in varying intervals, which is difficult to assess, is often encountered in clinical practice. OBJECTIVE: To investigate whether the cardioprotective effect of PC is preserved when it is applied after a period of ischemia of varying duration. METHODS: Male Wistar rats were used for this study. Isolated normal rat hearts were perfused in Langendorff mode. Before 20 min of zero flow global ischemia followed by 45 min of reperfusion, hearts were subjected to an initial 20-min period of ischemia followed by 10 min of reperfusion (group A1); an initial 20-min period of ischemia followed by 10 min of reperfusion and two-cycle PC (3 min of ischemia, 5 min of reperfusion followed by 5 min of ischemia and 5 min of reperfusion) (group A2); and two-cycle PC followed by the initial 20-min period of ischemia and 10 min of reperfusion (group A3). Groups B and C were subjected to an initial ischemia of 15 min and 10 min, respectively, and subgroups 1, 2 and 3 were treated as above. Left ventricular end-diastolic pressure was measured at 45 min of reperfusion (LVEDP45 in mmHg). Postischemic recovery of left ventricular developed pressure was expressed as a percentage of the initial value (LVDP%). RESULTS: LVDP% and LVEDP45 were similar between groups A1 and A2, while when ischemic preconditioning preceded the two periods of ischemia (group A3), it resulted in significantly higher LVDP% and significantly lower LVEDP45 compared with groups A1 and A2. Left ventricular functional recovery was not increased in group B2 compared with group B1. LVDP% and LVEDP45 were similar among groups C1, C2 and C3. CONCLUSION: Ischemic preconditioning does not improve functional recovery in isolated rat hearts that have been initially subjected to 20 min or 15 min of zero-flow global ischemia, while an initial 10-min ischemic period seems to precondition the heart. PMID- 19644578 TI - Pathogenesis of atherosclerosis: A multifactorial process. AB - Atherosclerosis is a leading cause of mortality and morbidity in the western world. It has been recognized for over a century, and the understanding of its pathogenesis has undergone many changes. Pathophysiological studies have unravelled the interactions of molecular and cellular elements involved in atherogenesis. The focus has shifted to the novel risk factors as well as characteristics and stability of atherosclerotic plaque; the genetic predisposition has further broadened the pathogenetic mechanisms. This review focuses on the molecular mechanisms involved in the evolution of the atherosclerotic plaque that may pave the way for selecting optimal therapies and preventing plaque complications. Atherosclerosis is no longer a disease attributed mainly to the high lipid content of the body. New insight into the disease pathology has shown it to be a disease of much greater ramifications. Endothelial damage and reactive oxygen species (and other free radicals) have predominantly emerged as factors in virtually all pathways leading to the development of atherosclerosis due to hyperlipidemia, diabetes, hypertension or smoking. Novel risk factors such as hyperhomocysteinemia, infections and systemic lupus erythematosus have emerged. Atherosclerosis has come to be regarded as a chronic inflammatory disease with an autoimmune component. The genetic basis of the disease assumes significance as candidate genes are identified and gene therapy becomes a promising new addition to the existing, less substantial conventional therapies. PMID- 19644581 TI - Immunohistological analyses of myocardial infiltrating cells in various animal models of myocarditis. AB - Animal models of myocarditis are of great value for studying the pathophysiology of the disease. To clarify the key factors for determining the severity of myocarditis, we analyzed immunohistological surface markers of myocardial infiltrating cells in various animal models, and the relationship between myocardiogenic antigens and abnormal behaviours of infiltrating cells was discussed. Myocarditis was induced in mice and rats by cardiotropic viruses and by porcine cardiac myosin. Animals were sacrificed at the peak of their disease. Pathological examinations were performed, and the severity of the lesions was scored semiquantitatively. There were striking differences in the severity of viral and autoimmune giant cell myocarditis among different animal models. However, the majority of myocardial infiltrating cells were comprised of macrophages and CD4+ T cells. Different immunological behaviours of myocardial infiltrating cells were demonstrated in these models of myocarditis. However, the development of severe myocardial lesions may depend on the macrophage-CD4 cell lineage in these animal models. PMID- 19644582 TI - Comparison of the effects of different magnesium administration times on infarct size. AB - BACKGROUND: The protection of high magnesium on infarct size remains controversial. OBJECTIVE: To examine the effects of magnesium administered before ischemia or early in reperfusion on infarct size in a rat model of global ischemia METHODS: Isolated rat hearts were submitted to 40 min of normothermic global ischemia and 2 h of reperfusion. After 20 min of stabilization, four protocols were performed: ischemic control (IC) hearts; 15 mM of magnesium chloride administered 15 min before ischemia (MgI); 15 mM of magnesium chloride administered during the first 15 min of reperfusion (MgR); or 15 mM magnesium plus 5 mM calcium (Mg+Ca) before ischemia. Infarct size was measured by triphenyltetrazolium staining. Contractile function was assessed by left ventricular developed pressure and the maximal velocity of rise of left ventricular presssure. RESULTS: The infarct size in IC hearts was 44+/-5%. In MgI and MgR hearts, the infarct diminished to 4.5+/-1.5% and 18+/-4%, respectively. In Mg+Ca hearts, the protection was also obtained (19+/-3%). Myocardial function also improved significantly by magnesium treatment. At the end of reperfusion, left ventricular developed pressure and maximal velocity of rise of left ventricular pressure values were 23+/-6% and 22+/-3% in MgI; and 10+/-3% and 9+/ 2.6% in MgR versus 2+/-0.7% and 2.3+/-0.8% in IC hearts, respectively. CONCLUSION: The treatment with magnesium either before ischemia or early in reperfusion has an infarct size limiting effect in a model of global ischemia. This protective effect is partially due to its calcium antagonistic action. PMID- 19644583 TI - Tibolone inhibits aortic atherosclerotic lesionformation in oophorectomized cholesterol-fed rabbits. AB - BACKGROUND: Tibolone is a synthetic steroid effective for the treatment of climacteric symptoms and osteoporosis. Long term treatment with tibolone is associated with a significant decrease in cholesterol levels due to a parallel decrease in high-density lipoprotein. However, the effect of these changes on atherogenesis is not known. OBJECTIVE: To investigate the effect of tibolone therapy on aorta atherogenesis. MATERIAL AND METHODS: Thirty-two New Zealand white rabbits were fed cholesterol-rich feed and studied for four months. The rabbits underwent laparotomy and were randomly assigned to four groups. Twenty four rabbits underwent bilateral ovariectomy; of these, eight received tibolone (group T), eight received estradiol valerate (group E), eight received placebo after sterilization (group C), and eight were sham operated (group S). RESULTS: After receiving the cholesterol-rich diet, total levels of cholesterol increased in group C from 3.17+/-0.72 mmol/L to 35.36+/-9.01 mmol/L, in group S from 2.88+/ 0.9 mmol/L to 28.76+/-9.442 mmol/L, in group E from 1.69+/-0.44 mmol/L to 1.69+/ 0.44 mmol/L and in group T from 2.03+/-0.22 mmol/L to 26.33+/-13.45 mmol/L (no significant differences were observed among the groups at the end of the study). At four months, the cholesterol- rich diet caused atherosclerotic lesions in both treated and untreated rabbits, affecting 30.47+/-12.2%, 24.51+/-16.1%, 17.91+/ 10.19% and 10.21+/-6.8% of the aortic surface for groups C, S, E and T, respectively (P<0.01 for treated groups). CONCLUSION: The principal result from this study was that treatment with tibolone in cholesterol-fed ovariectomized rabbits reduces aortic atherosclerotic lesion formation and that this reduction is not related to plasma lipid levels. PMID- 19644584 TI - Plasma nitric oxide metabolite levels increase during successive exercise stress testing - A link to delayed ischemic preconditioning? AB - BACKGROUND: Animal studies have shown that nitric oxide is involved in delayed ischemic preconditioning. OBJECTIVES: To determine whether plasma nitrates and nitrites (NO(x) (-), as measure of nitric oxide) are modified by two consecutive effort tests and whether these changes translate into clinical improvement METHODS: Twenty-two patients with ischemic heart disease each performed two effort tests at 24-h intervals. Plasma NO(x) (-) level was determined and compared before and after both stress tests. Peak effort, double product at peak effort and maximal ST segment depression were considered clinical endpoints and were compared between the two tests. RESULTS: Plasma NO(x) (-)increased slightly after the first exercise test compared with pretest value (17.05+/-1.6 mumol/mL versus 15.38+/-1.4 mumol/mL). In turn, after the second test there was a significant rise in NO(x) (-) level (23.65+/-2.2 mumol/mL versus 15.10+/-1.3 mumol/mL, P<0.03). The pretest values were almost identical between the two tests. Peak effort and double product at peak effort remained unchanged between the two tests. Although ischemic stress was the same, ST depression was significantly lower (P<0.01) for the second test (0.85+/-0.06 mm versus 1.73+/ 0.16 mm). CONCLUSION: Our study shows an increased plasma NO(x) (-)level after the second of two consecutive exercise stress tests at 24-h intervals, along with a decrease of electrocardiographic consequences of approximately the same ischemic stress. These findings are consistent with experimental data in animals, which point to nitric oxide as a trigger and effector of ischemic preconditioning. PMID- 19644585 TI - Can the amplitude of mitral annulus motion be used in the assessment of left ventricular systolic function in patients with left ventricular wall thickness in the upper limit of normal to mild hypertrophy? AB - BACKGROUND: Mitral annulus motion (MAM) obtained by echocardiography can be used in the assessment of left ventricular systolic function (LVSF). However, it has been shown that the amplitude of MAM is decreased in patients with left ventricular wall thickness (LVWT) greater than 14 mm. OBJECTIVE: To study if the amplitude of MAM can be used in the assessment of LVSF in patients with LVWT in the upper limit of normal to mild hypertrophy (12 mm to 14 mm). METHODS: Eighteen consecutive patients with LVWT of 12 mm to 14 mm were compared to 18 age- and sex matched patients with LVWT less than 12 mm. RESULTS: There was no significant difference between the amplitude of MAM in the two groups. CONCLUSIONS: MAM can be used in the assessment of LVSF in patients with LVWT in the upper limit of normal to mild hypertrophy and be related to reference values. PMID- 19644586 TI - Left cardiac sympathectomy prevents exercise-induced QTc prolongation in congenital long QT syndrome. AB - Congenital long QT syndrome (LQTS) is a group of ion channel disorders of ventricular myocytes caused by mutations of genes that encode these ion channels. The main clinical features of LQTS are syncope, cardiac arrest and QT prolongation on body surface electrocardiogram. The present study reports on the case of a 42-year-old female patient with a 10-year history of LQTS and syncopal attacks resistant to beta-blocker therapy. Treadmill exercise testing in this patient increased the corrected QT interval (QTc) from 0.48 s to 0.54 s and reduced the amplitude of the T wave. Left cardiac sympathectomy did not affect the resting heart rate or QTc but it prevented exercise-induced T wave reduction and QTc prolongation. Therefore, sympathetic activation plays a key role in exerciseinduced QT prolongation and changes in T wave morphology in patients with congenital LQTS. PMID- 19644587 TI - AVAPROMISE: A randomized clinical trial for increasing adherence through behavioural modification in essential hypertension. AB - BACKGROUND: Patients with hypertension often do not adhere to their medications. OBJECTIVE: To improve medication adherence in patients with essential hypertension by modifying their behaviours. PATIENTS AND METHODS: From general practice settings, 4864 patients with essential hypertension were recruited and randomly assigned to receive the angiotensin receptor blocker irbesartan (Avapro) with (intervention group) or without (nonintervention group) a behavioural modification program (Avapromise) based on a model of change. Patients were followed up for 12 months. Patients were subgrouped based on their stage of change in the behavioural change continuum, and the intervention was tailored to address the needs of the particular subgroup. The primary efficacy measure was rate and time to discontinuation with irbesartan. RESULTS: At the end of the study, there was no significant difference in the discontinuation rates between the intervention (25.4%, 95% CI 23.7 to 27.2) and nonintervention (25.5%, 95% CI 23.8 to 27.3) groups (P=0.94). The time to discontinuation (P=0.87) and the extrapolated rate of discontinuation estimated from the Kaplan-Meir curve (intervention 23.1%, 95% CI 21.3 to 24.8; nonintervention 23.5%, 95% CI 21.8 to 25.3) were not different between the groups. CONCLUSIONS: This behavioural modification intervention based on a model of change was not efficacious at increasing rates of adherence in patients with essential hypertension in this setting. More individualized interventions may be required to increase adherence in this population. PMID- 19644588 TI - Oxygen radicals mediate ultrastructural and metabolic protection of preconditioning in vivo in pig hearts. AB - Ischemic preconditioning (PC) preserves myocardial high-energy phosphate metabolites and intracellular pH during subsequent sustained ischemia. Generation of reactive oxygen species may be required to mediate PC, as seen in vitro. In the present study, the effects of inhibiting reactive oxygen species generation during a PC protocol in vivo using an open-chest porcine model were examined. Myocyte ultrastructural changes assessed by electron microscopy were correlated with phosphorus nuclear magnetic resonance spectroscopy data. Open-chest pigs underwent 60 min of left anterior descending coronary artery occlusion. PC was elicited by a single episode of 5 min occlusion and 5 min reperfusion. The cell diffusible hydroxyl radical and superoxide radical scavenger, N-2-mercapto propionyl glycine (MPG, 20 mg/kg), or placebo saline were infused for 40 min, starting 30 min before PC (PC plus MPG group, n=10; and PC group, n=9). After PC, ATP and intracellular pH were significantly preserved through 25 min of ischemia (control versus PC, 46+/-3% versus 55+/-5% of baseline [P<0.05]; and control versus PC, 6.18+/-0.08 versus 6.42+/-0.03 [P<0.05], respectively). Phosphocreatine was significantly preserved through 20 min of ischemia (control versus PC, 0+/-0% versus 7+/-2% of baseline [P<0.05]). The preservation of high energy phosphate metabolites and intracellular pH was abolished by inhibiting the generation of reactive oxygen species with MPG. Preservation of high-energy phosphate metabolites with PC was associated with reduced ultrastructural damage, as seen by electron microscopy, including less myocyte swelling, myofibrillar disruption and nuclear chromatin margination. The present study demonstrates the importance of reactive oxygen species generation in mediating PC preservation of myocyte ultrastructure and high-energy phosphate metabolites during prolonged ischemia in vivo. PMID- 19644589 TI - Afterload- and preload-dependent interactions in the isolated biventricular working rat heart. AB - OBJECTIVES: The afterload- (AL) and preload- (PL) dependent interactions between the left and right ventricle (LV, RV, respectively) of an isolated biventricular ejecting rat heart were measured in terms of left (L) and right (R) intraventricular peak pressure (LP(max) and RP(max), respectively) and aortic and pulmonary flow (AF, PF, respectively). METHODS: Starting with standardized loading conditions, LVPL was varied in six steps for each of five distinct LVALs (n=28) and then RVPL was varied in seven steps for each of five distinct RVALs (n=37). Thus, the entire range of loading conditions was covered. RESULTS: Identification of AL-dependent systolic interactions revealed an important DeltaLP(max)-DeltaRP(max) gain of 0.25 (r(2)=0.78) and a still more dominant DeltaRP(max)-DeltaPF gain of 0.45 (r(2)=0.84). At least 26% of maximal PF were attributable to LV systolic function. In contrast, R-L systolic interaction impeded PF; there was no global crosstalk pressure gain and no ipsilateral pressure-flow gain. Reduction of RV activity augmented AF by at least 15%. PL dependent L-R interactions were absent except for minimal LVAL. In contrast, the reverse interaction reflected an inverse correlation between RVPL and AF, which is coincidential with other studies (-11% AF for a doubling of the standard RVPL). For the minimal RVAL, there was a biphasic response of AF to RVPL. Unloading the maximally loaded RV revealed an overall inhibition of AF by 37% for the standardized LV. Unloading the standardized RV revealed a basal inhibition of AF by 6% for the standardized LV and a 4.5% augmentation for the highly loaded LV. Consequently, basal contribution of RV to LV performance depended on the conditions of LV loading. CONCLUSIONS: The authors suggest a unidirectional transseptal R-L mechanism for diastolic interactions, and transseptal L-R and paraseptal R-L mechanisms for systolic interactions. PMID- 19644590 TI - Optimal biphasic waveforms for internal defibrillation using a 60 muF capacitor. AB - The optimal capacitance for defibrillation is calculated to be 40 to 80 muF by theoretical models, assuming a heart chronaxie of 2 to 4 ms and a mean impedance of 40 ohms. The 60 muF capacitor is optimal for providing maximum defibrillation efficacy, which can reduce defibrillation energy. The purpose of the present study was to determine the optimal tilt to maximize defibrillation efficacy in a 60/60 muF biphasic waveform and to compare these waveforms with an optimized 60/15 muF waveform. The defibrillation thresholds (DFTs) were evaluated for five different 60/60 muF biphasic waveforms having 40%, 50%, 60%, 70% and 80% phase 1 tilt and a 60/15 muF biphasic waveform having 50% phase 1 tilt with a hot can electrode system in 15 pigs (20+/-2 kg). Phase 2 pulse widths were held constant at 3 ms in all waveforms. The DFT was measured by 'down-up, down-up' technique and was random in each waveform. The DFT energy in 60/60 muF waveforms (40%, 50%, 60%, 70% and 80%) and a 60/15 muF waveform (50%) were 6.9*, 6.9*, 7.1*, 7.8*, 8.4* and 6.0, respectively (*P<0.05 versus 60/15 muF waveform). A phase 1 tilt of 40% to 50% maximizes defibrillation efficacy for biphasic waveforms using 60/60 muF capacitors. Additionally, switching to a 15 muF capacitor for phase 2 can further reduce the DFT energy. PMID- 19644592 TI - Angiographic characteristics of the coronary artery in patients with type 2 diabetes. AB - OBJECTIVES: To investigate the adverse effect of type 2 diabetes on coronary artery anatomy. PATIENTS AND METHODS: The coronary angiograms of 1564 consecutive patients were analyzed. The coronary lesions of patients with and without type 2 diabetes were compared. RESULTS: Seventy-four diabetic and 824 nondiabetic patients were found to have coronary artery disease. Diabetic patients had more multivessel (48.7% versus 34.7%, P<0.01), multilesion (64.9% versus 46.1%, P<0.05), extensive (51.4% versus 7.8%, P<0.01) and small vessel disease (95.2% versus 39.8%, P<0.01) than nondiabetic patients. CONCLUSIONS: Type 2 diabetes is a significant risk factor for coronary artery disease. These findings may provide useful information for the future development of therapeutic strategies. PMID- 19644591 TI - Effects of AT1 receptor antagonist therapy in patients with severe heart failure pretreated with angiotensin-converting enzyme inhibitors. AB - BACKGROUND: The efficacy of angiotensin-converting enzyme (ACE) inhibitors is well documented in the treatment of chronic severe heart failure. Because pharmacological mechanisms of angiotensin II type 1 (AT1) receptor antagonists differ from the effects of ACE inhibitors, an additional positive effect can be expected by combining these drugs. METHODS: Sixty patients (mean age 68.3+/-10.0 years) with severe chronic heart failure receiving long term medication with digitalis, diuretics, ACE inhibitors and in part beta-blockers (68.3%) were randomly assigned after clinical recompensation to three groups: additional therapy with eprosartan (477.5+/-143.7 mg/day), telmisartan (65.9+/-17.7 mg/day) and control group according to a prospective study design. Hemodynamic measurements by impedance cardiography were performed before and during the observation period (9.6+/-3.4 days). RESULTS: Additional sartan treatment resulted in an improvement in cardiac output from 2.32+/-0.69 L/min to 3.12+/ 1.24 L/min (P=0.003) in the eprosartan group and from 2.24+/-0.59 L/min to 2.76+/ 0.91 L/min (P=0.001) in the telmisartan group; cardiac output in the control group did not increase. Furthermore, a significant decrease in total peripheral resistance was observed during treatment with eprosartan (23%, P=0.002) and telmisartan (18%, P=0.002). In the subgroup receiving combined therapy with beta blockers, ACE inhibitors and AT1 antagonists, a significant increase in cardiac output was also observed. CONCLUSIONS: The additional treatment with AT1 receptor antagonists resulted in an increase in the cardiac output and a decrease in the peripheral resistance. This beneficial effect may be due to the additional property of sartans to block the interaction of locally and non-ACE-generated angiotensin II with their respective vascular and myocardial AT1 receptors. PMID- 19644593 TI - Association of three polymorphisms in the gene coding for endothelin-1 with essential hypertension, overweight and smoking. AB - OBJECTIVE: To evaluate the association of three endothelin-1 (ET-1) gene polymorphisms with essential hypertension, as well as with two cardiovascular risk factors: body mass index (BMI) and smoking. DESIGN: Three gene polymorphisms and the genotype and allelic distributions were compared between normotensive healthy volunteers and patients with essential hypertension. The genetic association of the three genotypes with BMI and smoking status was calculated. PATIENTS AND METHODS: CA/CT dinucleotide repeat polymorphism, G(8002)A polymorphism and -3A/-4A polymorphism (-138 insertion/deletion) were examined in the gene coding for ET-1 (6p21.3) in 398 subjects: 192 normotensives (healthy volunteers) and 206 patients with essential hypertension. Normotension was verified by 24 h ambulatory blood pressure monitoring. RESULTS: Significant inner associations were observed between all three polymorphisms, which suggests possible complex interactions inside the gene. The only significant difference in a single gene case control study was in the lengths of allelic variants of CA/CT dinucleotide repeat polymorphism. In hypertensive patients, the alleles of G(8002)A and -3A/-4A ET-1 polymorphisms were found to be significantly associated (G with -3A and A with -4A). None of the ET-1 gene polymorphisms was associated with BMI. A highly significant increase of the -3A allele of the -3A/-4A ET-1 polymorphism was found in hypertensive men who were current smokers or had smoked at least seven cigarettes a week for at least one year at any time in their life compared with hypertensive men who had never smoked (odds ratio 1.54, 95% CI 1.03 to 2.32, P=0.009). CONCLUSIONS: Smoking seems to be an independent cardiovascular risk factor genetically codetermined by the ET-1 gene variant. PMID- 19644594 TI - The diabetic heart: A review of the lifework of Sophie Maria Koltai. AB - It is well known that cardiovascular alterations are the principal causes of mortality in patients with diabetes. Premature and accelerated atherosclerosis cannot be the sole cause of diabetic heart disease because functional disorders develop both in experimental and in clinical diabetes before the onset of the detectable morphological changes of the vessel wall. Namely, altered adrenergic responses and prostaglandin metabolism and diminished vasodilatory ability can be seen in diabetic vessels. This leads to enhanced vasoconstriction, which - combined with increased sympathetic activity - may induce myocardial edema and an increase in myocardial stiffness, resulting in diminished heart function. Increased myocardial stiffness due to myocardial dehydration caused by hyperglycemic hyperosmolality can also result in impaired heart function. Thus, myocardial water content plays a key role in the development of diabetic heart dysfunction. Disturbances in the myocardial energy metabolism may also contribute to the diminished cardiac performance in the diabetic state. Some antidiabetic agents may also have deleterious cardiovascular effects. Whether the functional abnormalities observed in the reviewed studies lead to clinically manifest heart disease in diabetes may depend on the superimposition of the classical cardiovascular risk factors. Thus, adequate control of carbohydrate and lipid metabolism and the possible concomitant hypertension may prevent the further impairment of heart function and the development of overt heart disease. PMID- 19644595 TI - Cardiac resynchronization therapy in congestive heart failure: The state of the art and future perspectives. AB - Congestive heart failure (CHF) is one of the leading causes of morbidity and mortality worldwide. Up to 50% of CHF patients have intraventricular conduction disturbances such as left bundle branch block or nonspecific wide QRS complex on the body surface ECG. Intraventricular conduction delays cause dyssynchrony of the ventricles which in turn leads to regional movement abnormalities and worsening of cardiac function. Recent clinical trials have indicated that cardiac resynchronization therapy or biventricular pacing in CHF patients with left bundle branch block or wide QRS complex improves cardiac function class, exercise tolerance, maximum oxygen consumption and quality of life within the first 12 months of therapy. The number of hospitalizations and the use of intravenous medications for worsening heart failure are also reduced by this new therapy. Apart from the short to medium term clinical benefits, cardiac resynchronization therapy has not been shown to reduce overall cardiac mortality. The present article reviews the pathophysiology of ventricular dyssynchrony and evaluates the results of recent clinical trials on resynchronization therapy. PMID- 19644596 TI - Factor Xa inhibitors--new anticoagulants for secondary haemostasis. AB - Oral factor Xa (FXa) inhibitors are a promising alternative to current anticoagulants. This paper reviews the latest developments of oral direct FXa inhibitors and focuses on those which have been approved for the prevention of venous thromboembolism (VTE) after total hip or knee replacement or are in advanced development and have passed phase II (proof of principle) testing. The most advanced drugs are apixaban, betrixaban, edoxaban, eribaxaban, rivaroxaban, LY517717, TAK-442, and YM150. Rivaroxaban (Xareltoa) is the first direct FXa inhibitor which has recently been approved for the prevention of VTE in adult patients after elective hip or knee replacement in several countries, including the European Union and Canada. Rivaroxaban has a flat dose-dependent anticoagulant response with a wide therapeutic window and low potential for drug drug and drug-food interactions. Rivaroxaban can be given in fixed doses without coagulation monitoring. This review describes the pharmacodynamic and pharmacokinetic profiles and the results of clinical trials with FXa inhibitors in the prevention and treatment of thromboembolic disorders. PMID- 19644597 TI - The present state of aspirin and clopidogrel resistance. AB - Antiplatelet therapy has demonstrated significant clinical benefit in the treatment of acute coronary syndrome. However, as with any treatment strategy it has been unable to prevent all cardiovascular events. This is far from surprising when considering the complexity of arterial thrombosis and more specifically platelet physiology. This lack of treatment success has provoked the introduction of various diagnostic tests and testing platforms with the intent of guiding and optimizing clinical treatment. Such tests have resulted in the generation of clinical data that suggest suboptimal response to antiplatelet agents such as aspirin and clopidogrel. In the case of both aspirin and clopidogrel, this suboptimal response has been termed resistance. Drug resistance would imply a lack of pharmacological response that has not been specifically investigated in many of the clinical studies performed to date. Rather, the term resistance has been used to describe various facets of platelet activation and aggregation relative to the testing method. Many of these measured parameters are not addressed in the therapeutic intent of the antiplatelet drug in question. PMID- 19644598 TI - [Anticoagulants of primary haemostasis]. AB - Inhibition of platelet function plays an important role in the treatment and secondary prevention of cardiovascular or cerebrovascular ischemic diseases. Established antiplatelet agents use different pharmacological targets for this role. Acetyl salicylic acid achieves a reduction of thromboxane A2 formation by inhibition of COX-1. Ticlopidine or clopidogrel are ADP-P2Y12 receptor antagonists. Tirofiban, abciximab or eptifibatid are used for the inhibition of the glycoprotein IIb/IIIa receptor which is activated at the surface of platelets preceding the final step of their aggregation. The mechanism of dipyridamole is based on the inhibition of adenosine uptake and of phosphodiesterase-5. Efforts are made to improve antiplatelet therapy with the aim to find agents with favorable clinical outcome and lower bleeding risk. Current clinical studies focus on a new generation of ADP receptor antagonists (prasugrel, cangrelor and ticagrelor) as successors of ticlopidine and clopidogrel after coronary arterial interventions. Developments using platelet targets different from established drugs are thrombin receptor antagonists (like SCH530348) or thromboxane receptor antagonists (like S18886/terutroban) in patients with cerebrovascular events. Results from recent experimental studies could lead to new strategies for antiplatelet therapy (like inhibition of GP Ib receptor, GP VI receptor, platelet leukocyte interaction, factor XII and others) in the future. PMID- 19644599 TI - [Patients with oral anticoagulation--bridging anticoagulation in the perioperative phase]. AB - Oral anticoagulation with a vitamin K-antagonist requires special consideration when surgery or interventional procedures are planned. This is mainly due to the half life of vitamin K-antagonists and to the need for safe and effective anticoagulation prior to and during surgery as well as in the postoperative period. So far, the continuous infusion of unfractionated heparin (UFH) has been the medication of choice to "bridge" patients to surgery. The use of low molecular weight heparins (LMWH) has been prospectively investigated in this setting and represents a safe alternative. The advantages of LMWH are the better dose-response relationship and reduced need for monitoring. This facilitates the bridging procedure to be started out of hospital, which may reduce hospital stay and associated costs. Furthermore, the so-called bridging of patients with oral anticoagulation prior to and during surgery reduces bleeding complications and maintains a safe anticoagulation for patients at risk. PMID- 19644600 TI - [Monitoring of anticoagulants of secondary haemostasis]. AB - Vitamin K-antagonists and heparin belong to the established indirect acting anticoagulants. For many years these drugs were the only possibility for prophylaxis and treatment of venous and arterial thrombosis. The challenges for the routine laboratory related to the treatment with vitamin K-antagonists and heparin can be regarded as solved. However, in recent years a rapid development of new anticoagulants began. Although they are developed with guidelines for use without monitoring, the control of effective levels may be necessary in selected cases. As a consequence new challenges for the routine laboratory have to be solved. This paper presents an overview concerning monitoring methods. PMID- 19644601 TI - Monitoring anticoagulation of primary haemostasis--estimation of platelet function in whole blood assays. AB - This article provides an overview on current commercially available methods to determine primary haemostasis as a target of drug-mediated anticoagulation. It focuses on whole blood methods only, and references the currently major achievements that have been reported with each method in respect to its clinical use. Advantages and disadvantages of the various methods are presented, based on considerations of platelet physiology, and on feasibility of the procedures. PMID- 19644602 TI - [Haemostaseologic effects of fractionated snake venoms]. AB - Comparative investigation concerning gelfiltration as well as haemostaseologic analysis of venoms and venom fractions of some snakes (elapidae and viperidae) have shown that in elapidae an inhibition of coagulation is dominant whilst in viperidae the stimulation of coagulation is of importance. Our investigations produce a basis to select substances for activation of coagulation and substances for inhibition of coagulation. Under pharmacological viewpoints the data may produce information to use snake fractions for anticoagulation or for procoagulant therapy in bleeding tendency. PMID- 19644603 TI - [Established anticoagulants in secondary haemostasis--Vitamin K antagonists, heparins]. AB - In respect to the actual discussion of new anticoagulants in secondary haemostasis, we will give a short review on established oral anticoagulation with vitamin K antagonists and parenteral anticoagulation by use of heparin. The different coumarin derivatives phenprocoumon, warfarin, and acenocoumarol are compared concerning to the management and influence of pharmacogenetic and pharmacokinetic factors. Studies to improve the safety of oral anticoagulation by vitamin K supplementation will be briefly discussed. The therapy with heparins include until now some problems of dose-response control. It is necessary to pay attention to contra-indications even for well known anticoagulants. Examples for that will be given. PMID- 19644604 TI - [New anticoagulants for secondary haemostasis--anti IIa inhibitors]. AB - In contrast to heparins and oral anticoagulants, anti IIa inhibitors (thrombin inhibitors) are able to directly inhibit the protease activity of thrombin and can thereby precisely control the blood coagulation process. Direct thrombin inhibitors are either biosimilars (r-hirudin) or synthetically produced substances (bivalirudin, argatroban, dabigatran). In 1997 r-hirudin was introduced into clinical practice, however due to its narrow therapeutic range and the necessity of drug monitoring it has not gained widespread clinical use by now. Since 2004 and 2005 the synthetic thrombin inhibitors bivalirudin and argatroban, respectively, are available. With dabigatran the first oral synthetic thrombin inhibitor followed in 2008. These four drugs can inhibit even clot bound thrombin and show low plasma protein binding. They differ in respect to route and duration of application as well as elimination from the body, thereby offering a precise inhibition of blood coagulation adjusted to the individual case and without danger of HIT II. These advantages shall be used and advanced by the development of further direct thrombin inhibitors. PMID- 19644605 TI - Anterior uveitis as a clinical presentation of orbital inflammatory disease in an adult. AB - We report an unusual case of orbital inflammatory disease presenting as anterior uveitis in an adult. A 35-year-old Chinese man presented with acute anterior uveitis unresponsive to topical steroids, and progressed to manifest optic disc swelling and posterior scleritis. Computed tomography showed a mass-like soft tissue swelling within the intraconal fat indenting the posterior medial aspect of the globe. The diagnosis of orbital inflammatory disease was made, and the patient was treated with systemic corticosteroids with prompt resolution of symptoms and signs. Anterior uveitis can be considered an unusual ophthalmic manifestation of orbital inflammatory disease in adults. PMID- 19644606 TI - Leucocoria in a boy with Kawasaki disease: a diagnostic challenge. AB - Retinoblastoma, the most common primary intraocular malignancy of childhood, usually presents in the first three years of life. Atypical presentation of retinoblastoma can masquerade as virtually any ocular or orbital pathology, which may lead to diagnostic dilemmas especially in the presence of other systemic diseases. We report a 20-month-old boy who was diagnosed with coronary aneurysm as a complication of Kawasaki disease, and presented with sudden left eye redness. His mother noticed the presence of white pupillary reflex three months earlier. Atypical acute ocular presentation secondary to Kawasaki disease was initially suspected, but the presence of multiple calcification and mild proptosis on imaging suggested characteristics of advanced retinoblastoma. Histopathological examination of the enucleated eye, which revealed a classical rosette pattern appearance, confirmed the diagnosis. Atypical presentations of retinoblastoma are usually associated with advanced disease. The presence of other systemic conditions further complicates the diagnosis. Early diagnosis is important to reduce the mortality and morbidity. PMID- 19644607 TI - Tuberculosis of the thyroid gland: magnetic resonance imaging appearances. AB - Tuberculosis involving the thyroid gland is a rare occurrence. We report a case of cytologically-diagnosed thyroid gland tuberculosis in a 21-year-old man who presented with thyroid swelling of short duration, and describe the magnetic resonance (MR) imaging appearances of the lesion, which to our knowledge, has not been previously described. We also report a rare complication of abscess formation in the track of the fine needle aspiration. The intermediate signal intensity of the lesions on both T1- and T2-weighted MR images may provide a clue about tuberculosis, as clinical suspicion is low due to the rarity of the disease. PMID- 19644608 TI - Malignant perivascular epithelioid cell tumour of the round ligament mimics leiomyoma on computed tomography. AB - We report a case of a 45-year-old woman who had a palpable mass in the left lower quadrant of the abdomen. Computed tomography (CT) showed a circumscribed mass in the left round ligament of the uterus. The mass had heterogeneous density and enhancement accompanied by mottled calcification, which was initially identified as a leiomyoma. A histopathological examination revealed a malignant perivascular epithelioid cell tumour (PEComa), which is a rare soft tissue tumour. This case demonstrates that the appearance of malignant PEComa on the CT can mimic leiomyoma, which is the most common tumour of the round ligament. To the best of our knowledge, this is the first report of a CT appearance of this round ligament tumour. The radiological features and differential diagnosis are discussed. PMID- 19644609 TI - Low insertion of a cystic duct into the common bile duct as a cause for a malpositioned biliary stent: demonstration with multidetector computed tomography. AB - Anatomical variations of the extrahepatic biliary system are common. Adequate knowledge of such variations and an appropriate roadmap before any surgical, endoscopic or percutaneous procedure/intervention help in preventing associated complications. Multiple imaging modalities can depict the anatomy of the extrahepatic biliary tree. High resolution magnetic resonance imaging and magnetic resonance cholangiopancreatography are increasingly used to delineate the hepatobiliary system. Multidetector computed tomography allows for high-speed volume scanning with an excellent spatial and temporal resolution. It also allows for multiplanar reconstructions in virtually any plane, with isotropic resolution. We describe an unusual complication of biliary stenting in a 62-year old man with low insertion of a cystic duct, resulting in the inadvertent placement of the common bile duct stent into the cystic duct. This was demonstrated well by multidetector computed tomography and confirmed thereafter, during surgery. PMID- 19644610 TI - Pulmonary atelectasis from compression of the left main bronchus by an aortic aneurysm. AB - Pulmonary atelectasis may be caused by endobronchial lesions or by extrinsic compression of the bronchus. However, lung collapse due to compression from a thoracic aneurysm is uncommon. We report a 76-year-old hypertensive female patient who has pulmonary atelectasis due to an extrinsic compression from a descending thoracic aortic aneurysm, and discuss possible treatment options. PMID- 19644611 TI - Pseudoaneurysm of a high origin radial artery treated by ultrasound-guided compression. AB - A high origin of the radial artery from the brachial artery is the most frequently encountered arterial anomaly in an upper extremity, and is reported in seven percent of individuals. This variant is vulnerable to injury because of its more superficial location. A 59-year-old man developed a pseudoaneurysm following the inadvertent cannulation of a high origin radial artery. We report the successful treatment of the pseudoaneurysm by ultrasound-guided compression. Ultrasound-guided compression is an available and simple method for the repair of arterial pseudoaneurysms, and delayed complete thrombosis can be expected even if a residual flow remains after the initial compression. PMID- 19644612 TI - Two cases of self-limiting nephropathies secondary to dengue haemorrhagic fever. AB - We report two cases of dengue haemorrhagic fever which developed self-limiting gross nephrotic-range proteinuria. One patient was a 32-year-old Bangladeshi and the other a 42-year-old Chinese national. Both patients did not have manifestations of renal damage, such as increase in serum creatinine, haematuria or urinary casts. Gross nephrotic-range proteinuria, which was self-limiting due to dengue haemorrhagic fever, has not been previously reported in Singapore. We postulate that this nephrotic-range proteinuria is a manifestation of increased glomerular leakage of protein, due to glomerulonephritis associated with dengue haemorrhagic fever. PMID- 19644613 TI - Acute renal failure following detergent ingestion. AB - A 42-year-old woman with a history of depression and epilepsy ingested two types of household detergent and developed gastrointestinal symptoms, and subsequently acute renal failure. Coingestants included nontoxic quantities of paracetamol and therapeutic doses of sodium valproate and fluoxetine. The patient developed acute renal failure, and also had fever and unilateral ear inflammation. The acute renal failure resolved four days later. Patients presenting with detergent poisoning are typically screened and treated for gastrointestinal and respiratory toxicity. We discuss the mechanism of development of acute renal failure in our patient, review the literature linking detergent poisoning and nephrotoxicity, and propose a direct relationship between detergent poisoning and acute renal failure. PMID- 19644614 TI - Gorham's disease with spontaneous recovery. AB - Gorham's disease is a rare benign cause of progressive massive idiopathic osteolysis. The clinician's acute awareness and high degree of suspicion are required for diagnosis because of its rarity and variable clinical presentation. Distinctive radiological and histopathological features may help in this regard. Though eventual stabilisation of the affected bone is the most common sequel, spontaneous recovery is very rarely reported in peer-reviewed literature. We report such a rare occurrence in a 17-year-old boy. PMID- 19644615 TI - Down syndrome in monochorionic twins. AB - Down syndrome in monochorionic twins has rarely been reported. We report such a case diagnosed prenatally. Maternal serum screening was performed at 15 weeks for a twin pregnancy which indicated a risk of greater than 1:50 for Down syndrome. The review of early ultrasonography confirmed monochorionic twins. Amniocentesis at 17 weeks' gestation was performed on one of the twin sacs, which confirmed Down syndrome. A screening scan at 19 weeks' gestation showed isolated absent nasal bones in both twins. Termination of pregnancy was performed subsequently. PMID- 19644617 TI - Language and multilingualism in scientific communication. PMID- 19644616 TI - IgA nephropathy associated with pleuropulmonary tuberculosis. AB - A 34-year-old man presented with polymerase chain reaction-positive pleuropulmonary tuberculosis with asymptomatic subnephrotic proteinuria and microscopic haematuria. He was diagnosed to have IgA nephropathy on renal biopsy. The patient was started on a four-drug anti-tuberculous therapy. Healing of the pleuropulmonary lesions along with disappearance of proteinuria and haematuria were seen both at one month and six months post-treatment, with no relapse of renal symptoms at one-year follow-up. PMID- 19644618 TI - Charles Laveran (1845-1922): Nobel laureate pioneer of malaria. PMID- 19644619 TI - Preparing the references. AB - In a scientific paper, the references serve to provide background information and allow the researcher to compare and contrast the work of others in relation to his own study. Authors are responsible for the accuracy of all references cited. The references quoted should be easily accessible and retrievable by anyone wishing to obtain further information. There is a strong preference for citing journal articles listed in PubMed. The two major reference format systems are the Vancouver and Harvard systems, with increasing preference for the Vancouver system. Authors should adhere exactly to the instructions to authors of the target journal. PMID- 19644620 TI - The use of antibodies in the treatment of infectious diseases. AB - There is a long history of the use of antibodies in the treatment and prophylaxis of infectious diseases, because these molecules play a critical role in directing the effector mechanisms of the immune system against the pathogens they recognise. However, the widespread application of this therapy has been hampered by allergic reactions, production costs and the availability of alternative drugs such as antibiotics. Some of these obstacles can now be overcome with advances in biotechnology, which has enabled the development of antibody-based drugs for use first in treating cancer, and recently, for treating infectious diseases. The efficacy of such antibodies has been demonstrated in various in vitro studies, animal models and clinical trials for a variety of both viral and bacterial pathogens. Antibodies appear to hold great promise as a new class of drugs against infectious diseases. PMID- 19644621 TI - Predictors of adverse neurological outcome following cardiac surgery. AB - INTRODUCTION: Stroke is a debilitating complication of cardiac surgery. Many intraoperative and postoperative factors predict the likelihood of post-cardiac surgery stroke. We evaluated preoperative parameters, seeking correlations with adverse neurological outcome following cardiac surgery. We investigated the possibility of preoperative carotid ultrasonography to select patients for carotid endarterectomy pre- or intraoperatively. METHODS: We conducted a retrospective analysis of 61 patients who suffered stroke post-cardiac surgery from 2003 to 2006. Data was collected for patient and disease characteristics, preoperative status, intraoperative events and postoperative course. Postoperative neurological complications were subdivided into three groups: mild/temporary events, moderate events such as seizures, and severe events such as stroke. A mild/temporary event was defined as a focal neurological deficit of less than 24 hours in duration. RESULTS: A total of 2,226 cardiac cases were retrospectively evaluated. The frequency of stroke was 61 patients (2.7 percent). The mean age of these patients was 63.7 +/- 7.4 years, and 40 (65.6 percent) were males. Logistic EuroSCORE, left ventricular ejection fraction (as determined by two-dimensional echocardiogram) and aortic cross-clamp time were significantly correlated with postoperative neurological complications, with a p-value of less than 0.05 for all subgroups. There was a significant correlation between the presence of preoperative carotid disease (as proven by pre- and postoperative carotid ultrasonography) and postoperative neurological events (p-value equals 0.033). However, atrial fibrillation did not correlate with postoperative stroke. CONCLUSION: The stage of cardiac disease (risk factor level, ejection fraction and presence of carotid stenosis) correlates with stroke and may predict an adverse neurological outcome. PMID- 19644622 TI - The age-specific clinical and anatomical profile of mitral stenosis. AB - INTRODUCTION: This cross-sectional study on the age-specific clinical and anatomical characteristics of mitral stenosis was conducted at the Department of Cardiology at Kottayam Medical College, South India. METHODS: The clinical profile, laboratory details and transthoracic echocardiographical features of 203 consecutive patients with mitral stenosis were studied. Wilkins score was used to assess the valve morphology and the feasibility of balloon mitral valvotomy (BMV)/closed mitral valvotomy (CMV). Patients were grouped according to age, into Group I (younger than 40 years; 68 cases), Group II (40-65 years; 78 cases) and Group III (older than 65 years; 57 cases) for analysis. RESULTS: The mean age of the patients was 53 years. History of rheumatic fever was less common in Group III (37 percent in Group I vs. 20 percent in Group III, p-value is equal to 0.05). Acute pulmonary oedema occurred commonly in Group III (six percent in Group I vs. 36 percent in Group III, p-value is less than 0.001). Incidence of ischaemic strokes increased with increasing age (three percent in Group I vs. 12 percent in Group II, p-value is equal to 0.05; 12 percent in Group II vs. 25 percent in Group III, p-value is equal to 0.05; and three percent in Group I vs. 25 percent in Group III, p-value is less than 0.001). Prevalence of atrial fibrillation (AF) increased progressively with increasing age (nine percent in Group I vs. 30 percent in Group II, p-value is less than 0.001; 30 percent in Group II vs. 64 percent in Group III, p-value equal to 0.003). Clinical features of pulmonary hypertension was highest among Group I (66 percent in Group I vs. 42 percent and 43 percent in Groups II and III, respectively, p-value is equal to 0.01). The mean duration of exertional dyspnoea, history of paroxysmal nocturnal dyspnoea, mean NYHA class, mean left atrial sizes, mean mitral valve areas and mean mitral valve gradients did not vary significantly among the three groups. Mitral valve scores were prohibitive for BMV/CMV in significant numbers of older patients (seven percent in Group I vs. 38 percent in Group II vs. 80 percent in Group III; p-value is less than 0.001). CONCLUSION: When compared to the trends in developed countries, the mean age at presentation of mitral stenosis is similar, but the degree of valve deformity is higher. Incidence of pulmonary oedema, AF and stroke increases with advancing age in mitral stenosis. PMID- 19644623 TI - Retention rates of disease-modifying anti-rheumatic drugs in patients with rheumatoid arthritis. AB - INTRODUCTION: Disease-modifying anti-rheumatic drugs (DMARDs) currently form the mainstay of treatment of rheumatoid arthritis (RA). We aimed to evaluate the retention rates of "therapeutic segments" of DMARDs in patients with RA. METHODS: This was a cross-sectional study of RA patients with at least one year of follow up. A therapeutic segment is said to begin when one DMARD combination is instituted and it ends with a subsequent change. The disability index for each patient was calculated using a modified health assessment questionnaire. Retention rates were calculated using the Kaplan Meier survival analysis. RESULTS: 375 DMARD courses in 102 patients were analysed. 99 courses were being continued at the time of the study and hence were censored for the purposes of analysis. The respective median (interquartile range [IQR]) retention period for segments containing methotrexate (MTX), sulfasalazine, hydroxychloroquine and leflunomide was 28 (15-45), 12 (3-20), 18 (9-24), 15 (4-32) months. The log-rank statistical test indicated that MTX was retained longer singly (median [IQR] 43 [32-70] months) than in combination (median [IQR] 19 [10-24] months) (p-value is 0.001). The commonest reason for the discontinuation of the DMARD segment was the disease "slipping out" of control (51.1 percent) followed by adverse effects (24.3 percent). Treatment termination on account of disease control was encountered in 16.3 percent of courses only. As many as 63 percent of single DMARD segments were changed because of disease "slip out" as compared to 41 percent of combination DMARD segments. Adverse effects were a more frequent cause of termination of the combination segments (32 vs. 15 percent). CONCLUSION: MTX, used singly, had the highest retention rates among all the DMARDs used in RA patients. Disease "slip out" and adverse effects frequently required a change of the therapeutic segment. PMID- 19644624 TI - B-Lynch suture for the treatment of uterine atony. AB - INTRODUCTION: Over 125,000 women die of postpartum haemorrhage (PPH) each year, with the commonest cause being uterine atony (75-90 percent). Failing conservative management, hysterectomy is usually the final resort. In 1997, Christopher B-Lynch devised an innovative technique to treat uterine atony, and it has been widely used around the world since its original report. However, there are hardly any reports of this technique being utilised in East Asian countries, including Singapore. Our study reviews the cases in which the B-Lynch suture was used to treat uterine atony, and the clinical outcomes of these cases. METHODS: A retrospective study of data of all women who delivered between May 2004 and June 2007 was collected from the department's database, to identify patients who had undergone the B-Lynch procedure. Primary PPH is defined as a blood loss of more than 500 ml at or within 24 hours of delivery. RESULTS: There were a total of 5,470 deliveries during this period, with primary PPH occurring in 100 cases. The B-Lynch procedure was performed in seven women, avoiding the need for a hysterectomy in five cases. CONCLUSION: Our series of cases treated with the B-Lynch procedure showed that it is an effective method of containing PPH. It has the advantage of being applied easily and rapidly, and should be taught to all trainees and registrars in obstetrics. It should be attempted when conservative management of PPH fails and before any radical surgery is considered. PMID- 19644625 TI - Erectile dysfunction as a sentinel marker of endothelial dysfunction disease. AB - INTRODUCTION: Vascular disease is the major underlying cause of erectile dysfunction (ED). Endothelial dysfunction acts as a marker of "peripheral vascular disease" that occurs prior to clinical vascular disease. ED is the first clinical manifestation of endothelial disease due to the small size of the penile artery. Brachial flow-mediated vasodilation (FMD) is one of the accurate tests for evaluating endothelial function. We compared the endothelial function by FMD between ED patients without clinical signs of vascular disease and non-ED patients. METHODS: 41 ED patients and 30 age-matched normal control subjects were assessed for cardiovascular risks and endothelial function. We measured the FMD in order to evaluate the endothelial function, by comparing the percentage change of the brachial arterial diameter after the brachial arterial occlusion. RESULTS: There were no significant differences in baseline characteristics, cardiovascular risks and lipid values between both groups, except that the high-density lipoprotein cholesterol was higher in the control group. The percentage change of the FMD was 8.7 +/- 1.0 percent and 5.1 +/- 0.6 percent in ED patients and control subjects, respectively (p-value is 0.007). CONCLUSION: ED is the first clinical presentation of sub-clinical endothelial dysfunction disease prior to the appearance of clinical cardiovascular disease or cardiovascular risk factors. ED can be the sentinel marker of early cardiovascular and other systemic vascular diseases and it should thus be employed in preventive strategies. PMID- 19644626 TI - Palmar pressure distribution during push-up exercise. AB - INTRODUCTION: Doing repetitive push-ups is among the most common exercise for the upper body and shoulder stabiliser muscle strength training. However, adverse effects such as neck pain, back pain, palmar pain and wrist pain have been reported. To date, to our knowledge, palmar pressure when performing push-ups has not been previously reported. We hypothesised that various hand positions during push-ups may provide different palmar pressures. METHODS: Bilateral palmar pressures were recorded in ten individual volunteers. All the subjects were set up for doing push-ups in five positions of the hand. Peak palmar pressure was recorded by Emed pressure platform system (Novel GmBH, Munich, Germany). The palm was divided into the following five anatomic regions, viz. thenar, lunate, hypothenar, metacarpals and fingers. Statistical comparison between the five positions of the hand was analysed using the analysis of variance test. RESULTS: A distribution of the mean peak pressure of the lunate and hypothenar areas were relatively higher than the other areas in both standby and full-elbow flexion positions. At the palmar position 30 cm wider than the shoulder width, the palmar pressure revealed significantly higher peak pressure in the lunate area in the standby and fully-flexed elbow positions (p-value is less than 0.05). At the palmar position 10 cm narrower than the shoulder width, palmar pressure showed significantly higher peak pressure in the hypothenar area only in the fully flexed elbow position. CONCLUSION: The information regarding palmar pressures while performing push-ups in different hand positions may be used as a guideline for exercise modification, especially in injured athletes. PMID- 19644627 TI - The usefulness of early ultrasonography, electroencephalography and clinical parameters in predicting adverse outcomes in asphyxiated term infants. AB - INTRODUCTION: The early identification of asphyxiated infants at high risk of adverse outcomes and the early selection of those who might benefit from neuroprotective therapies are required. A prospective observational study was conducted to determine if there were any early clinical, neuroimaging or neurophysiological parameters that might predict the outcome in term newborns with asphyxia. METHODS: 44 term newborns with acute asphyxia had a cranial ultrasonography (US), electroencephalography (EEG) and clinical examination performed between three and eight hours of life to determine the parameters that might predict outcome. US findings were classified as normal or abnormal (ventricular dilatation or compression and/or focal/diffuse echogenicities). EEG background activity was classified into two categories: normal/mildly abnormal/intermediate, or severely abnormal (low voltage activity or "suppression burst"). An intrapartum score (based on graded abnormalities of foetal heart monitoring, umbilical arterial base deficit and five-minute Apgar score) and a hypoxic ischaemic encephalopathy (HIE) score (based on graded abnormalities of the neurological and respiratory status at 3-8 hours of life) was also obtained. RESULTS: At one year of life, eight infants had died, six had defaulted follow up, five had major impairment, two minor impairment and 23 were normal. On univariate analysis, poor outcome (death or major impairment) was associated with abnormal cranial US, severely abnormal EEG and a high HIE score (greater than or equal to 15). The positive predictive value was 54.5, 100 and 100 percent, respectively, while the negative predictive value was 93.8, 80.6 and 80.6 percent, respectively. Combining these factors did not improve the predictive values. CONCLUSION: There was no added advantage in combining EEG or US parameters over a clinical neurological scoring system alone in predicting the outcome of asphyxiated term newborns. PMID- 19644628 TI - Utility of abdominal ultrasonography in HIV patients. AB - INTRODUCTION: Various diseases associated with human immunodeficiency virus (HIV) infection are often difficult to diagnose. A poor immune response, atypical presentations and opportunistic pathologies all contribute to this difficulty. We tried to evaluate the utility of routine abdominal ultrasonography (US) in new and follow-up HIV cases, and compared the results among those with a clinical need for US and those where US was performed as a routine screening. METHODS: 150 consecutive seropositive patients were subdivided into four groups depending on the necessity of abdominal US on the initial workup, i.e. Group A (38 patients) or B (112 patients), and whether they were newly-diagnosed HIV patients or follow up patients, i.e. Group X (62 patients) or Y (88 patients), giving us subgroups, AX (22 patients), AY (16 patients), BX (40 patients) and BY (72 patients). RESULTS: The prevalence of significant US findings was higher in those with CD4 less than 200 cells/ml (77.8 percent) compared to those with CD4 200-500 cells/ml and CD4 more than 500 cells/ml (65.5 percent and 37 percent, respectively). 24 out of 38 patients with clinical indications and 71 out of 112 patients without any obvious clinical need for US, had positive findings on US, the majority of which had a major therapeutic impact. CONCLUSION: We conclude that abdominal US is a simple and cost-effective tool in resource-poor countries like India, where HIV care is becoming more and more important. PMID- 19644629 TI - Some interesting observations on the surface features of the liver and their clinical implications. AB - INTRODUCTION: A sound knowledge of the normal and variant liver anatomy is a prerequisite to having a favourable surgical outcome. Knowledge of the commonly occurring variations assumes even more significance in the era of diagnostic imaging and minimally-invasive surgical approaches. Although the segmental anatomy of the liver has been extensively researched, very few studies have dealt with the surface variations of the liver. METHODS: 90 formalin-fixed livers were utilised for the study. Variations regarding the shapes of the caudate and the quadrate lobes as well as the normal fissures were observed. The presence of the accessory fissures and any other variations on the surface of the livers were noted. RESULTS: Varied shapes of the caudate and the quadrate lobes were encountered. Notching along the inferior border of the caudate lobe was seen in 18 percent of livers, a vertical fissure was observed in 30 percent, and prominent papillary process was seen in 32 percent. Accessory fissures and grooves were more common in the right lobe. Multiple prominent vertical grooves were observed on the anterosuperior surface of the liver in six percent of livers. Quadrate lobe was absent in four percent, and in two cases, it was found to be deeply buried. Presence of a pons hepatis, bridging the left and the quadrate lobes, was observed in 30 percent of the livers examined. CONCLUSION: Our study is expected to serve as a guide for proper interpretations of liver images using various imaging modalities. It will also be useful to the operating surgeons to be aware of the frequently-occurring morphological variations on the liver surface. PMID- 19644630 TI - A profile of cancer patient outcomes from a tertiary care teaching hospital in Malaysia. AB - INTRODUCTION: The aim of this paper was to determine the sociodemographic and cancer characteristics of patients with cancer at a tertiary care centre. METHODS: For the study, 80 newly-diagnosed cancer patients were selected and interviewed using structured questionnaires that included sociodemographic and cancer characteristic profiles. At the end of the study period of two years, the survivorship status of the patients was determined. RESULTS: Gender, occupational status, type of cancer and stage of cancer were found to be significantly associated with the survival status among the study group of cancer patients. Results of logistic regression analysis showed that deceased patients were significantly more likely to be pensioners rather than employed, aged 60-69 years rather than 40-49 years, to have all other types of cancer rather than breast cancer, and to be in Stage 3 or 4 of the disease rather than in Stage 1 of the disease. CONCLUSION: There is a greater necessity for psychosocial research in order to achieve optimal health for patients with cancer, and in turn, to improve the survival of cancer patients. PMID- 19644631 TI - Incidence of thyroid malignancy among goitrous thyroid lesions from the Sarawak General Hospital 2000-2004. AB - INTRODUCTION: Thyroid cancer is the most common among all endocrine malignancies. The worldwide prevalence of goitre in the general population is estimated at 4-7 percent and the incidence of malignancy in goitrous thyroid is about ten percent. It is postulated that goitrous thyroid is a precursor lesion to the development of malignant thyroid diseases. As Sarawak is a state well known for endemic goitre, this study focused on establishing the incidence of thyroid malignancy among goitrous thyroid swellings. METHODS: This study was a hospital-based retrospective study on the archived collection of the surgically-removed thyroid specimens from the Sarawak General Hospital, Malaysia. Cases were grouped into cancer and non-cancer groups. The cancer group included papillary thyroid carcinoma (PTC), PTC follicular variant, follicular carcinoma and anaplastic carcinoma (ANA). RESULTS: A total of 820 thyroid cases which underwent surgical removal in years 2000 to 2004 were collected. Of these, 143 (17.4 percent) were male and 677 (82.6 percent) female. It was observed that the highest prevalence of thyroid swelling cases occurred in the age group 41-60 years while the lowest prevalence occurred in the age group under 21 years, 371 (45.2 percent) vs. 31 (3.8 percent). By ethnicity, the Ibans and Malays were found to have a higher prevalence at 275 (33.5 percent) and 196 (23.9 percent), respectively, while the lowest prevalence was observed in Indians, 11 (1.3 percent). 55 cases (6.7 percent) were found to be cancerous and the rest (93.3 percent) were non cancerous thyroid swellings. Histologically, the highest incidence of carcinoma was PTC (4.0 percent) and the lowest was ANA (0.2 percent). CONCLUSION: Based on our observations, although goitrous thyroid swelling is quite a common problem in Sarawak, thyroid malignancy is not a major issue. Among thyroid malignancies, PTC is the most common histological type of malignancy. PMID- 19644633 TI - A new feeding tube which is secure and easy to change. AB - Loss of a normal swallowing reflex as in dysphagic stroke is the commonest indication for long-term tube feeding. For this, either the nasogastric tube or the percutaneous endoscopic gastrostomy tube is used, with the former being uncomfortable. The latter tube is neither secure nor easy to change. A new feeding tube invented in Singapore uses a loop and lock configuration to make it comfortable for the patient, impossible to pull out accidentally, and easy to change. This third-generation feeding tube has the potential to be the new global standard. PMID- 19644632 TI - Comparison of Ki-67 antigen expression and K-ras mutation in lung tumours induced by urethane in mice. AB - INTRODUCTION: This study aims to compare Ki-67 antigen expression and K-ras mutation in lung tumours induced by the interfering effects of urethane followed by sodium nitrite, sodium chloride and vitamin D3. METHODS: The samples were classified into six groups: control (C) group; urethane only (U) group; urethane and vitamin D (U+D) group which received 3.5 mg/kg vitamin D3 for four weeks; urethane and sodium nitrite (U+NS) group which was given sodium nitrite (50 mg/L); urethane and physiological serum (U+NaCl) group; and sodium nitrite and physiological serum (NS+NaCl) group which was given 50 mg/L sodium nitrite and physiological serum, instead of water. The four carcinogen groups receiving urethane were injected intraperitoneally with 600 mg/kg of urethane three times. After 20 weeks of intervention, the mice were killed; the tissues were removed and examined for histopathological changes and comparison of Ki-67 antigen expression and mutations in the exon 1 of the K-ras gene in lung tumours. RESULTS: There were significant differences in the Ki-67 index between the C group and the U (p-value is less than 0.006, 95 percent confidence interval [CI] 432.9 to -55.6), U+D (p-value is less than 0.05, 95 percent CI -408.3 to -4.6), U+NS (p-value less than 0.02, 95 percent CI -415.7 to -27.2), U+NaCl (p-value less than 0.002, 95 percent CI -478.8 to -90.3) groups. There was no difference between the C and NS+NaC1 groups. There was no mutation in the exon 1 of K-ras gene of the lung tumours. CONCLUSION: The expression of Ki-67 antigen was found to be increased by urethane in the present study. However, a study on a larger sample size may show anti-tumourogenic effect of vitamin D3. However, the K-ras exon 1 mutations do not play any role in the interfering effects of urethane followed by sodium nitrite and sodium chloride. PMID- 19644634 TI - Deja vu: swine flu. PMID- 19644635 TI - Omphalolith/umbolith: CT and MR imaging appearances in two patients. PMID- 19644636 TI - Hospital-based dermatology: my personal journey. PMID- 19644638 TI - No association between polymorphisms of peroxisome [corrected] proliferator activated receptor-gamma gene and peak bone mineral density variation in Chinese nuclear families. AB - Association between SNPs in polymorphism in peroxisome [corrected] proliferator activated receptor-gamma (PPARG) and peak bone mineral density (BMD) variation of women was measured in 401 Chinese nuclear families using quantitative transmission disequilibrium test (QTDT). The peak BMD variation was not attributable to PPARG in our sample. INTRODUCTION: The purpose of this study is to test whether genetic PPARG might play a role in normal variation in peak BMD. METHODS: We genotyped 10 tagging SNPs in PPARG using allele-specific polymerase chain reaction and further test whether these SNPs were associated with peak BMD variation at the lumbar spine and femoral neck of women in 401 Chinese nuclear families using QTDT. Furthermore, the association between these SNPs in PPARG and BMD in 710 postmenopausal Chinese women was measured. RESULTS: Using QTDT for within-family association, we failed to find that single SNP and haplotype were significantly associated with peak BMD at the lumbar spine and femoral neck. Meanwhile, we found that only rs1801282 was significantly associated with BMD at the lumbar spine in postmenopausal women (P = 0.013). CONCLUSIONS: Our present results suggest, for the first time, that the genetic polymorphism in PPARG is not a major contributor to the observed variability in peak BMD at the lumbar spine and femoral neck in Chinese women. PMID- 19644639 TI - Usefulness of percutaneous intervention with transarterial approach in the salvage of nonmaturing native fistulas status-post transvenous approach failure: transarterial approach in the salvage of nonmaturing native fistulas. AB - The purpose of this study was to assess the usefulness of percutaneous intervention with transarterial approach in the salvage of nonmaturing native fistulas status post transvenous approach failure. Eight patients (M:F=2:6; mean age, 56.8 years) underwent percutaneous intervention with antegrade transarterial approach when the retrograde transvenous approach failed. Mean time from fistula creation to fistulography was 80.5 days. Five patients had brachiocephalic fistulas and three had radiocephalic fistulas. Brachial or radial arterial access was performed using real-time ultrasound guidance, and balloon angioplasty was performed for hemodynamically significant (>50%) stenosis. Technical and clinical success and complications were evaluated. Patency following percutaneous intervention was estimated with the Kaplan-Meier method. Technical success was achieved in 87.5% (seven of eight patients). Clinical success of normal hemodialysis (fistula maturation) occurred in 87.5% (seven of eight patients). One minor complication (regional hematoma) occurred in one patient. Mean primary patency at 6, 12, and 18 months was 75%, 56.2%, and 37.5%, respectively. Additional angioplasty (n=3) resulted in mean secondary patency at 12 and 18 months of 87.5% and 87.5% of the patients, respectively. In conclusion, percutaneous intervention with the transarterial approach can be a useful method for salvage of nonmaturing native fistulas when the transvenous approach fails. PMID- 19644640 TI - Lifesaving embolization of coronary artery perforation. AB - Coronary artery perforation remains one of the most fearsome complications during cardiac catheterization procedures. Although emergent bypass surgery is the preferred treatment for cases with uncontrollable perforation, endovascular vessel sealing and arrest of bleeding with a combination of balloons, covered stents, or embolic materials have also been proposed. The authors describe a case of emergent lifesaving microcoil embolization of the distal right coronary artery in a patient with uncontrollable grade III guidewire perforation resulting in cardiac tamponade. The relevant literature is reviewed and the merits and limitations of the endovascular approach are highlighted. PMID- 19644641 TI - Primary stent in occluded femoropopliteal bypass graft in a patient with contraindications for thrombolytic therapy: case report. PMID- 19644642 TI - Percutaneous biopsy of osteoid osteomas prior to percutaneous treatment using two different biopsy needles. AB - Biopsy is usually performed as the first step in percutaneous treatment of osteoid osteomas prior to laser photocoagulation. At our institution, 117 patients with a presumed diagnosis of osteoid osteoma had a trephine biopsy before a percutaneous laser photocoagulation. Biopsies were made using two different types of needles. A Bonopty biopsy needle (14-gauge cannula, 16-gauge trephine needle; Radi Medical Systems, Uppsala, Sweden) was used in 65 patients, and a Laurane biopsy needle (11-gauge cannula, 12.5-gauge trephine needle; Laurane Medical, Saint-Arnoult, France) in 43 patients. Overall biopsy results were positive for osteoid osteoma in 83 (70.9%) of the 117 cases. The Laurane needle provided a significantly higher positive rate (81.4%) than the Bonopty needle (66.1%; p < 0.05). This difference was not due to the size of the nidus, which was similar in the two groups (p < 0.05) and may be an effect of differences in needle caliber (12.5 vs. 14 gauge) as well as differences in needle design. The rate of positive biopsy results obtained in the present series with the Laurane biopsy needle is, to our knowledge, the highest rate reported in series dealing with percutaneous radiofrequency ablation and laser photocoagulation of osteoid osteomas. PMID- 19644643 TI - British Society of Interventional Radiology Iliac Artery Angioplasty-Stent Registry III. AB - The objective of this study was to audit current practice in iliac artery intervention in the United Kingdom. In 2001 the British Society of Interventional Radiology Iliac Artery Angioplasty-Stent (BIAS) III registry provided the first national database for iliac intervention. It recommended that data collection needed to continue in order to facilitate the dissemination of comparative data to individual units. BIAS III was designed to continue this work and has a simplified data set with an online submission form. Interventionalists were invited to complete a 3-page tick sheet for all iliac angioplasties and stents. Questions covered risk factors, procedural data, and outcome. Data for 2233 patients were submitted from 37 institutions over a 43-month period. Consultants performed 80% of the procedures, 62% of which were for claudication. Fifty-four percent of lesions were treated with stents and 25% of patients underwent bilateral intervention, resulting in a residual stenosis of <50% in 98%. Ninety seven percent of procedures had no limb complication and there was a 98% inpatient survival rate. In conclusion, these figures provide an essential benchmark for both audit and patient information. National databases need to be expanded across the range of interventional procedures, and their collection made simple and, preferably, online. PMID- 19644645 TI - Symptomatic and hemodynamic benefit of pentaerythrityl tetranitrate and hydralazine in a case of congestive heart failure. PMID- 19644646 TI - A two-centre blinded randomised control study comparing the Lichtenstein patch, Perfix plug and ProLoop plug in the repair of primary inguinal hernia. AB - INTRODUCTION: Mesh plug is an established and effective method for repair of inguinal hernia. The ProLoop plug (Atrium) is a recently developed mesh plug with a novel configuration, which may offer advantages over the standard Prefix plug (Bard) or the Lichtenstein repair. This two-centre double-blinded randomised control trial assessed the short- and medium-term outcomes, comparing the above three methods. PATIENTS AND METHODS: Consecutive patients over the age of 18 years with primary unilateral inguinal hernia were randomised to receive a Lichtenstein tension free mesh repair (LTFM), Perfix plug (Bard) (PF) or ProLoop plug (Atrium) (PL) repair. Follow-up was at 2 weeks, 6 months and 12 months. Endpoints were operative time, hospital stay, bodily pain scores, return to daily activity and complications. RESULTS: A total of 295 consecutive patients were recruited to the study. Ninety-three patients were randomised to receive PL plug repairs, 101 PF plug repairs and 101 LTFM repairs. There was no significant difference among the three groups in terms of age, sex or BMI. There was no significant difference among the groups in terms of operative time (PL vs PF P = 0.92; PL vs LTFM P = 0.52), hospital stay (PL vs PF P = 0.74; PL vs LTFM P = 0.44), bodily pain scores (at 12 months PL vs PF P = 0.84, PL vs LTFM P = 0.85, PF vs LTFM P = 0.16), complication rates or return to daily activity. CONCLUSIONS: The ProLoop plug (Atrium) is a safe and effective method of repairing primary inguinal hernias. Its novel lightweight configuration does not increase the risk of recurrence when compared to thicker mesh plugs, and it may offer benefit in terms of long-term patient comfort. The ProLoop plug (Atrium) represents a new effective alternative to the established mesh repairs. PMID- 19644644 TI - Supporting cell characteristics in long-deafened aged mouse ears. AB - Significant sensory hair cell loss leads to irreversible hearing and balance deficits in humans and other mammals. Future therapeutic strategies to repair damaged mammalian auditory epithelium may involve inserting stem cells into the damaged epithelium, inducing non-sensory cells remaining in the epithelium to transdifferentiate into replacement hair cells via gene therapy, or applying growth factors. Little is currently known regarding the status and characteristics of the non-sensory cells that remain in the deafened auditory epithelium, yet this information is integral to the development of therapeutic treatments. A single high-dose injection of the aminoglycoside kanamycin coupled with a single injection of the loop diuretic furosemide was used to kill hair cells in adult mice, and the mice were examined 1 year after the drug insult. Outer hair cells are lost throughout the entire length of the cochlea and less than a third of the inner hair cells remain in the apical turn. Over 20% and 55% of apical organ of Corti support cells and spiral ganglion cells are lost, respectively. We examined the expression of several known support cell markers to investigate for possible support cell dedifferentiation in the damaged ears. The support cell markers investigated included the microtubule protein acetylated tubulin, the transcription factor Sox2, and the Notch signaling ligand Jagged1. Non-sensory epithelial cells remaining in the organ of Corti retain acetylated tubulin, Sox2 and Jagged1 expression, even when the epithelium has a monolayer like appearance. These results suggest a lack of marked SC dedifferentiation in these aged and badly damaged ears. PMID- 19644647 TI - 'Dissectalgia' following TEP, a new entity: its recognition and treatment. Results of a prospective randomized controlled trial. AB - PURPOSE: To find the effect of pre-peritoneal instillation of bupivacaine on 'dissectalgia' (pain over a wide area corresponding to the area of pre-peritoneal dissection) and return to work following totally extraperitoneal (TEP) repair for groin hernia in labor-active males. METHODS: Fifty-three consecutive ASA grade I adult males undergoing TEP for groin hernia were randomized to control group A (n = 28) and test group B (n = 25), receiving 30 ml saline or 0.25% bupivacaine pre peritoneally after placing mesh, respectively. Assessment parameters included time (h) to rescue analgesia, number of patients needing additional injectable analgesia at night during their hospital stay, visual analog scale (VAS) score for pain at 24 h, 48 h, and then weekly for 4 weeks, and time of resuming their job. RESULTS: The time to rescue analgesia was significantly shorter in group A (4.50 +/- 2.3) than in group B (7.00 +/- 4.1), P = 0.0077. A significantly greater number of group A patients needed additional injectable analgesia at bed time than group B patients (24 vs. 6, respectively, P < 0.0001 on the first night; 11 vs. 2, respectively, P = 0.008 on the second night). The VAS scores were significantly higher in group A patients than group B patients (3.47 +/- 1.04 vs. 1.69 +/- 1.04, respectively, at 24 h postoperatively, P < 0.0001; 2.29 +/- 1.44 vs. 1.36 +/- 0.81, respectively, at 48 h postoperatively, P = 0.0063). However, subsequent VAS scores up to 4 weeks postoperatively were comparable, as was the time of resuming their job. No patient had seroma/fluid collection, chronic pain, or recurrence, with the minimum follow-up being 3 years. CONCLUSIONS: Dissectalgia following TEP deserves its due recognition. Pre peritoneal bupivacaine instillation significantly reduces its occurrence, although the time of patients' resuming their jobs remains unaffected. PMID- 19644648 TI - Long-term results of local excision for T1 rectal carcinoma: the experience of two colorectal units. AB - BACKGROUND: Local excision for early rectal cancer has low morbidity and good functional results. Its use is limited by the inability to assess regional lymph nodes and by the uncertainty of oncologic outcome. METHODS: We conducted a retrospective chart review of all patients who underwent local excision of early rectal cancer in two colorectal units between 1995 and 2007. The retrieved and analyzed data were patient age and gender, tumor size, tumor distance from the anal verge, tumor differentiation, and additional treatment. RESULTS: There were 42 patients with T1 rectal cancer: 24 underwent transanal endoscopic microsurgery and 18 had a transanal excision. The surgical margins were free of tumor in 39 patients (93%), they were involved by tumor in one (2%) and margin status was unclear in two (5%). Seven patients (16%) had postoperative complications. There was no postoperative mortality. The mean hospital stay was 67 h. Thirty-nine patients (93%) were followed up for 57 months (mean). Two patients had local recurrence, at 7 and 41 months post-surgery. They had a tumor that invaded into the lower third of the submucosa, sm3. Both received chemoradiotherapy, and underwent an abdominoperineal resection and a low anterior resection. One of them died of metastatic disease 13 months later and the other is alive with no evidence of disease. Another two patients had salvage low anterior resection, one for suspected local recurrence and one for lymphovascular invasion: the specimens were tumor free. Six patients died of unrelated causes. CONCLUSIONS: Local excision of early rectal cancer is a feasible and acceptable alternative to radical resection. It has low complication and recurrence rates and a short postoperative hospital stay. PMID- 19644649 TI - An osteoporotic hip fracture in a 14-year-old girl undergoing chemotherapy and operated for knee osteosarcoma. AB - Non-weight-bearing, pre- and postsurgical immobilization, neoadjuvant and adjuvant chemotherapy are known to act on bone turnover, causing osteoporosis over short and long time periods. Treatment of fracture insurgence is very difficult because it really depends on being able to choose the right time (i.e., when immunodeficiency is less important). We report a case of spontaneous neck femur fracture during adjuvant chemotherapy in a young girl treated with resection and prosthesis reconstruction for distal femur osteosarcoma. Possible prevention and the correct approach and surgical timing are emphasized considering immunodeficiency following chemotherapy. PMID- 19644650 TI - Fibroma of tendon sheath located within the ankle joint capsule. AB - We report a very rare case of fibroma of the tendon sheath arising from the anteromedial ankle joint capsule, with no apparent connection to any tendon in the area, found in a 58-year-old patient complaining of progressive local swelling. This uncommon tumor has its usual localization in tendon sheaths, is extremely rare in joint capsules, and has never been described in this location previously. MRI showed nonuniform low signal intensity in T1- and T2-weighted images and high intensity in STIR images. The mass was completely excised by open surgery. Histopathological analysis later confirmed the diagnosis of a fibroma of the tendon sheath. PMID- 19644651 TI - The costs of limited health literacy: a systematic review. AB - OBJECTIVES: To summarize evidence about (1) the costs of limited health literacy (HL) and (2) the cost-effectiveness of interventions to improve limited HL. METHODS: We performed a systematic review searching electronic databases and additional information resources. We included observational studies and interventional studies with HL-outcomes. We included populations at high risk for low HL and patients with (1) diabetes mellitus or (2) hyperlipidemia. RESULTS: We retrieved 2,340 papers and included 10 studies for analysis. The prevalence of limited HL is considerable (range 34-59%). On the health system level, the additional costs of limited HL range from 3 to 5% of the total health care cost per year. On the patient level, the additional expenditures per year per person with limited HL compared to persons with adequate HL range from US $143 to 7,798. Data on the cost-effectiveness of interventions to improve limited HL are scarce. CONCLUSION: The costs of limited HL may be substantial, but few studies were retrieved and the results are heterogeneous. PMID- 19644652 TI - Different molecular patterns in glioblastoma multiforme subtypes upon recurrence. AB - One of the hallmarks of glioblastoma is its inherent tendency to recur. At this point patients with relapsed GBM show a survival time of only few months. The molecular basis of the recurrence process in GBM is still poorly understood. The aim of the present study was to investigate the genetic profile of relapsed GBM compared to their respective primary tumors. We have included 20 paired GBMs. In all tumor samples, we have analyzed p53 and PTEN status by sequencing analysis, EGFR amplification by semiquantitative PCR and a wide-genome fingerprinting was performed by microsatellite analysis. Among primary GBM, we observed twelve type 2 GBM, four type 1 GBM and four further GBM showing neither p53 mutations nor EGFR amplification (non-type 1-non-type 2 GBM). Upon recurrence, we have detected two molecular patterns of tumor progression: GBM initially showing either type 1 or type 2 profiles conserved them at the time of relapse. In contrast, non-type 1 non-type 2 GBM acquired the typical pattern of type 2 GBM and harbor EGFR amplification without p53 mutation. New PTEN mutations upon relapse were only detected in type 2 GBM. Additional LOH were more frequently identified in relapses of type 2 GBM than in those showing the type 1 signature. Taken together, our results strongly suggest that recurrences of GBM may display two distinct pattern of accumulation of molecular alterations depending on the profile of the original tumor. PMID- 19644653 TI - Microscopic observations and inflammatory cytokine productions of human macrophage phagocytising submicron titanium particles. AB - This study was performed to microscopically observe and measure inflammatory cytokine production by human macrophages phagocytosing submicron titanium (Ti) particles. Observations with secondary electron microscopy (SEM), SEM/electron probe microanalysis (EPMA) and transmission electron microscopy (TEM) indicated that macrophages [phorbol-12-myristate-13-acetate (PMA)-differentiated THP-1 cells] at 24 h in culture actively phagocytosed and accumulated submicron Ti particles in intracellular phagosomes, in which refinement of Ti particles occurred. The macrophages were also cultured for 24 h in four media with and without submicron Ti particles and lipopolysaccharide (LPS; components of bacteria). Whilst neither stimulus reduced cell viability, submicron Ti particles and LPS activation independently and synergistically caused the macrophages to produce three inflammatory cytokines (TNF-alpha, IL-1beta and IL-6) at high levels in the culture supernatants. The inflammatory and osteolysis conditions caused by macrophages phagocytosing submicron Ti particles would be worsened by challenge with LPS in patients wearing Ti prostheses. PMID- 19644654 TI - Effects of biosilicate and bioglass 45S5 on tibial bone consolidation on rats: a biomechanical and a histological study. AB - The purpose of this study was to investigate the effects of Bioglass 45S5 and Biosilicate, on bone defects inflicted on the tibia of rats. Fifty male Wistar rats were used in this study, and divided into five groups, including a control group, to test Biosilicate and Bioglass materials of two different particle sizes (180-212 microm or 300-355 microm). All animals were sacrificed 15 days after surgery. No significant differences (P > 0.05) were found when values for Maximal load, Energy Absorption and Structural Stiffness were compared among the groups. Histopathological evaluation revealed osteogenic activity in the bone defect for the control group. Nevertheless, it seems that the amount of fully formed bone was higher in specimens treated with Biosilicate (granulometry 300-355 microm) when compared to the control group. The same picture occurred regarding Biosilicate with granulometry 180-212 microm. Morphometric findings for bone area results (%) showed no statistically significant differences (P > 0.05) among the groups. Taken together, such findings suggest that, Biosilicate exerts more osteogenic activity when compared to Bioglass under subjective histopathological analysis. PMID- 19644655 TI - Density functional calculations of chemical shielding of backbone 15N in helical residues of protein G. AB - We performed density functional calculations of backbone (15)N chemical shielding tensors in selected helical residues of protein G. Here we describe a computationally efficient methodology to include most of the important effects in the calculation of chemical shieldings of backbone (15)N. We analyzed the role of long-range intra-protein electrostatic interactions by comparing models with different complexity in vacuum and in charge field. Our results show that the dipole moment of the alpha-helix can cause significant deshielding of (15)N; therefore, it needs to be considered when calculating (15)N chemical shielding. We found that it is important to include interactions with the side chains that are close in space when the charged form for ionizable side chains is adopted in the calculation. We also illustrate how the ionization state of these side chains can affect the chemical shielding tensor elements. Chemical shielding calculations using a 8-residue fragment model in vacuum and adopting the charged form of ionizable side chains yield a generally good agreement with experimental data. PMID- 19644656 TI - Partially folded equilibrium intermediate of the villin headpiece HP67 defined by 13C relaxation dispersion. AB - Identification and characterization of ensembles of intermediate states remains an important objective in describing protein folding in atomic detail. The 67 residue villin headpiece, HP67, consists of an N-terminal subdomain (residues 10 42) that transiently unfolds at equilibrium under native-like conditions and a highly stable C-terminal subdomain (residues 43-76). The transition between folded and unfolded states of the N-terminal domain has been characterized previously by (15)N NMR relaxation dispersion measurements (Grey et al. in J Mol Biol 355:1078, 2006). In the present work, (13)C spin relaxation was used to further characterize backbone and hydrophobic core contributions to the unfolding process. Relaxation of (13)C(alpha) spins was measured using the Hahn echo technique at five static magnetic fields (11.7, 14.1, 16.4, 18.8, and 21.1 T) and the Carr-Purcell-Meiboom-Gill (CPMG) relaxation dispersion method at a static magnetic field of 14.1 T. Relaxation of methyl (13)C spins was measured using CPMG relaxation dispersion experiments at static magnetic fields of 14.1 and 18.8 T. Results for (13)C and (15)N spins yielded a consistent model in which the partially unfolded intermediate state of the N-terminal subdomain maintains residual structure for residues near the unprotonated His41 imidazole ring and in the interface between the N- and C-terminal subdomains. In addition, a second faster process was detected that appears to represent local dynamics within the folded state of the molecule and is largely confined to the hydrophobic interface between the N- and C-terminal subdomains. PMID- 19644657 TI - Insulin mimetic effect of tungsten compounds on isolated rat adipocytes. AB - Investigations of effective, orally active, and safe antidiabetic metallopharmaceuticals have been carried out during the last two decades. It has been reported that tungsten compounds mimic the action of insulin in intact cell systems. As insulin mimetics, the most investigated tungsten compound was sodium tungstate (ST), rarely investigated was tungstophosphoric acid (WPA), but never alanine complex of tungstophosphoric acid (WPA-A). In this study, the insulin mimetic activity of three different tungsten compounds, ST, WPA, and WPA-A, was evaluated by means of in vitro measurements of the glucose uptake and inhibition of free fatty acids release from epinephrine-treated isolated rat white adipocytes. We investigated the influence of concentration (lower and higher, 0.1 and 1.0 mM, respectively) and solvent: isotonic salt solution-saline (0.9% w/v of NaCl) and dimethyl sulfoxide (DMSO; 2% v/v), on the biological effect of tested compounds. Our experimental data showed that all of the three investigated tungsten compounds possess insulin mimetic activity in vitro on the isolated adipocytes. Influence of concentration and solvents on insulin mimetic effect for the certain tungsten compounds were: WPA was shown effect independently of concentration and solvents; higher concentration and DMSO were significant decreasing insulin mimetic effect of ST; lower concentration and saline led to decreasing effect of WPA-A. Generally, there were no differences in insulin mimetic effect of three tungsten compounds in lower concentration and dissolved in DMSO. When saline was used as solvent, it was needed higher concentration of investigated compounds to accomplish the same effect. In conclusion, our results suggest that low concentration (0.1 mM) of ST, WPA, and WPA-A dissolved in 2% DMSO could be the good candidates for in vivo investigation of their antidiabetic properties. PMID- 19644658 TI - Significance of trace element profile of blood of persons with multiple caries versus sound teeth. AB - In order to determine any possible relation between chemical composition of a person's blood to formation of dental caries, whole blood was analyzed for 35 inorganic elements (Si, Al, Fe, Ca, Mg, K, Mn, Ti, P, Li, Be, B, V, Cr, Co, Ni, Cu, Zn, As, Sr, Y, Nb, Mo, Ag, Cd, Sn, Sb, Ba, La, Ce, W, Pb, Bi, Zr, and F) in the 15 people having sound teeth as well as an equal number of those having multiple caries. The results showed the absence of 13 elements (Si, Al, Mn, Ti, Be, Co, As, Y, Cd, Ba, La, Ce, and Zr) in the blood of both groups. Of the remaining 22 elements, the results of only seven elements (Fe, P, B, V, Sr, Sn, and F) were significantly different between the two groups. The most remarkable finding of this study was significantly decreased amount of phosphorus, strontium, and fluorine and perhaps increased boron in the blood of persons with caries. PMID- 19644659 TI - Comparison of trace elements in the scalp hair of malignant and benign breast lesions versus healthy women. AB - Trace elements including Al, Ca, Cd, Co, Cr, Cu, Fe, K, Mg, Mn, Na, Ni, Pb, Sb, Sr, and Zn were analyzed in the scalp hair samples of women with malignant breast lesions, women with benign breast lesions, and healthy donors using atomic absorption spectrophotometric method. In the scalp hair of malignant-tumor patients, the highest average concentration was shown by Ca (1,187 microg/g), followed by Na (655 microg/g), Mg (478 microg/g), Zn (391 microg/g), Sr (152 microg/g), Fe (114 microg/g), and K (89.8), while in the case of benign-tumor patients, the average estimated element levels were 1,522, 1,093, 572, 457, 217, 80.4, and 74.7 microg/g, respectively. Most of the elements exhibited non-normal distribution evidenced by large spread, standard error, and skewness values. Mean concentrations of Ca (634 microg/g), Zn (206 microg/g), Mg (162 microg/g), Fe (129 microg/g), and Na (82.1 microg/g) were noteworthy in the scalp hair of healthy women. Average levels of Na, Sr, K, Cd, Co, Pb, Mg, Ca, Zn, Ni, Sb, and Mn were revealed to be significantly higher in the hair of malignant and benign patients compared to the healthy women; however, Fe, Cu, Al, and Cr were not significantly different in the scalp hair of the three groups. The quartile distributions of Ca, Cd, Co, Cr, K, Mg, Mn, Na, Ni, Pb, Sb, and Sr revealed maximum spread in the scalp hair of malignant and benign groups; nevertheless, Al, Cu, Fe, and Zn exhibited almost comparable quartile levels in the three groups. Strong correlation coefficients were found between Fe and Cd, Al and Na, Mn and Sr, Co and Cr, Cd and Cr, Pb and K, Pb and Mn, Cu and Na, and Al and Fe in the scalp hair of malignant-tumor patients, while Fe and K, Cd and Co, Na and Co, and Cr and Pb showed strong correlations in the scalp hair of benign-tumor patients, both of which were significantly different compared with the healthy subjects. Multivariate cluster analysis also revealed divergent clustering of the elements in the scalp hair of malignant and benign patients in comparison with the healthy women. PMID- 19644660 TI - p38 MAP kinase inhibitor prevents diastolic dysfunction in rats following HIV gp120 injection in vivo. AB - HIV infection in patients is associated with a surprisingly high frequency of diastolic dysfunction followed by the development of a dilated cardiomyopathy. Potential mechanisms include direct effects of HIV proteins, including gp120. We have previously reported direct inotropic and p38 MAP kinase signaling effects of HIV gp120 on isolated cardiac myocytes in vitro. We now report effects of a single injection of HIV gp120 on cardiac hemodynamics in vivo. HIV gp120 (50 microg/kg) was injected intravenously and hemodynamics assessed at 1, 24, 48 and 72 h in freely ambulatory, awake rats. Rats injected with gp120 demonstrated a blunted diastolic response to increasing intravenous (IV) injections of the beta adrenergic agonist, isoproterenol (ISO), compared with similarly instrumented controls at 48 h (gp120 vs. control, P < 0.01; n = 6, for each). Pre-treatment with the p38 MAP kinase inhibitor, SB 203580, prevented the diastolic dysfunction (gp120 + SB vs. control, P = NS; n = 6, for each). Hemodynamic changes correlated with inhibition of both p38 MAP kinase and troponin I phosphorylation by SB in vivo. There were no differences in ISO dose-response curves between gp120-treated and control rats at 1, 24 or 72 h (P = NS; n = 6, for each). Thus, evidence of diastolic dysfunction is apparent in vivo in rats following a single dose of HIV gp120. To our knowledge, this is the first report of a hemodynamic effect of an HIV protein in vivo. These findings lend further support to the hypothesis that the HIV virus, itself, may contribute to myocardial dysfunction in patients infected with HIV via a p38 MAP kinase mechanism. PMID- 19644661 TI - [Therapy of occupational skin diseases]. AB - Hand eczema is one of the most frequent skin diseases. About 5-10% of population has chronic hand eczema. In addition, hand eczema accounts for more than 90% of occupational skin diseases. The therapy of hand eczema is expensive and often leads to a loss in quality of life. The therapy is complex, not always successful and can lead in the worst case to the patient being forced to give up or change their profession. We review the therapeutic options to treat occupational hand eczema. PMID- 19644662 TI - [Skin protection. From TRGS 401 to guidelines on "occupational skin protection products"]. AB - The technical standards for hazardous substances (TRGS) reflect the currently achievable technical safety, occupational-medical, hygienic and scientific standards for production, distribution and handling of hazardous substances. The TRGS 401 "Risks resulting from skin contact--determination, evaluation, measures" gives important information regarding occupational hazardous exposure of the skin and the measures for prevention. A definition for wet work is given under which occlusion by moisture impermeable protective gloves and contacts to wet environments are included. Both the TRGS 401 and the AWMF S1 guidelines on "Occupational protection products" place emphasis on the fact that the protective effectiveness of topical skin products for protection, care and cleansing should be proven by in vivo methods. PMID- 19644663 TI - Frontiers in the pathogenesis of kidney disease. PMID- 19644664 TI - [Safe:Trac course series of the German Society for Trauma Surgery on patient safety]. AB - Based on crew resource management of the airline industry the German Society for Trauma Surgery (Deutsche Gesellschaft fur Unfallchirurgie, DGU) was the first scientific community in Germany to develop and implement a training course for patient safety. The S:training courses contain four course formats which focus on the prehospital life support (S:PLS), the operating room (S:OR), the trauma room (S:TR) and the intensive care unit (S:ICU). In the training the importance of the human factor for the management of acute major trauma is developed by means of presentations, training videos, practical training, discussions and realistic case scenarios associated with the special working environment of the participants. A specially developed course manual acts as a work and reference book and course booking is possible at http://www.safe-trac.de. PMID- 19644665 TI - [Qualitative and quantitative CT analysis of acute pulmonary failure]. AB - Since its first application in patients with acute lung injury 25 years ago, computed tomography (CT) has significantly influenced the understanding of the pathophysiology, diagnosis and management of acute lung injury and has become an important diagnostic modality for these patients. The aim of this article is to review important disease-specific aspects of CT acquisition and qualitative and quantitative analyses of CT data. Morphological changes seen on CT and associated functional alterations are discussed. Methods used for the quantification of lung aeration are described and their limitations outlined. PMID- 19644666 TI - Identifying QTL for high-temperature adult-plant resistance to stripe rust (Puccinia striiformis f. sp. tritici) in the spring wheat (Triticum aestivum L.) cultivar 'Louise'. AB - Over time, many single, all-stage resistance genes to stripe rust (Puccinia striiformis f. sp. tritici) in wheat (Triticum aestivum L.) are circumvented by race changes in the pathogen. In contrast, high-temperature, adult-plant resistance (HTAP), which only is expressed during the adult-plant stage and when air temperatures are warm, provides durable protection against stripe rust. Our objective was to identify major quantitative trait loci (QTL) for HTAP resistance to stripe rust in the spring wheat cultivar 'Louise'. The mapping population consisted of 188 recombinant inbred lines (RIL) from a Louise (resistant) by 'Penawawa' (susceptible) cross. F(5:6) lines were evaluated for stripe rust reaction under natural infection in replicated field trials at five locations in the US Pacific Northwest in 2007 and 2008. Infection type (IT) and disease severity were recorded for each RIL 2-4 times per location. In all environments, Penawawa, the susceptible parent, was rated with an IT ranging from 6 to 8 at all growth stages evaluated. In contrast, Louise, the resistant parent, was rated with an IT of 2 or 3 across growth stages. Distribution of IT values was bimodal, indicating a single major gene was affecting the trait. The parents and RIL population were evaluated with 295 polymorphic simple sequence repeat and one single nucleotide polymorphism markers. One major QTL, designated QYrlo.wpg-2BS, associated with HTAP resistance in Louise, was detected on chromosome 2BS (LOD scores ranging from 5.5 to 62.3 across locations and years) within a 16.9 cM region flanked by Xwmc474 and Xgwm148. SSR markers associated with QYrlo.wpg-2BS are currently being used in marker-based forward breeding strategies to transfer the target region into adapted germplasm to improve the durability of resistance in resulting cultivars. PMID- 19644667 TI - Perinatal survivin is essential for the establishment of pancreatic beta cell mass in mice. AB - AIMS/HYPOTHESIS: Pancreatic beta cells undergo dynamic remodelling during the perinatal period, with enhanced neogenesis, proliferation and apoptosis observed. The molecular mechanisms responsible for these processes have yet to be elucidated. Survivin is an inhibitor of apoptosis, first described as being exclusively expressed in tumour and embryonic tissues with regulatory functions in mitosis and apoptosis. The aim of the present study was to define the essential physiological role of survivin in the pancreas. METHODS: The expression profile of survivin was assessed in the mouse pancreas, and we generated a Pdx1 promoter-driven Survivin (also known as Birc5) knockout mouse using the Cre-loxP recombination system to determine the essential physiological function of survivin in the pancreas. RESULTS: Survivin is transiently expressed in mouse pancreatic islets during the embryonic and neonatal periods. Targeted deletion of Survivin in the pancreas resulted in a significant decline in beta cell mass throughout the perinatal period, leading to glucose intolerance in the adult. Survivin-deficient islets showed decreased cell proliferation as a result of a delay in cell cycle progression with perturbations in cell cycle proteins. Survivin did not, however, play an essential role in beta cell apoptosis either during the physiological remodelling period or in response to streptozotocin. Islet development, islet architecture, microvasculature and apoptosis were not affected by the absence of survivin in the pancreas. CONCLUSIONS/INTERPRETATION: Survivin expression in the pancreatic islets during the perinatal remodelling period is essential for the establishment of beta cell mass through cell cycle regulation. PMID- 19644668 TI - Optimal insulin regimens in type 2 diabetes mellitus: systematic review and meta analyses. AB - AIMS/HYPOTHESIS: We compared the effect of biphasic, basal or prandial insulin regimens on glucose control, clinical outcomes and adverse events in people with type 2 diabetes. METHODS: We searched the Cochrane Library, MEDLINE, EMBASE and major American and European conference abstracts for randomised controlled trials up to October 2008. A systematic review and meta-analyses were performed. RESULTS: Twenty-two trials that randomised 4,379 patients were included. Seven trials reported both starting insulin dose and titration schedules. Hypoglycaemia definitions and glucose targets varied. Meta-analyses were performed pooling data from insulin-naive patients. Greater HbA(1c) reductions were seen with biphasic and prandial insulin, compared with basal insulin, of 0.45% (95% CI 0.19-0.70, p = 0.0006) and 0.45% (95% CI 0.16-0.73, p = 0.002), respectively, but with lesser reductions of fasting glucose of 0.93 mmol/l (95% CI 0.21-1.65, p = 0.01) and 2.20 mmol/l (95% CI 1.70-2.70, p < 0.00001), respectively. Larger insulin doses at study end were reported in biphasic and prandial arms compared with basal arms. No studies found differences in major hypoglycaemic events, but minor hypoglycaemic events for prandial and biphasic insulin were inconsistently reported as either higher than or equivalent to basal insulin. Greater weight gain was seen with prandial compared with basal insulin (1.86 kg, 95% CI 0.80 2.92, p = 0.0006). CONCLUSIONS/INTERPRETATION: Greater HbA(1c) reduction may be obtained in type 2 diabetes when insulin is initiated using biphasic or prandial insulin rather than a basal regimen, but with an unquantified risk of hypoglycaemia. Studies with longer follow-up are required to determine the clinical relevance of this finding. PMID- 19644672 TI - Reduction of ventilator-associated pneumonia: enhancing knowledge is important. PMID- 19644669 TI - Metabolic effects of diets differing in glycaemic index depend on age and endogenous glucose-dependent insulinotrophic polypeptide in mice. AB - AIMS/HYPOTHESIS: High- vs low-glycaemic index (GI) diets unfavourably affect body fat mass and metabolic markers in rodents. Different effects of these diets could be age-dependent, as well as mediated, in part, by carbohydrate-induced stimulation of glucose-dependent insulinotrophic polypeptide (GIP) signalling. METHODS: Young-adult (16 weeks) and aged (44 weeks) male wild-type (C57BL/6J) and GIP-receptor knockout (Gipr ( -/- )) mice were exposed to otherwise identical high-carbohydrate diets differing only in GI (20-26 weeks of intervention, n = 8 10 per group). Diet-induced changes in body fat distribution, liver fat, locomotor activity, markers of insulin sensitivity and substrate oxidation were investigated, as well as changes in the gene expression of anorexigenic and orexigenic hypothalamic factors related to food intake. RESULTS: Body weight significantly increased in young-adult high- vs low-GI fed mice (two-way ANOVA, p < 0.001), regardless of the Gipr genotype. The high-GI diet in young-adult mice also led to significantly increased fat mass and changes in metabolic markers that indicate reduced insulin sensitivity. Even though body fat mass also slightly increased in high- vs low-GI fed aged wild-type mice (p < 0.05), there were no significant changes in body weight and estimated insulin sensitivity in these animals. However, aged Gipr ( -/- ) vs wild-type mice on high-GI diet showed significantly lower cumulative net energy intake, increased locomotor activity and improved markers of insulin sensitivity. CONCLUSIONS/INTERPRETATION: The metabolic benefits of a low-GI diet appear to be more pronounced in younger animals, regardless of the Gipr genotype. Inactivation of GIP signalling in aged animals on a high-GI diet, however, could be beneficial. PMID- 19644673 TI - Bacteraemia following single-stage percutaneous dilatational tracheostomy. AB - OBJECTIVE: Surgical tracheostomy in critically ill adults has largely been replaced by physicians performing percutaneous dilatational tracheostomy (PDT) at the bedside. Complications associated with this technique include haemorrhage, wound infection, barotrauma, false passage, ruptured tracheal ring and bacteraemia. Prophylactic antibiotics are not generally used with this procedure, however the incidence of bacteraemia following PDT has not been extensively studied. DESIGN: Prospective observational study. SETTING: Adult intensive care unit of a university medical centre. METHODS: Peripheral venous blood cultures were obtained immediately before and after PDT in 118 consecutive patients. Surveillance cultures of potential respiratory pathogens were also recorded using routine non-directed broncholalveolar lavage. RESULTS: Forty-three female and 75 male patients underwent PDT. Fifty-seven patients (48.3%) were not receiving antibiotics on the day of PDT, whilst the remaining 61 individuals (51.7%) were on antibiotic therapy at the time of the procedure. Bacteraemia following PDT occurred in six out of 113 patients (5.3%), five of which occurred in patients not receiving antibiotics (9.2%). Unexpected bacteraemia (positive pre-and post PDT blood cultures) was identified in five patients, two of whom were on antibiotic therapy. CONCLUSION: The incidence of bacteraemia following a single stage PDT was similar to other manipulations of the aerodigestive tract such as intubation, insertion of an LMA or tooth brushing. We suggest that routine antibiotic prophylaxis is unnecessary for this procedure. PMID- 19644674 TI - Management of patients transferred to the ICU during the conditioning phase of allogeneic hematopoietic stem cell transplantation. PMID- 19644675 TI - PIP5K2A-dependent regulation of excitatory amino acid transporter EAAT3. AB - INTRODUCTION: According to previous observations, the gene encoding the phosphatidylinositol-4-phosphate 5-kinase II alpha (PIP5K2A) is associated with schizophrenia. Specifically, the mutation (N251S)PIP5K2A has been discovered in schizophrenic patients but not in healthy individuals. A defect of the excitatory amino acid transporter EAAT3 has similarly been implicated in the development of schizophrenia. The present study thus explored whether PIP5K2A is involved in the regulation of EAAT3 activity. MATERIALS AND METHODS: EAAT3 was expressed in Xenopus oocytes either without or with PIP5K2A, and EAAT3 transporter activity was estimated from the glutamate (2-mM)-induced current (I(glu)) in dual electrode voltage clamp experiments. EAAT3 protein abundance in the cell membrane was estimated by Western blotting and confocal microscopy. RESULTS: In EAAT3 expressing oocytes, I(glu) was enhanced by coexpression of wild type PIP5K2A. Coexpression of the schizophrenia-associated mutant (N251S)PIP5K2A significantly decreased I(glu) in oocytes expressing EAAT3 with or without additional expression of wild type PIP5K2A. Thus, (N251S)PIP5K2A exerts a dominant inhibitory effect. DISCUSSION: Membrane abundance of EAAT3 was increased by wild type PIP5K2A and decreased by (N251S)PIP5K2A in both EAAT3-expressing oocytes and human embryonic kidney cells. The present observations disclose a novel mechanism of EAAT3 regulation, which may contribute to the deranged regulation of excitability in schizophrenic patients. PMID- 19644676 TI - Analytical strategies for characterizing the surface chemistry of nanoparticles. AB - Chemical modifications of nanoparticle (NP) surfaces are likely to regulate their activities, remove their toxic effects, and enable them to perform desired functions. It is urgent to develop analytical strategies for acquiring structural and quantitative information about small molecules linked to the surface of NP. Recent progress in characterizing the surface chemistry of NPs using nuclear magnetic resonance (NMR) spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, liquid chromatography-mass spectroscopy (LC-MS), X-ray photoelectron spectroscopy (XPS), and combustion elemental analysis are reviewed. PMID- 19644677 TI - New directions in medical biosensors employing poly(3,4-ethylenedioxy thiophene) derivative-based electrodes. AB - Demand is growing in the field of medical diagnostics for simple, disposable devices that also demonstrate fast response times, are easy to handle, are cost efficient, and are suitable for mass production. Polymer-based microfluidic devices meet the requirements of cost efficiency and mass production and they are suitable for biosensor applications. Conducting polymer-based electrochemical sensors have shown numerous advantages in a number of areas related to human health, such as the diagnosis of infectious diseases, genetic mutations, drug discovery, forensics and food technology, due to their simplicity and high sensitivity. One of the most promising group of conductive polymers is poly(3,4 ethylenedioxythiophene) (PEDOT) and its derivatives due to their attractive properties: high stability, high conductivity (up to 400-600 S/cm) and high transparency. This review paper summarizes newly developed methods associated with the application of PEDOT to diagnostic sensing. PMID- 19644679 TI - Current trends in the detection of peroxide-based explosives. AB - The increased use of peroxide-based explosives (PBEs) in criminal and terrorist activity has created a demand for continued innovation in the detection of these agents. This review provides an update to a previous 2006 review on the detection of PBEs, with a focus in this report on luminescence and fluorescence methods, infrared and Raman spectroscopy, mass spectrometry, and electrochemical techniques. Newer developments in gas chromatography and high performance liquid chromatography methods are also discussed. One recent trend that is discussed is an emphasis on field measurements through the use of portable instruments or portable assay formats. An increase in the use of infrared spectroscopy and mass spectrometry for PBE analysis is also noted. The analysis of triacetone triperoxide has been the focus in the development of many of these methods, although hexamethylene triperoxide diamine has received increased attention in PBE detection during the last few years. PMID- 19644678 TI - Comparison of protein immobilisation methods onto oxidised and native carbon nanofibres for optimum biosensor development. AB - The properties of native and oxidised graphene layered carbon nanofibres are compared, and their utilisation in enzyme biosensor systems using different immobilisation methods are evaluated. The efficient oxidation of carbon nanofibres with concentrated H(2)SO(4)/HNO(3) is confirmed by Raman spectroscopy while the introduction of carboxylic acid groups on the surface of the fibres by titration studies. The oxidised fibres show enhanced oxidation efficiency to hydrogen peroxide, while at the same time they exhibit a more efficient and selective interaction with enzymes. The analytical characteristics of biosensor systems based on the adsorption or covalent immobilisation of the enzyme glucose oxidase on carbon nanofibres are compared. The study reveals that carbon nanofibres are excellent substrates for enzyme immobilisation allowing the development of highly stable biosensor systems. PMID- 19644680 TI - An associativity requirement for locus coeruleus-induced long-term potentiation in the dentate gyrus of the urethane-anesthetized rat. AB - Norepinephrine has been hypothesized to provide a learning and memory signal. Norepinephrine long-term potentiation of perforant path input to the dentate gyrus of the hippocampus provides a model for norepinephrine initiated memory processes. However, in vitro, the pairing of perforant path stimulation and norepinephrine is not required for the occurrence of norepinephrine-dependent long-term potentiation. Since bath application of norepinephrine induces long term changes in 2nd messenger signalling and differs in a number of ways from physiological norepinephrine release, the present study is an in vivo test of the associative requirement for the pairing of perforant path input with norepinephrine to induce long-term potentiation. Phasic activation of the locus coeruleus is provided by glutamate infusion into the locus coeruleus to initiate transient norepinephrine release in the hippocampus of urethane-anesthetized Sprague-Dawley rats. Perforant path stimulation (0.067 Hz) was given throughout the experiment in the paired condition. In the unpaired condition perforant path stimulation was interrupted 10 min prior to locus coeruleus activation and resumed 10 min after locus coeruleus activation. Locus coeruleus-induced long term potentiation of both EPSP slope and population spike only occurred in the pairing condition. This result argues that, in vivo, temporal proximity of locus coeruleus-associated norepinephrine release and perforant path stimulation are required to induce long-term plasticity. The associativity requirement for locus coeruleus activation and perforant path stimulation in vivo is consistent with the hypothesis that norepinephrine can initiate circuit changes supporting learning and memory. PMID- 19644681 TI - Saccadic eye movements as an index of perceptual decision-making. AB - One of the most common decisions we make is the one about where to move our eyes next. Here we examine the impact that processing the evidence supporting competing options has on saccade programming. Participants were asked to saccade to one of two possible visual targets indicated by a cloud of moving dots. We varied the evidence which supported saccade target choice by manipulating the proportion of dots moving towards one target or the other. The task was found to become easier as the evidence supporting target choice increased. This was reflected in an increase in percent correct and a decrease in saccade latency. The trajectory and landing position of saccades were found to deviate away from the non-selected target reflecting the choice of the target and the inhibition of the non-target. The extent of the deviation was found to increase with amount of sensory evidence supporting target choice. This shows that decision-making processes involved in saccade target choice have an impact on the spatial control of a saccade. This would seem to extend the notion of the processes involved in the control of saccade metrics beyond a competition between visual stimuli to one also reflecting a competition between options. PMID- 19644682 TI - Association between the use of anticholinergic antiparkinson drugs and safety and receptor drug-binding profiles of antipsychotic agents. AB - PURPOSE: The use of anticholinergic antiparkinson drugs is almost exclusively confined to treating antipsychotic-induced extrapyramidal side effects (EPS). We investigated the prevalence of concomitant prescription of anticholinergics as a proxy for antipsychotic-induced EPS and compared variance in prevalence with differences in the assumed mechanisms of action of antipsychotics on central nervous system (CNS) transmitter systems (i.e., receptor drug-binding profiles). We paid special attention to potential differences between typical and atypical antipsychotics. METHODS: Data were drawn from the Norwegian Prescription Database on sales of antipsychotic and anticholinergic antiparkinson drugs to a total of 57,130 outpatients in 2004. We assessed concomitant dispensations of antipsychotic and anticholinergic drugs and correlated the prevalence of concomitantly prescribed anticholinergics to previously assessed receptor-binding profiles of antipsychotics. RESULTS: The concurrent use of anticholinergics varied between 0.4% and 26.0% for patients using a single antipsychotic agent. The prevalence of anticholinergic comedication was more than twice as high in patients using two or more antipsychotic drugs. Four typical antipsychotics (fluphenazine, zuclopenthixol, haloperidol, and perphenazine) were associated with higher concomitant use of anticholinergics than the rest. For the remaining 14 antipsychotic agents, the difference between typical and atypical antipsychotics was neither pronounced nor systematic. A high degree of D2 receptor antagonism and a high 5-HT2A/D2-receptor-affinity ratio coincided with the use of anticholinergics. CONCLUSIONS: The liability of antipsychotic drugs to cause EPS seemed to vary considerably and largely independently of the distinction between typical and atypical antipsychotics. PMID- 19644683 TI - Coil embolization of anterior circulation aneurysms supported by the Solitaire AB Neurovascular Remodeling Device. AB - INTRODUCTION: The purpose of the study is to evaluate patients with wide-necked or complex aneurysms of the anterior circulation who underwent Solitaire AB Neurovascular Remodeling Device-assisted coil embolization. METHODS: From February 2008 to March 2009, consecutive data were collected from 45 patients with anterior circulation aneurysms. Eighteen of the patients presented with acute subarachnoid hemorrhage. Forty-six aneurysms were treated with the aid of different applications (n = 49) of the Solitaire AB Remodeling Device followed by standard coiling procedure (n = 43) using bioactive coils or/and bare coils. RESULTS: Successful positioning of the remodeling device was obtained in 95.9% of the cases. There were two thromboembolic complications (4.1%) and one severe vasospasm requiring retrieval of the device. Permanent procedural morbidity was observed in one patient (2%). The proportion of patients in whom Raymond class 1 occlusion was obtained was 53.5% (n = 23). Raymond class 2 occlusion was achieved in 42% (n = 18) and Raymond class 3 occlusion in 4.7% (n = 2). Thirty-nine patients left the hospital with a good clinical status. CONCLUSION: The initial technical and clinical results of Solitaire AB device-assisted coiling of aneurysms in the anterior circulation are highly encouraging. This technique may enhance the possibilities of the endovascular treatment of these aneurysms in clinical routine. PMID- 19644684 TI - Clinical image. MR angiography of midaortic syndrome. PMID- 19644685 TI - CT angiography of mildly symptomatic, isolated, unilateral right pulmonary vein atresia. AB - We report a mildly symptomatic 12-year-old boy with a very rare congenital anomaly-isolated unilateral pulmonary vein atresia. Diagnosis was made using CT angiography and its role in diagnosis is discussed. PMID- 19644686 TI - On the analysis of sedimentation velocity in the study of protein complexes. AB - Sedimentation velocity analytical ultracentrifugation has experienced a significant transformation, precipitated by the possibility of efficiently fitting Lamm equation solutions to the experimental data. The precision of this approach depends on the ability to account for the imperfections of the experiment, both regarding the sample and the instrument. In the present work, we explore in more detail the relationship between the sedimentation process, its detection, and the model used in the mathematical data analysis. We focus on configurations that produce steep and fast-moving sedimentation boundaries, such as frequently encountered when studying large multi-protein complexes. First, as a computational tool facilitating the analysis of heterogeneous samples, we introduce the strategy of partial boundary modeling. It can simplify the modeling by restricting the direct boundary analysis to species with sedimentation coefficients in a predefined range. Next, we examine factors related to the experimental detection, including the magnitude of optical aberrations generated by out-of-focus solution columns at high protein concentrations, the relationship between the experimentally recorded signature of the meniscus and the meniscus parameter in the data analysis, and the consequences of the limited radial and temporal resolution of the absorbance optical scanning system. Surprisingly, we find that large errors can be caused by the finite scanning speed of the commercial absorbance optics, exceeding the statistical errors in the measured sedimentation coefficients by more than an order of magnitude. We describe how these effects can be computationally accounted for in SEDFIT and SEDPHAT. PMID- 19644687 TI - Analysis of aldehyde reductases from Gluconobacter oxydans 621H. AB - Two cytosolic nicotinamide adenine dinucleotide phosphate-dependent aldehyde reductases, Gox1899 and Gox2253, from Gluconobacter oxydans 621H were overproduced and purified from Escherichia coli. The purified proteins exhibited subunit masses of 26.4 (Gox1899) and 36.7 kDa (Gox2253). Both proteins formed homo-octamers exhibiting native masses of 210 and 280 kDa, respectively. The substrate spectra, optimal reaction conditions, and kinetic constants were determined for Gox1899 and Gox2253. Both enzymes efficiently catalyzed the reduction of medium/long-chain aldehydes. However, Gox1899 had a wider substrate spectrum and was more catalytically efficient. The best activity with Gox1899 was found for aliphatic aldehydes of C6-C10. In contrast, Gox2253 had a limited substrate spectrum and reduced octanal, nonanal, and decanal. Both enzymes were unable to oxidize primary alcohols. Aldehyde removal may be of particular importance for Gluconobacter because the membrane-bound alcohol dehydrogenase rapidly oxidizes short to long-chain alcohols, and large quantities of aldehydes could enter the cell, making detoxification necessary. PMID- 19644688 TI - Occurrence, properties, and applications of feruloyl esterases. AB - Feruloyl esterases hydrolyze the ester linkages of ferulic and diferulic acids present in plant cell walls. This interesting group of enzymes also has a potentially broad range of applications in the pharmaceutical and agri-food industries. An overview of the current knowledge of fungal feruloyl esterases focusing on the diverse of substrate specificity and potential applications is presented in this review. Furthermore, biological functions of ferulic acid are discussed. PMID- 19644689 TI - Efficient methods for large-area surface sampling of sites contaminated with pathogenic microorganisms and other hazardous agents: current state, needs, and perspectives. AB - The recovery operations following the 2001 attacks with Bacillus anthracis spores were complicated due to the unprecedented need for large-area surface sampling and decontamination protocols. Since this event, multiple reports have been published describing recovery efficiencies of several surface sampling materials. These materials include fibrous swabs of various compositions, cloth wipes, vacuum socks, and adhesive tapes. These materials have reported recovery efficiencies ranging from approximately 20% to 90% due to the many variations in their respective studies including sampling material, composition of surface sampled, concentration of contaminant, and even the method of deposition and sample processing. Additionally, the term recovery efficiency is crudely defined and could be better constructed to incorporate variations in contaminated surface composition and end user needs. While significant efforts in devising protocols for large-area surface sampling have been undertaken in the years since the anthrax attacks, there is still a general lack of consensus in optimal sampling materials and the methodology in which they are evaluated. Fortunately, sampling efforts are continuing to be supported, and the knowledge gaps in our procedures, methodology, and general understanding of sampling mechanisms are being investigated which will leave us better prepared for the future. PMID- 19644690 TI - Methyl-branched poly(hydroxyalkanoate) biosynthesis from 13-methyltetradecanoic acid and mixed isostearic acid isomer substrates. AB - Pseudomonas resinovorans, a known medium-chain-length (mcl-) poly(hydroxyalkanoate) (PHA) producer, was grown on 13-methyltetradecanoic acid (13-MTDA) and a mixture of isostearic acid (IA) isomers to produce methyl branched mcl-PHA polymers. Shake-flask experiments revealed polymer productivities (the percent of the cell mass that is polymer) of 31 +/- 1% (n = 3) and 23 +/- 3% (n = 3) when grown in 13-MTDA and IA, respectively. Monomer content was determined by a combination of gas chromatography/mass spectrometry (GC/MS) of the acid hydrolyzed, silylated methyl esters, and nuclear magnetic resonance spectroscopy. Results showed that the mcl-PHA polymer derived from 13 MTDA was primarily composed of 3-hydroxy-7-methyloctanoic acid and 3-hydroxy-9 methyldecanoic acid (67 and 16 mol% by GC/MS, respectively). In contrast, the mcl polymers synthesized from the IA isomeric mixture were more complex, containing both even and odd chain-length monomers as well as varying distributions of methyl-branched derivatives. The PHA distributions among the C8, C10, C12, and C14 carbon chain-length monomers included three isomers of C8, five isomers of C10, seven isomers of C12, and nine isomers of C14 each containing one linear chain derivative and n-6 methyl-branched derivatives where n equals the total number of carbon atoms in each monomer unit (C8-C14). PMID- 19644691 TI - Effects of therapeutic ultrasound and electrical stimulation program on pain, trunk muscle strength, disability, walking performance, quality of life, and depression in patients with low back pain: a randomized-controlled trial. AB - The aim of this trial is to investigate and compare the effects of electrical stimulation (ES) program and ultrasound (US) therapy on pain, disability, trunk muscle strength, walking performance, spinal mobility, quality of life (QOL), and depression in the patients with chronic low back pain (CLBP). A total of 59 patients with definite CLBP were enrolled in this study. These patients were randomized into three groups. Group 1 (n = 20) was given an ES program and exercises. Group 2 (n = 19) was given an US treatment and exercises. Group 3 (n = 20) was accepted as the control group and was given only exercises. All of the programs were performed 3 days a week, for 6 weeks. The patients were evaluated according to pain, disability, walking performance, endurance, mobility, QOL, depression. The trunk muscle strength was measured with a hand-held dynamometer. All of the groups showed stastically significant improvements in pain, disability, muscle strength, endurance, walking performance, mobility, sub-scores of SF 36, and depression when compared with their initial status. The intergroup comparison showed significant difference in physical function, energy and social function sub-groups of SF-36, VAS pain, extensor muscle strength, between three groups. This difference was statistically significant in the groups 1 and 2 compared to the control group. There was also no significant difference between the groups 1 and 2. We observed that US treatment and ES treatment were effective in improving pain, isometric extensor muscle strength, and QOL in patients with CLBP. PMID- 19644693 TI - Modified transoral approach for resection of skull base chordomas in children. AB - PURPOSE: Chordomas are rare slow growing, locally destructive tumours originating from remnants of the primitive notocord and are found most commonly in the clivus and saccrococcygeal region. These tumours usually present in early adult life but on occasion can present in childhood. The combination of the skull base location and paediatric patient size makes access to these tumours particularly challenging. METHODS AND RESULTS: We report a multidisciplinary technique used in two cases in children where a modified extended palatal split was undertaken to allow greater access for tumour excision. CONCLUSION: This approach allows for good access to the skull base region to allow for maximal tumour resection. This technique also appears to have minimal impact on palatal function and no adverse effects on the upper airway management. PMID- 19644692 TI - Trilateral retinoblastoma: an institutional experience and review of the literature. AB - BACKGROUND: Retinoblastoma is the most common pediatric intraocular neoplasm. The association of uni- or bilateral retinoblastoma with synchronic or metachronic ectopic midline intracranial tumor [trilateral retinoblastoma (TRB)] is uncommon. MATERIALS AND METHODS: MR examinations of 202 children with retinoblastoma treated at our institute were retrospectively reviewed. MR images and clinical data of children with TRB were evaluated for the patient's age at diagnosis of the intracranial tumor and intraocular lesions, tumor size, signal characteristics, and further course in follow-up MR examinations. RESULTS: There were three patients with TRB in our group of patients. All three children had had a negative family history. Two of them had a primary midline intracranial tumor and intraocular lesions at the time of the first diagnosis. In the third case, the first diagnosis was intracranial midline primitive neuroectodermal tumor. Diagnosis of lesions in both eyes was confirmed in ophthalmologic examination 1 month later. In one case, the intracranial tumor was in the pineal region and, in the other two cases, in the sellar and suprasellar regions. There was no evidence of leptomeningeal spread of the tumors in any patient. CONCLUSIONS: Patients with uni- and bilateral intraocular tumors should receive brain screening by MR imaging. We also recommend that patients under the age of 4 years with midline tumors should be carefully diagnosed for ocular neoplasms. PMID- 19644694 TI - Analysis of albumin fatty acid binding capacity in patients with benign and malignant colorectal diseases using electron spin resonance (ESR) spectroscopy. AB - INTRODUCTION: In colorectal cancer (CRC), no biological marker is known that could serve both as a marker for detection and prognosis. Electron spin resonance (ESR) spectroscopy of spin-labeled fatty acid (FA) molecules binding to human serum albumin is a suitable method for the detection of conformational changes and alterations of transport function of albumin through changes in its FA binding capabilities. OBJECTIVE: The aim of this study was to examine whether the FA binding to albumin is detectably and significantly altered in CRC patients when compared with patients having benign colorectal diseases. MATERIALS AND METHODS: One hundred four patients operatively or endoscopically treated for CRC, sigmoid diverticulitis, or a colorectal adenoma were examined before procedure. Albumin was analyzed by ESR with spin-labeled FA. A determination ratio (DR) was calculated from the measured ESR spectra as ratios of the fraction of FA that is tightly bound vs. the fractions that are loosely interacting with albumin or are unbound. RESULTS AND DISCUSSIONS: Patients with CRC showed significantly lower DR values (DR, -0.09 +/- 0.98 vs. 0.61 +/- 1.43) than patients with benign colorectal diseases, consistent with a change of conformation and transport function of albumin in CRC. Within the CRC group, with advanced tumor stage, the difference in DR values increased. ESR of FA binding to albumin thus seems to be suitable for detection of patients with CRC. Furthermore, a correlation with advanced tumor stage can be established. CONCLUSIONS: These results suggest that a further evaluation of the role of ESR in patients with all stages of CRC should take place. It should also be examined whether ESR might play a role in detecting CRC in a larger panel of patients. PMID- 19644695 TI - Total femur replacement. AB - BACKGROUND: Total femoral replacement after massive resection of bone and soft tissue sarcoma of the thigh can restore femoral integrity and allow patients to resume ambulation, albeit at a compromised level. This compromised functional capacity is superior to that achieved after hip disarticulation. Most reports of total femoral replacements are isolated case studies. Only few reported series have been identified. METHODS: We treated nine consecutive patients by total femur resection and reconstruction with total femur replacement between 1993 and 2007. Four had a primary malignant bone tumor, four had a primary malignant soft tissue tumor, and one had a metastatic disease. RESULTS: After a mean follow-up of 51 (8-200) months, four patients were still alive, whereas five patients died of malignant disease. Mechanical loosening of the tibial component was seen in one patient. Infection was encountered in two patients. Four patients had excellent outcomes. Competence of the extensor mechanism is the major determinant of functional outcome of these patients. The flexion range of knee motion ranged from 20 to 120 degrees (mean 60 degrees ). According to Enneking's functional evaluation method, the function ranged from 30 to 93% (mean 72%). Using the International Society of Limb Salvage radiographic evaluation method, all the available radiographs show excellent results. Excellent results also were seen for the radiographic evaluation of the hip. CONCLUSION: Endoprosthetic femoral replacement is a reliable mean to restore mechanical and functional results after extensive resection of the femur. PMID- 19644697 TI - A randomised controlled study comparing Drotaverine hydrochloride and Valethamate bromide in the augmentation of labour. AB - OBJECTIVES: Cervical dilatation is a poorly understood process. Various drugs have been used to facilitate this process and reduce the duration of labour and thereby reduce feto-maternal complications. The present study is an attempt to compare and evaluate the efficacy of Drotaverine hydrochloride and Valethamate bromide in the process of cervical dilatation and labour augmentation. STUDY DESIGN: A prospective randomised trial of 146 low-risk women in spontaneous labour was conducted. 49 women were given Drotaverine (Group 1), 49 women were given Valethamate (Group 2) and 48 women were given placebo (Group 3). At 4 cm of cervical dilatation, elective amniotomy was done and the injection was given intramuscularly, and repeated every hour for a maximum of three doses. RESULTS: There was a statistically significant difference in the mean injection-delivery times (time from first injection to delivery of the baby), which was 183.2 min (SD 78.8) in the Drotaverine group compared to 206.5 min (SD 69.7) in the Valethamate group, and 245 min (SD 70.9) in the control group. The mean cervical dilatation rate (cm/h) was 3 (SD 1.4), 2.4 (SD 0.9) and 1.9 (SD 0.6) in groups 1, 2 and 3, respectively, and these differences were statistically significant. There were no statistically significant differences in the duration of second and third stage of labour. Transient side effects such as foeto-maternal tachycardia, flushing of the face and dryness of mouth were noted with Valethamate. A few patients complained of headache in the Drotaverine group. CONCLUSIONS: Both Drotaverine and Valethamate appear to significantly help cervical dilatation and augment first stage of labour. But, Drotaverine is superior to Valethamate with fewer side effects. PMID- 19644696 TI - The pathophysiology of endometriosis and adenomyosis: tissue injury and repair. AB - INTRODUCTION: This study presents a unifying concept of the pathophysiology of endometriosis and adenomyosis. In particular, a physiological model is proposed that provides a comprehensive explanation of the local production of estrogen at the level of ectopic endometrial lesions and the endometrium of women affected with the disease. METHODS: In women suffering from endometriosis and adenomyosis and in normal controls, a critical analysis of uterine morphology and function was performed using immunohistochemistry, MRI, hysterosalpingoscintigraphy, videohysterosonography, molecular biology as well as clinical aspects. The relevant molecular biologic aspects were compared to those of tissue injury and repair (TIAR) mechanisms reported in literature. RESULTS AND CONCLUSIONS: Circumstantial evidence suggests that endometriosis and adenomyosis are caused by trauma. In the spontaneously developing disease, chronic uterine peristaltic activity or phases of hyperperistalsis induce, at the endometrial-myometrial interface near the fundo-cornual raphe, microtraumatizations with the activation of the mechanism of 'tissue injury and repair' (TIAR). This results in the local production of estrogen. With ongoing peristaltic activity, such sites might increase and the increasingly produced estrogens interfere in a paracrine fashion with the ovarian control over uterine peristaltic activity, resulting in permanent hyperperistalsis and a self-perpetuation of the disease process. Overt auto-traumatization of the uterus with dislocation of fragments of basal endometrium into the peritoneal cavity and infiltration of basal endometrium into the depth of the myometrial wall ensues. In most cases of endometriosis/adenomyosis, a causal event early in the reproductive period of life must be postulated leading rapidly to uterine hyperperistalsis. In late premenopausal adenomyosis, such an event might not have occurred. However, as indicated by the high prevalence of the disease, it appears to be unavoidable that, with time, chronic normoperistalsis throughout the reproductive period of life leads to the same extent of microtraumatization. With the activation of the TIAR mechanism followed by infiltrative growth and chronic inflammation, endometriosis/adenomyosis of the younger woman and premenopausal adenomyosis share in principle the same pathophysiology. In conclusion, endometriosis and adenomyosis result from the physiological mechanism of 'tissue injury and repair' (TIAR) involving local estrogen production in an estrogen-sensitive environment normally controlled by the ovary. PMID- 19644698 TI - The relation between the presence of a giant primary ovarian leiomyoma and the occurrence of epilepsy as a paraneoplastic syndrome. AB - INTRODUCTION: Primary ovarian leiomyoma is a quite rare tumor and usually it is small and unilateral. Most cases are asymptomatic. This benign tumor is usually diagnosed incidentally on routine pelvic examination or in pathologic specimens at surgery or at autopsy. CASE PRESENTATION: In this case, a patient with her first epileptic seizure was admitted to our emergency department. Following the initial treatment in neurology clinics, patient claimed of an abdominal pain, so by abdominal ultrasonography, it was determined that the patient had a giant abdominal mass measured 30 x 28 x 15 cm in diameter which was clinically diagnosed as malign ovarian tumor. CONCLUSION: At laparotomy, a radical hysterectomy was performed. It was reported as ovarian leiomyoma on pathological evaluation. After 15 days of surgery, patient is discharged without any complications and also no more epileptic seizures. PMID- 19644700 TI - Tips and pitfalls in 23-gauge vitrectomy surgery: does one size fits (almost) all? PMID- 19644699 TI - Effect of multiple injections of small divided doses vs single injection of intravitreal bevacizumab on retinal neovascular model in rabbits. AB - BACKGROUND: To compare effects of multiple injections of small divided doses of intravitreal bevacizumab vs a single injection using a retinal neovascular model in rabbits. METHODS: We assigned 12 pigmented rabbits to four groups of three each. All groups received an intravitreal injection of vascular endothelial growth factor (VEGF, 10 microg) on the first day. Group A received an intravitreal loading dose of bevacizumab (0.5 mg) on day 3, followed by five smaller injections (0.15 mg), one every third day. Those in groups B and C received a single intravitreal injection of bevacizumab (1.25 mg) on day 3, followed by five injections of sham, one every third day in group C. Group D received only intravitreal VEGF. Follow-up examinations were performed for 26 days. RESULTS: In groups A and B, vascular changes associated with VEGF injection decreased substantially in the first 3 days, and continued to show gradual regression during each follow-up interval. No statistically significant differences were found between the changes of mean retinal thicknesses in groups A and B in both areas. In group C, the extra sham injections did not lead to any further vascular changes. The mean retinal thickness in groups B and C did not have a statistically significant difference during the follow-up period. In group D, vascular changes resolved more gradually than in other groups. The difference in retinal thickness between group D and the other groups was statistically significant on day 6 in both groups (medullary and inferior part; p = 0.0003) and in medullary wing on day 12 (p = 0.03). CONCLUSIONS: Frequent smaller doses of bevacizumab can control VEGF-induced vascular changes as well as the currently utilized model of single large monthly injections. Dividing of currently used single injection (1.25 mg) of bevacizumab to multiple small doses can control VEGF-induced vascular changes as effectively as one large injection. PMID- 19644701 TI - Atypical fast SERCA1a protein expression in slow myofibers and differential S nitrosylation prevented by exercise during long term bed rest. AB - We monitored changes in SERCA isoform specific expression and S-nitrosylation in myofibers of lower limb soleus (SOL) and vastus lateralis (VL) muscle biopsies before and after 60 days of voluntary long term bed rest (BR) without (BR-CTRL group, n = 8) and with exercise countermeasure (BR-EX group, n = 8). Before BR, a typical myofiber type-specific distribution of fast and slow SERCA1/2a isoforms was seen. After BR, a subpopulation (approx. 15%) of slow myofibers in BR-CTRL additionally expressed the fast SERCA1a isoform which was not seen in BR-EX. After BR, SERCA1a S-nitrosylation patterns analyzed by the biotin-switch assay decreased in disused SOL only but increased in both muscles following exercise. Differential SERCA1a S-nitrosylation and SERCA1a/2a co-expression in subsets of slow myofibers should be considered as signs of an altered cytosolic Ca(2+) homeostasis following chronic muscle disuse. Exercise preserved myofiber type specific SERCA1a expression and S-nitrosylation in VL and SOL in a different way, suggesting muscle-specific responses to the countermeasure protocol applied during bed rest. PMID- 19644702 TI - Reply to "IL6 genotype and creatine kinase response to exercise". PMID- 19644704 TI - Transinguinal preperitoneal memory ring patch versus Lichtenstein repair for unilateral inguinal hernias. AB - PURPOSE: The aim of this study was to compare the transinguinal preperitoneal technique (TIPP) using a memory ring patch versus the Lichtenstein technique in relation to acute and chronic pain, post-operative complications and recurrence rates. METHODS: During an 18-month period, all adult patients that needed treatment for a unilateral inguinal or femoral hernia were treated by the TIPP repair using the Polysoft mesh. This group was retrospectively compared with a historical cohort of patients treated by the Lichtenstein technique. Our policy concerning type of anaesthesia, post-operative pain management and visual analogue scale measurements did not change over the study period. For post operative pain evaluation, the visual analogue scale was used (0-10) and scores were measured after 6 h, 24 h, 1 week, 1 month, 1 year and yearly thereafter. Recurrence rates were evaluated at time of clinical examinations. RESULTS: In total, 142 patients have been analysed with the TIPP technique (group I) versus 136 patients operated in the previous 2 years with a Lichtenstein repair (group II). In group I, 112 patients (78.9%) received a medium size patch of 14 x 7.5 cm and 30 patients (21.1%) had a large patch (16 x 9 cm). The mean operative time for a TIPP procedure was statistically shorter than for a Lichtenstein repair, 33 versus 44 min, respectively (p = 0.04). After 24 h, 1 week and 1 month post surgery, there was significantly less post-operative pain observed in the TIPP group than in the Lichtenstein group. In total, four recurrences were observed in the TIPP group (2.8%), of which one laterally and three medially. In group II, seven recurrences were observed in total (5.1%), of which five were detected within 2 years of follow-up (3.7%). CONCLUSION: For surgeons performing the Lichtenstein repair but looking for modifications concerning pain relief and a quicker procedure, the TIPP approach is a feasible alternative that seems to be associated with less post-operative pain. PMID- 19644705 TI - Larvicidal activities of three plants against filarial vector Culex quinquefasciatus Say (Diptera: Culicidae). AB - The present study was carried out to establish the larvicidal properties of crude extracts of three plants, viz. Carica papaya, Murraya paniculata and Cleistanthus collinus against Culex quinquefasciatus as target species. The relative efficacy of the plant extracts in vector control was as follows: C. papaya seed extract > M. paniculata fruit extract > M. paniculata leaf extract > C. collinus leaf extract. Result of log-probit analysis (at 95% confidence level) revealed that LC(50) and LC(95) values gradually decreased with the exposure periods similar to the result in bioassay experiment for each of the plant extract. The results of preliminary qualitative phytochemical analysis of all the plants revealed the presence of many bioactive principles such as steroids, alkaloids, terpenes, saponins, etc. that may be responsible for their biocontrol potentiality. The appropriate lethal concentrations at 24 h for each of the extracts were also studied on non-target organisms such as Diplonychus annulatum and Chironomus circumdatus, and no change in the swimming behaviour and survivality was noticed, which indicates that all the extracts are safe for the aquatic ecosystem. PMID- 19644703 TI - The possible use of stem cells in regenerative medicine: dream or reality? AB - Stem cells are one of the most fascinating areas in regenerative medicine today. They play a crucial role in the development and regeneration of human life and are defined as cells that continuously reproduce themselves while maintaining the ability to differentiate into various cell types. Stem cells are found at all developmental stages, from embryonic stem cells that differentiate into all cell types found in the human body to adult stem cells that are responsible for tissue regeneration. The general opinion postulates that clinical therapies based on the properties of stem cells may have the potential to change the treatment of degenerative diseases or important traumatic injuries in the "near" future. We here briefly review the literature in particularly for the liver, heart, kidney, cartilage, and bone regeneration. PMID- 19644706 TI - Mechanism involved in phagocytosis and killing of Listeria monocytogenes by Acanthamoeba polyphaga. AB - Intra-cellular pathogen, Listeria monocytogenes, is capable of invasion and survival within mammalian cells. However, Acanthamoeba polyphaga trophozoites phagocytose and rapidly degrade Listeria cells. In order to provide more information on amoeba phagocytosis and killing mechanisms, this study used several inhibitor agents known to affect the phagocytosis and killing of bacteria by eukaryotes. Amoebae were pre-treated with mannose, cytochalasin D, wortmannin, suramin, ammonium chloride, bafilomycin A and monensin followed by co-culture with bacteria. Phagocytosis and killing of bacterial cells by amoeba trophozoites was assessed using plate counting methods and microscopy. The data presented indicates that actin polymerisation and cytoskeletal rearrangement are involved in phagocytosis of L. monocytogenes cells by A. polyphaga trophozoites. Further, both phagosomal acidification and phagosome-lysosome fusion are involved in killing and degradation of L. monocytogenes cells by A. polyphaga. However, the mannose-binding protein receptor does not play an important role in uptake of bacteria by amoeba trophozoites. In conclusion, this data reveals the similar principles of molecular mechanisms used by different types of eukaryotes in uptake and killing of bacteria. PMID- 19644707 TI - Comprehensive resequence analysis of a 97 kb region of chromosome 10q11.2 containing the MSMB gene associated with prostate cancer. AB - Genome-wide association studies of prostate cancer have identified single nucleotide polymorphism (SNP) markers in a region of chromosome 10q11.2, harboring the microseminoprotein-beta (MSMB) gene. Both the gene product of MSMB, the prostate secretory protein 94 (PSP94) and its binding protein (PSPBP), have been previously investigated as serum biomarkers for prostate cancer progression. Recent functional work has shown that different alleles of the significantly associated SNP in the promoter of MSMB found to be associated with prostate cancer risk, rs10993994, can influence its expression in tumors and in vitro studies. Since it is plausible that additional variants in this region contribute to the risk of prostate cancer, we have used next-generation sequencing technology to resequence a ~97-kb region that includes the area surrounding MSMB (chr10: 51,168,025-51,265,101) in 36 prostate cancer cases, 26 controls of European origin, and 8 unrelated CEPH individuals in order to identify additional variants to investigate in functional studies. We identified 241 novel polymorphisms within this region, including 142 in the 51-kb block of linkage disequilibrium (LD) that contains rs10993994 and the proximal promoter of MSMB. No sites were observed to be polymorphic within the exons of MSMB. PMID- 19644708 TI - Novel human pathological mutations. Gene symbol: HEXA. Disease: Tay-Sachs disease. PMID- 19644709 TI - Kinetic study on succinic acid and acetic acid formation during continuous cultures of Anaerobiospirillum succiniciproducens grown on glycerol. AB - Succinic acid-producing Anaerobiospirillum succiniciproducens was anaerobically grown in a glycerol-fed continuous bioreactor in order to investigate the physiological responses of the cell to different pH values (5.9, 6.2, or 6.5) and various dilution rates, D. In these experiments, A. succiniciproducens showed a pH-dependent glycerol consumption behavior. When pH was maintained at 5.9 or 6.5, glycerol started to accumulate even at a very low D of 0.027 h(-1). Succinic acid yield was not significantly affected by the pH of the culture or the Ds. However, more acetic acid formation was observed when the growth rate of A. succiniciproducens was fast on glycerol at pH 6.2 (at D > or = 0.15 h(-1)). The highest obtainable succinic acid/acetic acid ratio was 40:1, which was 10 times higher than that obtained by batch cultures grown on glucose. The maximum obtainable productivity of succinic acid was 2.1 g L(-1) h(-1)), which was 14 times higher than that obtained by batch culture. PMID- 19644710 TI - Simulating inadequate dialysis and its correction using an individualized patient derived nomogram. AB - Optimization of the peritoneal dialysis prescription is dependent on proper characterization of the peritoneal membrane, as obtained by the peritoneal equilibration test (PET) or similar procedure. For any individual, certain predictions can be made to allow for decisions as to number of cycles, bag strength, and other options in order to maximize both small-solute clearance and ultrafiltration. In this paper, designed to address questions around correcting nonadherence to a prescribed peritoneal dialysis (PD) prescription, Lee et al. remind us that by using modeling programs, a series of theoretical prescriptions can be generated for each patient based on changes in cycle number or bag strength. From a selection of these prescriptions and using the current cycler technology that allows for downloading recent patient run data, and uploading new prescriptions, they demonstrate that one can correct for (scripted) nonadherent dialysis in relation to small-solute clearance. Currently, PD programs should be capable of making use of concepts from this study, as well as the ability to provide prescriptive changes via multiple preprogrammed memory cards or over modem/Internet, to provide patients with individually modeled and optimized options to correct certain forms of inadequate dialysis, for example, missed cycles or hours due to power failures. PMID- 19644711 TI - Biologically active ADAMTS13 is expressed in renal tubular epithelial cells. AB - ADAMTS13 mRNA, which encodes the von Willebrand factor-cleaving protease, has been detected in a variety of tissues, including the kidney. The aim of our study was to characterize tubular expression and bioactivity of ADAMTS13. ADAMTS13 mRNA was detected in cultured primary human renal tubular epithelial cells (HRTEC) and in A498 cells, a human renal carcinoma cell line, by real-time PCR. Protein was detected using immunofluorescence and immunoblotting. Immunoblots demonstrated that the protein was secreted. The protease was proteolytically active in both cell lysates and cleaved the FRETS-VWF73 substrate. ADAMTS13 was demonstrated in situ in the renal cortex by immunohistochemistry. Protease was detected in both the proximal and distal renal tubules in normal renal tissue (n=3) as well as in patients with tubular disorders (n=3). Immunoblotting revealed that ADAMTS13 was present in the urine of patients with tubulopathy (n=5) but not in normal urine. ADAMTS13 in urine had a molecular size similar to that in plasma, which indicates that the protease originates in the tubuli because such large proteins do not normally pass the glomerular filter. In conclusion, human renal tubular epithelial cells synthesize biologically active ADAMTS13 which may, after release from tubuli, regulate hemostasis in the local microenvironment. PMID- 19644712 TI - Oxidant stress in primary nephrotic syndrome: does it modulate the response to corticosteroids? AB - In order to assess the oxidative stress in newly diagnosed children with primary nephrotic syndrome (PNS), we serially measured serum total antioxidant capacity (TAC) and malondialdehyde (MDA) in 33 children with PNS and ten healthy matched controls. Patients were classified into two groups: those who had steroid sensitive nephrotic syndrome (SSNS; n = 26) and those who had steroid-resistant nephrotic syndrome (SRNS; n = 7). Of the patients with SSNS, 15 were non relapsers and 11 were relapsers. At the proteinuric phase, all patients had significantly higher MDA levels and lower TAC than the controls. These changes were more marked in patients with SRNS than in those with SSNS. During remission and still on corticosteroids, patients had higher TAC and similar MDA levels as in the proteinuric phase, but the TAC and MDA levels still significantly differed from those of the controls. More improvement in TAC and MDA levels occurred in patients following the weaning of corticosteroids, but TAC was still lower in the patients than in the controls. Moreover, TAC was higher in non-relapsers than in relapsers. Using a receiver operating characteristic curve, the initial response to corticosteroids could be predicted at serum TAC level > or =0.73 mM/L (sensitivity 89%, specificity 86%), while serum TAC levels < or = 1.14 mM/L after the weaning of corticosteroids could predict that the patient would not relapse (sensitivity 91%, specificity 80%). In conclusion, based on our results, PNS can be considered to be associated with oxidative stress even during remission. This stress may modulate the response to corticosteroids. Further prospective studies using larger numbers of patients are needed to validate these results. PMID- 19644713 TI - Ideal screw entry point and projection angles for posterior lateral mass fixation of the atlas: an anatomical study. AB - Although various posterior insertion angles for screw insertion have been proposed for C1 lateral mass, substantial conclusions have not been reached regarding ideal angles and average length of the screw yet. We aimed to re consider the morphometry and the ideal trajections of the C1 screw. Morphometric analysis was performed on 40 Turkish dried atlas vertebrae obtained from the Department of Anatomy at the Medical School of Ankara University. The quantitative anatomy of the screw entry zone, trajectories, and the ideal lengths of the screws were calculated to evaluate the feasibility of posterior screw fixation of the lateral mass of the atlas. The entry point into the lateral mass of the atlas is the intersection of the posterior arch and the C1 lateral mass. The optimum medial angle is 13.5 +/- 1.9 degrees and maximal angle of medialization is 29.4 +/- 3.0 degrees . The ideal cephalic angle is 15.2 +/- 2.6 degrees , and the maximum cephalic angle is 29.6 +/- 2.6 degrees . The optimum screw length was found to be 19.59 +/- 2.20 mm. With more than 30 degrees of medial trajections and cephalic trajections the screw penetrates into the spinal canal and atlantooccipital joint, respectively. Strikingly, in 52% of our specimens, the height of the inferior articular process was under 3.5 mm, and in 70% was under 4 mm, which increases the importance of the preparation of the screw entry site. For accommodation of screws of 3.5-mm in diameter, the starting point should be taken as the insertion of the posterior arch at the superior end of the inferior articular process with a cephalic trajection. This study may aid many surgeons in their attempts to place C1 lateral mass screws. PMID- 19644714 TI - Prevalence of antibodies against Ascaris suum and its association with allergic manifestations in 4-year-old children in The Netherlands: the PIAMA birth cohort study. AB - The association between helminth infections and childhood atopic diseases remains controversial. The majority of studies have been carried out in tropical areas, whereas less information is available from western countries with low intensity of helminth infections. In the Netherlands, the infection of pigs with Ascaris suum is very common, particularly on pig farms with outdoor facilities. This helminth can also infect humans, causing visceral larva migrans. This study aims at determining the prevalence of antibodies against A. suum and its association with allergic symptoms and sensitisation in a population of 4-year-old children living in The Netherlands. Blood samples from 629 children from the prospective birth cohort Prevention and Incidence of Asthma and Mite Allergy (PIAMA) study were examined for Ascaris antibodies. Data on allergic symptoms and sensitisation were collected using questionnaires and radioallergosorbent tests (RAST). A total of 45 out of 629 (7%) were found to be Ascaris-seropositive. In addition, a positive association between Ascaris seropositivity and wheeze in the last year, doctor-diagnosed asthma and food and aero-allergen sensitisation was found. These results support the hypothesis that low-level or transient infection with helminths enhances allergic reactivity. PMID- 19644716 TI - Two-dimensional perturbations in a scalar model for shear banding. AB - We present an analytical study of a toy model for shear banding, without normal stresses, which uses a piecewise linear approximation to the flow curve (shear stress as a function of shear rate). This model exhibits multiple stationary states, one of which is linearly stable against general two-dimensional perturbations. This is in contrast to analogous results for the Johnson-Segalman model, which includes normal stresses, and which has been reported to be linearly unstable for general two-dimensional perturbations. This strongly suggests that the linear instabilities found in the Johnson-Segalman can be attributed to normal stress effects. PMID- 19644715 TI - Dura splitting decompression in Chiari type 1 malformation: clinical experience and radiological findings. AB - To restore the cerebrospinal fluid (CSF) flow at the craniocervical junction in Chiari I malformation (CM-I), most surgeons practice a suboccipital craniectomy with duraplasty. To reduce the risk of CSF leak, a dura splitting decompression is created removing only the dural outer layer. We report on a series of 11 patients with CM-I (five with syringomyelia) operated on between 2000 and 2007 using this technique. Neurological examination and cerebro-spinal MRI scan were performed before and after surgery. Symptoms improved completely in six patients. Headaches and cervicalgias disappeared for all patients. Dizziness and paresthesia in the upper limb remained unchanged for three and two patients, respectively. We observed no complications such as CSF leak, meningocele, or meningitis. Postoperative MRI scan showed a significant craniocervical decompression in ten patients. Four patients had a new cisterna magna. Two syringomyelias completely disappeared, two decreased, and one was stable. Dural splitting can be practiced to treat CM-I. Clinical results are similar to the other techniques with less complications. Radiological findings show satisfying posterior fossa decompression. PMID- 19644717 TI - Proton transport through aqueous Nafion membrane. AB - We introduce a new model for proton transport through a single proton-conducting channel of an aqueous Nafion membrane based on a mechanism in which protons move under electrostatic effect provided by the sulfonate (SO3-)groups of the Nafion side chains, the spin effect of active components, the hydrogen bonding effect with water molecules, and the screening effect of water media. This model can describe the proton transport within various levels of humidification ranging from the low humidity to the high humidity as a function of operating temperature. At low humidity, this model approaches to the so-called surface mechanism, while at high humidity, it approaches the well-known Grotthuss one. Proton motion is considered as the transfer from cluster to cluster under a potential energy. A proton-proton interaction is comprised in the calculation. Using Green function method, we obtained the proton current as a function of the Nafion membrane temperature. We found that the lower the temperature, the higher the proton current transfer through the Nafion membrane in low temperatures compared to the critical point 10K, which separates magnetic regime from non magnetic regime. The increasing of proton current at very low temperatures is attributed to the spin effect. As the membrane temperature is higher than 40 ( degrees ) C , the decreasing of proton current is attributed to the loss of water uptake and the polymer contraction. The results of this study are qualitatively in good agreement with experiments. The expression for the critical temperature is also presented as a function of structural and tunable parameters, and interpreted by experimental data. PMID- 19644718 TI - Biomechanics of single chondrocytes under direct shear. AB - Articular chondrocytes experience a variety of mechanical stimuli during daily activity. One such stimulus, direct shear, is known to affect chondrocyte homeostasis and induce catabolic or anabolic pathways. Understanding how single chondrocytes respond biomechanically and morphologically to various levels of applied shear is an important first step toward elucidating tissue level responses and disease etiology. To this end, a novel videocapture method was developed in this study to examine the effect of direct shear on single chondrocytes, applied via the controlled lateral displacement of a shearing probe. Through this approach, precise force and deformation measurements could be obtained during the shear event, as well as clear pictures of the initial cell-to probe contact configuration. To further study the non-uniform shear characteristics of single chondrocytes, the probe was positioned in three different placement ranges along the cell height. It was observed that the apparent shear modulus of single chondrocytes decreased as the probe transitioned from being close to the cell base (4.1 +/- 1.3 kPa), to the middle of the cell (2.6 +/- 1.1 kPa), and then near its top (1.7 +/- 0.8 kPa). In addition, cells experienced the greatest peak forward displacement (approximately 30% of their initial diameter) when the probe was placed low, near the base. Forward cell movement during shear, regardless of its magnitude, continued until it reached a plateau at ~35% shear strain for all probe positions, suggesting that focal adhesions become activated at this shear level to firmly adhere the cell to its substrate. Based on intracellular staining, the observed height-specific variation in cell shear stiffness and plateau in forward cell movement appeared to be due to a rearrangement of focal adhesions and actin at higher shear strains. Understanding the fundamental mechanisms at play during shear of single cells will help elucidate potential treatments for chondrocyte pathology and loading regimens related to cartilage health and disease. PMID- 19644719 TI - Modeling of drug delivery into tissues with a microneedle array using mixture theory. AB - In this paper, we apply mixture theory to quantitatively predict the transient behavior of drug delivery by using a microneedle array inserted into tissue. In the framework of mixture theory, biological tissue is treated as a multi-phase fluid saturated porous medium, where the mathematical behavior of the tissue is characterized by the conservation equations of multi-phase models. Drug delivery by microneedle array imposes additional requirements on the simulation procedures, including drug absorption by the blood capillaries and tissue cells, as well as a moving interface along its flowing pathway. The contribution of this paper is to combine mixture theory with the moving mesh methods in modeling the transient behavior of drug delivery into tissue. Numerical simulations are provided to obtain drug concentration distributions into tissues and capillaries. PMID- 19644720 TI - Utilizing different methods for visualizing susceptibility from a single multi gradient echo dataset. AB - PURPOSE: Objects that cause a susceptibility gradient can generate regions of hypo-intensity in MRI. MR techniques developed for positive enhancement of such objects require sequence parameter optimization. Thus comparison of images acquired successively using different techniques is difficult since different parameter settings result in variations in signal and noise. A new method is presented that allows production of positive contrast images, a relaxation rate R*2-map and negative contrast images from a single dataset by post-processing. METHODS: Positive contrast techniques considered include the "white marker" technique, inversion-recovery on-resonance (IRON) and susceptibility gradient mapping (SGM). The new method was tested in phantoms of iron-oxide agent gel solutions and prostate marker seeds. Images produced by post-processing were compared with those obtained directly. The post-processing technique was applied in vivo for the visualization of iron-oxide contrast agent uptake in a balloon injured swine carotid model. RESULTS: The images produced in the post-processing step allowed determination of optimal parameter settings for each technique. SGM was found to provide the greatest positive contrast, whilst the T*2-weighted images provide more sensitivity to regions that exhibited weaker susceptibility effects. CONCLUSIONS: Combined T*2-weighted imaging and SGM using the same complex image data was found to provide complementary information and high sensitivity to detect distortion inducing agents. PMID- 19644722 TI - The role of BRAFV600E mutation and ultrasonography for the surgical management of a thyroid nodule suspicious for papillary thyroid carcinoma on cytology. AB - BACKGROUND: This study was designed to investigate the role of BRAFV600E mutation status in cytology specimens and ultrasonography (US) when planning surgery for thyroid nodules with cytologic results suspicious for papillary thyroid carcinoma (PTC). METHODS: From July 2008 to November 2008, 91 consecutive patients with cytologic results of suspicious for PTC underwent thyroidectomy. Before surgery, all patients received US-guided fine needle aspiration biopsy (US-FNAB) solely for the purpose of BRAFV600E mutation analysis of thyroid nodules suspicious for PTC on cytology. BRAFV600E mutations were tested by direct sequencing. We investigated the role of BRAFV600E mutation and US in planning the thyroid surgery. RESULTS: Of 91 nodules suspicious for PTC, 42 (46.2%) were positive for the BRAFV600E mutation and confirmed to be PTC by histopathology. The positive predictive values of BRAFV600E mutation was 100%. Of the 49 nodules without the BRAFV600E mutation, 42 (85.7%) proved to be PTC. Thirty-nine of 42 (92.9%) PTCs were suspicious for malignant features on US. Two of seven (28.6%) benign lesions showed probably benign features. The sensitivity, positive predictive value, and accuracy of US in thyroid nodules without BRAFV600E mutations was 92.9% (39/42), 88.6% (39/44), and 83.7% (41/49), respectively. CONCLUSIONS: The BRAFV600E mutation is a useful molecular marker for preoperative diagnosis of PTC and an indicator for therapeutic thyroid surgery in the nodule with cytologic results suspicious for PTC. In thyroid nodules without the BRAFV600E mutation, suspicious malignant features on US may help in planning the extent of thyroid surgery. PMID- 19644723 TI - Mastectomies on the rise for breast cancer: "the tide is changing". PMID- 19644724 TI - Numerical equilibrium analysis for structured consumer resource models. AB - In this paper, we present methods for a numerical equilibrium and stability analysis for models of a size structured population competing for an unstructured resource. We concentrate on cases where two model parameters are free, and thus existence boundaries for equilibria and stability boundaries can be defined in the (two-parameter) plane. We numerically trace these implicitly defined curves using alternatingly tangent prediction and Newton correction. Evaluation of the maps defining the curves involves integration over individual size and individual survival probability (and their derivatives) as functions of individual age. Such ingredients are often defined as solutions of ODE, i.e., in general only implicitly. In our case, the right-hand sides of these ODE feature discontinuities that are caused by an abrupt change of behavior at the size where juveniles are assumed to turn adult. So, we combine the numerical solution of these ODE with curve tracing methods. We have implemented the algorithms for "Daphnia consuming algae" models in C-code. The results obtained by way of this implementation are shown in the form of graphs. PMID- 19644725 TI - A model of hydrodynamic interaction between swimming bacteria. AB - We study the dynamics and interaction of two swimming bacteria, modeled by self propelled dumbbell-type structures. We focus on alignment dynamics of a coplanar pair of elongated swimmers, which propel themselves either by "pushing" or "pulling" both in three- and quasi-two-dimensional geometries of space. We derive asymptotic expressions for the dynamics of the pair, which complemented by numerical experiments, indicate that the tendency of bacteria to swim in or swim off depends strongly on the position of the propulsion force. In particular, we observe that positioning of the effective propulsion force inside the dumbbell results in qualitative agreement with the dynamics observed in experiments, such as mutual alignment of converging bacteria. PMID- 19644726 TI - [Torsades de pointes during general anesthesia for Cesarean delivery in a pre eclamptic patient]. PMID- 19644727 TI - Effects of omega-3 essential fatty acids (omega-3 EFAs) on motor disorders and memory dysfunction typical neuroleptic-induced: behavioral and biochemical parameter. AB - The effects of fish oil supplementation on motor disorders, memory dysfunction, and lipid peroxidation (LP) induced by typical neuroleptics were studied. Wistar rats received a suspension prepared with fish oil containing omega-3 fatty acids, water, and Tween 80 (1%) in the place of drinking water (FO group) or vehicle (C group) for 8 weeks. After 4 weeks of treatment, half of the animals of both groups were treated with haloperidol (H and FO + H groups; experiment 1), fluphenazine (F and FO + F groups; experiment 2), or vehicle (C group), administered once a week (12 mg/kg/im) for 4 weeks, maintaining the treatment with FO. Extrapyramidal motor disorders by haloperidol and fluphenazine were observed by an increase in vacuous chewing movements and catalepsy (P < 0.05). These effects were reduced by FO treatment (P < 0.05). Both neuroleptics displayed impairment in memory retention observed by latency time to find the original location of platform in water-maze task, after 4 days of training performed in the last treatment week. This effect was reduced by FO (P < 0.05) to both haloperidol and fluphenazine treatments. Haloperidol increased the LP in plasma and hippocampus, and these effects were decreased by FO treatment (P < 0.05). Fluphenazine increased the LP in plasma and substantia nigra, which were completely decreased by FO treatment (P < 0.05). The FO decreased the motor disorders, memory dysfunction, and oxidative damage typical neuroleptic-induced. Our results indicate that FO exhibits a neuroprotector role useful on diseases related to oxidative damages, and may be considered in the prevention of motor and memory side effects induced by the antipsychotic treatment. PMID- 19644728 TI - Polyunsaturated fatty acids protect against prion-mediated synapse damage in vitro. AB - A loss of synapses is characteristic of the early stages of the prion diseases. Here we modelled the synapse damage that occurs in prion diseases by measuring the amount of synaptophysin, a pre-synaptic membrane protein essential for neurotransmission, in cortical or hippocampal neurones incubated with the disease associated isoform of the prion protein (PrP(Sc)), or with the prion-derived peptide PrP82-146. The addition of PrP(Sc) or PrP82-146 caused a dose-dependent reduction in the synaptophysin content of PrP wildtype neurones indicative of synapse damage. They did not affect the synaptophysin content of PrP null neurones. The loss of synaptophysin in PrP wildtype neurones was preceded by the accumulation of PrP82-146 within synapses. Since supplements containing polyunsaturated fatty acids (PUFA) are frequently taken for their perceived health benefits including reported amelioration of neurodegenerative conditions, the effects of some common PUFA on prion-mediated synapse damage were examined. Pre-treatment of cortical or hippocampal neurones with docosahexaenoic (DHA) or eicosapentaenoic acids (EPA) protected neurones against the loss of synaptophysin induced by PrP82-146 or PrP(Sc). This effect of DHA and EPA was selective as they did not alter the loss of synaptophysin induced by a snakevenom neurotoxin. The effects of DHA and EPA were associated with a significant reduction in the amount of FITC-PrP82-146 that accumulated within synapses. Such observations raise the possibility that supplements containing PUFA may protect against the synapse damage and cognitive loss seen during the early stages of prion diseases. PMID- 19644730 TI - Rare association of motor neuron disease and spinocerebellar ataxia type 2 (SCA2): a new case and review of the literature. AB - We report a rare association of spinocerebellar ataxia and motor neuron disease (MND) in a woman with genetically confirmed SCA2 who subsequently developed a rapidly progressive and fatal form of MND. Considering the rarity of these two neurological conditions, it is interesting to note that the concomitant occurrence of SCA mutations and MND have been previously observed in three cases: in one patient affected by SCA6 and two other cases with SCA2. PMID- 19644729 TI - Reduced hippocampal neurogenesis in the GR(+/-) genetic mouse model of depression. AB - Glucocorticoid receptor (GR) heterozygous mice (GR(+/- )) represent a valuable animal model for major depression. GR(+/- ) mice show a depression-related phenotype characterized by increased learned helplessness on the behavioral level and neuroendocrine alterations with hypothalamo-pituitary-adrenal (HPA) axis overdrive characteristic of depression. Hippocampal brain-derived neurotrophic factor (BDNF) levels have also been shown to be reduced in GR(+/- ) animals. Because adult hippocampal neurogenesis has been implicated in the pathophysiology of affective disorders, we studied here the effects of the GR(+/- ) genotype on neurogenesis in vivo. In a 2 x 2 design, GR(+/- ) mice and GR(+/+) littermate controls were either subjected to 1 h of restraint stress or left undisturbed in their home cages after intraperitoneal injection of BrdU. Stress exposure and BrdU injections were performed once daily for 7 days and neurogenesis analyzed 4 weeks later. BrdU cell counts were significantly reduced as an effect of GR(+/- ) genotype and as an effect of stress. Majority of the BrdU+ cells showed co labeling with mature neuronal marker NeuN or astrocytic marker S100beta with no further significant effect of either experimental condition or of genotype. In sum, this results in reduced neurogenesis in GR(+/- ) mice which is further repressed by restraint stress. Our results, thus, reinforce the link between reduced neurogenesis, stress, neurotrophins, and behavioral symptoms of and susceptibility to depression. PMID- 19644731 TI - Does inhibitory control capacity in overweight and obese children and adolescents predict success in a weight-reduction program? AB - It has been assumed that inhibitory control capacity might influence the success of overweight or obese subjects in reducing weight. However, empirical research on this association is scarce. The present study, therefore, examines whether success in an outpatient weight-reduction program for children and adolescents can be predicted by pre-intervention inhibitory control capacity. The study sample consisted of 111 overweight and obese children and adolescents (7.5-15 years) who attended an outpatient weight-reduction program of 1 year's duration. Inhibitory control was assessed by two computerized neuropsychological procedures, a Go-NoGo and an interference task. Principal component analysis revealed "impulsivity" (fast but less valid reactions) and "inattention" (slow and highly variable reaction times) component. Those who succeeded in the intervention (losing more than 5% of BMI-SDS; n = 63) scored significantly higher in the first component than those who failed, while controlling for pre intervention BMI-SDS, age, gender, and maternal education level. The association was moderated by age. Although in younger children no effect was found, in adolescents high "impulsivity" predicted success. Our result supports the scant evidence for a role of inhibitory control. However, further studies are required to substantiate that weak inhibitory control, and thus high reactivity to external cues, entails a better outcome in behavior modification interventions. PMID- 19644732 TI - Mental health of adolescents reared in institutional care in Turkey: challenges and hope in the twenty-first century. AB - The objectives of the study are (i) to describe and compare the epidemiology of emotional/behavioral problems and associated risk/protective factors among nationally representative samples of institutionally reared and similarly aged community-based adolescents brought up in their natural homes by means of youth self-reports, caregiver/parent, and teacher informants; and (ii) to identify mental health service needs and utilization. A cross-sectional survey was conducted between November 2005 through April 2006 using an equal probability cluster sample of 11-18 year old adolescents in institutional care settings (N = 350; 163 males, 187 females) and results were compared with similarly aged community sample of youth living in their natural homes (N = 2,206). The Sociodemographic Information Form, Youth Self Report (YSR), Child Behavior Checklist (CBCL) by caregivers for institutional sample and parents for the community sample, and Teacher's Report Form (TRF) were used to obtain standardized data on demographic characteristics, emotional/behavioral problems, and risk/protective factors. The prevalence of problems behaviors by YSR, caregiver/parent CBCL, and TRF were: 47, 15.1, 20.5% for the institutional versus 10.1, 7.5 and, 9.5% for the community samples, respectively (p < 0.05). Youth self-reports were fourfold, and all informant reports were twofold higher for institutional versus community comparisons. Furthermore, institutional sample had consistently higher rates, not only of Externalizing, but Internalizing, Social Problems, Attention Problems, and Thought Problems, as well as discrete DSM oriented scales, suggesting that labeling of institutional youth as simply aggressive and delinquent contributes to their further marginalization and does not comprehensively address their mental health needs. In terms of protective factors, we found that: perceived social support, high competency scores, supportive caregiving, getting along well with peers and relatives (positive relationships), and problem solving skills were significantly protective of mental health. On the other hand fatalistic beliefs, cigarette and alcohol use were significantly associated with increased risk for problem behaviors (p < 0.05). The primary reason for institutional placement was family disruption (68.9%), poverty (15.7%), abandonment (8.4%), and physical or sexual abuse (5.4%). Only 31.2% of the youth were in fact true orphans (loss of one or both parents). It is therefore remarkable that in terms of service use, despite consistently high prevalence of problem behaviors across all informant sources, only 2.4% of the youth had received any speciality mental health services during institutional care. In conclusion, there is a pressing need to transform the social and health care policy and to provide family and community-based alternatives for youth currently in institutional care in Turkey. Before this goal is achieved, it is necessary to address their mental health needs urgently and comprehensively. The highest rates of problems by youth self-report also support the view that the youths' own voices ought to be heard and need to inform the reform process regarding their future care. PMID- 19644733 TI - Transthyretin: the servant of many masters. AB - Transthyretin (TTR) (formerly, thyroxine binding prealbumin) is an evolutionarily conserved serum and cerebrospinal fluid protein that transports holo-retinol binding protein and thyroxine. Its serum concentration has been widely used to assess clinical nutritional status. It is also well known that wild-type transthyretin and approximately 100 different mutants give rise to a variety of forms of systemic amyloid deposition. It has been suspected and recently established that TTR can suppress the Alzheimer's disease phenotype in transgenic animal models of cerebral Abeta deposition. Thus, while TTR is a systemic amyloid precursor, in the brain it seems to have an anti-amyloidogenic effect. TTR is found in other organs as a result of local synthesis or transport, suggesting that it may have other, as yet undiscovered, functions. It is possible that its capacity to bind many classes of compounds allows it to serve as an endogenous detoxifier of molecules with potential pathologic effects. PMID- 19644734 TI - Cyanobacterial psbA gene family: optimization of oxygenic photosynthesis. AB - The D1 protein of Photosystem II (PSII), encoded by the psbA genes, is an indispensable component of oxygenic photosynthesis. Due to strongly oxidative chemistry of PSII water splitting, the D1 protein is prone to constant photodamage requiring its replacement, whereas most of the other PSII subunits remain ordinarily undamaged. In cyanobacteria, the D1 protein is encoded by a psbA gene family, whose members are differentially expressed according to environmental cues. Here, the regulation of the psbA gene expression is first discussed with emphasis on the model organisms Synechococcus sp. and Synechocystis sp. Then, a general classification of cyanobacterial D1 isoforms in various cyanobacterial species into D1m, D1:1, D1:2, and D1' forms depending on their expression pattern under acclimated growth conditions and upon stress is discussed, taking into consideration the phototolerance of different D1 forms and the expression conditions of respective members of the psbA gene family. PMID- 19644735 TI - Regulation of Plasmodium falciparum Pfnek3 relies on phosphorylation at its activation loop and at threonine 82. AB - A mitogen-activated protein kinase (MAPK), Pfmap2, has been identified in Plasmodium falciparum. However, its bona fide activator remains elusive as no MAPK kinase (MAPKK) homologues have been found so far. Instead, Pfnek3, a NIMA (never in mitosis, Aspergillus)-related kinase, was earlier reported to display a MAPKK-like activity due to its activating effect on Pfmap2. In this study, the regulatory mechanism of Pfnek3 was investigated. Pfnek3 was found to possess a SSEQSS motif within its activation loop that fulfills the consensus SXXXS/T phospho-activating sequence of MAPKKs. Functional analyses of the SSEQSS motif by site-directed mutagenesis revealed that phosphorylation of residues S221 and S226 is essential for mediating Pfnek3 activity. Moreover, via tandem mass spectrometry, residue T82 was uncovered as an additional phosphorylation site involved in Pfnek3 activation. Collectively, these results provide valuable insights into the potential in vivo regulation of Pfnek3, with residues T82, S221 and S226 functioning as phospho-activating sites. PMID- 19644736 TI - Enhanced topical delivery and ex vivo anti-inflammatory activity from a betamethasone dipropionate formulation containing fish oil. AB - OBJECTIVE AND DESIGN: To probe ex vivo the influence of fish oil (FO) on the topical delivery and anti-inflammatory properties of betamethasone dipropionate (BD). MATERIALS OR SUBJECTS: Freshly excised porcine ear skin. TREATMENT: Ointment formulations containing BD + salicylic acid (SA), BD + SA + FO, or base as control, applied to the skin mounted in Franz cells. METHODS: Comparative depth profiling; skin probed by immunohistochemistry for cyclooxygenase-2 (COX-2) and by ELISA for prostaglandin E2 (PGE2). RESULTS: More BD was obtained in the first 30 layers and the remaining epidermis with BD + SA. However, more penetrants were recovered from the remaining skin treated with BD + SA + FO. Although BD + SA reduced COX-2 expression within the epidermis, greater reduction was observed with BD + SA + FO as indicated by reduced COX-2 expression. FO alone had a comparable effect on the expression of COX-2. Modulation of PGE2 production also supported the anti-inflammatory properties of fish oil, reducing PGE2 levels by an amount comparable to the reduction by BD. Combining FO and BD, however, did not provide the anticipated potentiation effect. CONCLUSIONS: Fish oil enhanced the delivery of BD and SA across skin. Addition of fish oil also enhanced the anti-inflammatory activity of BD, attributed to increased amounts of BD present in the skin and/or the intrinsic anti-inflammatory activity of fish oil. PMID- 19644737 TI - The interaction of serum albumin with cholesterol containing lipid vesicles. AB - In this paper, the interaction of both human blood serum (the primary fraction of which is serum albumin) and pure human serum albumin (HSA) with surface immobilised lipid vesicles was measured by combined Surface Plasmon Resonance (SPR) and Surface Plasmon enhanced Fluorescence (SPEFS), and fluorescence microscopy. It was found that both blood serum and HSA showed specific binding to vesicles which contained cholesterol, resulting in increased membrane permeability and release of encapsulated fluorescent dye. This effect was not seen with heat inactivated blood serum, heat inactivated HSA or in vesicles not containing cholesterol. These results suggest that HSA may have a physiological role over and beyond that of fatty acid carrier, possibly acting to regulate vascular endothelial cell cholesterol concentration. PMID- 19644738 TI - Fast and slow tracks in lysozyme folding elucidated by the technique of disulfide scrambling. AB - GdmCl (6 M) unfolded lysozyme was previously shown to refold via kinetically partitioned pathways (Kiefhaber in Proc Natl Acad Sci 92:9029-9033, 1995). About 80% of the unfolded lysozyme molecules refold on a slow pathway with well populated intermediates. The remaining 20% of denatured lysozyme refold on a fast track without detectable intermediate. This kinetic heterogeneity has been proposed to originate from the collapsed state of lysozyme folding. Using the method of disulfide scrambling, we demonstrate in this report that these two populations of unfolded lysozyme can be isolated and analyzed separately. GdmCl (6 M) denatured lysozyme actually comprises two major populations of unfolded isomers, namely X-LYZ-a and X-LYZ-b with molar ratio of about 80:20. X-LYZ-a and X-LYZ-b exist in equilibrium in the unfolded state. Their disulfide structures and CD properties indicate that X-LYZ-a is more extensively unfolded than X-LYZ b. Refolding experiments using the method of disulfide scrambling also show that folding kinetics of X-LYZ-a is about 8-10 times slower than that of X-LYZ-b and folding intermediates of X-LYZ-a is far more heterogeneous than that of X-LYZ-b. The results highlight the implication of the conformational heterogeneity of 6 M GdmCl denatured proteins for the interpretation of the initial stage of protein folding mechanism. PMID- 19644739 TI - Self-reported false confessions and false guilty pleas among offenders with mental illness. AB - Persons with mental illness may be at risk for false admissions to police and to prosecutors because of the defining characteristics of mental illness, but potentially because of heightened recidivism rates and increased opportunities. We surveyed 1,249 offenders with mental disorders from six sites about false confessions (FCs) and false guilty pleas (FGPs). Self-reports of FC ranged from 9 to 28%, and FGPs ranged from 27 to 41% depending upon site. False admissions to murder and rape were rarely reported. We also examined differences between those claiming false admissions and those not. Minorities, offenders with lengthier criminal careers, and those who were more symptomatic were more likely to have self-reported false admissions than their counterparts. PMID- 19644740 TI - The effects of rehabilitative voir dire on juror bias and decision making. AB - During voir dire, judges frequently attempt to "rehabilitate" venirepersons who express an inability to be impartial. Venirepersons who agree to ignore their biases and base their verdict on the evidence and the law are eligible for jury service. In Experiment 1, biased and unbiased mock jurors participated in either a standard or rehabilitative voir dire conducted by a judge and watched a trial video. Rehabilitation influenced insanity defense attitudes and perceptions of the defendant's mental state, and decreased scaled guilt judgments compared to standard questioning. Although rehabilitation is intended to correct for partiality among biased jurors, rehabilitation similarly influenced biased and unbiased jurors. Experiment 2 found that watching rehabilitation did not influence jurors' perceptions of the judge's personal beliefs about the case. PMID- 19644742 TI - How increased contraceptive use has reduced maternal mortality. AB - It is widely recognized that family planning contributes to reducing maternal mortality by reducing the number of births and, thus, the number of times a woman is exposed to the risk of mortality. Here we show evidence that it also lowers the risk per birth, the maternal mortality ratio (MMR), by preventing high-risk, high-parity births. This study seeks to quantify these contributions to lower maternal mortality as the use of family planning rose over the period from 1990 to 2005. We use estimates from United Nations organizations of MMRs and the total fertility rate (TFR) to estimate the number of births averted-and, consequently, the number of maternal deaths directly averted-as the TFR in the developing world dropped. We use data from 146 Demographic and Health Surveys on contraceptive use and the distribution of births by risk factor, as well as special country data sets on the MMR by parity and age, to explore the impacts of contraceptive use on high-risk births and, thus, on the MMR. Over 1 million maternal deaths were averted between 1990 and 2005 because the fertility rate in developing countries declined. Furthermore, by reducing demographically high-risk births in particular, especially high-parity births, family planning reduced the MMR and thus averted additional maternal deaths indirectly. This indirect effect can reduce a county's MMR by an estimated 450 points during the transition from low to high levels of contraceptive use. Increases in the use of modern contraceptives have made and can continue to make an important contribution to reducing maternal mortality in the developing world. PMID- 19644741 TI - Maternal social support and neighborhood income inequality as predictors of low birth weight and preterm birth outcome disparities: analysis of South Carolina Pregnancy Risk Assessment and Monitoring System survey, 2000-2003. AB - Effects of income inequality on health and other social systems have been a subject of considerable debate, but only a few studies have used multilevel models to evaluate these relationships. The main objectives of the study were to (1) Evaluate the relationships among neighborhood income inequality, social support and birth outcomes (low birth weight, and preterm delivery) and (2) Assess variations in racial disparities in birth outcomes across neighborhood contexts of income distribution and maternal social support. We evaluated these relationships by using South Carolina Pregnancy Risk Assessment and Monitoring System (PRAMS) survey for 2000-2003 geocoded to 2000 US Census data for South Carolina. Multilevel analysis was used to simultaneously evaluate the association between income inequality (measured as Gini), maternal social relationships and birth outcomes (low birth weight and preterm delivery). The results showed residence in neighborhoods with medium levels of income inequality was independently associated with low birth weight (OR: 2.00; 95% CI 1.14-3.26), but not preterm birth; low social support was an independent risk for low birth weight or preterm births. The evidence suggests that non-Hispanic black mothers were at increased risks of low birth weight or preterm birth primarily due to greater exposures of neighborhood deprivations associated with low income and reduced social support and modified by unequal income distribution. PMID- 19644743 TI - Factors that affect parent perceptions of provider-family partnership for children with special health care needs. AB - Partnering between families and their children's providers is a cornerstone of family-centered care. This study aimed to identify factors associated with family provider partnership and determine the association between partnership and other outcome measures for children with special health care needs (CSHCN). Descriptive, bivariate, and multivariate analyses were conducted using data from the 2005-2006 National Survey of Children with Special Health Care Needs. Multivariate models showed that CSHCN who are White non-Hispanic, younger than 12, reside in households with incomes above 400% of the federal poverty level, and have a usual source of care were associated with family-provider partnership. Multivariate models showed that family-provider partnership was significantly associated with adequate insurance, early and continual screening, organized health care services, and transition preparedness. Family-provider partnership was associated with 20% fewer emergency department visits and 9% fewer school days missed. This study suggests that policies aimed at promoting family-provider partnership could increase health outcomes for CSHCN. PMID- 19644744 TI - Breastfeeding ambivalence among low-income African American and Puerto Rican women in north and central Brooklyn. AB - This study explores low-income African American and Puerto Rican women's conceptions and practices around breastfeeding. It examines the impact of such diverse factors as social constructions of the body, local mores around infant care, the practicalities of food availability, in the context of interactions with family members and friends, institutions, and others in women's neighborhoods. The study employed ethnographic methods, including interviews and participant observation, with 28 families in two low-income Brooklyn neighborhoods. While women in this study felt that breastfeeding was the best way to feed their infants, their commitment turned to ambivalence in the face of their perceptions about the dangers of breast milk, the virtues of formula, and the practical and sociocultural challenges of breastfeeding. Women's ambivalence resulted in a widespread complementary feeding pattern that included breast milk and formula, and resulted in short breastfeeding durations. Findings suggest the critical role of breastfeeding "ambivalence" in driving thought and action in women's lives. Ambivalence erodes the permanence of breastfeeding intention, and makes feeding practices provisional. Ambivalence challenges breastfeeding promotion strategies, resulting in weakened public health messages and a difficult-to-realize public health goal. PMID- 19644746 TI - Sensory processing subtypes in autism: association with adaptive behavior. AB - Children with autism are frequently observed to experience difficulties in sensory processing. This study examined specific patterns of sensory processing in 54 children with autistic disorder and their association with adaptive behavior. Model-based cluster analysis revealed three distinct sensory processing subtypes in autism. These subtypes were differentiated by taste and smell sensitivity and movement-related sensory behavior. Further, sensory processing subtypes predicted communication competence and maladaptive behavior. The findings of this study lay the foundation for the generation of more specific hypotheses regarding the mechanisms of sensory processing dysfunction in autism, and support the continued use of sensory-based interventions in the remediation of communication and behavioral difficulties in autism. PMID- 19644745 TI - Causal pattern recovery from neural spike train data using the Snap Shot Score. AB - We present a new approach to learning directed information flow networks from multi-channel spike train data. A novel scoring function, the Snap Shot Score, is used to assess potential networks with respect to their quality of causal explanation for the data. Additionally, we suggest a generic concept of plausibility in order to assess network learning techniques under partial observability conditions. Examples demonstrate the assessment of networks with the Snap Shot Score, and neural network simulations show its performance in complex situations with partial observability. We discuss the application of the new score to real data and indicate how it can be modified to suit other neural data types. PMID- 19644747 TI - Resolution of the diagnosis among parents of children with autism spectrum disorder: associations with child and parent characteristics. AB - Resolution with the diagnosis of one's child involves coming to terms with and accepting the diagnosis and its implications. Parental resolution with the diagnosis was examined among 61 mothers and 60 fathers of 61 children with autism spectrum disorders aged 2-17 years. We investigated resolution rates and subtypes, and associations between resolution status and child characteristics (CA, gender, MA, adaptive behavior, diagnosis type, time elapsed since diagnosis) and parent characteristics (age, gender, IQ, broad autism phenotype index, special needs' impact on family). Nearly half of the parents were classified as resolved. Maternal but not paternal resolution status was associated with reported negative impact of raising a child with a disability on family life, but not with other characteristics of the child or the parent. PMID- 19644748 TI - Food insecurity among homeless and marginally housed individuals living with HIV/AIDS in San Francisco. AB - Food insecurity is a risk factor for both HIV transmission and worse HIV clinical outcomes. We examined the prevalence of and factors associated with food insecurity among homeless and marginally housed HIV-infected individuals in San Francisco recruited from the Research on Access to Care in the Homeless Cohort. We used multiple logistic regression to determine socio-demographic and behavioral factors associated with food insecurity, which was measured using the Household Food Insecurity Access Scale. Among 250 participants, over half (53.6%) were food insecure. Higher odds of food insecurity was associated with being white, low CD4 counts, recent crack use, lack of health insurance, and worse physical and mental health. Food insecurity is highly prevalent among HIV infected marginally housed individuals in San Francisco, and is associated with poor physical and mental health and poor social functioning. Screening for and addressing food insecurity should be a critical component of HIV prevention and treatment programs. PMID- 19644749 TI - Early adolescents' perceptions of their mother's anxious parenting as a predictor of anxiety symptoms 12 months later. AB - Parental overprotection and modeling of fearful behaviors have been proposed to play a central role in the development of anxiety. Yet there have been few longitudinal examinations of these relationships and virtually none focusing on the adolescent period. The current study measured adolescent perceptions of maternal anxious parenting (a combination of overprotection and expression of anxiety), mothers' levels of anxiousness, and adolescents' anxiety symptoms in 421 girls in grade 7 and their mothers. Measures were repeated 12 months later. When the adolescent's self report of anxiety was used as the outcome, the adolescent's perception of maternal anxious parenting significantly predicted adolescent anxiety 12 months later. When the mother's report of adolescent anxiety was used as the outcome adolescent anxiety significantly predicted adolescent perceptions of maternal anxious parenting 12 months later. Maternal anxiousness predicted the adolescent's perception of anxious parenting, but meditational relationships were not significant in either model. The data are partly consistent with reciprocal influence models of parent/child relationships but point to the importance of informant perspectives in determining relationships between these complex variables. PMID- 19644751 TI - Children's peer victimization, empathy, and emotional symptoms. AB - This study investigated the concurrent and longitudinal relations among children's peer victimization, empathy, and emotional symptoms. The sample consisted of 175 children (85 girls, mean age = 6.1 years) recruited from kindergartens in Switzerland and followed for 1 year (Time 2). Parents and teachers reported on the children's emotional symptoms, empathy, and victimization. Children reported their empathy and victimization experiences. Peer victimization was a predictor of emotional symptoms at Time 1; this association was stronger for children with average or high levels of empathy. Increases in peer victimization predicted increases in boys' emotional symptoms, and increases in victimization were related to decreases in empathy. The results emphasize the role of negative peer relations and children's social-emotional information processing for the development of emotional symptoms. PMID- 19644752 TI - Fluroxypyr triggers oxidative damage by producing superoxide and hydrogen peroxide in rice (Oryza sativa). AB - The present study has evaluated effect of fluroxypyr concentrations 0-0.8 mg l( 1) (a widely-used herbicide for controlling annual or perennial weeds growth) on selected metabolic and stress-related parameters in Oryza sativa plants after 6 days of exposure. Increasing concentrations decreased shoot growth and accumulation of chlorophylls but had no effect on root biomass. Increasing doses led also to increase in superoxide radical, hydrogen peroxide and proline accumulation, while malondialdehyde, an indicator of lipid peroxidation, was constitutively elevated. Histochemical staining with nitroblue tetrazolium and 3, 3-diaminobenzidine were positively correlated with the generation of superoxide radical and H(2)O(2). The fluroxypyr-induced oxidative stress triggered significant changes in activities of superoxide dismutase, catalase, ascorbate peroxidase and peroxidase (POD). Activities of the antioxidant enzymes show a general increase at low fluroxypyr concentrations and a decrease at high fluroxypyr levels (except for POD). Analysis of naturing polyacrylamide gel electrophoresis confirmed these results. These data support the observation that fluroxypyr-triggered oxidative stress was responsible for the disturbance of the growth in the rice plants. PMID- 19644753 TI - Study on tracheal collapsibility, compliance, and stress by considering nonlinear mechanical property of cartilage. AB - Tracheal cartilage has been widely regarded as a linear elastic material either in experimental studies or in analytic and numerical models. However, it has been recently demonstrated that, like other fiber-oriented biological tissues, tracheal cartilage is a nonlinear material, which displays higher strength in compression than in extension. Considering the nonlinearity requires a more complex theoretical frame work and costs more to simulate. This study aims to quantify the deviation due to the simplified treatment of the tracheal cartilage as a linear material. It also evaluates the improved accuracy gained by considering the nonlinearity. Pig tracheal rings were used to exam the mechanical properties of cartilage and muscular membrane. By taking into account the asymmetric shape of tracheal cartilage, the collapse behavior of complete rings was simulated, and the compliance of airway and stress in the muscular membrane were discussed. The results obtained were compared with those assuming linear mechanical properties. The following results were found: (1) Models based on both types of material properties give a small difference in representing collapse behavior; (2) regarding compliance, the relative difference is big, ranging from 10 to 40% under negative pressure conditions; and (3) the difference in determining stress in the muscular membrane is small too: <5%. In conclusion, treating tracheal cartilage as a linear material will not cause big deviations in representing the collapse behavior, and mechanical stress in the muscular part, but it will induce a big deviation in predicting the compliance, particularly when the transmural pressure is lower than -0.5 kPa. The results obtained in this study may be useful in both understanding the collapse behavior of trachea and in evaluating the error induced by the simplification of treating the tracheal cartilage as a linear elastic material. PMID- 19644754 TI - New cardiac MRI gating method using event-synchronous adaptive digital filter. AB - When imaging the heart using MRI, an artefact-free electrocardiograph (ECG) signal is not only important for monitoring the patient's heart activity but also essential for cardiac gating to reduce noise in MR images induced by moving organs. The fundamental problem in conventional ECG is the distortion induced by electromagnetic interference. Here, we propose an adaptive algorithm for the suppression of MR gradient artefacts (MRGAs) in ECG leads of a cardiac MRI gating system. We have modeled MRGAs by assuming a source of strong pulses used for dephasing the MR signal. The modeled MRGAs are rectangular pulse-like signals. We used an event-synchronous adaptive digital filter whose reference signal is synchronous to the gradient peaks of MRI. The event detection processor for the event-synchronous adaptive digital filter was implemented using the phase space method-a sort of topology mapping method-and least-squares acceleration filter. For evaluating the efficiency of the proposed method, the filter was tested using simulation and actual data. The proposed method requires a simple experimental setup that does not require extra hardware connections to obtain the reference signals of adaptive digital filter. The proposed algorithm was more effective than the multichannel approach. PMID- 19644755 TI - Linguistic markers and emotional intensity. AB - The purpose of this experiment is to explore possible relationships between the intensity of emotions and the lexical modalities for expressing those emotions. In this experiment, 60 Hebrew-speaking subjects were asked to watch four short films that aroused emotion. Two of the films gave rise to different degrees of happiness, and two produced sadness. At the end of each film, subjects were asked to report on their emotions. This experiment was based on the supposition that there is a relationship between the various lexical modalities used by the subjects when writing about their emotions and the intensity of those emotions. The lexical modalities examined included intensifiers, the use of emotion words, repetitions, the use of first person singular, the use of metaphors, and the use of exclamations, among others. This experiment supported the research hypothesis, as it confirmed that significant differences existed between the lexical modalities found in texts written with lower emotional intensity (for both happiness and sadness) and those written with greater emotional intensity. PMID- 19644756 TI - Phonological constraints on the assembly of skeletal structure in reading. AB - Linguistic research suggests that certain skeletal frames (e.g., CVC) are preferred to others (e.g., VCC). We examine whether such preferences constrain reading in the Stroop task. We demonstrate that CCVC nonwords facilitate naming the color black (/blaek/, a CCVC frame) relative to CVC controls. Conversely, CCVC items inhibit red (a CVC frame) relative to CVC controls. These results suggest that readers are sensitive to the congruency between the skeletal structure of color names and printed nonwords. However, various frames are not all equally preferred: the color black is named faster with a VCC frame, an infrequent and ill-formed frame, relative to a CVC frame, a frequent and grammatically preferred frame. These findings suggest that the representation of printed words specifies distinct slots for consonants and vowels, and readers are equipped with preferences (either grammatical or statistical) concerning skeletal frames. These conclusions underscore the contribution of linguistic knowledge to skilled reading. PMID- 19644757 TI - Doomed to read in a second language: implications for learning. AB - The aim of the study was to elucidate whether and how reliance on a second language impacts the learning of new information under very basic learning conditions. The paradigm used to investigate this issue required individuals to learn a series of associations between numerals and particular letter strings. Participants were two groups of university students: (1) individuals for whom spoken Hebrew was the mother tongue and written Hebrew a primary orthography (L1 group), and (2) individuals for whom Hebrew, both spoken and written, was a second language (L2 group). Data were collected under two conditions. In the language-dependent condition (LDC), the paradigm required learning associations between eight numerals and the letter strings of eight familiar Hebrew words. In the language-independent condition (LIC), it required learning associations between eight numerals and eight random letter strings in Hebrew. Results suggest that learners may be significantly disadvantaged when compelled to learn new information mediated in a second language. This disadvantage appears to manifest itself at a very basic learning level and in instances where new information is mediated by language that is fairly overlearned by the L2 learner. PMID- 19644758 TI - Re-evaluating the time course of gender and phonological encoding during silent monitoring tasks estimated by ERP: serial or parallel processing? AB - Neurolinguistic and psycholinguistic studies suggest that grammatical (gender) and phonological information are retrieved independently and that gender can be accessed before phonological information. This study investigated the relative time courses of gender and phonological encoding using topographic evoked potentials mapping methods. Event-related brain potentials (ERPs) were recorded using a high resolution electroencephalogram (EEG) system (128 channels) during gender and phoneme monitoring in silent picture naming. Behavioural results showed similar reaction times (RT) between gender and word onset (first phoneme) monitoring, and longer RT when monitoring the second syllable onset. Temporal segmentation analysis (defining dominant map topographies using cluster analysis) revealed no timing difference between gender monitoring and word onset monitoring: both effects fall within the same time window at about 270-290 ms after picture presentation. Monitoring a second syllable onset generated a later effect at about 480 ms. Direct comparison between gender and first phoneme monitoring revealed a difference of only 10 ms between tasks at approximately 200 ms. Taken together, these results suggest that lemma retrieval and phonological encoding may proceed in parallel or overlap. Word onset is retrieved simultaneously with gender, while the longer RT and the later ERP effect for second syllable onset reflect that segmental encoding continues incrementally to the following phonemes. PMID- 19644759 TI - Adopting best practices: lessons learned in the Collaborative Initiative to Help End Chronic Homelessness (CICH). AB - The Collaborative Initiative to Help End Chronic Homelessness (CICH) was established to provide housing and supportive services for individuals experiencing chronic homelessness. As part of this initiative, 11 projects across the country received funding to apply models of best practices to support their clients in housing. This paper reports on the experiences of the CICH projects in their use of Assertive Community Treatment (ACT) and Motivational Interviewing (MI), clinical practice models commonly used by CICH projects. A qualitative analysis identified five areas of challenge for the projects: (1) Incomplete and underdeveloped staff teams; (2) Incomplete understanding of the practice models; (3) Using the elements of the practice models; (4) Interagency teaming; and (5) Competing expectations of multiple federal agencies. The paper describes the specific challenges in each of the five areas as well as training approaches and gaps in training and the perceived benefits of the practice models as reported by project staff. PMID- 19644760 TI - Quantum dots as new-generation fluorochromes for FISH: an appraisal. AB - In the field of nanotechnology, quantum dots (QDs) are a novel class of inorganic fluorochromes composed of nanometre-scale crystals made of a semiconductor material. Given the remarkable optical properties that they possess, they have been proposed as an ideal material for use in fluorescent in-situ hybridization (FISH). That is, they are resistant to photobleaching and they excite at a wide range of wavelengths but emit light in a very narrow band that can be controlled by particle size and thus have the potential for multiplexing experiments. The principal aim of this study was to compare the potential of QDs against traditional organic fluorochromes in both indirect (i.e. QD-conjugated streptavidin) and direct (i.e. synthesis of QD-labelled FISH probes) detection methods. In general, the indirect experiments met with a degree of success, with FISH applications demonstrated for chromosome painting, BAC mapping and use of oligonucleotide probes on human and avian chromosomes/nuclei. Many of the reported properties of QDs (e.g. brightness, 'blinking' and resistance to photobleaching) were observed. On the other hand, signals were more frequently observed where the chromatin was less condensed (e.g. around the periphery of the chromosome or in the interphase nucleus) and significant bleed-through to other filters was apparent (despite the reported narrow emission spectra). Most importantly, experimental success was intermittent (sometimes even in identical, parallel experiments) making attempts to improve reliability difficult. Experimentation with direct labelling showed evidence of the generation of QD-DNA constructs but no successful FISH experiments. We conclude that QDs are not, in their current form, suitable materials for FISH because of the lack of reproducibility of the experiments; we speculate why this might be the case and look forward to the possibility of nanotechnology forming the basis of future molecular cytogenetic applications. PMID- 19644761 TI - Prevalence of brucellosis and infectious bovine rhinotracheitis in organized dairy farms in India. AB - This study was carried out to investigate the prevalence of bovine brucellosis and infectious bovine rhinotracheitis (IBR) in organized dairy farms with history of abortion in India. ELISA and Rose Bengal Plate Test (RBPT) were used to detect the seropositive animals and the test results indicated that 22.18% and 13.78% animals were declared as sero-positive by ELISA and RBPT, respectively. Milk Ring Test (MRT) was carried out only in one farm and 12.82% of the tested animals were turned positive. Culture examination analysis of milk samples, two animals revealed the presence of organisms indistinguishable from Brucella spp. The organism was confirmed as brucella by morphological characteristics and biochemical tests. An overall sero-prevalence of antibodies against IBR was found to be 60.84%. None of the genital and nasal swab samples was found to be positive for presence of bovine herpesvirus -1 (BHV-1) on repeated passage in Madin-Darby Bovine Kidney (MDBK) cell lines. Brucella and IBR considered as the causal agent for abortions in these farms. The present study indicates the urgent need and the necessity for control of these infectious diseases which cause heavy economic losses to the organized farms. PMID- 19644762 TI - Exceptional survivors have lower age trajectories of blood glucose: lessons from longitudinal data. AB - Exceptional survival results from complicated interplay between genetic and environmental factors. The effects of these factors on survival are mediated by the biological and physiological variables, which affect mortality risk. In this paper, we evaluated the role of blood glucose (BG) in exceptional survival using the Framingham heart study data for the main (FHS) and offspring (FHSO) cohorts. We found that: (1) the average cross-sectional age patterns of BG change over time; (2) the values of BG level among the longest lived individuals in this study differ for different sub-cohorts; (3) the longitudinal age patterns of BG differ from those of cross-sectional ones. We investigated mechanisms forming average age trajectories of BG in the FHS cohort. We found that the two curves: one, characterizing the average effects of allostatic adaptation, and another, minimizing mortality risk for any given age, play the central role in this process. We found that the average BG age trajectories for exceptional survivors are closer to the curve minimizing mortality risk than those of individuals having shorter life spans. We concluded that individuals whose age trajectories of BG are located around the curve minimizing chances of premature death at each given age have highest chances of reaching exceptional longevity. PMID- 19644763 TI - Introduction to theory/modeling methods in photosynthesis. AB - Theory and molecular modeling play an increasingly important role in complementing the experimental findings and supporting the interpretation of the data. Owing to the increase in computational power combined with the development of more efficient methods, computer simulations and modeling have emerged as primary ingredients of modern scientific inquiry. Here, we introduce the methods that in our view bring the largest promises in photosynthesis research, indicate how they have already contributed, and can in the near future assume a significant role in this field. Particular emphasis is given to density functional theory and its combination with molecular dynamics simulations. We point out the need for a multi-scale approach in facing the challenging task of describing processes which cover several orders of magnitude both in the time scale and in the size of the systems of interest. PMID- 19644765 TI - Lack of apoE causes alteration of cytokines expression in young mice liver. AB - To investigate the effect of apolipoprotein E (apoE) on cytokine expression profile of the liver of young mice, quantitative RT-PCR (qRT-PCR) assay and cytokine antibody array for multiplex analysis of 62 cytokines have been used to analyze characteristics of expression of cytokines in the liver of 6-week-old apoE-null (apoE(-/-)) mice. The levels of plasma cytokines were also analyzed. The mRNA level of IL-1 beta, IL-2, IL-6, ICAM-1, VCAM-1, MCP-1, NF-kappaB (p65), IFN-gamma and I kappaB-alpha were increased significantly in apoE(-/-) mice comparative to wild-type (WT) mice. IL-4, IL-10 and GM-CSF, however, were slightly decreased. Compared with WT, levels of 21 cytokines altered twofold or more in apoE(-/-) mice, including 10 cytokines increased and 11 decreased. Expression patterns of IL-1 beta, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-gamma and VCAM-1 showed identical trend between cytokine antibody array and qRT-PCR analysis. Moreover, levels of IL-1 beta, IFN-gamma and IL-6 in the plasma were elevated, while IL-4 was lightly decreased in apoE(-/-) mice compared to those in WT mice. These results implied that promotion of type I immune response in the liver of young apoE(-/-) mice due to alteration of these cytokines, and the phenotypes may be caused by the regulation of NF-kappaB. The inflammation and lipid metabolism dysfunction in the liver cooperated in dysfunction of the liver in young apoE(-/-) mice. PMID- 19644764 TI - Updating corneofungimetry: a bioassay exploring dermatomycoses and antifungal susceptibility. AB - Superficial dermatomycoses are frequent conditions in humans and animals. Specific treatment modalities have been designed using a variety of different antifungal compounds. The need for antifungal susceptibility testing (AST) has been growing steadily over the last two decades due to the extending number of newer antifungal agents. Objective inter- and intraindividual comparisons of their respective efficacies are nearly impossible to perform in vivo. Currently, a series of standardized AST methods and interpretative guidelines have been designed. However, their clinical relevance for dermatomycoses is not consistent. The corneofungimetry bioassay was designed to test comparatively a series of antifungals on pathogenic fungi growing on sheets of human stratum corneum. Computerized morphometric assessments bring numerical values allowing statistical comparisons. Variants of corneofungimetry address more specific aspects related to fungal cell adhesion, fungitoxicity and lipid-dependent fungi. PMID- 19644766 TI - Development of cell culture system from the giant freshwater prawn Macrobrachium rosenbergii (de Man). AB - A new cell culture system (MRH) was developed for the first time from 2 months old freshwater prawn, Macrobrachium rosenbergii. Primary cultures were developed from heart tissues by explant culture technique. Cell outgrowth was obtained from the heart explant after 14 days of explant culture. The culture medium used was Leibovitz-15 supplemented with 20% Fetal Bovine Serum along with 1% prawn hemolymph serum, 0.1% glucose, 0.5% NaCl and antibiotics (Penicillin 10,000 Units ml(-1), Streptomycin 10,000 microg ml(-1), Amphotericin B 500 mg ml(-1)) with a final osmomolality of 470-550 mmol kg(-1). The pH of the growth medium found suitable for the growth of the cells was 7.20. The viability of cells was found to be 60% when revived after a month of storage in liquid nitrogen. PMID- 19644767 TI - Molecular regulation of mast cell development and maturation. AB - Mast cells play a crucial role in the pathogenesis of allergic diseases. In recent years, tremendous progresses have been made in studies of mast cell origination, migration, proliferation, maturation and survival, and the cytokines regulating these activities. These advances have significantly improved our understandings to mast cell biology and to the molecular mechanisms of mast cells in the pathogenesis of allergic diseases. PMID- 19644768 TI - A clinical perspective on ethical arguments around prenatal diagnosis and preimplantation genetic diagnosis for later onset inherited cancer predispositions. AB - Prenatal diagnosis (PND) and preimplantation genetic diagnosis (PGD) for later onset and/or reduced penetrance inherited cancer predispositions, e.g. familial adenomatous polyposis, hereditary non-polyposis colorectal cancer/Lynch syndrome and hereditary breast and ovarian cancer, raise a number of ethical issues. Some of these are the same as for conditions which present early in childhood, are fully penetrant and for which no/limited treatment options are possible; others relate to whether reduced penetrance and/or the availability of treatment mean that these are not serious (enough) conditions to warrant tests prior to/during pregnancy or to justify termination of pregnancy. However, attempts to reach a consensus on what counts as a serious (enough) condition in the context of PND and PGD have been unsuccessful. Such a definition may anyway be unhelpful if it cannot also take into account, for example, the woman's/couple's awareness and experience of the condition and the impact of the condition on affected individuals and their families. Individuals affected by, or at high risk of, later onset and/or reduced penetrance inherited cancer predispositions are generally supportive of access to PND and PGD for their own conditions, even if they would not consider using it themselves. Professionals working in clinical cancer genetics need to be prepared to discuss PND and PGD with this group of patients. PMID- 19644769 TI - More on enrolling female students in science and engineering. AB - This paper investigates reasons for practices and policies that are designed to promote higher levels of enrollment by women in scientific disciplines. It challenges the assumptions and problematic arguments of a recent article questioning their legitimacy. Considering the motivations for and merits of such programs suggests a practical response to the question of whether there should be programs to attract female science and engineering students. PMID- 19644770 TI - On genies and bottles: scientists' moral responsibility and dangerous technology R&D. AB - The age-old maxim of scientists whose work has resulted in deadly or dangerous technologies is: scientists are not to blame, but rather technologists and politicians must be morally culpable for the uses of science. As new technologies threaten not just populations but species and biospheres, scientists should reassess their moral culpability when researching fields whose impact may be catastrophic. Looking at real-world examples such as smallpox research and the Australian "mousepox trick", and considering fictional or future technologies like Kurt Vonnegut's "ice-nine" from Cat's Cradle, and the "grey goo" scenario in nanotechnology, this paper suggests how ethical principles developed in biomedicine can be adjusted for science in general. An "extended moral horizon" may require looking not just to the effects of research on individual human subjects, but also to effects on humanity as a whole. Moreover, a crude utilitarian calculus can help scientists make moral decisions about which technologies to pursue and disseminate when catastrophes may result. Finally, institutions should be devised to teach these moral principles to scientists, and require moral education for future funding. PMID- 19644771 TI - Toward an horizon in design ethics. AB - This paper suggests that design ethics can be enriched by considering ethics beyond the traditional approaches of deontology, teleology, and virtue ethics. Design practice and design ethics literature tend to frame ethics in design according to these approaches. The paper argues that a fundamental and concrete ethical understanding of design ethics can also be found in Sartrean Existentialism, a philosophy centered on the individual and his/her absolute freedom. Through the analysis of four core concepts of Sartrean Existentialism that define a specific ethics, the paper illustrates why such philosophical approach is relevant to design ethics. The paper also shows how Sartrean Existentialism and its ethics apply to critical issues of professional practice in design such as professional engagement and design decision-making. The paper finally argues that Sartre's philosophy and ethics is a perspective that offers the designer in design practice a solid ground to engage his/her ethical dilemma. PMID- 19644772 TI - Chronic administration with rotenone does not enhance MPTP neurotoxicity in C57BL/6 mice. AB - Systematic administration of rotenone as one of pesticides is known to produce degeneration of nigral dopaminergic neurons and motor deficits in experimental animals. Here, we investigated to determine whether systematic administration of rotenone causes the increased susceptibility in 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)-treated mice. Rotenone was injected into MPTP-treated mice over a period of 4 weeks. Thereafter, we evaluated the effect of rotenone 1, 3, and 6 weeks after the cessation of treatment with rotenone. In the present study with HPLC analysis, rotenone did not enhance MPTP-induced dopaminergic neurotoxicity in mice. Furthermore, MPTP + rotenone (9 mg/kg)-treated mice exhibit a significant loss of motor activity 1 day after the cessation of treatment with rotenone, However, no significant change of motor activity was found in MPTP-treated and MPTP + rotenone (9 mg/kg)-treated animals 6 weeks after the cessation of treatment with 0.5% carboxymethyl cellulose or rotenone. Our Western blot analysis study demonstrated that the change of tyrosine hydroxylase and glial fibrillary acidic protein protein levels in MPTP-treated mice was similar than that in MPTP + rotenone-treated animals. These results suggest that rotenone did not enhance MPTP neurotoxicity in mice. Our findings suggest that rotenone is not a reliable model for PD. Thus, our findings provide further valuable information for the pathogenesis of PD for exposure to agricultural pesticides. PMID- 19644773 TI - Contemporary management of traumatic intracranial hypertension: is there a role for therapeutic hypothermia? AB - OBJECTIVE: Intracranial hypertension (ICH) remains the single most difficult therapeutic challenge for the acute management of severe traumatic brain injury (TBI). We reviewed the published trials of therapeutic moderate hypothermia to determine its effect on ICH and compared its efficacy to other commonly used therapies for ICH. METHODS: A PubMed database search was done using various combinations of the search terms "brain injury," "therapeutic hypothermia," "intracranial hypertension," "barbiturates," "mannitol," "hypertonic saline," "hyperventilation," "decompressive craniectomy," and "CSF drainage." RESULTS: We identified 11 prospective randomized clinical TBI trials comparing hypothermia vs. normothermia treatment for which intracranial pressure (ICP) data was provided, and 6 prospective cohort studies that provided ICP data before and during hypothermia treatment. In addition, we identified 37 clinical TBI studies of lumbar CSF drainage, mannitol, hyperventilation, barbiturates, hypertonic saline, and decompressive craniectomy that provided pre- and posttreatment ICP data. Hypothermia was at least as effective as the traditional therapies for ICH (hyperventilation, mannitol, and barbiturates), but was less effective than hypertonic saline, lumbar CSF drainage, and decompressive craniectomy. Ultimately, however, therapeutic hypothermia does appear to have a favorable risk/benefit profile. CONCLUSION: Therapeutic moderate hypothermia is as effective, or more effective, than most other treatments for ICH. If used for 2-3 days or less there is no evidence that it causes clinically significant adverse events. The lack of consistent evidence that hypothermia improves long-term neurologic outcome should not preclude consideration of its use for the primary treatment of ICH since no other ICP therapy is held to this standard. PMID- 19644774 TI - Effects of the neurological wake-up test on intracranial pressure and cerebral perfusion pressure in brain-injured patients. AB - OBJECTIVE: To evaluate the effects of the neurological "wake-up test" (NWT), defined as interruption of continuous propofol sedation and evaluation of the patient's level of consciousness, on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with severe subarachnoid hemorrhage (SAH) or traumatic brain injury (TBI). METHODS: A total of 127 NWT procedures in 21 severely brain-injured adult patients with either TBI (n = 12) or SAH (n = 9) were evaluated. ICP and CPP levels prior to, during and after the NWT procedure were recorded. RESULTS: During the NWT, ICP increased from 13.4 +/- 6 mmHg at baseline to 22.7 +/- 12 (P < 0.05) and the CPP increased from 75.6 +/- 11 to 79.1 +/- 21 mmHg (P < 0.05) in TBI patients. Eight patients showed a reduced CPP during the NWT due to increased ICP. In SAH patients, ICP increased from 10.6 +/- 5 to 16.8 +/- 8 mmHg (P < 0.05) and the CPP increased from 76.9 +/- 13 to 84.6 +/ 15 mmHg (P < 0.05). CONCLUSION: When continuous propofol sedation was interrupted and NWT was performed in severely brain-injured patients, the mean ICP and CPP levels were modestly increased. A subset of patients showed more pronounced changes. To date, the role of the NWT in the neurointensive care of TBI and SAH patients is unclear. Although the NWT is safe in the majority of patients and may provide useful clinical information about the patient's level of consciousness, alternate monitoring methods are suggested in patients showing marked ICP and/or CPP changes during NWT. PMID- 19644775 TI - Autoreactive B cells and epigenetics. AB - Autoreactive B cells are central in the pathogenesis of autoimmune diseases (AID) not only by producing autoantibodies but also by secreting cytokines and by presenting autoantigens. Changes in DNA methylation, histone modifications, and miRNA expression, the hallmarks of epigenetic failure, characterize B cells isolated from patients with AID, highlighting the contribution of epigenetic processes to autoreactivity. Additional evidence of epigenetic involvement in the development of B cell autoreactivity comes from in vivo and in vitro studies using DNA demethylating agents as accelerating factors or histone deacetylase inhibitors as repressing factors. As a result, a better understanding of the altered epigenetic processes in AID and in particular in B cells opens perspectives for the development of new therapeutics. PMID- 19644778 TI - Role of low dose capecitabine combined to irinotecan in advanced and metastatic gastric cancer. AB - Chemotherapy has a proven role in advanced and metastatic gastric cancer (AMGC) significantly improving quality of life and prolonging survival compared with best supportive care alone. Multiple regimens have been explored. The choice of treatment should be individualized and tailored to the patient's overall conditions and preference. This manuscript is divided into two sections. The first section illustrates the results of a phase II trial combining weekly irinotecan and low dose capecitabine in the management of untreated AMGC patients. The second section aims to identify the current optimal place of this combination in the management of AMGC in the light of the latest advances. In this manuscript we detail our phase II trial which showed objective response rate of 47% (15 patients), disease stabilization of 28% (9 patients), and overall tumor control rate of 75% (24 patients). Median time to progression and overall survival were 5.8 and 8 months, respectively. Grades III-IV toxicities were reported in 7 cases. Low-dose capecitabine plus irinotecan is effective in the treatment of AMGC with an acceptable toxicity profile. Compared to the recent published data, this combination is indicated in the second-line treatment of AMGC and in the first-line treatment where a contraindication for docetaxel- and/or oxaliplatin-based regimen is present. PMID- 19644779 TI - Ballistics reviews: mechanisms of bullet wound trauma. AB - The location of an entrance wound (bullet placement) and the projectile path are the most important factors in causing significant injury or death following a shooting. The head followed by the torso are the most vulnerable areas, with incapacitation resulting from central nervous system (brain or cord) disruption, or massive organ destruction with hemorrhage. Tissue and organ trauma result from the permanent wound cavity caused by direct destruction by the bullet, and also from radial stretching of surrounding tissues causing a temporary wound cavity. The extent of tissue damage is influenced by the type of bullet, its velocity and mass, as well as the physical characteristics of the tissues. The latter includes resistance to strain, physical dimensions of an organ, and the presence or absence of surrounding anatomical constraints. Bullet shape and construction will also affect tissue damage and bullets which display greater yaw will be associated with increased temporary cavitation. Military bullet designs do not include bullets that will expand or flatten as these cause greater wound trauma and are regulated by convention. PMID- 19644776 TI - Epigenetic therapeutics in autoimmune disease. AB - Several lines of evidence suggest the involvement of disturbance in epigenetic processes in autoimmune disease. Most noteworthy is the global DNA hypomethylation seen in lupus. Epigenetic states in difference from genetic lesions are potentially reversible and hence candidates for pharmacological intervention. Potential targets for drug development are histone modification and DNA methylating and demethylating enzymes. The most advanced set of drugs in clinical development are histone deacetylase (HDAC) inhibitors. However, the prevalence of DNA hypomethylation in lupus suggests that we should shift our attention from HDAC inhibitors to DNA demethylation inhibitors. MBD2 was recently proposed to be involved in demethylation in T cells in lupus and is, therefore, a candidate target. Although this field is at its infancy, it carries great promise. PMID- 19644780 TI - [Pulmonary rehabilitation after total laryngectomy using a heat and moisture exchanger (HME)]. AB - A complete removal of the larynx has profound consequences for a patient. Since laryngectomy involves the separation of the upper airway from the lower airway, it not only implies a loss of the voice organ but also leads to chronic lung problems such as increased coughing, mucus production and expectoration. In addition, laryngectomees complain of fatigue, sleeping problems, a reduced sense of smell and taste, and a loss of social contact. A heat and moisture exchanger (HME) cassette can replace a function of the upper airway which consists in conditioning inspired air. It can improve pulmonary symptoms in three ways. 1. An HME cassette heats and moisturises inhaled air and thus creates nearly physiological conditions in the region of the deep airway. 2. The use of an HME cassette leads to an increase in breathing resistance, thereby reducing dynamic airway compression and improving lung ventilation. 3. An HME cassette acts as a filter and removes larger particles from incoming air. This review examines the current understanding of lung physiology after laryngectomy and assesses the effects of HME cassettes on the conditioning of respiratory air, lung function and psychosocial problems. PMID- 19644777 TI - Advances in progenitor cell therapy using scaffolding constructs for central nervous system injury. AB - Traumatic brain injury (TBI) is a major cause of morbidity and mortality in the United States. Current clinical therapy is focused on optimization of the acute/subacute intracerebral milieu, minimizing continued cell death, and subsequent intense rehabilitation to ameliorate the prolonged physical, cognitive, and psychosocial deficits that result from TBI. Adult progenitor (stem) cell therapies have shown promise in pre-clinical studies and remain a focus of intense scientific investigation. One of the fundamental challenges to successful translation of the large body of pre-clinical work is the delivery of progenitor cells to the target location/organ. Classically used vehicles such as intravenous and intra arterial infusion have shown low engraftment rates and risk of distal emboli. Novel delivery methods such as nanofiber scaffold implantation could provide the structural and nutritive support required for progenitor cell proliferation, engraftment, and differentiation. The focus of this review is to explore the current state of the art as it relates to current and novel progenitor cell delivery methods. PMID- 19644782 TI - [Injuries of the pharyngeal posterior wall in tonsillectomy as a serious malpractice]. PMID- 19644783 TI - [Reconstructive surgery for patients with facial palsy]. AB - Patients with chronic facial palsy first need an exact classification of the palsy etiology. A standardised clinical examination, if necessary MRI imaging and an electromyographic examination allow a determination of the severity of the palsy and the functional deficits. Considering the patient's desire, age and life expectancy an individual surgical concept using three main categories is developed: a) early reconstruction of extratemporal reconstruction, b) early reconstruction of proximal lesions or impossibility of extratemporal reconstruction or c) late reconstruction or congenital palsy. Twelve to 24 months after the last step of surgical reconstruction a standardised evaluation of the therapeutic result is recommended on the one hand to evaluate the necessity for adjuvant procedures and on the other hand as a tool of quality management and to develop new techniques in this field of relatively of infrequent surgery. Principally, controlled trials on the value of physiotherapy and other adjuvant measures are missing to give recommendation for optimal application of adjuvant therapies. PMID- 19644784 TI - [Addiction in DSM V and ICD-11 state of the art]. AB - Diagnoses are made for identifying rather homogeneous groups of patients being thereby relevant for research and for therapy. Therefore diagnostic manuals, like the DSM-IV and the ICD-10 are subjected to changing knowledge derived from research on one hand and to changes of clinical necessities. The diagnosis of substance related disorders, published for DSM-IV in 1994 and for the ICD-10 in 1992, has proven of value for epidemiological research and economic validation. In spite of these advantages the concept has prove to be too broad and rather unspecific for research, specific therapeutic strategies and for defining an illness course. During the last 20 years research has yielded many criteria of interest, which never entered DSM IV or ICD-10, remaining therefore on the level of single items, which are nowadays additionally assigned to all patients (like e. g. early versus late onset) or on the level of typologies (like e. g. Lesch's typology) demanding different treatments. To give an example: acamprosate has lasting relapse preventing effects in Lesch types I and II, while naltrexone is effective in types III and IV. For rendering an expertise in Germany, the referring literature recommends to utilize Lesch's typology additionally to the ICD-10 diagnosis, especially when prognosis or therapeutic strategies are demanded. Since 1999 different expert groups strive for including new criteria into DSM IV and ICD-10. The revised manuals should include easily assignable items for severity of different arrays (time illness onset, co-morbidity, withdrawal symptoms, bridge symptoms and neurological sequela). Different therapy stages (e. g. withdrawal or relapse prevention) need a different weighting of individual symptoms (e. g. degree of intoxication, severity of withdrawal is needed for acute treatment, while an assignment of co-morbidity and personality factors is necessary for relapse prevention). This quantifier is rendered by Lesch's typology, which is available in the form of a computer programme, based on a decision tree (see also www.ausam.at - Typology according to Lesch). Non substance related disorders should enter other diagnostic categories, like e. g. impulse control disorders. A revised diagnostic classification suggests presently offered therapeutic strategies to follow up with necessary modifications. A tailor made therapy according to subgroups can result in better long term performance of therapies offered to persons suffering form substance related disorders. PMID- 19644785 TI - [Usage of drugs with potential adverse effects on cognition in a memory-clinic]. AB - Cognitive decline is a frequent clinical symptom in elderly patients. In particular, memory disturbances are an early sign and a risk factor for subsequent development of neurodegenerative dementia. At the same time, elderly patients often receive multiple medications due to an increasing number of acquired diseases. Certain drugs have adverse side effects on cognition due to interference with the cholinergic or GABA-ergic system. This could lead to underestimation of the actual cognitive status at initial clinical presentation. In the present study we included 221 patients (mean age 68,5 years) who presented for the first time in a specialized memory-clinic and who had or developed dementia during follow up. Most patients had mixed vascular-degenerative dementia (57 %). On average, patients took 2.1 drugs. 19.9 % of the patients had medications with potential adverse effects on cognition. Patients with medication affecting cognition had a worse cognitive performance than patients with a medication not influencing cognitive functioning (Mini-Mental vs. 18.8. 22.01, p = 0.01) in univariate analysis. Psychotropic drugs were used less frequently (38 %) than primary non-CNS medication. The results remained unchanged even after performing a case-control study with the mixed dementia population with age and gender matched patients. However, in multivariate analysis, only the absolute number of medication taken remained as an independent factor. Our data highlight the clinical importance of medication history in the diagnostic work-up of cognitive impairment. The absolute number of medication taken seems to be more important than medication with possible adverse side effects on cognition. PMID- 19644786 TI - [Asperger syndrome]. PMID- 19644787 TI - Second-trimester serum cytokines in women who develop spontaneous preterm labor at less than 28 weeks' gestation versus term labor. AB - We sought to determine if there is a relationship between serum concentrations of cytokines and the development of preterm labor. A panel of 28 cytokines was measured using the multiplex assay in serum samples collected between 15 and 18 weeks' gestation from women who developed spontaneous preterm labor and delivered between 24 and 28 weeks' gestation (N = 25) and from women who delivered at term (>or=37 weeks; N = 25). Sixteen of the 28 cytokines measured were detected. Except for vascular endothelial growth factor, which showed a trend toward a significant increase in patients who developed preterm labor, there was no difference in cytokine levels between groups in preterm labor and in term labor. Serum cytokine changes in women who develop spontaneous preterm labor possibly occur in the period between 18 weeks' gestation and the onset of labor. PMID- 19644788 TI - Uterine activity in women receiving 17 alpha-hydroxyprogesterone caproate for the prevention of preterm birth: an observational study. AB - We evaluated uterine contraction frequency in women receiving 17 alpha hydroxyprogesterone caproate (17-OHP-C) for the prevention of preterm delivery. Women with singleton pregnancies and receiving weekly 17-OHP-C and outpatient tococardiography were identified from a database. The mean and maximum contraction frequencies per hour were compared from 3 days before to 3 days after 17-OHP-C dosing. McNemar chi(2), Mann-Whitney U, and Friedman test statistics were used for analysis. Data were obtained from 388 women. Median contraction frequency was greater for women with subsequent preterm birth versus those delivering at term (1.5 [range 0, 14.5] versus 1.2 [range 0, 21.0] contractions per hour, P < 0.001). No reduction in contraction frequency was observed after 17 OHP-C administration, and in fact, the converse was observed for the average contractions 3 days prior compared with 3 days posttreatment ( P < 0.001). In the subgroup of women with a subsequent spontaneous preterm, the proportion who had an average contraction frequency of more than five per hour 1 day preinjection versus 1 day postinjection was not significantly different (2.6% versus 3.0%, P = 1.0). Administration of 17-OHP-C was not associated with a reduction in contraction frequency. To be effective, this drug likely has effects by mechanisms other than tocolysis. Although a statistically significant increase in contractions was identified posttherapy versus pretherapy, the clinical importance of this observation is unknown. PMID- 19644789 TI - Transabdominal measurement of placental oxygenation by near-infrared spectroscopy. AB - We evaluated the clinical usefulness of near-infrared spectroscopic quantitative measurement of placental tissue oxygenation for noninvasive estimation of uteroplacental function in pregnant women. We performed a prospective observational clinical study. Women without complications (N = 15) and women with pregnancy-induced hypertension (PIH; N = 6) were enrolled. Measurements of placental tissue oxygenation index (TOI) using NIRO-300 (Hamamatsu Photonics, Hamamatsu City, Japan) were recorded. The mean TOI in women without complications was 72.36 +/- 5.36% and 80.28 +/- 2.78% in pregnant women with PIH. The mean TOI in pregnant women with PIH was higher than that of pregnant women without complications. There were no differences in the TOI in relation to gestational age at onset of PIH, forms of PIH, or severity of hypertension. Higher TOIs in pregnant women suggest the reduced ability of the placental function. Monitoring the TOI by near-infrared spectroscopic quantitative measurement may have a high potential for clinical application, particularly in prenatal management. PMID- 19644790 TI - Do neonatal outcomes differ depending on the cause of preterm birth? A comparison between spontaneous birth and iatrogenic delivery for preeclampsia. AB - We compared short-term neonatal outcomes between premature infants with spontaneous preterm birth (s-PTB) and those delivered due to preeclampsia (PEC). Data were collected from women with singleton pregnancies admitted with spontaneous preterm labor (PTL) (2002 to 2005) and PEC (2005 to 2007). Patients delivering 24 to 36(6/7) weeks were analyzed. The incidence of adverse outcomes was compared. Chi-square and Fisher exact tests compared outcomes between neonates of varying gestational ages, and Poisson regression was used to control for confounders. Data describing 368 infants are included (PTL: n = 224; PEC: n = 144). Overall, s-PTB infants had less favorable outcomes at earlier gestational ages, and at later gestational ages those born preterm secondary to PEC (pec-PTB) had less favorable outcomes. s-PTB infants 24 to 27(6/7) weeks were 21% more likely to stay in the neonatal intensive care unit (NICU) > or = 8 days than pec PTB infants (incident rate ratios [IRR] 0.79, P = 0.002, 95% confidence interval [CI] 0.68 to 0.92). Pec-PTB infants 32 to 33(6/7) weeks were 6 times more likely to stay in the NICU > or = 31 days than s-PTB infants (IRR 5.82, P = 0.03, 95% CI 1.20 to 28.31). Short-term neonatal outcomes differ by the etiology of preterm birth. These data can help facilitate proper patient counseling and allocation of resources. Future studies should address mechanisms by which the etiology of PTB leads to specific adverse outcomes, thus allowing for more direct interventional strategies. PMID- 19644791 TI - Two cases of pontocerebellar hypoplasia: ethical and prenatal diagnostic dilemma. AB - We report the clinical characteristics and the outcome of two cases of pontocerebellar hypoplasia (PCH) in one family. The objective of this report is to describe the mode of presentation, discuss the clinical course, and address the dilemma of prenatal diagnosis and the prospects for genetic diagnosis for PCH. The first case is a 4-year-old boy in whom the diagnosis was made in the neonatal period. Despite extensive prenatal follow-up during the mother's subsequent pregnancy, prenatal diagnosis could not be made and a second affected child was born. Both siblings have severe developmental delay. The cases raise an important ethical dilemma about the most appropriate intervention if the mother of a child affected with PCH becomes pregnant. PCH is considered to have an autosomal-recessive mode of inheritance and a recurrence risk of 25% in each pregnancy. Until recently when genetic mutations in PCH types 2, 4, and 6 began to be identified, the lack of well-recognized genetic testing precluded experts from making clear recommendations. The best advice to these parents was difficult or elusive. With two children currently affected, should the parents terminate or continue with the latest pregnancy? Extensive monitoring with serial prenatal ultrasound failed in the previous pregnancy and resulted in the birth of the second affected child. It is evident that serial ultrasound scan may not be helpful in making the diagnosis prenatally. Therefore, other diagnostic modalities such as magnetic resonance imaging may be necessary and should be considered. With the identification of genetic basis or mutations in PCH types 2, 4, and 6 and possible development of commercial genetic testing for these types of PCH, reproductive decision or genetic testing during pregnancy should be recommended to affected families to enable informed choices. PMID- 19644792 TI - [Submucous cleft palate--an often late diagnosed malformation]. AB - BACKGROUND: Submucous cleft palate (SMCP) is often diagnosed very late and can cause velopharyngeal insufficiency with open nasal speech and Eustachian tube dysfunction. METHODS: A retrospective analysis of 106 patients (100 children, 6 adults) who had been surgically treated for SMCP was made. Age of diagnosis, physician who initially diagnosed the SMCP, typical symptoms for cleft palate, clinical examination of the palate, therapy options and accompanying diseases were evaluated. RESULTS: SMCP was diagnosed in 79 cases by a specialist for Phoniatrics/ENT surgery of the University and in 21 cases by a physician, who does not work at hospital at the age of 4.9 years. Main symptoms were Eustachian tube dysfunctions (61.3%) and hypernasal speech (48.1%). Typical findings of the palate were: reduced contraction (69.8%), lack of posterior nasal spine (55.7%) and bifid uvula (51.9%). In 18 patients a dysmorphic syndrome was observed and in 83% a conductive hearing loss which resolved after palatoplasty (often in combination with adenotomy and insertion of ventilation tubes). Following surgery 18 patients required speech therapy and of these 6 needed velopharyngoplasty due to continuing open nasal speech. CONCLUSIONS: SMCP is often diagnosed very late, though symptoms of velopharyngeal insufficiency such as open nasal speech, Eustachian tube dysfunction and reduced contraction of the palate with bifid uvula are present. It is also often found in children with craniofacial dysmorphic syndromes. We therefore recommend that all patients with such findings are examined by an appropriate specialist such as Phoniatrics, ENT-Surgeon and Oral-Maxillofacial Surgeon so that early diagnosis and palatoplasty can be performed. PMID- 19644793 TI - [Amyloidosis of the tongue - case report]. PMID- 19644795 TI - Antibacterial compounds from mushrooms I: a lanostane-type triterpene and prenylphenol derivatives from Jahnoporus hirtus and Albatrellus flettii and their activities against Bacillus cereus and Enterococcus faecalis. AB - Antibacterial bioassay-guided fractionation of two American mushroom species, Jahnoporus hirtus and Albatrellus flettii, led to the isolation and identification of their major antibacterial constituents: 3,11-dioxolanosta-8,24( Z)-diene-26-oic acid (1) from J. hirtus and confluentin (2), grifolin (3), and neogrifolin (4) from A. flettii. Compound 1 is a new lanostane-type triterpene. All purified compounds were evaluated for their ability to inhibit the growth of Bacillus cereus and Enterococcus faecalis using standard MIC assays. Compounds 1- 4 demonstrated MIC values of 40, 20, 10, and 20 microg/mL, respectively, against B. cereus and MIC values of 32, 1.0, 0.5, and 0.5 microg/mL, respectively, against E. faecalis. Thus, one novel compound and three others were shown to possess antimicrobial activities against these gram-positive bacteria employed as surrogates for more virulent and dangerous pathogens. PMID- 19644794 TI - Synergistic anti-candidal activity of tetrandrine on ketoconazole: an experimental study. AB - With the widespread use of azoles, drug resistant Candida albicans strains are increasing. The study examined the synergism of tetrandrine (TET) on ketoconazole (KCZ) candidacidal activity. The protocol M27-A2 of the Clinical and Laboratory Standards Institute (CLSI) was adopted and the minimum inhibitory concentrations (MICs) were determined for KCZ alone and in combination with a TET level that was noncytotoxic for C. albicans strains CA-1 through CA-17, with no CA-10. Colony counting techniques were used to construct time-kill curves. CA-15 was used to build the mouse candidal vaginitis model. After randomization, drugs were administered vaginally once daily from days 3-10 (both KCZ and TET were 26 mg/kg/day and 13 mg/kg/day, respectively, administered in different combinations). Mouse vaginal lavage fluid was obtained at days 2, 6, and 11 after inoculation for fungal load analysis, and vaginal tissue was obtained for pathological examination. MICs of KCZ alone and combined with 30 microg/mL TET for the C. albicans strains were 1-32 microg/mL and 0.0038-0.2500 microg/mL, respectively ( T = 24.624, p = 0.000). Time-kill curves showed that at 48 h the viable cell counts of strains treated with KCZ + TET were at least 2 log(10) CFU/mL lower compared to strains treated with corresponding doses of KCZ (p = 0.000). At day 6, the fungal load in the KCZ 26 mg/kg/day + TET 26 mg/kg/day mice was significantly lower than the KCZ 26 mg/kg/day mice (1.17 +/- 1.17 x 10(4) CFU/mL and 9.33 +/- 3.08 x 10(4) CFU/mL, respectively, p = 0.000). Mucosal and submucosal fungal clearances were complete and vaginal mucosal edema was slight with minimal inflammatory cell infiltration. We conclude that noncytotoxic doses of TET synergistically enhance KCZ candidacidal activity in vitro and in vivo. PMID- 19644796 TI - Activity of ladanein on leukemia cell lines and its occurrence in Marrubium vulgare. AB - Three methoxylated flavones isolated from Marrubium peregrinum - ladanein, scutellarein-5,7,4'-trimethyl ether, and scutellarein-5,6,7,4'-tetramethyl ether were assayed for their cytotoxicity towards a recently developed dasatinib resistant murine leukemia cell line (DA1-3b/M2 (BCR-ABL)), together with the structurally related non-methylated flavone scutellarein. The most active compound, ladanein, was looked for in 20 common Lamiaceae species by a quick HPLC screening. Among the possible positive results, the most interesting source was found to be Marrubium vulgare, which led to the isolation and identification of ladanein for the first time in this species. Ladanein also displayed moderate (20 40 microM) activities against K562, K562R (imatinib-resistant), and 697 human leukemia cell lines but was toxic neither to MOLM13 nor to human peripheral blood mononuclear cells. This work provides a common natural source for the hemi synthesis of future ladanein-derived flavones and the study of their antileukemic activity. PMID- 19644797 TI - [Composite Tissue Allotransplantation (CTA): organ or tissue transplantation?]. AB - Plastic surgery has a long tradition in transplantation issues. Skin transplantation has been introduced by plastic surgeons Padgett and Brown. The first kidney transplantation was performed by Dr. Murray, a plastic surgeon. Composite tissue allotransplantation (CTA) is an evolving new field with transplantation of hand, vascularised knees or partial faces. With the European Union (EU) directive 2004/23/EC come into effect with the German tissue law at August 1, 2007 one has question the classification of transplantation of the hands, arms or the face as tissue or organ transplantation. While solid organs are allocated based on the German Deutsche Stiftung Organspende (DSO) and EuroTransplant, this is not the case for tissues. While for example thoracic organ procurement is performed in heart-beating organ donors with established hemodynamics, this is not the case for tissues, either. Given the complexity of a hand or a face as a sample of bones, muscles, nerves, vessels, and skin this has to be taken into account for example in comparison to a cornea as a tissue graft. As such, Dr. Siemionow has proposed a face to be regarded as an organ when comparing it to a kidney. Currently, allocation procedures as well as procurement issues in CTA are much more similar to organ- rather than tissue transplantation. Thus, we believe that CTA of hands or partial faces has more similarities to organ than to mere tissue transplantation. PMID- 19644798 TI - [Commentary on the article of P. S. Harenberg and D. Erdmann: academic plastic surgery: a comparison of residency models in Germany and the USA]. AB - The postgraduate training in plastic surgery in Germany has to be considered as young. A direct comparison of the postgraduate training in Germany with that of the United States of America is possible on an equal basis, as the quality of postgraduate training has a high standard in both countries. Nevertheless, further corrections are necessary. In the end only competent and well qualified board certified plastic surgeons are in the position to represent this specific field of surgery on a skilled and a political basis. PMID- 19644799 TI - [Surgical correction of eyelid malpositions]. AB - PURPOSE: It is anticipated that in the light of demographic changes a further increase, particularly in senile eyelid malpositions will occur. METHODS: Using case studies, this article presents the most common surgical procedures for correction of ectropion, entropion, trichiasis, ptosis and eyelid anomalies in facial nerve palsy and socket anophthalmic syndrome. RESULTS: In general, most eyelid malpositions can be corrected with excellent cosmetic and functional results. It is, however, difficult to reconstruct eyelid malpositions occurring in conjunction with systemic diseases. CONCLUSIONS: The choice of surgical procedure considering the age of the patient, the genesis and the exact localisation of the pathology is of utmost importance in order to achieve ideal post-operative results. PMID- 19644800 TI - [Stem cell therapy for corneal defects]. AB - BACKGROUND: The healing process of corneal defects requires functioning limbus stem cells. Their loss will lead to secondary wound healing problems. Stem cell research offers new treatment options. MATERIAL AND METHODS: A Medline search of the U. S. National Library of Medicine was carried out. RESULTS: The autologous limbus stem cell transplantation is currently the treatment of choice. Amniotic membrane transplantation, previously settled with limbus stem cells, is a clinically proven method. In animal experiments bone marrow-derived mesenchymal stem cells or epidermal stem cells can be used to improve healing of corneal defects. Adipose-derived stem cells may support the regenerative ability of the cornea as well. Moreover, membrane transplantation of epithelial cells from the buccal mucosa cultivated in vitro was clinically tested. DISCUSSION AND CONCLUSIONS: Limbus stem cell failure of both eye is the limiting factor for autologous limbus stem cell transplantation. Epithelial cells, epidermal stem cells, bone marrow- or adipose-derived mesenchymal stem cells promote the regeneration of the cornea and have become established for the treatment of corneal defects. Additionally, mesenchymal stem cells offer the advantage of immunosuppressive and anti-inflammatory effects. PMID- 19644801 TI - [Orbital and periorbital complications in acute sinusitis]. AB - BACKGROUND: Orbital and periorbital complications due to acute paranasal sinusitis can be treated surgically or conservatively. In many cases the type of treatment depends on the ophthalmological findings. In the context of this clinical analysis we explored whether a conservative rather than an surgical therapy should be chosen for specific otorhinolaryngological or ophthalmological findings. METHODS: 32 patients were treated conservatively, whereas 4 patients had to be operated. Before therapy and after completion of the treatment otorhinolaryngologistical and ophthalmological findings were recorded and these findings as well as the two therapy options were compared with each other. RESULTS: In the cases of the 32 conservatively treated patients plus the 4 patients, who were treated surgically, a complete restitutio ad integrum could be observed at the end of the treatment period. DISCUSSION: A conservative therapy is obsolete in cases with specific ophthalmological findings such as reduction of vision, significant increase of exophthalmos, extreme limitation of motility. In all other cases, a conservative attempt can be made first, because the results of this therapy are as good as the results of surgical intervention but with less exposure for the patient. So the choice of therapy depends the ophthalmological findings. PMID- 19644802 TI - [Efficacy and safety of etofibrate in patients with non-proliferative diabetic retinopathy]. AB - INTRODUCTION: Diabetic retinopathy is the leading cause of vision loss or blindeness in working-age adults in the developed and developing countries. No curative treatments are available for diabetic retinopathy and the most common symptomatic treatment, laser photocoagulation, provides only partial and temporary relief from the progressive vascular damage caused by this disease. Etofibrate (Lipo-Merz) is an orally-administered treatment for lipid disorders that combines fibrate and nicotinic acid in a slow-release formulation. PATIENTS AND METHODS: This report describes the results of a double-blind, randomised, placebo-controlled study, performed to evaluate the efficacy and safety of etofibrat in patients with type 2 diabetes mellitus and concomitant diabetic retinopathy. They received either placebo or 1000 mg/day etofibrate for up to 12 months. Efficacy analyses were based on visual acuity assessment and blinded expert ratings of ocular fundus pathology, as well as laboratory analyses of serum lipid parameters. RESULTS: The evaluable population comprised 296 patients, 148 in each treatment group, of whom 89% completed the study and 73% completed according to protocol. After 12 months of treatment, a significantly larger population of etofibrate-treated patients than placebo-treated patients showed improvements in ocular pathology (46% versus 32%, respectively, p < 0.001); similar findings were already apparent after 6 months of treatment (43% versus 31%, respectively p < 0.001). Etofibrate treatment also produced significant improvements in total cholesterol, LDL-cholesterol and HDL-cholesterol in comparison to the placebo treatment group. Safety evaluations (adverse events, laboratory parameters) did not reveal any clinically significant adverse effects of etofibrate in comparison to placebo. CONCLUSION: Etofibrate provides a safe and effective treatment for ocular pathology resulting from type 2 diabetes mellitus. PMID- 19644803 TI - [A new haploscopic test device excludes blinking induced monocular perception]. AB - BACKGROUND: Haploscopic tests like the pola-test are used to detect functional loss of vision, aggravation or simulation. They aim at confusing the tested person about the relation of disparate monocular visual perceptions to the right and left eyes. The haploscopic confusion can be overcome easily by single sided blinking. Other investigators have faced this problem by presenting optotypes very briefly, thus excluding blinking artefacts. We introduce a new device for shutting off the optotype projection whenever blinking occurs. MATERIALS AND METHODS: A newly developed mechanism slightly presses small lever-switches onto each upper eyelid of a test person while performing the pola test. The levers move up and down following eyelid movements. Lid closure triggers a shut off of the optotype projector. The device was tested on 30 persons. RESULTS: The device worked properly on 59/60 eyes. 24/30 persons did not realize the haploscopic confusion at the beginning, but 6/30 did right away. 18/30 would not realize the haploscopic confusion even after some experience. CONCLUSIONS: The new device worked on nearly all patients and effectively kept most of them from overcoming the haploscopic confusion. It is a useful upgrading for haploscopic tests, making them applicable even in repeated examinations. It should be helpful to detect single-sided functional loss of vision. PMID- 19644804 TI - [Preseptal cellulitis as a complication of surgical treatment of migraine headaches]. PMID- 19644806 TI - [Secondary glaucoma as a masquerade for cutaneous melanoma metastatic to the vitreous and anterior chamber of the eye]. PMID- 19644805 TI - [Subconjunctival injection of bevacizumab for treatment of corneal neovascularization after perforating keratoplasty]. PMID- 19644807 TI - [Development of acute cataract as complication of diabetes mellitus type I]. PMID- 19644808 TI - [Central retinal artery occlusion after embolization in juvenile nasopharyngeal angiofibroma]. PMID- 19644809 TI - [Iodine and folic acid in food: prevention or paternalism?]. PMID- 19644812 TI - [Risk factors for renal disease in cardiac patients]. AB - There are interconnections between the kidney, which regulates the extracellular volume, and the heart, which regulates the systemic circulation. In normal and minor pathological conditions or in those with a slow onset, a self-regulatory mechanism between the two systems is created in our organism to maintain a balance that permits good survival. In acute or severe pathological conditions, this reciprocal correlation between the two systems may fail, creating situations where it is necessary to intervene rapidly to bring the organism back to a condition of balance compatible with life. Moreover, many disorders, such as acute or chronic inflammation of the endothelium, vascular alteration processes of metabolic origin, arteriosclerosis, and vascular calcifications, involve both the cardiocirculatory system and the kidney. Therefore, the cardiologist often has to treat cardiac patients who, besides their cardiocirculatory problems, present kidney involvement, a situation which significantly complicates patient management and may increase the mortality. PMID- 19644810 TI - Effect of astilbin on experimental diabetic nephropathy in vivo and in vitro. AB - Astilbin, a flavonoid compound, was isolated from the rhizome of Smilax glabra Roxb. This study was conducted to investigate the efficacy of astilbin on experimental diabetic nephropathy (DN) in vivo and in vitro and its possible mechanisms. Astilbin was added in high glucose stimulated HK-2 cells, streptozotocin-induced experimental DN, randomized to receive intragastric ( I. G.) astilbin to observe its anti-renal lesion effect. Results showed that astilbin inhibited high glucose stimulated HK-2 cell production of transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor (CTGF) in vitro, especially CTGF; analogic results was also found in vivo. I. G. of astilbin 2.5 mg/kg or 5 mg/kg significantly ameliorated renal function, reduced kidney index, while it increased body weight and survival time in animals. In addition there was no significant difference in blood glucose level between the STZ-treated group and the astilbin groups. Furthermore, astilbin ameliorated the pathological progress of renal morphology. Astilbin can exert an early renal protective role to DN, inhibit production of TGF-beta1 and especially of CTGF. We suggest that astilbin inhibition of CTGF may be a potential target in DN therapy. This work provides the first evidence for astilbin as a new candidate of DN therapeutic medicine. PMID- 19644813 TI - [Inflammation, oxidative stress and kidney function in arterial hypertension]. AB - Traditional risk factors such as hypertension, diabetes, dyslipidemia, obesity and metabolic syndrome, as well as additional nontraditional risk factors, can damage the kidney directly and by promoting intrarenal atherogenesis. Evidence indicates that increased oxidative stress and inflammation may mediate most of the effects of risk factors on the kidney. An early sign of impending nephropathy is microalbuminuria, defined as urinary excretion of albumin at a rate of 20-200 mg/min. Patients with microalbuminuria, especially in diabetes, may progress along the renal continuum to chronic kidney disease (CKD) (indicated by macroalbuminuria or proteinuria), increased serum creatinine concentration and decreased glomerular filtration rate. Microalbuminuria is now recognized as an important marker not only for renal disease, but above all for cardiovascular risk. Clinical studies have demonstrated a relationship between oxidative stress and inflammatory biomarkers, and a few studies indicate an inverse correlation of oxidative stress biomarkers, assessed by 8-isoprostaglandin F2 alpha, with estimated glomerular filtration rate (eGFR). Moreover, plasma concentrations of high-sensitivity C-reactive protein have been shown to be increased and related to left ventricular mass in CKD individuals having left ventricular hypertrophy. Further, surrogate indexes of atherosclerosis such as intima-media thickness and aortic pulse wave velocity have been demonstrated to be related to plasma concentrations of markers of endothelial activation, inflammation and fibrosis in patients with different stages of CKD. In conclusion, current evidence supports a central role for inflammation in all phases of the atherosclerotic process. On the other hand, in arterial hypertension experimental and clinical data suggest a possible interplay of inflammatory molecules with both oxidative stress and endothelial activation markers. The identification of novel biomarkers and cardiovascular risk factors is needed for prognostic evaluation, cardiovascular and renal prevention, and slowing renal function decline. PMID- 19644814 TI - [Inherited thrombophilia]. AB - The paradigm of inherited thrombophilia as a cause of unprovoked venous thrombosis among young people and associated with a high clinical penetrance among members of the same kindred is challenged by many diagnosed cases not fitting this paradigm, although inherited thrombophilia is still the most likely diagnosis in most cases. However, all patients with venous thromboembolism are potential candidates for screening, regardless of the age at which the event occurs, the circumstances of thrombosis, and the severity of the clinical manifestations. A possible exclusion criterion is the contemporary presence of a high-risk disease for thrombosis such as cancer, since in such situations the presence of thrombophilic polymorphisms associated with a moderate risk for venous thromboembolism is not considered a significant additive risk factor. Potential candidates for screening are also women who have suffered from complications, other than venous thromboembolism, of a pregnancy. The inclusion of a large number of individuals with venous thromboembolism (or obstetric complications) in a diagnostic panel for inherited thrombophilia needs to be counterbalanced by a stringent selection of the laboratory tests. Screening should be limited to those traits that are more frequent or carry a higher thrombotic risk. A first-line diagnostic panel should include antithrombinheparin cofactor assay (functional amidolytic method), protein C assay (functional clotting or amidolytic method), and protein S assay (total and free fraction, measured by immunological methods). Analysis of DNA should include the search for factor V Leiden and the prothrombin G20210A. Genotyping for the C677T polymorphism in the methylenetetrahydrofolate reductase gene is quite meaningless, while homocysteine measurement is recommended. With the use of this panel, at least one third of the patients with venous thromboembolism can be diagnosed as carrying inherited thrombophilia; homocysteine measurement allows identification of at least a further 10% of patients with thrombophilia, achieving an overall diagnostic yield of more than 40%. PMID- 19644815 TI - [Role of hyperviscosity in cardiovascular and microvascular diseases]. AB - Blood viscosity plays a key role in regulating microvascular flow and alterations of hemorheological variables can lead to hyperviscosity, thus favoring the occurrence of occlusive thrombotic events. In the last few years an association between alterations in the hemorheologic profile and the severity of blood flow disturbances has been emphasized in several clinical and experimental conditions, possibly contributing to a better understanding of the pathophysiology of vascular disorders. The presence of alterations in hemorheological variables proved to be associated in several studies with an increased risk of cardiovascular disease and a higher mortality. The role of blood viscosity has also been analyzed in retrospective studies, which demonstrated that alterations in some hemorheological variables may increase the incidence of embolic events in patients with atrial fibrillation and may influence the responsiveness to antiplatelet drugs in patients with acute coronary syndromes. Recently, alterations of some hemorheological parameters were shown to be associated with complete occlusion of coronary arteries, favoring the occurrence of myocardial infarction with ST-segment elevation. In patients with this clinical condition, an increase in blood viscosity and some of its determinants was associated with increased infarct size and worse acute left ventricular dysfunction. Finally, the results of some observational clinical studies have shown that alterations of hemorheological variables may help to explain the pathophysiological mechanisms of some clinical disorders in which microvascular damage has been demonstrated, such as idiopathic sudden sensorineural hearing loss, retinal vein occlusion, and systemic sclerosis. PMID- 19644816 TI - [Factors determining cardiovascular disease progression after kidney transplant]. AB - Cardiovascular disease is the leading cause of mortality and morbidity in renal transplant recipients as well as the leading cause of death with a functioning graft. The high cardiovascular risk is attributable to the prolonged exposure to multiple traditional and nontraditional risk factors in the pretransplant and posttransplant period. Particular attention must be paid to cardiovascular screening of candidates for kidney transplantation. After a transplant, treatment and prevention strategies should be focused on the modifiable risk factors including smoking, dietary habits, physical activity, weight control, hypertension, and dyslipidemia. Further studies on these factors are needed to better define the pharmacological approaches (hypotensive or hypolipemic drugs) and therapeutic targets. In view of the role of immunosuppressive therapy in the onset or worsening of several risk factors, it is important to tailor the treatment approach and dosage to the cardiovascular risk profile of the individual patient. PMID- 19644817 TI - [Is intermittent peritoneal dialysis with icodextrin a valid option in the long term treatment of refractory congestive heart failure?]. AB - Refractory congestive heart failure (CHF) is affected by a very high morbidity and mortality. We report our experience in the long-term treatment of refractory CHF (NYHA class IV) by means of intermittent peritoneal dialysis (PD) with icodextrin (ICO) solutions in 4 male patients with a mean age of 71.5 + or - 5.6 (standard deviation) years and with a variable degree of chronic renal failure: 1 nocturnal exchange with ICO in 3 patients and 2 exchanges (ICO + isotonic dextrose solution) in 1 patient. The mean PD follow-up period was 24.3 + 15.6 months. After stabilization on PD, all patients had a statistically significant increase in daily diuresis (from 587.5 + or - 165.2 to 1700.0 + or - 141.4 mL, p < 0.003), a statistically significant decrease in body weight (11.3 + or - 3.4 kg, p < 0.007), and a statistically significant improvement in NYHA class (from 4.0 + or - 0.0 to 2.5 + or - 2.6, p < 0.01). Three patients had no hospitalizations due to cardiac illness in the PD follow-up period. No episodes of peritonitis occurred. Three patients died after 11, 13 and 43 months of PD treatment: 2 because of sudden death and 1 because of neoplastic cachexia. No death could be attributed to any complication related to PD treatment. Intermittent PD with ICO solutions can be proposed as a long-term treatment modality for refractory CHF. It allows an improvement in quality - if not quantity - of life. Randomized controlled trials are needed to confirm the evidence derived from case reports. PMID- 19644818 TI - [Long-term sustained low efficiency dialysis in eight patients with class IV NYHA heart failure resistant to high-dose diuretic treatment]. AB - Many of the patients hospitalized for congestive heart failure have concurrent renal failure. Most patients with heart failure present NYHA class III dysfunction, but when the heart failure progresses to NYHA class IV, replacement therapy may be necessary to remove the salt and water overload and mitigate the clinical, prevalently respiration-related symptoms. We report the clinical cases of 8 patients with NYHA class IV heart failure resistant to multidrug treatment and high-dose diuretics who were treated with sustained low efficiency dialysis (SLED). We evaluated the survival rates of the patients, their clinical improvement and cardiac performance. The obtained results suggested that treatment with SLED is the most indicated in NYHA class IV heart failure. PMID- 19644819 TI - [Understanding the different functions of vitamin D]. AB - Exposure of the skin to sunlight is now considered the most important source of vitamin D in Western countries. It is presumed to contribute approximately two thirds of the total requirement, leaving the remaining one third to the few foods naturally rich in this vitamin. In the skin, vitamin D is synthesized as a cholesterol chain which undergoes structural modifications following exposure to UVB rays. Once produced in the skin or absorbed in the gut as cholecalciferol, vitamin D enters the blood to be transported by a specific vitamin D binding protein, which is synthesized in the liver and has a powerful buffering capacity. The transport system carries the metabolites to the sites of further activation (25-hydroxylation in the liver and 1alpha-hydroxylation in the kidney), ultimately resulting in the production of calcitriol. This last compound, now regarded as a hormone, circulates freely in minimal amounts and, compared with the other metabolites, shows the highest affinity for the vitamin D receptor (VDR). The mechanism of VDR activation is rather complex, resulting in either stimulation or inhibition of protein synthesis. Importantly, besides its presence in parathyroid, bone, kidney and intestine, this receptor has been demonstrated in several tissues, where its stimulation results in a reduced proliferation rate and increased differentiation. Accordingly, vitamin D is now regarded as a complex hormonal system, involved not only in the regulation of divalent ions and bone, but also in the proliferation and differentiation of numerous cell types with potential involvement in several diseases like cancer, immune diseases, diabetes, hypertension and heart failure. PMID- 19644820 TI - [Management of hyperphosphatemia in patients with chronic kidney disease]. AB - Hyperphosphatemia is a common finding in patients with chronic kidney disease (CKD) undergoing hemodialysis or receiving conservative treatment. Recent papers have reported a link between hyperphosphatemia, soft tissue calcifications, and cardiovascular events responsible for high morbidity and mortality in these patients. Our group identified in salivary phosphate secretion a method to study the phosphate balance in CKD. Moreover, we found that CKD patients on hemodialysis usually drink beverages with a high phosphate content that may increase their serum phosphorus levels. Hyperphosphatemia is currently treated with diet, phosphate-binding drugs, and drugs acting on bone metabolism. Despite such treatment, only half of the patients with end-stage renal disease fall within the K/DOQI guidelines range for serum phosphorus levels. This paper reports positive results obtained with the use of the polymer chitosan as a phosphatebinding chewing gum in CKD patients undergoing periodic hemodialysis. PMID- 19644821 TI - [Endothelial dysfunction and diabetes: possible role in kidney damage]. AB - Endothelial damage, with loss of the vascular protective effects of nitric oxide (NO), is an important early step in the development of microvascular and macrovascular complications of diabetes. Endothelial dysfunction is closely associated with diabetic nephropathy in type 1 and 2 diabetes. In this review we will discuss the mechanisms by which hyperglycemia may cause kidney damage and endothelial dysfunction. Hyperglycemia causes microvascular dysfunction, which contributes to the development of end stage renal disease. Determining the role of endothelial abnormalities in the development of diabetic nephropathy is critical to understanding the etiology and pathogenesis of the microvascular complications of diabetes. Endothelial function can be assessed by invasive and noninvasive techniques both in the coronary and peripheral circulation. Endothelial dysfunction is considered a reversible phenomenon; pharmacological intervention with hypolipidemic agents, insulin sensitizers, ACE inhibitors and angiotensin II receptor blockers (ARB) as well as dietary and lifestyle modifications have been shown to reverse it. PMID- 19644822 TI - [Diabetes worsens the clinical manifestations and prognosis of concurrent cardiovascular and kidney disease]. AB - Numerous studies have shown a marked increase in the incidence of diabetes mellitus worldwide. Diabetes mellitus is currently considered equivalent to coronary artery disease in terms of prognostic risk stratification, and its high prevalence makes this clinical condition the first cause of end-stage renal disease requiring chronic hemodialysis or kidney transplant. Even if chronic kidney disease remains the ''Cinderella of the cardiovascular profile'', the presence of microalbuminuria is closely related to a high risk of development of coronary artery disease. The same risk factors that impair heart function are also harmful to the kidney, and the common pathophysiological features of the two systems are at the origin of a new subspecialty, cardionephrology. A crucial task of cardiologists and nephrologists is the early identification of high risk patients with concurrent cardiovascular and kidney disease. The utilization of simple screening methods such as assessment of microalbuminuria and glomerular filtration rate by family doctors may help in establishing prevention strategies directed towards cardiovascular risk and progression of kidney disease. In conclusion, early stratification of cardiovascular risk, coupled with primary prevention strategies aimed at the general population, is warranted to obtain a significant reduction of kidney and cardiovascular disease and of the need for chronic hemodialysis treatment. This strategy is safe and cost-effective in comparison with the costs of chronic dialysis of patients affected by chronic kidney disease. PMID- 19644823 TI - [Renal dysfunction as a marker of cardiovascular risk]. AB - The evaluation of urinary albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) is suggested for the assessment of cardiovascular risk. It is unclear whether UAE and eGFR provide complementary information. UAE, eGFR, cardiovascular risk factors, and the incidence of cardiovascular disease were analyzed in 45- to 64-year-old individuals involved in the Gubbio study. UAE in the highest decile was defined as high (microng/min: > or = 18.6 in men and > or = 15.7 in women), eGFR in the lowest decile as low (mL/min/1.73 m(2): <64.2 in men and <57.9 in women). Kidney dysfunction was more frequent when defined by both markers than when defined by one marker only (UAE or eGFR) because high UAE and low eGFR tended to cluster in different individuals. The hazard ratio (HR) for incident cardiovascular disease was 1.85 in individuals with high UAE only (95%CI 1.04-3.25), 1.84 in individuals with low eGFR only (95%CI 1.04-3.26), and 5.93 in individuals with high UAE and low eGFR (95%CI 2.58-13.61). Concomitant evaluation of UAE and eGFR should be considered to adequately assess kidney dysfunction and cardiovascular risk. PMID- 19644824 TI - [Effectiveness of daptomycin in the treatment of patients on hemodialysis affected by CVC infection]. AB - The use of tunneled central venous catheters (CVCs) has grown exponentially in recent years. It has increased particularly for elderly patients, patients with severe heart failure, and patients on chronic hemodialysis. In such patients there is a great risk of infection. This led us to search for a new-generation antibiotic able to resolve infection rapidly and effectively. In our experience, administration of daptomycin resulted in rapid resolution of infection without the necessity of CVC removal or its replacement by another system. PMID- 19644825 TI - [Presentation of the issue dedicated to living donor kidney transplant]. PMID- 19644826 TI - [Cyclosporine and proteinuria: the hidden connection]. PMID- 19644827 TI - [Systemic congestion in heart failure: an old and underestimated enemy of the kidney]. PMID- 19644828 TI - [Clinical testing and evidence-based medicine: when the absence of evidence doesn't mean evidence of absence]. PMID- 19644829 TI - [Hyperhomocysteinemia and treatment with folates: what's new?]. PMID- 19644830 TI - [Calcimimetic or calcitriol? A new class struggle]. PMID- 19644831 TI - [Prophylaxis or no prophylaxis after urinary infection in children?]. PMID- 19644832 TI - [The role of steroids in the treatment of IgA nephropathy]. AB - IgA nephropathy (IgAN) is characterized by a variable natural history. Welldefined risk factors from a clinical point of view are renal function impairment, associated hypertension, and proteinuria, while tubular-interstitial fibrosis constitutes a histological risk factor. These are serious clinical symptoms and histological signs, indicating long-lasting and severe damage. The available therapeutic tools belong essentially to two categories: 1) angiotensin inhibitors and 2) steroids, associated or not with immunosuppressive drugs. ACE inhibitors have limited toxicity and no significant side effects, and nephrologists are inclined to use them in case of moderate proteinuria. Steroids, in some cases associated with immunosuppressive agents, are obviously more demanding for the patient. Decisions must be made by the clinicians regarding the timing and the possible presence of contraindications. Furthermore, the treatment may not yield the expected results and a critical approach by the nephrologist is necessary. This controversy highlights the theoretical and practical issues related to steroid therapy in IgAN and here we discuss the different approaches to indications, doses, duration and route of administration. PMID- 19644833 TI - [Renal transplantation from living donor in Italy and Europe]. AB - Renal transplantation from a living donor shows a better graft and patient survival when compared with cadaver donor grafts. Moreover, since surgery can be planned in advance when a living donor is available, the time spent on dialysis while awaiting transplantation can be greatly reduced and dialysis treatment can be completely avoided in some cases. Only few risks for the donor have been reported as a consequence of nephrectomy, both in the short and long term. Nevertheless, despite these advantages, the number of living donor renal transplants carried out in Europe each year varies greatly from country to country and is particularly low in Spain and Italy. Several factors account for these differences, mainly the effectiveness of the organ procurement system, which could make people reluctant to living donation, and doctors' and patients' limited knowledge about living donor transplants. Nephrologists have the responsibility to identify patients eligible for transplant early in the course of the disease, and to inform them and their relatives about living donor transplantation, enabling them to make informed choices among the various treatment options in end-stage renal disease. PMID- 19644834 TI - [Clinical evaluation of living donor]. AB - When possible, living donor transplantation represents the best therapeutic strategy for patients suffering from chronic renal failure. Studying the donor allows a complete and thorough clinical, laboratory and instrumental assessment that guarantees good organ function whilst protecting the health of the donor. The main parameters considered within this framework are age, renal function, nephrological complications, comorbidities (diabetes, hypertension, obesity, etc.), malignancies, and infection. Moreover, particular attention is paid to the sociopsychological aspects of the donation, particularly related to the donor, the recipient, and the entire family situation. PMID- 19644835 TI - [Follow-up of the kidney donor]. AB - Kidney transplant from a living donor is known to be the best renal replacement therapy. While not as common as in northern Europe and the USA, living donor transplants are on the rise in Italy. Although there is a large body of evidence in the literature about the safety of the surgical procedure, the risk of long term complications for the donor has not been clearly defined because of the lack of studies with adequate follow-up and a sufficient number of subjects involved. The main questions concern the development of chronic kidney disease in the donor, expressed as a GFR decline or the presence of microalbuminuria. The physiopathological basis of GFR decline and proteinuria development may differ from the model of nephropathy in patients with two kidneys, and this could involve prognostic differences too, particularly with regard to the cardiovascular risk. Detailed and prolonged follow-up programs are needed to monitor and, if necessary, treat long-term complications in kidney donors. PMID- 19644836 TI - [Selection and follow-up of living donor kidney transplant recipients]. AB - The objectives of pre-transplant assessment are: a) to ensure that transplantation is technically possible; b) to ensure that the recipient's chances of survival are not compromised by transplantation; c) to ensure that graft survival is not limited by premature death; d) to ensure that pre-existing conditions are not exacerbated by transplantation; e) to identify measures to be taken to minimize perioperative and postoperative complications; f) to inform patients of the likely risks and benefits of transplantation. During the long term follow-up of living donor kidney transplant recipients, clinicians have to pay attention to the possible recurrence of the primary renal disease, to the identification and, if possible, prevention of noncompliance, and, finally, to immunological monitoring. PMID- 19644837 TI - [Preemptive living donor kidney transplant]. AB - We analyze and describe the epidemiology, characteristics and outcome of patients who underwent preemptive kidney transplants from living donors. The outcome of preemptive transplants from deceased donors and that of living donor transplants in patients who have started dialysis are often compared with the outcome of preemptive transplants from living donors. The causes of the better outcome of preemptive kidney transplants are analyzed here. We have examined data from large registries including the Collaborative Transplant Study, USRDS and ANZDATA registry as well as the results of single-center studies and data from developing countries. Overall, preemptive transplantation is more frequently performed with living donors. Recipients are often younger and have fewer vascular comorbidities. Also late referrals are less frequent with preemptive kidney transplantation. The data described by different studies may be discordant, but this is caused by different factors linked to the studies, as well as donor type, recipient age and residual renal function at transplant. Preemptive transplant usually has a better outcome because of the avoidance of dialysis-related comorbidities. Preemptive transplant is associated with less delayed graft function, fewer acute rejections, and better graft and patient survival rates. PMID- 19644838 TI - [Living donor kidney transplant: the crossover modality]. AB - Living donor kidney transplantation (LKD) has to be considered the best transplant choice for ESRD patients in terms of organ quality and survival. ABO incompatibility and positive cross-match frequently impede LKD. Recently, options based on stronger immunosuppression, apheresis techniques and Ig administration have been proposed to overcome the biological barriers. International guidelines on LKD advise paired exchange as the preferable transplant option to avoid the hazard of blood type or cross-match incompatibility. Since 1986 many paired exchange LKD programs have been started in the world including the USA, Japan, South Korea and, in Europe, the Netherlands, Switzerland, Romania, Germany and Italy. The first Italian paired exchange LKD was performed at the Pisa Transplant Center in November 2005 between three couples of spouses. One year later a National Program was established by the Italian National Transplant Center. The second experience in Italy was again in Pisa in December 2007 between two couples of spouses. International reports have shown that paired exchange LKD offers good clinical results comparable to direct LKD. In our experience paired exchange LKD is to be considered a quality choice for uremic patients, in that it allows them to obtain the benefit of an LKD that would otherwise not be practicable. PMID- 19644839 TI - [Desensitization protocols in immunized living donor kidney transplant recipients]. AB - It is well known that the presence of alloantibodies against human HLA class I (A, B, C) and class II (DR, DQ) antigens in transplant recipients waiting for a first or subsequent kidney transplant has a significant negative impact on graft outcome, with increased acute and chronic rejection rates. HLA antibodies, present in hyperimmunized patients (PRA > 80%) as a result of pregnancies, blood transfusions and previous failed grafts, once thought to be a formidable barrier to renal transplantation, can now be overcome with excellent results by means of desensitization protocols in kidney transplant recipients from living or cadaver donors. Such pretransplant desensitization protocols consist of high-dose intravenous immunoglobulin infusions (IVIg-HD), plasmapheresis associated with low-dose IVIg (IVIg-LD) and immunoabsorption by protein-A sepharose or Ig sepharose columns. All of the above treatments, associated in many cases with the anti-CD20 monoclonal antibody Rituximab, have been widely applied in living donor kidney transplant recipients showing donor-specific anti-HLA antibodies. Similar desensitization protocols have been used for non-A2 AB0-incompatible living donor kidney transplants. These techniques have allowed successful transplantation in this high-risk patient category by providing live donor kidneys that function promptly with minimal risk of early loss, and have consequently increased the organ donor pool. Long-term follow- up of these patients and the application on a wider scale of these techniques, which for many patients may represent the only realistic chance of a successful transplant, will provide the definitive answers about their real efficacy. PMID- 19644840 TI - [Living donor kidney transplant: the surgical procedure]. AB - The ideal nephrectomy technique for living donors should preserve donor safety and maximize graft quality for the recipient. The laparoscopic technique performs as well as the traditional open technique and has become the procedure of choice in up to 70% of the transplant centers in the US. Since November 2001, 70 living donor kidney transplants have been performed at the Transplant Center of Padua: 42 of the donors underwent laparoscopic left nephrectomy, 28 standard open nephrectomy. Donor and recipient results were analyzed retrospectively. After a mean follow-up of 38+/-26 months (laparoscopic group) and 40+/-27 months (open nephrectomy group) no deaths had occurred among the donors. Only one minor surgical complication was registered (hernia at the port site in a laparoscopic donor). Renal function was optimal in both groups of recipients, without significant differences in the incidence of delayed graft function and acute rejection. Minimally invasive approaches to donor nephrectomy are as safe and effective as the traditional open technique, minimizing postoperative pain and disability, and providing a better cosmetic result. PMID- 19644841 TI - [Report of the National Renal Ultrasound Study Group on the ultrasound activity of nephrology care units in Italy]. AB - The presence of operational and organizational differences in the use of ultrasonography in Italian nephrology units has prompted this survey on a nationwide scale. The survey was carried out by questionnaire and included questions about the activity and equipment of each nephrology unit, dedicated personnel and relevant training, and the fields of ultrasonography application. Seventy-five percent of the contacted care units replied to the questionnaire. Twenty-six percent of these performed their ultrasound examinations outside the care unit, sharing equipment with other units. The mean lifetime of ultrasound devices was longer (5.8 years) than allowed by the electro-medical equipment regulations. In spite of an increasing number of nephrologists with ultrasonographic expertise, in each care unit the percentage of physicians performing ultrasound examinations was very low. The number of operators who learned this methodology directly at surgeries using ultrasound devices was higher than that of operators who attended training courses and obtained the relevant certificates. In addition to the kidneys and urinary tract, other body districts investigated included abdominal organs, parathyroids, vascular access for hemodialysis treatment, and the bone-joint system. Moreover, ultrasonography was widely used for surgical procedures in nephrology. However, in spite of the widespread application of ultrasound imaging, the use of radiology was unexpectedly high (80%). Finally, the questionnaire results evidenced the particular care of nephrologists towards follow-up for situations of nephrological interest, such as acquired renal cysts, vascular access visualization, and monitoring of parathyroids. PMID- 19644842 TI - [Calciphylaxis: a multidisciplinary approach]. AB - Calcific uremic arteriolopathy (CUA) is a rare syndrome characterized by medial calcification of the small arteries and ischemia of the subcutaneous tissue that progresses to non-healing ulcers and gangrene. It is common in patients with end stage renal disease (ESRD), associated with high morbidity and mortality, and there is no standard treatment at the present time. We report a case of CUA developing in a 70-year-old woman on dialysis, with a normal plasma concentration of parathyroid hormone but a body mass index of 40 kg/m(2) and receiving oral anticoagulant therapy. She was successfully treated with a multidisciplinary approach focused on medical and surgical therapy. PMID- 19644843 TI - [Risk management in nephrology]. PMID- 19644844 TI - Childhood risk factors for offending before first psychiatric admission for people with schizophrenia: a case-control study of high security hospital admissions. AB - BACKGROUND: People with schizophrenia who offend do not constitute a homogenous population. Pre-illness characteristics may distinguish groups. AIMS: To test for differences in prevalence of childhood risk factors for offending between serious offenders with schizophrenia who had started offending before their first ever psychiatric admission (pre-admission offenders) and those who had started after it (post-admission offenders). Our hypothesis was that such adverse childhood factors would be more prevalent in the pre-admission offenders. METHOD: Retrospective interview and records case-control study of all first high security hospital admissions diagnosed with schizophrenia in England 1972-2000. Risk factors were identified by multivariate logistic regression. RESULTS: 853 patients were pre- and 741 post-admission offenders. Our hypothesis was confirmed in that factors associated with pre-admission offending were paternal criminal convictions, larger family size, and younger age at first use of illicit drugs, on first smoking cigarettes, and at maternal separation. There were differences too in pre-high security hospital treatment: pre-admission offenders had been younger at first court appearance and had more criminal justice system disposals, post-admission offenders were younger at first ever psychiatric hospital admission and more often hospitalized. CONCLUSIONS: While early offending among people with schizophrenia may delay treatment, making the distinction between pre admission and post-admission offending may be useful in understanding the aetiology of the offending, and establishment of such a history may help in targeting interventions supplementary to treatment specific for the psychosis. PMID- 19644845 TI - Estimation of intragastric drug solubility in the fed state: comparison of various media with data in aspirates. AB - The suitability of various media to forecast the solubility of ketoconazole and dipyridamole in the fed stomach at various periods after meal administration was evaluated. Solubilities were measured with the shake-flask method in gastric fluids aspirated 30, 60 and 120 min after administration of 500 ml Ensure plus to healthy fasted adults, in three sets of simulated gastric fluids based on milk, and in simple aqueous buffered media. Simple aqueous buffered media vastly underestimated the intragastric solubility of model compounds in the fed state. When using undigested milk-based media, the solubilities of model compounds in aspirates were also underestimated by a factor of 2.5-27. Solubility in milk digested with pepsin was useful for estimating the intragastric solubility of ketoconazole (within 20%) but overestimated the intragastric values of dipyridamole by a factor of 2-19. For both drugs, the solubility in milk digested with pepsin and lipase predicted the solubility in aspirates collected 60 min after meal administration, whereas at other times it overestimated the intragastric solubility (by a factor of <5). Both the use of biorelevant media and simulation of intragastric digestion are necessary for the prediction of drug solubility in the fed stomach. Milk digested with pepsin and lipase enabled the estimation of the intragastric solubility of dipyridamole and ketoconazole at 1 h after meal intake. Simulation of vesicle/micellar structures seems to be key for the prediction of intragastric solubility in the fed stomach. PMID- 19644846 TI - Prevalence of and predictive factors for sustained disease-modifying antirheumatic drug-free remission in rheumatoid arthritis: results from two large early arthritis cohorts. AB - OBJECTIVE: Remission has become an attainable goal of rheumatoid arthritis (RA) treatment, especially since the advent of biologic antirheumatic therapy. Because little is known about patients who achieve disease remission with conventional treatment, we used 2 large independent inception cohorts to study the prevalence of and predictive factors for disease-modifying antirheumatic drug (DMARD)-free sustained remission after treatment with conventional therapy. METHODS: Remission of disease was assessed in 454 patients from the Leiden Early Arthritis Clinic (EAC) and in 895 patients from the British Early Rheumatoid Arthritis Study (ERAS) who fulfilled the American College of Rheumatology 1987 revised criteria for the classification of RA and were treated with conventional therapy. Sustained DMARD-free remission was defined as fulfilling the following criteria for at least 1 year: 1) no current DMARD use, 2) no swollen joints, and 3) classification as DMARD-free remission by the patient's rheumatologist. Predictive factors were identified by Cox regression analysis. RESULTS: Sustained DMARD-free remission was achieved by 68 of 454 patients (15.0%) in the Leiden EAC and by 84 of 895 patients (9.4%) in the ERAS. Six factors were associated with sustained DMARD-free remission in both cohorts: acute onset, short symptom duration before inclusion, not smoking, little radiographic damage at baseline, absence of IgM rheumatoid factor (IgM-RF), and absence of HLA shared epitope alleles. In the ERAS, low disease activity at baseline was also predictive of remission. Multivariate analyses revealed symptom duration and the absence of autoantibodies (anti-cyclic citrullinated peptide 2 and IgM-RF) as independent predictors. CONCLUSION: Sustained DMARD-free remission in RA patients treated with conventional therapy is not uncommon. Symptom duration at presentation and the absence of autoantibodies are associated with sustained DMARD-free remission. PMID- 19644847 TI - Profiling microRNA expression in bovine articular cartilage and implications for mechanotransduction. AB - OBJECTIVE: Articular cartilage is an avascular tissue with precise polarity and organization comprising 3 distinct functional zones: the surface, middle, and deep zones. Each zone has a different gene expression pattern that plays a specific role in articular cartilage development and maintenance. MicroRNA (miRNA) are small noncoding gene products that play an important regulatory role in determining cell differentiation and function. The purpose of this study was to test our hypothesis that miRNA expression profiles in the different articular cartilage zones as well as between regions subjected to different levels of weight-bearing stresses are unique. METHODS: Using an miRNA microarray approach in conjunction with quantitative reverse transcription-polymerase chain reaction, we identified miRNA in bovine articular cartilage that were differentially expressed in the different functional zones and in the anterior weight-bearing and posterior non-weight-bearing regions of the medial femoral condyle (M1 and M4, respectively). RESULTS: We identified miRNA-221 and miR-222 as part of a subset of differentially expressed miRNA that were up-regulated in articular cartilage in the anterior, M1, greater weight-bearing location. Additionally, miR 126, miR-145, and miR-335 were down-regulated in monolayers of tissue-cultured chondrocytes as compared with levels determined directly from intact native cartilage. CONCLUSION: In conclusion, miR-222 expression patterns in articular cartilage are higher in the weight-bearing anterior medial condyle as compared with the posterior non-weight-bearing medial condyle. Thus, miR-222 might be a potential regulator of an articular cartilage mechanotransduction pathway. These data implicate miRNA in the maintenance of articular cartilage homeostasis and are therefore targets for articular cartilage tissue engineering and regenerative medicine. PMID- 19644848 TI - The role of neutrophil apoptosis in juvenile-onset systemic lupus erythematosus. AB - OBJECTIVE: Accumulation of apoptotic cells may lead to the development of systemic lupus erythematosus (SLE) through a breakdown in immune tolerance. Altered neutrophil apoptosis may contribute to nuclear autoantigen exposure, ultimately leading to autoantibody generation. This study aimed to determine whether neutrophil apoptosis is altered in patients with juvenile-onset SLE as compared with controls. METHODS: Apoptosis was measured in neutrophils from patients with juvenile-onset SLE (n=12), adult-onset SLE (n=6), and pediatric patients with inflammatory (n=12) and noninflammatory (n=12) conditions. Annexin V staining and flow cytometry were used to determine neutrophil apoptosis. Proapoptotic and antiapoptotic proteins were measured in sera and in neutrophil cell lysates. RESULTS: Neutrophil apoptosis was significantly increased in patients with juvenile-onset SLE as compared with the noninflammatory controls at time 0. Incubation of neutrophils with sera from patients with juvenile-onset SLE further increased neutrophil apoptosis as compared with incubation with sera from pediatric controls. Concentrations of TRAIL and FasL were significantly increased in sera from patients with juvenile-onset SLE, whereas interleukin-6, tumor necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor (GM CSF) were significantly decreased. Addition of GM-CSF to sera from patients with juvenile-onset SLE significantly decreased neutrophil apoptosis as compared with juvenile-onset SLE sera alone. The expression of proapoptotic proteins (caspase 3, Fas, and FADD) was elevated in juvenile-onset SLE neutrophils, whereas the expression of antiapoptotic proteins (cellular inhibitor of apoptosis 1 and 2 and X-linked inhibitor of apoptosis) was decreased. Neutrophil apoptosis correlated with biomarkers of disease activity (erythrocyte sedimentation rate and double stranded DNA concentration) and the British Isles Lupus Assessment Group disease activity score. CONCLUSION: Our data demonstrate an imbalance in proapoptotic and antiapoptotic factors in both neutrophils and sera from patients with juvenile onset SLE. This imbalance results in increased neutrophil apoptosis in these patients. Correlations with markers of disease activity indicate that altered neutrophil apoptosis in juvenile-onset SLE patients may play a pathogenic role in this condition. PMID- 19644849 TI - Golimumab, a human anti-tumor necrosis factor alpha monoclonal antibody, injected subcutaneously every four weeks in methotrexate-naive patients with active rheumatoid arthritis: twenty-four-week results of a phase III, multicenter, randomized, double-blind, placebo-controlled study of golimumab before methotrexate as first-line therapy for early-onset rheumatoid arthritis. AB - OBJECTIVE: To assess the safety and efficacy of golimumab in methotrexate (MTX) naive patients with active rheumatoid arthritis (RA). METHODS: MTX-naive patients with RA (n = 637) were randomized to receive placebo plus MTX (group 1), golimumab 100 mg plus placebo (group 2), golimumab 50 mg plus MTX (group 3), or golimumab 100 mg plus MTX (group 4). Subcutaneous injections of golimumab or placebo were administered every 4 weeks. The dosage of MTX/placebo capsules started at 10 mg/week and escalated to 20 mg/week. The primary end point, the proportion of patients meeting the American College of Rheumatology 50% improvement criteria (achieving an ACR50 response) at week 24, required significant differences between groups 3 and 4 combined (combined group) versus group 1 and significant differences in a pairwise comparison (group 3 or group 4 versus group 1). RESULTS: An intent-to-treat (ITT) analysis of the ACR50 response at week 24 did not show a significant difference between the combined group and group 1 (38.4% and 29.4%, respectively; P=0.053), while a post hoc modified ITT analysis (excluding 3 untreated patients) of the ACR50 response showed statistically significant differences between the combined group and group 1 (38.5% versus 29.4%; P=0.049) and between group 3 (40.5%; P=0.038) but not group 4 (36.5%; P=0.177) and group 1. Group 2 was noninferior to group 1 for the ACR50 response at week 24 (33.1%; 95% confidence interval lower bound -5.2%; predefined delta value for noninferiority -10%). The combination of golimumab plus MTX demonstrated a significantly better response compared with placebo plus MTX in most other efficacy parameters, including response/remission according to the Disease Activity Score in 28 joints. Serious adverse events occurred in 7%, 3%, 6%, and 6% of patients in groups 1, 2, 3, and 4, respectively. CONCLUSION: Although the primary end point was not met, the modified ITT analysis of the primary end point and other prespecified efficacy measures demonstrated that the efficacy of golimumab plus MTX is better than, and the efficacy of golimumab alone is similar to, the efficacy of MTX alone in reducing RA signs and symptoms in MTX-naive patients, with no unexpected safety concerns. PMID- 19644850 TI - Regulation of plasminogen activator inhibitor 1 expression in human osteoarthritic chondrocytes by fluid shear stress: role of protein kinase Calpha. AB - OBJECTIVE: To test a fluid flow system for the investigation of the influence of shear stress on expression of plasminogen activator inhibitor 1 (PAI-1) in human osteoarthritic (OA) articular chondrocytes (from lesional and nonlesional sites) and human SW-1353 chondrocytes. METHODS: Human SW-1353 chondrocytes and OA and normal human articular chondrocytes were cultured on type II collagen-coated glass plates under static conditions or placed in a flow chamber to form a closed fluid-circulation system for exposure to different levels of shear stress (2-20 dyn/cm2). Real-time polymerase chain reaction was used to analyze PAI-1 gene expression, and protein kinase C (PKC) inhibitors and small interfering RNA were used to investigate the mechanism of shear stress-induced signal transduction in SW-1353 and OA (lesional and nonlesional) articular chondrocytes. RESULTS: There was a significant reduction in PAI-1 expression in OA chondrocytes obtained from lesional sites compared with those obtained from nonlesional sites. In SW-1353 chondrocytes subjected to 2 hours of shear flow, moderate shear stresses (5 and 10 dyn/cm2) generated significant PAI-1 expression, which was regulated through PKCalpha phosphorylation and Sp-1 activation. These levels of shear stress also increased PAI-1 expression in articular chondrocytes from nonlesional sites and from normal healthy cartilage through the activation of PKCalpha and Sp-1 signal transduction, but no effect of these levels of fluid shear stress was observed on OA chondrocytes from lesional sites. CONCLUSION: OA chondrocytes from lesional sites and those from nonlesional sites of human cartilage have differential responses to shear stress with regard to PAI-1 gene expression, and therefore diverse functional consequences can be observed. PMID- 19644851 TI - Course of the modified Rodnan skin thickness score in systemic sclerosis clinical trials: analysis of three large multicenter, double-blind, randomized controlled trials. AB - OBJECTIVE: To assess the course of the modified Rodnan skin thickness score (MRSS) in 3 large, multicenter, double-blind, randomized controlled trials (RCTs) of patients with diffuse cutaneous systemic sclerosis (dcSSc) with different baseline disease durations, as defined from the date of onset of the first dcSSc symptom (excluding Raynaud's phenomenon) or from the date of onset of the first dcSSc-related symptom (including Raynaud's phenomenon). METHODS: Data from 3 RCTs examining high-dose versus low-dose D-penicillamine (D-Pen Trial), recombinant human relaxin versus placebo (Relaxin Trial), and oral bovine type I collagen versus placebo (Collagen Trial) treatment in patients with dcSSc were pooled and analyzed. Patients were divided into 5 groups according to their disease duration at baseline. The linear mixed model for correlated data was used to model the 2 predictors of MRSS: time in study (expressed in months after baseline) and baseline disease duration (expressed in months, calculated from the date of onset of the first symptom characteristic of dcSSc with and without Raynaud's phenomenon). RESULTS: At study entry, the mean MRSS value was 21.0 in the D-Pen Trial cohort, 27.3 in the Relaxin Trial cohort, and 26.1 in the Collagen Trial cohort. Time in study was a significant predictor of improvement in MRSS regardless of the disease duration at baseline (P<0.0001). Patients with a disease duration of >or=24 months showed a greater rate of decline as compared with patients with a disease duration of <24 months (P<0.05). Similar results were obtained when disease duration was reclassified by including the time of the first Raynaud's phenomenon symptom in the definition. CONCLUSION: Our study confirms recent findings that in patients entered into these 3 RCTs, skin thickening did not follow the same trend in natural history as that seen in the dcSSc populations entered into early, open longitudinal studies previously reported. These findings have important implications for study design, in which "prevention of worsening" is the main objective. PMID- 19644852 TI - Amelioration of alphavirus-induced arthritis and myositis in a mouse model by treatment with bindarit, an inhibitor of monocyte chemotactic proteins. AB - OBJECTIVE: Alphaviruses such as chikungunya virus, Sindbis virus, o'nyong-nyong virus, Mayaro virus, and Ross River virus (RRV), are commonly associated with arthralgias and overt arthritides worldwide. Understanding the processes by which arthritogenic viruses cause disease is a prerequisite in the quest for better treatments. In this regard, we have recently established that monocyte/macrophages are mediators of alphavirus-induced arthritis in mice. We hypothesized that chemokines associated with monocyte/macrophage recruitment may play an important role in disease. The aim of the present investigations was to determine whether bindarit, an inhibitor of monocyte chemotactic protein (MCP) synthesis, could ameliorate alphavirus-induced rheumatic disease in mice. METHODS: Using our recently developed mouse model of RRV-induced arthritis, which has many characteristics of RRV disease (RRVD) in humans, the effects of bindarit treatment on RRVD in mice were determined via histologic analyses, immunohistochemistry, flow cytometry, real-time polymerase chain reaction analysis, enzyme-linked immunosorbent assay, and electrophoretic mobility shift assay. RESULTS: Bindarit-treated RRV-infected mice developed mild disease and had substantially reduced tissue destruction and inflammatory cell recruitment as compared with untreated RRV-infected mice. The virus load in the tissues was not affected by bindarit treatment. Bindarit exhibited its activity by down regulating MCPs, which in turn led to inhibition of cell infiltration and lower production of NF-kappaB and tumor necrosis factor alpha, which are involved in mediating tissue damage. CONCLUSION: Our data support the use of inhibitors of MCP production in the treatment of arthritogenic alphavirus syndromes and suggest that bindarit may be useful in treating RRVD and other alphavirus-induced arthritides in humans. PMID- 19644853 TI - Determinants of red blood cell methotrexate polyglutamate concentrations in rheumatoid arthritis patients receiving long-term methotrexate treatment. AB - OBJECTIVE: Methotrexate (MTX) is the most commonly used disease-modifying antirheumatic drug (DMARD) in the management of rheumatoid arthritis (RA). MTX is transported into cells, where additional glutamate moieties are added and it is retained as MTX polyglutamates (MTXGlu [referred to as a group as MTXGlun]). There is large interpatient variability in MTXGlun concentrations. This study was undertaken to determine nongenetic factors that influence red blood cell (RBC) MTXGlun concentrations in patients receiving long-term stable low-dose oral MTX. METHODS: One hundred ninety-two patients receiving long-term oral MTX for the treatment of RA were recruited. Trough MTXGlun concentrations were measured by high-performance liquid chromatography. Univariate analysis was performed to determine variables influencing MTXGlun concentrations. Backward stepwise multivariate regression analysis was done to determine variables that affect individual MTXGlun concentrations; variables with P values of <0.1 in the univariate analysis for any MTXGlun were included. RESULTS: Univariate analysis revealed that increased age, lower estimated glomerular filtration rate (GFR), higher MTX dosage, longer duration of MTX treatment, and use of prednisone were associated with significantly higher MTXGlun concentrations. Smokers had significantly lower concentrations of MTXGlu3, MTXGlu3-5, and MTXGlu1-5. Sex, rheumatoid factor and anti-cyclic citrullinated peptide status, RBC folate level, and body mass index had no significant effect on MTXGlun levels. Concomitant use of other DMARDs was associated with lower MTXGlu2 levels, and treatment with nonsteroidal antiinflammatory drugs was associated with lower MTXGlu3 and MTXGlu1 5 concentrations. Multivariate regression analysis revealed that age, MTX dosage, and estimated GFR were the major determinants of MTXGlun concentrations. CONCLUSION: Large interpatient variability in MTXGlun concentrations can be explained, at least in part, by a combination of factors, particularly age, MTX dosage, and renal function. There are complex interactions between smoking, RBC folate levels, and concentrations of MTXGlun. PMID- 19644855 TI - Hypoxia and glucocorticoid signaling converge to regulate macrophage migration inhibitory factor gene expression. AB - OBJECTIVE: Macrophage migration inhibitory factor (MIF) is a proinflammatory mediator involved in the pathogenesis of rheumatoid arthritis. This study was undertaken to identify the MIF promoter elements responsible for regulating gene expression. METHODS: Luciferase reporter gene assays were used to identify the MIF promoter sequence responsible for basal activity. Bioinformatic analysis was used to predict transcription factor binding sites, and electrophoretic mobility shift assay (EMSA) was used to demonstrate transcription factor binding. Chromatin immunoprecipitation (ChIP) was used to demonstrate transcription factor loading on the MIF promoter. RESULTS: We identified the minimal promoter sequence required for basal MIF promoter activity that was also capable of conferring glucocorticoid-dependent inhibition in a T lymphocyte model cell line. Deletion studies and EMSA revealed 2 elements in the MIF promoter that were responsible for basal promoter activity. The 5' element binds CREB/activating transcription factor 1, and the 3' element is a functional hypoxia-responsive element binding hypoxia-inducible factor 1alpha. Further studies demonstrated that the cis elements are both required for glucocorticoid-dependent inhibition. ChIP demonstrated glucocorticoid-dependent recruitment of glucocorticoid receptor alpha to the MIF promoter in lymphocytes within 1 hour of treatment and a concomitant decrease in acetylated histone H3. CONCLUSION: Our findings indicate that hypoxia and glucocorticoid signaling converge on a single element regulating MIF; this regulatory unit is a potential interacting node for microenvironment sensing of oxygen tension and glucocorticoid action in foci of inflammation. PMID- 19644856 TI - Vascular cell adhesion molecule 1 as a predictor of severe osteoarthritis of the hip and knee joints. AB - OBJECTIVE: Osteoarthritis (OA) is a leading cause of pain and physical disability in middle-aged and older individuals. We undertook this study to determine predictors of the development of severe OA, apart from age and overweight. METHODS: Joint replacement surgery due to severe hip or knee OA was recorded over a 15-year period in the prospective Bruneck cohort study. Demographic characteristics and lifestyle and biochemical variables, including the level of soluble vascular cell adhesion molecule 1 (VCAM-1), were assessed at the 1990 baseline visit and tested as predictors of joint replacement surgery. RESULTS: Between 1990 and 2005, hip or knee joint replacement due to OA was performed in 60 subjects. VCAM-1 level emerged as a highly significant predictor of the risk of joint replacement surgery. Intervention rates were 1.9, 4.2, and 10.1 per 1,000 person-years in the first, second, and third tertiles, of the VCAM-1 level, respectively. In multivariable logistic regression analysis, the adjusted relative risk of joint replacement surgery in the highest versus the lowest tertile group of VCAM-1 level was 3.9 (95% confidence interval 1.7-8.7) (P<0.001). Findings were robust in various sensitivity analyses and were consistent in subgroups. Addition of the VCAM-1 level to a risk model already including age, sex, and body mass index resulted in significant gains in model discrimination (C statistic) and calibration and in more accurate risk classification of individual participants. CONCLUSION: The level of soluble VCAM 1 emerged as a strong and independent predictor of the risk of hip and knee joint replacement due to severe OA. If our findings can be reproduced in other epidemiologic cohorts, they will assist in routine risk classification and will contribute to a better understanding of the etiology of OA. PMID- 19644854 TI - A polymorphism within IL21R confers risk for systemic lupus erythematosus. AB - OBJECTIVE: Interleukin-21 (IL-21) is a member of the type I cytokine superfamily that has a variety of effects on the immune system, including B cell activation, plasma cell differentiation, and immunoglobulin production. The expression of IL 21 receptor (IL-21R) is reduced in the B cells of patients with systemic lupus erythematosus (SLE), while serum IL-21 levels are increased both in lupus patients and in some murine lupus models. We recently reported that polymorphisms within the IL21 gene are associated with increased susceptibility to SLE. The aim of this study was to examine the genetic association between single-nucleotide polymorphisms (SNPs) within IL21R and SLE. METHODS: We genotyped 17 SNPs in the IL21R gene in 2 large cohorts of lupus patients (a European-derived cohort and a Hispanic cohort) and in ethnically matched healthy controls. RESULTS: We identified and confirmed the association between rs3093301 within the IL21R gene and SLE in the 2 cohorts (meta-analysis odds ratio 1.16 [95% confidence interval 1.08-1.25], P=1.0x10(-4)). CONCLUSION: Our findings indicate that IL21R is a novel susceptibility gene for SLE. PMID- 19644859 TI - Association of a single-nucleotide polymorphism in CD40 with the rate of joint destruction in rheumatoid arthritis. AB - OBJECTIVE: The severity of joint destruction in rheumatoid arthritis (RA) is highly variable from patient to patient and is influenced by genetic factors. Genome-wide association studies have enormously boosted the field of the genetics of RA susceptibility, but risk loci for RA severity remain poorly defined. A recent meta-analysis of genome-wide association studies identified 6 genetic regions for susceptibility to autoantibody-positive RA: CD40, KIF5A/PIP4K2C, CDK6, CCL21, PRKCQ, and MMEL1/TNFRSF14. The purpose of this study was to investigate whether these newly described genetic regions are associated with the rate of joint destruction. METHODS: RA patients enrolled in the Leiden Early Arthritis Clinic were studied (n=563). Yearly radiographs were scored using the Sharp/van der Heijde method (median followup 5 years; maximum followup 9 years). The rate of joint destruction between genotype groups was compared using a linear mixed model, correcting for age, sex, and treatment strategies. A total of 393 anti-citrullinated protein antibody (ACPA)-positive RA patients from the North American Rheumatoid Arthritis Consortium (NARAC) who had radiographic data available were used for the replication study. RESULTS: The TT and CC/CG genotypes of 2 single-nucleotide polymorphisms, rs4810485 (CD40) and rs42041 (CDK6), respectively, were associated with a higher rate of joint destruction in ACPA-positive RA patients (P=0.003 and P=0.012, respectively), with rs4810485 being significant after Bonferroni correction for multiple testing. The association of the CD40 minor allele with the rate of radiographic progression was replicated in the NARAC cohort (P=0.021). CONCLUSION: A polymorphism in the CD40 locus is associated with the rate of joint destruction in patients with ACPA positive RA. Our findings provide one of the first non-HLA-related genetic severity factors that has been replicated. PMID- 19644860 TI - Delayed acquisition of somatic hypermutations in repopulated IGD+CD27+ memory B cell receptors after rituximab treatment. AB - OBJECTIVE: Transient B cell depletion by rituximab has been used with clinical efficacy in the treatment of patients with rheumatoid arthritis (RA). Previous studies of B cell repopulation have shown long-term numerical reduction in memory B cells. Non-class-switched IgD+CD27+ memory B cells, in particular, repopulate slowly. This study was undertaken to determine whether mutational acquisition in individual B cell receptors in repopulating class-switched and non-class-switched memory B cells is affected by rituximab. METHODS: Cells obtained from 16 RA patients, 4 healthy donors, and 3 patients who underwent allogeneic stem cell transplantation (ASCT) were analyzed using single B cell sorting followed by nested polymerase chain reaction and Ig V(H)3 sequencing. RESULTS: There was a delayed acquisition of mutations in Ig receptors of IgD+ memory B cells over a period of 6 years after a single course of rituximab. One year after rituximab treatment, 84% of single repopulating IgD+CD27+ B cells were unmutated, and no highly mutated Ig receptors were found (compared with 52% before therapy). Over time, increasing numbers of mutations were detected. Even 6 years after rituximab treatment, however, mutations in IgD+ memory B cells were still significantly reduced. In contrast, class-switched memory B cells repopulated with quantitatively normal mutations. In comparison, in patients undergoing ASCT, IgD+ memory cells repopulated earlier with higher mutations in Ig receptors. CONCLUSION: Our data suggest that IgD+ memory B cells are particularly susceptible to the effects of rituximab, with delayed acquisition of mutations in their Ig receptors still evident 6 years after a single course of rituximab. Our findings indicate that these cells have different requirements for mutational acquisition compared with class-switched memory B cells. PMID- 19644861 TI - Clinical images: Otalgia, an unusual complication of Sjogren's syndrome. PMID- 19644862 TI - Pathogenetic mechanisms, new drugs, and old problems in idiopathic recurrent pericarditis: comment on the article by Picco et al. PMID- 19644864 TI - Apoptotic cell blebs: repositories of autoantigens and contributors to immune context. PMID- 19644865 TI - Changes in surface markers of human mesenchymal stem cells during the chondrogenic differentiation and dedifferentiation processes in vitro. AB - OBJECTIVE: To investigate surface markers showing specific changes during the chondrogenic differentiation and dedifferentiation of human mesenchymal stem cells (MSCs). METHODS: Human MSCs from adult bone marrow were subjected to chondrogenic differentiation in 3-dimensional (3-D) alginate culture with or without transforming growth factor beta3 (TGFbeta3) for 2 weeks, followed by dedifferentiation in monolayer for 1 week. Surface antigens were selected from those previously reported to show changes in expression during dedifferentiation of human articular chondrocytes (HACs). RESULTS: Flow cytometry was used to identify 3 groups of surface antigens with differential expression patterns that were quite different from those previously reported on HACs. Two groups of antigens were expressed at high levels on human MSCs. The expression of the first group of antigens (CD44, CD58, CD81, CD90, CD105, and CD166) was decreased reversibly by the 3-D alginate culture and irreversibly in the presence of TGFbeta3, except for CD81, which showed reversible changes regardless of TGFbeta3. The expression of the second group of antigens (CD49c, CD49e, and CD151) was decreased during chondrogenic differentiation only in the presence of TGFbeta3. During all experimental stages, the expression of the third group of antigens (CD14, CD26, CD49f, CD54, CD106, CD119, and CD140a) was maintained at low levels (expressed on <30% of cells), although with some fluctuations. CONCLUSION: We speculate that the second group of surface antigens could be negative markers for chondrogenic differentiation of human MSCs. PMID- 19644870 TI - The effects of phosphatidylserine-dependent antiprothrombin antibody on thrombin generation. AB - OBJECTIVE: Antibodies to prothrombin (APTs) and to beta2-glycoprotein I are the major autoantibodies responsible for lupus anticoagulant (LAC) activity. APTs comprise antibodies against prothrombin alone as well as antibodies against phosphatidylserine/prothrombin complex (anti-PS/PT), the latter being highly associated with the antiphospholipid syndrome (APS). The effect of anti-PS/PT on thrombin generation has not been elucidated, and the paradoxical effect of LAC (an anticoagulant in vitro, but a procoagulant in vivo) remains an enigma. The purpose of this study was to investigate the effects of anti-PS/PT on thrombin generation and to examine the LAC paradox. METHODS: We evaluated 36 anti-PS/PT positive APS patients and 127 healthy subjects. Markers of in vivo thrombin/fibrin generation, including prothrombin fragment F1+2, thrombin antithrombin III complex, soluble fibrin monomer, D-dimer, and fibrin degradation products, were measured. Mouse monoclonal anti-PS/PT antibody 231D was established, and its effects on in vitro thrombin generation were investigated by chromogenic assay. RESULTS: Significantly elevated levels of markers of thrombin/fibrin generation were observed in anti-PS/PT-positive patients, regardless of the presence or absence of anticardiolipin antibodies, as compared with healthy subjects. In the presence of low concentrations of human activated factor V (FVa), monoclonal antibody 231D increased thrombin generation in a dose dependent manner. In contrast, when high concentrations of FVa were added, monoclonal antibody 231D decreased thrombin generation. Under a constant concentration of FVa, a high concentration of human FXa enhanced the effect of 231D. CONCLUSION: The presence of anti-PS/PT greatly correlated with increased thrombin generation in APS patients. The in vitro effects of monoclonal antibody 231D on thrombin generation are "biaxial" according to the FVa/FXa balance. These data may serve as a clue to understanding the LAC paradox and the thrombogenic properties of anti-PS/PT. PMID- 19644866 TI - Fcgamma receptor-dependent expansion of a hyperactive monocyte subset in lupus prone mice. AB - OBJECTIVE: Lupus-prone BXSB mice develop monocytosis characterized by selective accumulation of the Gr-1- monocyte subset. The aim of this study was to explore the possible role of activating IgG Fc receptors (FcgammaR) in the development of monocytosis and to characterize the functional phenotype of the Gr-1- subset that accumulates in lupus-prone mice bearing the NZB-type defective Fcgr2b allele for the inhibitory FcgammaRIIB. METHODS: The development of monocytosis was analyzed in BXSB and anti-IgG2a rheumatoid factor-transgenic C57BL/6 mice deficient in activating FcgammaR. Moreover, we assessed the expression levels of activating FcgammaR and inhibitory FcgammaRIIB on Gr-1+ and Gr-1- monocyte subsets in C57BL/6 mice bearing the C57BL/6-type or the NZB-type Fcgr2b allele. RESULTS: We observed monocytosis with expansion of the Gr-1- subset in anti-IgG2a-transgenic C57BL/6 mice expressing IgG2a, but not in those lacking IgG2a. Moreover, monocytosis barely developed in BXSB and anti-IgG2a-transgenic C57BL/6 mice deficient in activating FcgammaR. The Gr-1- subset that accumulated in lupus prone mice displayed a unique hyperactive phenotype. It expressed very low levels of inhibitory FcgammaRIIB, due to the presence of the NZB-type Fcgr2b allele, but high levels of activating FcgammaRIV. This was in contrast to high levels of FcgammaRIIB expression and no FcgammaRIV expression on the Gr-1+ subset. CONCLUSION: Our results demonstrated a critical role of activating FcgammaR in the development of monocytosis and in the expansion of a Gr-1 FcgammaRIIB(low)FcgammaRIV+ hyperactive monocyte subset in lupus-prone mice. Our findings further highlight the importance of the NZB-type Fcgr2b susceptibility allele in murine lupus, the presence of which induces increased production of hyperactive monocytes as well as dysregulated activation of autoreactive B cells. PMID- 19644871 TI - Anti-adalimumab antibodies in rheumatoid arthritis patients are associated with interleukin-10 gene polymorphisms. PMID- 19644872 TI - Value of anti-modified citrullinated vimentin and third-generation anti-cyclic citrullinated peptide compared with second-generation anti-cyclic citrullinated peptide and rheumatoid factor in predicting disease outcome in undifferentiated arthritis and rheumatoid arthritis. AB - OBJECTIVE: Autoantibodies such as rheumatoid factor (RF) and anti-citrullinated protein autoantibodies (ACPAs) determined by testing with second-generation anti cyclic citrullinated peptide (anti-CCP-2) are frequently measured in clinical practice because of their association with disease outcome in undifferentiated arthritis (UA) and rheumatoid arthritis (RA). Recently, 2 new ACPA tests were developed: third-generation anti-CCP (anti-CCP-3) and anti-modified citrullinated vimentin (anti-MCV) autoantibody tests. To facilitate the decision on which autoantibody to test in daily practice, this study evaluated the capability of these autoantibodies and combinations of them to predict 3 outcome measures: progression from UA to RA, the rate of joint destruction in RA, and the chance of achieving sustained disease-modifying antirheumatic drug (DMARD)-free remission in RA. METHODS: Patients with UA (n=625) were studied for whether UA progressed to RA after 1 year. Patients with RA (n=687) were studied for whether sustained DMARD-free remission was achieved and for the rate of joint destruction during a median followup of 5 years. Positive predictive values (PPVs) for RA development and for associations with the disease course in RA were compared between single tests (anti-CCP-2, anti-CCP-3, anti-MCV, and RF) and between combinations of these tests. RESULTS: Among the single tests performed in patients with UA, anti CCP-2 tended to have the highest PPV for RA development (67.1%), but the 95% confidence intervals of the other tests overlapped. Among the single tests in patients with RA, all 4 tests showed comparable associations with the rate of joint destruction and with the achievement of remission. In both ACPA-positive and ACPA-negative RA, the presence of RF was not associated with more joint destruction. For all outcome measures, performing combinations of 2 or 3 autoantibody tests did not increase the predictive accuracy compared with performing a single test. CONCLUSION: For clinical practice, a single autoantibody test is sufficient for risk estimation in UA and RA. PMID- 19644873 TI - Down-regulation of cathepsin K in synovium leads to progression of osteoarthritis in rabbits. AB - OBJECTIVE: The hypothesis of this study was that synovial factors playing a pivotal role in the pathogenesis of osteoarthritis (OA) and thus gene expression in the synovium would be altered at the initial stage of OA. The aims of this study were to identify the candidate genes in synovium related to OA initiation, to evaluate cartilage degeneration after knockdown of the gene using small interfering RNA (siRNA) gene silencing in the knee joints at the initial stage of OA, and to determine the potential role of the knocked-down gene in OA initiation. METHODS: Genes overexpressed in synovium at the initial stage of disease in a rabbit model of anterior cruciate ligament transection (ACLT) induced OA were identified using the suppression subtractive hybridization technique and differential screening. Candidate gene expression in the synovium of the knees of rabbits with OA was manipulated with electroporation-assisted siRNA transduction 4 times before and after operation. Four weeks after surgery, histologic analysis was performed. RESULTS: Cathepsin K gene and protein expression was significantly up-regulated in synovium at the initial stage of OA in rabbits. Down-regulation of cathepsin K in synovium at the initial stage of OA significantly accelerated cartilage degeneration. CONCLUSION: These results indicate that cathepsin K plays a protective role in cartilage degeneration at the initial stage of OA. We believe that the current results obtained from models of the early phase of OA will provide useful information for developing a novel strategy to prevent disease progression. PMID- 19644874 TI - Mouse dendritic cells matured by ingestion of apoptotic blebs induce T cells to produce interleukin-17. AB - OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the formation of antinuclear autoantibodies. Increased apoptosis and reduced clearance of apoptotic material have been assigned a role in the pathogenesis of SLE, but the underlying mechanisms remain elusive. During apoptosis apoptotic blebs are formed in which autoantigens are clustered. The cellular remnants after blebbing are referred to as apoptotic cell bodies. We undertook this study to compare the effects of apoptotic blebs and apoptotic cell bodies on maturation of dendritic cells (DCs) and their T cell stimulatory capacity in a murine setting. METHODS: The uptake by DCs of apoptotic blebs and apoptotic cell bodies was analyzed by flow cytometry and confocal microscopy. DC maturation and DC-induced T cell activation were determined by measuring expression of costimulatory molecules using flow cytometry and by measuring production of cytokines using enzyme-linked immunosorbent assay. RESULTS: DCs internalized apoptotic blebs more efficiently than apoptotic cell bodies. Incubation of DCs with apoptotic blebs resulted in increased CD40 and CD86 expression and increased interleukin-6 (IL-6) and tumor necrosis factor alpha production, while apoptotic cell bodies had no stimulatory effects. Using chloroquine, apoptotic bleb-induced DC maturation was shown to be independent of Toll-like receptors 3, 7, and 9. Interestingly, in cocultures with allogeneic T cells, bleb-matured DCs induced production of IL-2, interferon-gamma, and, in particular, IL-17, suggesting a Th1/Th17 response. CONCLUSION: Apoptotic blebs, in contrast to apoptotic cell bodies, induce DC maturation, thereby providing DCs with increased Th17 cell stimulatory capacity. These data imply that apoptotic bleb-induced DC maturation represents an important driving force in the autoimmune response in SLE. PMID- 19644875 TI - Interleukin-1beta suppression in Blau syndrome: comment on the article by Martin et al. PMID- 19644876 TI - Association of STAT4 and BLK, but not BANK1 or IRF5, with primary antiphospholipid syndrome. AB - OBJECTIVE: Primary antiphospholipid syndrome (APS) is formally classified by the presence of antiphospholipid antibodies, recurrent thrombosis, and/or pregnancy morbidity in the absence of any underlying full-blown systemic autoimmune disease. However, systemic manifestations in patients with primary APS have been recently reported, as has the presence of serologic markers in common with systemic lupus erythematosus (SLE). In spite of similarities between the 2 diseases, only a minority of cases of primary APS evolve into full-blown SLE, even after a long followup period. The aim of this study was to investigate whether the analysis of SLE susceptibility genes may provide at least a partial explanation for such a discrepancy. METHODS: One hundred thirty-three patients with primary APS classified according to the Sydney criteria and 468 healthy control subjects from the same geographic area were recruited. We genotyped 3 single-nucleotide polymorphisms (SNPs) in IRF5 (rs2004640, rs2070197, and rs10954213), 4 SNPs in STAT4 (rs1467199, rs3821236, rs3024866, and rs7574865), 2 SNPs in BANK1 (rs10516487 and rs3733197), and 1 SNP in BLK (rs2736340). RESULTS: STAT4 and BLK displayed a strong genetic association with primary APS (for rs7574865, odds ratio [OR] 2.19, P=5.17x10(-7); for rs2736340, OR 2.06, P=1.78x10(-6)), while a weak association with IRF5 and no association with BANK1 were observed. CONCLUSION: The presence of a strong genetic association with only a few SLE susceptibility genes and the absence of a more complex gene association may contribute to the lack of cases of full-blown SLE developing in patients with primary APS, in spite of the clinical and serologic similarities between SLE and primary APS. PMID- 19644877 TI - Ultraviolet radiation intensity predicts the relative distribution of dermatomyositis and anti-Mi-2 autoantibodies in women. AB - OBJECTIVE: Because studies suggest that ultraviolet (UV) radiation modulates the myositis phenotype and Mi-2 autoantigen expression, we conducted a retrospective investigation to determine whether UV radiation may influence the relative prevalence of dermatomyositis and anti-Mi-2 autoantibodies in the US. METHODS: We assessed the relationship between surface UV radiation intensity in the state of residence at the time of onset with the relative prevalence of dermatomyositis and myositis autoantibodies in 380 patients with myositis from referral centers in the US. Myositis autoantibodies were detected by validated immunoprecipitation assays. Surface UV radiation intensity was estimated from UV Index data collected by the US National Weather Service. RESULTS: UV radiation intensity was associated with the relative proportion of patients with dermatomyositis (odds ratio [OR] 2.3, 95% confidence interval [95% CI] 0.9-5.8) and with the proportion of patients expressing anti-Mi-2 autoantibodies (OR 6.0, 95% CI 1.1-34.1). Modeling of these data showed that these associations were confined to women (OR 3.8, 95% CI 1.3-11.0 and OR 17.3, 95% CI 1.8-162.4, respectively) and suggests that sex influences the effects of UV radiation on autoimmune disorders. Significant associations were not observed in men, nor were UV radiation levels related to the presence of antisynthetase or anti-signal recognition particle autoantibodies. CONCLUSION: This first study of the distribution of myositis phenotypes and UV radiation exposure in the US showed that UV radiation may modulate the clinical and immunologic expression of autoimmune disease in women. Further investigation of the mechanisms by which these effects are produced may provide insights into pathogenesis and suggest therapeutic or preventative strategies. PMID- 19644879 TI - Efficacy and tolerability of rituximab with or without PEGylated interferon alfa 2b plus ribavirin in severe hepatitis C virus-related vasculitis: a long-term followup study of thirty-two patients. AB - OBJECTIVE: To report on the long-term followup of a cohort of patients with hepatitis C virus (HCV)-related vasculitis treated with rituximab with or without PEGylated interferon alfa-2b (PEG-IFN alfa-2b) plus ribavirin. METHODS: The study group comprised 32 HCV RNA-positive patients with HCV-related vasculitis: 20 patients were treated with rituximab and PEG-IFN alfa-2b (9 of whom had not previously received antiviral treatment and 11 of whom had experienced disease resistance to or relapse with antiviral treatment), and 12 antiviral-intolerant patients were treated with rituximab alone. RESULTS: Treatment with rituximab and PEG-IFN alfa-2b plus ribavirin induced a complete clinical response and a partial clinical response in 80% and 15% of patients, respectively, a complete immunologic response and a partial immunologic response in 67% and 33% of patients, respectively, and a sustained virologic response in 55% of patients. Treatment with rituximab alone induced a complete clinical response and a partial clinical response in 58% and 9% of patients, respectively, and a complete immunologic response and a partial immunologic response in 46% and 36% of patients, respectively. B cell depletion was achieved in 96% of patients, and B cell recovery began after a median delay of 12 months. After a mean+/-SD followup period of 23+/-12 months, 22% of patients experienced a clinical relapse, and 34% of patients experienced an immunologic relapse. All relapses were associated with the absence of virologic control, and 78% of relapses were associated with B cell recovery. Six patients were re-treated with rituximab. All 6 of these patients had a complete clinical response, 50% had a complete immunologic response, and 50% had a partial immunologic response. Rituximab was well tolerated overall. CONCLUSION: Rituximab is an effective treatment of severe and/or refractory HCV related vasculitis. Relapses were consistently associated with the absence of virologic control. The clinical and immunologic efficacy of rituximab after repeated infusion appeared to be the same as that observed after induction therapy. PMID- 19644878 TI - Abrogation of antibody-induced arthritis in mice by a self-activating viridin prodrug and association with impaired neutrophil and endothelial cell function. AB - OBJECTIVE: To test a novel self-activating viridin (SAV) prodrug that slowly releases wortmannin, a potent phosphoinositide 3-kinase inhibitor, in a model of antibody-mediated inflammatory arthritis. METHODS: The SAV prodrug was administered to K/BxN mice or to C57BL/6 (B6) mice that had been injected with K/BxN serum. Ankle thickness was measured, and histologic changes were scored after a 10-day disease course (serum-transfer arthritis). Protease activity was measured by a near-infrared imaging approach using a cleavable cathepsin selective probe. Further near-infrared imaging techniques were used to analyze early changes in vascular permeability after serum injection, as well as neutrophil-endothelial cell interactions. Neutrophil functions were assessed using an oxidative burst assay as well as a degranulation assay. RESULTS: SAV prevented ankle swelling in mice with serum-transfer arthritis in a dose dependent manner. It also markedly reduced the extent of other features of arthritis, such as protease activity and histology scores for inflammation and joint erosion. Moreover, SAV was an effective therapeutic agent. The underlying mechanisms for the antiinflammatory activity were manifold. Endothelial permeability after serum injection was reduced, as was firm neutrophil attachment to endothelial cells. Endothelial cell activation by tumor necrosis factor alpha was impeded by SAV, as measured by the expression of vascular cell adhesion molecule. Crucial neutrophil functions, such as generation of reactive oxygen species and degranulation of protease-laden vesicles, were decreased by SAV administration. CONCLUSION: A novel SAV prodrug proved strongly antiinflammatory in a murine model of antibody-induced inflammatory arthritis. Its activity could be attributed, at least in part, to the inhibition of neutrophil and endothelial cell functions. PMID- 19644880 TI - Sera from anti-Jo-1-positive patients with polymyositis and interstitial lung disease induce expression of intercellular adhesion molecule 1 in human lung endothelial cells. AB - OBJECTIVE: To investigate whether sera or purified IgG from patients with polymyositis (PM) and patients with dermatomyositis (DM), with or without interstitial lung disease (ILD), can activate endothelial cells (ECs). METHODS: Patients' sera were selected based on the presence or absence of anti-Jo-1, anti SSA, or anti-U1 small nuclear RNP autoantibodies. The presence of autoantibodies was determined by line blot assays. Cultured human microvascular ECs derived from lung tissue (HMVEC-L) were incubated with sera or purified IgG from 22 patients with PM, 7 patients with DM, and 10 healthy individuals as controls. Assessment of intercellular adhesion molecule 1 (ICAM-1) expression was conducted by immunofluorescence (n=22) and by cell-based enzyme-linked immunosorbent assay (ELISA) (n=20). Serum levels of soluble ICAM-1 (sICAM-1) were determined by ELISA. RESULTS: Sera from PM patients with ILD who were positive for anti-Jo-1 autoantibodies had a significantly stronger effect on the expression of ICAM-1 by HMVEC-L in comparison with sera from healthy controls and patients with other autoantibodies. Purified IgG did not induce ICAM-1 expression. Higher serum levels of sICAM-1 were found in patients with myositis compared with healthy controls. CONCLUSION: EC activation with ICAM-1 expression could contribute to the multiorgan involvement, including the development of myositis and ILD, in patients carrying anti-Jo-1 autoantibodies. The EC-activating factors are not the autoantibodies themselves, but might be systemic factors associated with these autoantibodies. PMID- 19644881 TI - Anti-cyclic citrullinated peptide testing for the diagnosis of rheumatoid arthritis and the quest for improved sensitivity and predictive value. PMID- 19644883 TI - Using "real clinic" definitions to predict the course of juvenile dermatomyositis: comment on the article by Stringer et al. PMID- 19644882 TI - Independent association of anti-beta(2)-glycoprotein I antibodies with macrovascular disease and mortality in scleroderma patients. AB - OBJECTIVE: Systemic sclerosis (SSc; scleroderma) is characterized by a unique widespread vascular involvement that can lead to severe digital ischemia, pulmonary arterial hypertension (PAH), or other organ dysfunction. Microthrombotic events and procoagulation factors such as anti-beta2-glycoprotein I (anti-beta2GPI) or anticardiolipin antibodies (aCL) may be implicated in the development of these manifestations. This study was undertaken to investigate whether anti-beta2GPI and aCL are correlated with macrovascular disease, including ischemic digital loss and PAH, in SSc patients. METHODS: Seventy-five SSc patients with a history of ischemic digital loss and 75 matched SSc controls were evaluated. Anticentromere antibodies (ACAs), anti-beta2GPI, and aCL were measured, and clinical associations were determined using conditional and simple logistic regression models. RESULTS: Positivity for anti-beta2GPI was significantly more frequent in SSc patients with digital loss than in patients without digital loss (P=0.017), with the IgA isotype of anti-beta2GPI showing the strongest association (odds ratio [OR] 4.0). There was no significant difference in aCL frequency between patients with digital loss and control patients. After adjustment for demographic characteristics, disease type, smoking, and ACA, anti beta2GPI positivity was significantly associated with active digital ischemia (OR 9.4), echocardiographically evident PAH (OR 4.8), and mortality (OR 2.9). ACA positivity was associated with history of digital loss (OR 3.28), but not with PAH or mortality. History of digital loss was strongly associated with increased mortality (OR 12.5). CONCLUSION: Anti-beta2GPI is significantly associated with macrovascular disease in SSc and independently predicts mortality. It is unclear whether it has a pathogenetic role or simply reveals the presence of underlying endothelial injury. The use of anti-beta2GPI as a biomarker of vascular disease in SSc should be further explored. PMID- 19644884 TI - Methotrexate catabolism to 7-hydroxymethotrexate in rheumatoid arthritis alters drug efficacy and retention and is reduced by folic acid supplementation. AB - OBJECTIVE: To assess the catabolism of methotrexate (MTX) to 7-hydroxy-MTX (7-OH MTX) in patients with rheumatoid arthritis as well as the effect of folic acid and folinic acid on this catabolism. METHODS: Urinary excretion of MTX and its catabolite, 7-OH-MTX, was measured in 2 24-hour urine specimens collected after MTX therapy. Urine samples were collected from patients after the sixth and seventh weekly doses of MTX. MTX and 7-OH-MTX concentrations were determined by high-performance liquid chromatography mass spectrometry. Swelling and pain/tenderness indices were used to measure symptoms before and at 6 and 7 weeks of therapy. Patients received either folic acid or folinic acid supplements (1 mg/day) from week 6 to week 7. RESULTS: Folic acid inhibited aldehyde oxidase (AO), the enzyme that produces 7-OH-MTX, but folinic acid did not. Excretion of 7 OH-MTX (determined as a percentage of the dose of MTX or as mg 7-OH-MTX/gm creatinine) was not normally distributed (n=39). Patients with marked improvement in swelling and pain/tenderness indices had a lower mean 7-OH-MTX excretion level (P<0.05). Patients who received folic acid supplements had decreased 7-OH-MTX excretion (P=0.03). Relatively high 7-OH-MTX excretion was correlated with relatively high MTX excretion and with relatively low MTX retention in vivo (P<0.05) (n=35). CONCLUSION: Our findings of a non-normal distribution of 7-OH MTX excretion suggest that there are at least 2 phenotypes for this catabolism. Decreased 7-OH-MTX formation suggests folic acid inhibition of AO and a better clinical response, while increased 7-OH-MTX formation may interfere with MTX polyglutamylation and binding to enzymes and, therefore, may increase MTX excretion and decrease MTX retention and efficacy in vivo. PMID- 19644885 TI - Regulation of the interferon-alpha production induced by RNA-containing immune complexes in plasmacytoid dendritic cells. AB - OBJECTIVE: Interferon-alpha (IFNalpha) is produced in several autoimmune diseases, including systemic lupus erythematosus (SLE), and may be important in their pathogenesis. We undertook this study to investigate how IFNalpha production induced by RNA-containing immune complexes (ICs) in plasmacytoid dendritic cells (PDCs) is regulated. METHODS: Normal PDCs purified from peripheral blood mononuclear cells (PBMCs) were cocultivated with other cell populations isolated from healthy individuals or SLE patients. IFNalpha production was induced by RNA-containing ICs, which consisted of anti-RNP autoantibodies and U1 small nuclear RNP particles, and the effects of prostaglandin E2 (PGE2), reactive oxygen species (ROS), or the cytokines IFNalpha2b, granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-10 (IL-10), or tumor necrosis factor alpha (TNFalpha) were explored. RESULTS: Monocytes inhibited IFNalpha production by PDCs in PBMC cultures, while natural killer (NK) cells were stimulatory. The monocytes had little effect on IFNalpha production by pure PDCs but inhibited its stimulation by NK cells. Monocytes from SLE patients were less inhibitory. Exposure of PBMCs or PDCs to IFNalpha2b/GM-CSF increased their IFNalpha production. RNA-containing ICs caused production of ROS, PGE2, and TNFalpha, especially in monocytes. These mediators and IL-10 suppressed IFNalpha production in PBMC cultures, with ROS and PGE2 also inhibiting IFNalpha production by purified PDCs. Inhibition by all of these agents, except for ROS, was abolished by IFNalpha2b/GM-CSF. The inhibitory effect of monocytes was significantly counteracted by the ROS scavengers serotonin and catalase. CONCLUSION: IFNalpha production induced by RNA-containing ICs in PDCs is regulated by a network of interactions between monocytes, NK cells, and PDCs, involving several pro- and antiinflammatory molecules. This should be considered when designing and applying new therapies. PMID- 19644886 TI - Gamma/delta T cells are the predominant source of interleukin-17 in affected joints in collagen-induced arthritis, but not in rheumatoid arthritis. AB - OBJECTIVE: Although interleukin-17 (IL-17)-producing gamma/delta T cells were reported to play pathogenic roles in collagen-induced arthritis (CIA), their characteristics remain unknown. The aim of this study was to clarify whether gamma/delta T cells or CD4+ T cells are the predominant IL-17-producing cells, and to determine what stimulates gamma/delta T cells to secret IL-17 in mice with CIA. The involvement of IL-17-producing gamma/delta T cells in SKG mice with autoimmune arthritis and patients with rheumatoid arthritis (RA) was also investigated. METHODS: IL-17-producing cells in the affected joints of mice with CIA were counted by intracellular cytokine staining during 6 distinct disease phases, and these cells were stimulated with various combinations of cytokines or specific antigens to determine the signaling requirements. Similar studies were performed using SKG mice with arthritis and patients with RA. RESULTS: Gamma/delta T cells were the predominant population in IL-17-producing cells in the swollen joints of mice with CIA, and the absolute numbers of these cells increased in parallel with disease activity. IL-17-producing gamma/delta T cells expressed CC chemokine receptor 6, were maintained by IL-23 but not by type II collagen in vitro, and were induced antigen independently in vivo. Furthermore, IL-17 production by gamma/delta T cells was induced by IL-1beta plus IL-23 independently of T cell receptor. In contrast to what was observed in mice with CIA, IL-17-producing gamma/delta T cells were nearly absent in the affected joints of SKG mice and patients with RA, and Th1 cells were predominant in the joints of patients with RA. CONCLUSION: Gamma/delta T cells were antigen independently stimulated by inflammation at affected joints and produced enhanced amounts of IL-17 to exacerbate arthritis in mice with CIA but not in SKG mice with arthritis or patients with RA. PMID- 19644887 TI - STAT4 is a genetic risk factor for systemic sclerosis having additive effects with IRF5 on disease susceptibility and related pulmonary fibrosis. AB - OBJECTIVE: Systemic sclerosis (SSc) belongs to the group of connective tissue disorders (CTDs), among which are several disorders characterized by a type I interferon (IFN) signature. The recent identification of an association between IRF5 and SSc further highlights a key role for IFN. STAT4, which encodes STAT-4, contributes to IFN signaling, and its genetic variants were found to be associated with CTDs. The aim of this study was to determine whether the STAT4 rs7574865 single-nucleotide polymorphism is associated with SSc, and whether it interacts with IRF5. METHODS: Both the STAT4 rs7574865 and IRF5 rs2004640 polymorphisms were genotyped in 1,855 individuals of French Caucasian origin comprising a discovery set of 440 patients with SSc and 485 control subjects and a replication set of 445 patients with SSc and an additional 485 control subjects. RESULTS: STAT4 rs7574865 was shown to be associated with SSc (P=0.001, odds ratio [OR] 1.29, 95% confidence interval [95% CI] 1.11-1.51). This association was not restricted to a particular phenotype. An additive effect of the STAT4 rs7574865 T allele and the IRF5 rs2004640 T allele was observed, resulting in a multiple increased 1.28-fold risk of SSc. The OR for SSc was 2.72 (95% CI 1.86-3.99) for combinations of genotypes with >or=3 risk alleles. An additive effect was also detected for fibrosing alveolitis: carriage of at least 3 risk alleles appeared to be an independent risk factor (P=2.2x10(-4), OR 1.97, 95% CI 1.28-3.04). CONCLUSION: Our results establish STAT4 rs7574865 as a new SSc genetic susceptibility factor. STAT4 and IRF5 act with additive effects in terms of susceptibility to both SSc and SSc-related fibrosing alveolitis. PMID- 19644889 TI - Accelerated development of aging-associated and instability-induced osteoarthritis in osteopontin-deficient mice. AB - OBJECTIVE: To investigate the role of osteopontin (OPN) in the development of osteoarthritis (OA) under in vivo and in vitro conditions. METHODS: Both instability-induced and aging-associated OA models were generated using OPN deficient (OPN-/-) and control wild-type (WT) mice. An in vitro cartilage degradation model was also used, to evaluate the effect of OPN on proteoglycan loss from joint cartilage. RESULTS: OPN deficiency exacerbated both aging associated and instability-induced OA. Both structural changes and an increased loss of proteoglycan from cartilage tissue were augmented in the absence of OPN. OPN deficiency also led to the induction of matrix metalloproteinase 13 (MMP-13), which degrades a major component of the cartilage matrix protein type II collagen. Both the loss of proteoglycan and the induction of the collagen degrading enzyme MMP-13 facilitated the development of OA. CONCLUSION: OPN plays a pivotal role in the progression of both instability-induced and aging associated spontaneous OA. OPN is a critical intrinsic regulator of cartilage degradation via its effects on MMP-13 expression and proteoglycan loss. PMID- 19644888 TI - Therapeutic effects of interleukin-6 blockade in a murine model of polymyositis that does not require interleukin-17A. AB - OBJECTIVE: To explore new molecular targets in the treatment of polymyositis (PM) by examining a recently established murine model of PM, C protein-induced myositis (CIM), for involvement of an interleukin-6 (IL-6)/IL-17A pathway. METHODS: CIM was induced by immunizing wild-type mice as well as IL-6-null and IL 17A-null C57BL/6 mice with recombinant mouse skeletal C protein fragments. Some mice were treated with anti-IL-6 receptor (anti-IL-6R) monoclonal antibodies or control antibodies. Muscle tissue samples were examined histologically and immunohistochemically. RESULTS: The syngeneic C protein fragments successfully induced inflammation in the skeletal muscles of wild-type mice. IL-6 was expressed by mononuclear cells, especially in macrophages, infiltrating in the muscles. IL-6-null mice developed myositis with significantly lower incidence and milder severity than wild-type mice. In contrast, IL-17A-null mice were as susceptible to CIM as wild-type mice. Intraperitoneal administration of anti-IL 6R monoclonal antibodies, but not of control monoclonal antibodies, ameliorated CIM both preventively and therapeutically. CONCLUSION: Our findings indicate that IL-6 is critically involved in the development of CIM. Although many other autoimmune models require IL-6 for differentiation of pathogenic T cells producing IL-17A, IL-17A was dispensable in CIM. Nevertheless, treatment with anti-IL-6R antibodies was effective. IL-6 blockade is potentially a new approach to the treatment of autoimmune myositis, via processes distinct from interference in the IL-6/IL-17A pathway. PMID- 19644890 TI - Role of p53 in human chondrocyte apoptosis in response to shear strain. AB - OBJECTIVE: Chondrocyte apoptosis plays an important role in cartilage degeneration in osteoarthritis (OA), and mechanical injury to cartilage induces chondrocyte apoptosis. In response to DNA damage, p53 expression is up-regulated, transcription activity is increased, and apoptosis signals are initiated. The p53 regulated apoptosis-inducing protein 1 (p53AIP-1) is one of the p53-regulated genes, and is activated in response to DNA damage. This study was undertaken to analyze p53 function after induction of apoptosis by shear strain in chondrocytes. METHODS: OA cartilage samples were obtained from subjects undergoing total knee replacement surgery, and normal cartilage samples were obtained from subjects undergoing surgery for femoral neck fracture. Chondrocytes were isolated from human cartilage and cultured. Expression of p53 and p53AIP in chondrocytes was detected by reverse transcriptase-polymerase chain reaction and Western blotting. Shear strain was introduced in normal human knee chondrocytes. To explore p53 function, normal human knee chondrocytes were pretreated with pifithrin-alpha or p53 small interfering RNA (siRNA) before induction of shear strain. Chondrocyte apoptosis was detected by expression of cleaved caspase 9 with Western blotting and TUNEL staining. Expression of p53 and p53AIP-1 was analyzed by Western blotting. RESULTS: OA and normal chondrocytes expressed p53. OA chondrocytes showed much higher expression of p53 and p53AIP-1 than did normal chondrocytes. TUNEL-positive cells and expression of p53, p53AIP-1, and cleaved caspase 9 were increased by shear strain, but chondrocyte apoptosis was suppressed after pretreatment with pifithrin-alpha or p53 siRNA. CONCLUSION: Our findings indicate that p53 and p53AIP-1 play important roles in human chondrocyte apoptosis. Down-regulation of p53 expression prevents cartilage from undergoing apoptosis introduced by shear strain. PMID- 19644891 TI - Treatment disparity related to race/ethnicity and education in rheumatoid arthritis patients: comment on the article by Constantinescu et al. PMID- 19644892 TI - Determinants of self-reported health status in a population-based sample of persons with radiographic knee osteoarthritis. AB - OBJECTIVE: Knee osteoarthritis (OA) is highly prevalent and disabling. Patients with radiographic knee OA may experience pain and functional impairment, which can diminish their health status. Our objective was to determine factors associated with self-reported health status in a national population-based sample with radiographic knee OA. METHODS: Our sample included all of the Third National Health and Nutrition Examination Survey (NHANES-III) participants who underwent a knee radiograph and were found to have radiographic OA (defined as Kellgren/Lawrence grade 2 or higher). Self-reported health status was determined by asking the participant to rate their overall health as excellent, very good, good, fair, or poor. Self-reported health status was analyzed as an ordinal variable using cumulative logit regression, as a dichotomous variable (excellent/very good/good versus fair/poor) using logistic regression, and as a continuous variable after transformation using linear regression. RESULTS: A total of 1,021 (42%) of NHANES-III participants with a knee radiograph were included in this analysis. The multivariable analyses were performed on 1,009 (99%) of the eligible participants with complete data. We found that nonwhite race, lower income, more comorbidities, and greater functional limitation were associated with worse self-reported health status in all 3 multivariable analyses. CONCLUSION: This study has quantified the role of clinical, radiographic, and socioeconomic factors associated with self-reported health status in a population-based sample of patients with knee OA. Self-reported health status in patients with knee OA was associated with functional status and comorbidity. PMID- 19644893 TI - Noninvasive imaging techniques in the assessment of scleroderma spectrum disorders. AB - OBJECTIVE: Systemic sclerosis (SSc) affects both microvascular structure and function. Laser Doppler imaging (LDI) and thermal imaging can be used to measure cutaneous blood vessel function. Nailfold capillaroscopy (NC) measures capillary morphology. The aim of this study was to investigate the relationship between capillary morphology and blood flow, and to determine which combination of techniques allows the best discrimination between patients with SSc, primary Raynaud's phenomenon (RP), and healthy controls. METHODS: NC was performed in 16 patients with SSc, 14 patients with primary RP, and 16 healthy controls. In addition, participants underwent cold stimulus with cold water. Hands were imaged to monitor rewarming and reperfusion. Nailfold morphologic features were measured and baseline images and rewarming curves were analyzed. RESULTS: Significant differences were found between groups (analysis of variance) for capillary morphologic features and rewarming curve characteristics. A correlation (P < 0.001) was found between LDI and thermal imaging at baseline (0.667) and maximum (0.729) blood flow and skin temperature, and for the areas under the rewarming curves (0.684). Receiver operating characteristic curves indicated that NC, thermal imaging, and LDI allowed 89%, 74%, and 72%, respectively, of SSc patient data to be correctly classified versus primary RP patients and controls. CONCLUSION: NC, LDI, and thermal imaging each independently provide good discrimination between patients with SSc and those with primary RP and healthy controls (NC being the most suitable technique for classifying patient groups). However, a combination of all 3 techniques improves classification. LDI and thermal imaging give equivalent information on dynamic changes in the cutaneous microcirculation; however, these only weakly correspond to capillary morphology. PMID- 19644894 TI - Depression, inflammation, and pain in patients with rheumatoid arthritis. AB - OBJECTIVE: An association between depression and inflammation has been suggested. In patients with rheumatoid arthritis (RA), pain is a major symptom associated with depression and inflammation. We examined the independent associations between depression, the inflammation marker C-reactive protein (CRP) level, and pain in patients with RA. METHODS: In total, 218 RA outpatients completed self administered questionnaires, using the Beck Depression Inventory II to measure depressive symptoms and a visual analog scale to quantify their perceived pain. Functional disability and CRP level were also measured. RESULTS: Depression scores were mildly and positively correlated with the CRP level (r = 0.46, P < 0.001). Both the depression score (standardized beta = 0.35, P < 0.001) and the CRP level (standardized beta = 0.35, P < 0.001) were significantly associated with pain, even after adjustment for clinical covariates in regression analysis. In logistic analysis, the combined effects on the risk of severe pain (pain score in the upper tertile) increased with depression scores and CRP levels linearly. CONCLUSION: Depression severity and inflammation were associated with each other and appeared to have independent effects on perceived pain. Therefore, a clinical approach that takes into account both the body and the mind could have benefits and could enable optimal pain control. PMID- 19644895 TI - Longitudinal effect of vigorous physical activity on patella cartilage morphology in people without clinical knee disease. AB - OBJECTIVE: There are few data concerning possible long-term effects of physical activity on cartilage change in the patellofemoral compartment. We examined the effect of participation in vigorous physical activity on changes to patella cartilage over 2 years. METHODS: A total of 297 healthy adults ages 50-79 years with no history of knee injury or symptoms were recruited from an existing study. Physical activity data were obtained by questionnaire at baseline (2003-2004). Patella cartilage volume and defects were determined by magnetic resonance imaging at baseline (2003-2004) and followup (2006-2007). RESULTS: Participation in vigorous physical activity at baseline was associated with a reduced rate of patella cartilage volume loss (-21.2 mm(3) per annum [95% confidence interval (95% CI) -41.5, -1.0; P = 0.04]) and a trend toward less risk of worsening patella cartilage defects (odds ratio 0.4; 95% CI 0.2, 1.1 [P = 0.07]) over the subsequent 2 years. In the subgroup with no significant patella cartilage defects at baseline (n = 192), participation in vigorous physical activity was associated with a reduced annual rate of patella cartilage volume loss (95% CI -53.8, -7.8; P = 0.03) and a trend for fewer new patella cartilage defects (95% CI 0.1, 1.1; P = 0.08). No significant relationships were found between vigorous physical activity and cartilage volume change or defect progression in the subgroup with prevalent patella cartilage defects at baseline. CONCLUSION: These observations suggest that vigorous physical activity is beneficial to patellofemoral joints for people without preexisting cartilage damage. Weight-bearing vigorous physical activity might, therefore, be useful in the prevention of patellofemoral osteoarthritis. PMID- 19644896 TI - Improvement in hemoglobin levels in patients with ankylosing spondylitis treated with infliximab. AB - OBJECTIVE: Anemia is a common complication in patients with inflammatory diseases such as ankylosing spondylitis (AS). This post hoc analysis of a large, randomized, placebo-controlled trial examined the effect of infliximab on hemoglobin levels, physical function, and fatigue in patients with AS. METHODS: Patients received infliximab 5 mg/kg (n = 188) or placebo (n = 68) at weeks 0, 2, 6, 12, and 18. Hemoglobin, interleukin-6 (IL-6), and C-reactive protein (CRP) levels, fatigue (visual analog scale [VAS]), physical function (Bath Ankylosing Spondylitis Functional Index [BASFI]), and disease activity were evaluated at baseline and week 24. Anemia was defined as a hemoglobin level <12 gm/dl for women and <13 gm/dl for men. RESULTS: At baseline, 11 placebo group patients (16.2%) and 37 infliximab group patients (19.7%) had anemia. Of these, more infliximab-treated patients achieved normal hemoglobin levels at week 24 compared with patients receiving placebo (70.3% versus 27.3%; P = 0.0155). Infliximab treated patients had significant improvements in mean hemoglobin concentration (0.7 gm/dl versus -0.3 gm/dl), BASFI score (-2.1 versus -0.2), and fatigue VAS score (-2.4 versus -0.4) compared with placebo patients (P < 0.001). Multiple regression analyses showed that improvements in hemoglobin level were significantly and independently associated with improvements in physical function and fatigue. Infliximab-treated patients with elevated CRP or IL-6 levels at baseline were more likely than those with low levels to have improvement in hemoglobin levels. CONCLUSION: Infliximab treatment significantly decreased the proportion of AS patients with anemia and improved hemoglobin levels compared with placebo. Improvement in hemoglobin level was independently associated with improvements in physical function and fatigue. PMID- 19644897 TI - Effectiveness of two finger splints for swan neck deformity in patients with rheumatoid arthritis: a randomized, crossover trial. AB - OBJECTIVE: To compare the effectiveness and acceptability of silver ring splints (SRS) and commercial prefabricated thermoplastic splints (PTS) in treating swan neck deformities in patients with rheumatoid arthritis (RA). METHODS: Consecutive patients with RA and a mobile swan neck deformity were included in a randomized, crossover trial. In 2 different sequences, patients used both splints for 4 weeks, with a washout period of 2 weeks. Afterward, patients used the preferred splint for another 12 weeks. The primary outcome measure was dexterity measured with the Sequential Occupational Dexterity Assessment (SODA). Secondary outcome measures included other measures of hand function, satisfaction with the splints, and splint preference. RESULTS: Fifty patients were included, and 47 (94%) of those completed the study. Eighteen patients (36%) had 1 swan neck deformity, whereas the other patients had 2 or more. The improvement of the total SODA score with the SRS (11.2; 95% confidence interval [95% CI] 8.1, 14.3) and PTS (10.8; 95% CI 7.5, 14.1) was similar (difference -0.5; 95% CI -2.2, 1.2). In addition, there were no significant differences in change scores regarding the other clinical outcome measures, or satisfaction. Twenty-four patients preferred the SRS, 21 preferred the PTS, and 2 patients chose neither. A comparison in the 12 week followup period yielded similar clinical outcomes, with the exception of a significantly higher score in 3 items of satisfaction in the SRS group. CONCLUSION: For patients with RA and a mobile swan neck deformity, SRS and PTS are equally effective and acceptable. PMID- 19644900 TI - Total knee replacement and health-related quality of life: factors influencing long-term outcomes. AB - OBJECTIVE: To evaluate health-related quality of life (HRQOL) in patients with osteoarthritis undergoing total knee replacement (TKR); identify the influence of sociodemographic, clinical, intraoperative, and postoperative variables on HRQOL; and determine patient perceptions at 7 years. METHODS: We conducted a prospective study with 7 years of followup. HRQOL measures (Western Ontario and McMaster Universities Osteoarthritis Index [WOMAC] and Short Form 36 [SF-36]); sociodemographic, clinical, intraoperative, inpatient, and postoperative data; patient perceptions of TKR outcomes; and physical activity at 7 years were determined. Associations were analyzed using linear regression models. RESULTS: Of 146 eligible patients, 112 (86 women, mean age 67.3 years) completed followup data. There were significant differences between pre- and postoperative WOMAC pain, stiffness, and function scores (P < 0.001). Variables retained in each of the models explained 14-32% (adjusted R(2)) of variability of the WOMAC dimensions. Obesity and postdischarge complications were associated with worse scores in all WOMAC dimensions (P < 0.05). Eighty-six percent of patients were satisfied with TKR, 80% would undergo the operation again, and 56% did regular physical activity and had better WOMAC scores (P < 0.05, except for stiffness [not significant]). Mean +/- SD SF-36 scores for men and women at 7 years were 55.1 +/- 27.1 and 39.5 +/- 22.9 for physical function, 71.2 +/- 36.5 and 51.5 +/- 42.7 for physical role, 66.2 +/- 26 and 55.6 +/- 28.9 for bodily pain, and 60.7 +/- 17.1 and 50.7 +/- 21.2 for general health, respectively. CONCLUSION: WOMAC dimension scores, especially pain, significantly improved at 7 years and were negatively influenced by obesity and postdischarge complications. HRQOL measures may help identify an increased risk of negative outcomes after TKR. PMID- 19644901 TI - Physical activity in women with arthritis: examining perceived barriers and self regulatory efficacy to cope. AB - OBJECTIVE: To examine whether the theory-based social cognitions of perceived barrier frequency, barrier limitation, and self-regulatory efficacy to cope were predictors of planned physical activity among adult women with arthritis. A secondary purpose was to identify and provide a phenomenologic description of the relevant barriers and coping strategies reported by study participants. METHODS: Eighty adult women (mean +/- SD age 49.09 +/- 12.89 years) with self-reported doctor-diagnosed arthritis participated in this observational study. Participants completed online survey measures of barriers to physical activity and, for each barrier, reported the frequency of occurrence and the extent of limitation. Measures of coping strategies for each barrier, efficacy to cope, and physical activity were also obtained. RESULTS: A multiple hierarchical regression analysis resulted in a model that significantly predicted physical activity (F[9,70] = 6.80, P < 0.01, adjusted R(2) = 0.40). Barrier limitation (standardized beta = 0.56) and efficacy (standardized beta = 0.20) were significant independent predictors. Phenomenologic findings indicated that arthritis-specific personal barriers (e.g., pain and fatigue due to arthritis) and arthritis-specific coping strategies (e.g., activity modification) were more commonly reported than generic barriers and coping strategies. CONCLUSION: Self-regulatory efficacy to cope and relevant perceived physical activity barriers, which were primarily arthritis specific and moderately or more limiting to planned physical activity, were important social cognitive predictors of physical activity, a key nonpharmacologic arthritis treatment, among women with arthritis. Future research direction should examine potential moderators of the relationship between these predictors and physical activity, such as pain acceptance. PMID- 19644902 TI - Spouse depression and disease course among persons with rheumatoid arthritis. AB - OBJECTIVE: To examine the role of spouse mood in the disability and disease course of persons with rheumatoid arthritis (PWRA). METHODS: A total of 133 married PWRA completed questionnaires, including the Rheumatoid Arthritis Disease Activity Index and the Disabilities of the Arm, Shoulder, and Hand, assessing PWRA arthritis disease activity and disability, respectively, at 2 time points 1 year apart. In addition, both PWRA and their spouses completed the Center for Epidemiologic Studies Depression Scale, a standardized community measure of depression at both time points. RESULTS: Multiple regression analysis revealed spouse depressive symptoms at initial assessment to be predictive of followup PWRA disability and disease activity, even after controlling for initial levels of PWRA depression, disability, disease activity, age, number of years married, education, disease duration, and employment. Specifically, higher levels of spouse depression predicted worse disease course over a 1-year period for PWRA, as indicated by higher reports of subsequent PWRA disability and disease activity. CONCLUSION: Our findings highlight the key role played by the spouse in PWRA disease course, and point to the importance of including the spouse in clinical interventions. Implications for theory, research, and treatment are discussed with a focus on examining pathways through which spouse depressive symptoms may affect PWRA disease course and disability. PMID- 19644903 TI - Predictors of early inactive disease in a juvenile idiopathic arthritis cohort: results of a Canadian multicenter, prospective inception cohort study. AB - OBJECTIVE: To determine early predictors of 6-month outcomes in a prospective cohort of patients with juvenile idiopathic arthritis (JIA). METHODS: Patients selected were those enrolled in an inception cohort study of JIA, the Research in Arthritis in Canadian Children Emphasizing Outcomes Study, within 6 months after diagnosis. The juvenile rheumatoid arthritis core criteria set and quality of life measures were collected at enrollment and 6 months later. Outcomes evaluated included inactive disease, Juvenile Arthritis Quality of Life Questionnaire (JAQQ) scores, and Childhood Health Assessment Questionnaire (C-HAQ) scores at 6 months. RESULTS: Thirty-three percent of patients had inactive disease at 6 months. Onset subtype and most baseline core criteria set measures correlated with all 3 outcomes. Relative to oligoarticular JIA, the risks of inactive disease were lower for enthesitis-related arthritis, polyarthritis rheumatoid factor (RF)-negative JIA, and polyarthritis RF-positive JIA, and were similar for psoriatic arthritis. In multiple regression analyses, the baseline JAQQ score was an independent predictor of all 3 outcomes. Other independent baseline predictors included polyarthritis RF-negative and systemic JIA for inactive disease; C-HAQ score and polyarthritis RF-positive JIA for the 6-month C-HAQ score; and active joint count, pain, and time to diagnosis for the 6-month JAQQ score. CONCLUSION: Clinical measures soon after diagnosis predict short-term outcomes for patients with JIA. The JAQQ is a predictor of multiple outcomes. Time to diagnosis affects quality of life in the short term. PMID- 19644904 TI - Illness perceptions in patients with osteoarthritis: change over time and association with disability. AB - OBJECTIVE: To investigate changes in illness perceptions in patients with osteoarthritis (OA) and the association of those changes with disability, and to determine the predictive value of illness perceptions in disability. METHODS: Illness perceptions and disability were measured at baseline and after 6 years in 241 patients with OA at multiple sites (mean age 59.0 years, 82.2% women) using the revised Illness Perception Questionnaire (IPQ-R) and the Health Assessment Questionnaire (HAQ), respectively. Mean changes for each IPQ-R dimension were reported and related to progression of disability, defined as the highest quartile of HAQ score change. The predictive value of baseline illness perceptions in disability at 6 years (with high disability defined as the highest quartile of HAQ score) was assessed using logistic regression. RESULTS: Illness perceptions changed over time, and these changes were related to the progression of disability. Patients with progression of disability had an increase in symptoms attributed to OA, perceived consequences, perceived disease chronicity, negative emotions associated with OA and beliefs about immunity as causal factor, and a decrease in perceived control and understanding of OA compared with patients without progression of disability. Moreover, a higher number of symptoms attributed to OA, less perceived control, and more perceived consequences of OA at baseline were predictive of high disability after 6 years. CONCLUSION: Illness perceptions in patients with OA changed over time, and these changes were related to outcome. Moreover, illness perceptions were predictive of disability. This may imply that interventions aimed at changing illness perceptions can contribute to better functional outcome. PMID- 19644905 TI - Naturopathic treatment of rotator cuff tendinitis among Canadian postal workers: a randomized controlled trial. AB - OBJECTIVE: To explore the effectiveness of naturopathic care (NC) on rotator cuff tendinitis using a prospective randomized clinical trial design. METHODS: Canadian postal workers with rotator cuff tendinitis for a duration of >6 weeks were randomized to receive NC (n = 43) or standardized physical exercises (PEs; n = 42) over 12 weeks. Participants in the NC group received dietary counseling, acupuncture, and Phlogenzym (2 tablets 3 times/day). The PE intervention group received passive, active-assisted, and active range of motion exercises and matched placebo. The primary outcome measure was the Shoulder Pain and Disability Index (SPADI), and secondary outcomes were the pain visual analog scale (VAS), Short Form 36 (SF-36), Measure Yourself Medical Outcomes Profile (MYMOP), and shoulder maximal range of motion. Participants and assessors were blinded to group and placebo allocation. RESULTS: Seventy-seven participants (87%) completed >or=8 weeks of the trial. Final total SPADI scores decreased by 54.5% (P < 0.0001) in the NC group and by 18% (P = 0.0241) in the PE group. Between-group differences in changes to SPADI scores showed statistically significant decreases in shoulder pain and disability in the NC group compared with the PE group (P < 0.0001). Significant differences between groups were also observed in the pain VAS, MYMOP, SF-36, and shoulder extension, flexion, and abduction, with the NC group showing superiority in each outcome. No serious adverse reactions were observed. CONCLUSION: NC and PE provided significant improvements, with greater improvement in shoulder function in the NC group compared with the PE group. Statistically significant improvements in quality of life measures were observed in the NC group as compared with the PE group. PMID- 19644906 TI - Health-related quality of life in systemic sclerosis: a systematic review. AB - OBJECTIVE: A number of studies (all n <200) have assessed health-related quality of life (HRQOL) in patients with systemic sclerosis (SSc), but no systematic review of the effect of SSc on HRQOL has been done. The objective of this study was to systematically review the literature on HRQOL in SSc measured using the Medical Outcomes Trust Short Form 36 (SF-36). METHODS: A comprehensive search was conducted in August 2007 using Medline, CINAHL, and EMBase to identify original research studies reporting SF-36 scores of SSc patients. Selected studies were reviewed and characteristics of the study samples and SF-36 data were extracted. Bayesian meta-analysis and meta-regression were performed to obtain pooled estimates of SF-36 physical component summary (PCS) and mental component summary (MCS) scores for all patients as well as by limited and diffuse disease status. RESULTS: Twelve data sets with a total of 1,127 SSc patients were included in the systematic review. HRQOL was impaired in patients with SSc, with pooled SF-36 PCS scores being more than 1 SD below the general population (38.3; 95% credible interval [95% CI] 35.2, 41.5) and pooled SF-36 MCS scores being approximately 0.5 SDs below the general population (46.6; 95% CI 44.2, 49.1). SF-36 PCS scores were 3.5 points (95% CI -1.0, 8.0) lower in patients with diffuse compared with limited disease. CONCLUSION: This study provides robust evidence of the presence and magnitude of impairment in HRQOL in patients with SSc. Although the impairment appears greater in physical health, mental health impairment is also reported. PMID- 19644907 TI - Demonstration of a link between spouse depression and disability and disease activity of persons with rheumatoid arthritis. PMID- 19644908 TI - Pseudoseptic arthritis due to acute lipoarthrosis in a systemic lupus erythematosus patient with osteonecrosis. PMID- 19644910 TI - A 58-year-old woman with a droopy left eye and vision loss. PMID- 19644909 TI - Detection of coronary artery lesions and myocardial necrosis by magnetic resonance in systemic necrotizing vasculitides. AB - OBJECTIVE: Myocardium and coronary arteries can occasionally be affected in patients with systemic necrotizing vasculitides; however, such involvement has not been systematically assessed using cardiovascular magnetic resonance imaging (MRI). METHODS: Magnetic resonance angiography and contrast-enhanced MRI were applied for the assessment of coronary arteries (the left anterior descending [LAD], left circumflex [LCx], and right coronary artery [RCA]) and myocardium, respectively, in 39 patients with vasculitis who were asymptomatic for cardiac disease (16 with microscopic polyangiitis [MPA], 11 with Wegener's granulomatosis [WG], 9 with Churg-Strauss syndrome [CSS], and 3 with polyarteritis nodosa [PAN]). Data were compared with age-matched disease-control patients with rheumatoid arthritis (n = 20) or systemic lupus erythematosus (n = 13), and with healthy control individuals with normal coronaries (n = 40). RESULTS: Patients with MPA, WG, and PAN (but not with CSS) were found to display significantly increased maximal diameters of coronary arteries compared with healthy controls (for MPA and WG; P < 0.001 for LAD and RCA, and P < 0.01 for LCx) and with both disease-control groups (for only MPA; P < 0.01 for LAD and RCA, and P < 0.05 for LCx). Fusiform coronary aneurysms were detected in patients with MPA (4/16) and PAN (2/3), whereas coronary ectasias were evident in patients with MPA (14/16) and WG (2/11). The presence of myocardial necrosis (by assessment of late gadolinium-enhanced images) was identified only in patients with MPA (2/16) and CSS (3/8 studied). CONCLUSION: Cardiovascular MRI assessment of patients with systemic vasculitis revealed coronary ectatic disease in the majority of patients with MPA and PAN, as well as in several patients with WG. Myocardial necrosis can be detected in MPA and CSS. PMID- 19644911 TI - The effects of impaired joint position sense on the development and progression of pain and structural damage in knee osteoarthritis. AB - OBJECTIVE: Although cross-sectional studies have reported impaired proprioceptive acuity in people with osteoarthritis (OA), there have been no longitudinal studies to evaluate whether those with such impairments increase the risk of OA or its worsening. METHODS: We studied subjects from the Multicenter Osteoarthritis Study study, a longitudinal study of people with or at high risk of knee OA. At baseline, we quantified acuity as the amount of a subject's error when attempting to reproduce a test knee flexion angle (a measure of joint position sense). We tested proprioception 10 times in the right leg and used a person's worst score as their proprioceptive acuity. At baseline and the 30-month followup, we assessed the presence of frequent pain, obtained Western Ontario and McMasters Universities OA Index (WOMAC) scores, and acquired posteroanterior and lateral weight-bearing knee radiographs read for Kellgren/Lawrence grade and individual radiographic features. We examined the relation of baseline proprioceptive acuity in quartiles with baseline knee pain (frequent pain yes/no), WOMAC pain score, self-reported physical function, and radiographic OA, and with changes from baseline in pain, physical function, and radiographic OA adjusted for age, sex, body mass index, and quadriceps strength. RESULTS: At baseline, proprioceptive acuity was associated with the presence and severity of knee pain but not with the presence of radiographic OA. However, among the 2,243 subjects with baseline acuity assessments and 30-month followup, there were no strong associations between proprioceptive acuity and development of adverse OA outcomes. Acuity was not significantly associated with the new onset of frequent knee pain. Those with the worst acuity at baseline had slightly greater worsening of WOMAC pain scores (0.47 on a 20-point scale) and physical function scores (by 1.5 points on a 0-68-point scale) compared with those with the best proprioceptive acuity, whose pain and physical function score deteriorated less (for pain P = 0.05; for physical function P = 0.02). Radiographic worsening was not significantly associated with proprioceptive acuity. CONCLUSION: Proprioceptive acuity as assessed by the accuracy of reproduction of the angle of knee flexion had modest effects on the trajectory of pain and physical functional limitation in knee OA. PMID- 19644912 TI - Health care transition counseling for youth with arthritis: comment on the article by Scal et al. PMID- 19644913 TI - Body image in gay and straight men: a qualitative study. AB - OBJECTIVE: Recent research has emphasized vulnerability to eating disorders in gay men, with calls for research on causality, cultural factors and focus on a younger age cohort. This study aimed to examine body image and related eating behaviours in younger gay and straight men. METHOD: Qualitative study using a sample of gay and straight male university students, applying audiotaped and transcribed depth interview subjected to interpretative phenomenological analysis. RESULTS: Fifteen young men (18-24) with a spectrum of sexual orientation (gay, straight and bisexual) agreed to participate. Five dominant categories emerged: body image ideal, external influences, perception of body image, dieting, mechanisms for modification (diet, exercise, cosmetics) and sexual orientation. CONCLUSION: Health and aesthetic ideals appear less divorced for young men than women, offering some degree of protection from eating disorders. Nonetheless there is widespread body dissatisfaction. Media and social influences are powerful, particularly for single gay men, but the study suggests fewer differences than similarities between gay and straight men. PMID- 19644915 TI - RNA biophysics has come of age. PMID- 19644916 TI - Evolutionary formation of new protein folds is linked to metallic cofactor recruitment. AB - To explore whether the generation of new protein folds could be linked to metallic cofactor recruitment, we identified the oldest examples of folds for manganese, iron, zinc, and copper proteins by analyzing their fold-domain mapping patterns. We discovered that the generation of these folds was tightly coupled to corresponding metals. We found that the emerging order for these folds, i.e., manganese and iron protein folds appeared earlier than zinc and copper counterparts, coincides with the putative bioavailability of the corresponding metals in the ancient anoxic ocean. Therefore, we conclude that metallic cofactors, like organic cofactors, play an evolutionary role in the formation of new protein folds. This link could be explained by the emergence of protein structures with novel folds that could fulfill the new protein functions introduced by the metallic cofactors. These findings not only have important implications for understanding the evolutionary mechanisms of protein architectures, but also provide a further interpretation for the evolutionary story of superoxide dismutases. PMID- 19644917 TI - Mammalian prenatal development: the influence of maternally derived molecules. AB - Normal fetal development is dependent upon an intricate exchange between mother and embryo. Several maternal and embryonic elements can influence this intimate interaction, including genetic, environmental or epigenetic factors, and have a significant impact on embryo development. The interaction of the genetic program of both mother and embryo, within the uterine environment, can shape the development of an individual. Accumulating data from animal models indicate that prenatal events may well initiate long-term changes in the expression of the embryo genetic program, which persist, or may only become apparent, much later in the individual's life. Also, environmental conditions during prenatal development may prompt the adoption of different developmental pathways, leading to alternative life histories. This review focuses on environmental factors, specifically maternally derived molecules, to illustrate how they can influence in utero embryonic development and, by extension, adult life. PMID- 19644918 TI - Pannexins, distant relatives of the connexin family with specific cellular functions? AB - Intercellular communication (IC) is mediated by gap junctions (GJs) and hemichannels, which consist of proteins. This has been particularly well documented for the connexin (Cx) family. Initially, Cxs were thought to be the only proteins capable of GJ formation in vertebrates. About 10 years ago, however, a new GJ-forming protein family related to invertebrate innexins (Inxs) was discovered in vertebrates, and named the pannexin (Panx) family. Panxs, which are structurally similar to Cxs, but evolutionarily distinct, have been shown to be co-expressed with Cxs in vertebrates. Both protein families show distinct properties and have their own particular function. Identification of the mechanisms that control Panx channel gating is a major challenge for future work. In this review, we focus on the specific properties and role of Panxs in normal and pathological conditions. PMID- 19644919 TI - Expanding roles for AMP-activated protein kinase in neuronal survival and autophagy. AB - AMP-activated protein kinase (AMPK) is an evolutionarily conserved cellular switch that activates catabolic pathways and turns off anabolic processes. In this way, AMPK activation can restore the perturbation of cellular energy levels. In physiological situations, AMPK senses energy deficiency (in the form of an increased AMP/ATP ratio), but it is also activated by metabolic insults, such as glucose or oxygen deprivation. Metformin, one of the most widely prescribed anti diabetic drugs, exerts its actions by AMPK activation. However, while the functions of AMPK as a metabolic regulator are fairly well understood, its actions in neuronal cells only recently gained attention. This review will discuss newly emerged functions of AMPK in neuroprotection and neurodegeneration. Additionally, recent views on the role of AMPK in autophagy, an important catabolic process that is also involved in neurodegeneration and cancer, will be highlighted. PMID- 19644921 TI - Trans-splicing of organelle introns--a detour to continuous RNAs. AB - In eukaryotes, RNA trans-splicing is an important RNA-processing form for the end to-end ligation of primary transcripts that are derived from separately transcribed exons. So far, three different categories of RNA trans-splicing have been found in organisms as diverse as algae to man. Here, we review one of these categories: the trans-splicing of discontinuous group II introns, which occurs in chloroplasts and mitochondria of lower eukaryotes and plants. Trans-spliced exons can be predicted from DNA sequences derived from a large number of sequenced organelle genomes. Further molecular genetic analysis of mutants has unravelled proteins, some of which being part of high-molecular-weight complexes that promote the splicing process. Based on data derived from the alga Chlamydomonas reinhardtii, a model is provided which defines the composition of an organelle spliceosome. This will have a general relevance for understanding the function of RNA-processing machineries in eukaryotic organelles. PMID- 19644920 TI - Genomic mutation rates: what high-throughput methods can tell us. AB - High-throughput DNA analyses are increasingly being used to detect rare mutations in moderately sized genomes. These methods have yielded genome mutation rates that are markedly higher than those obtained using pre-genomic strategies. Recent work in a variety of organisms has shown that mutation rate is strongly affected by sequence context and genome position. These observations suggest that high throughput DNA analyses will ultimately allow researchers to identify trans acting factors and cis sequences that underlie mutation rate variation. Such work should provide insights on how mutation rate variability can impact genome organization and disease progression. PMID- 19644923 TI - Controlled intracellular release of peptides from microcapsules enhances antigen presentation on MHC class I molecules. AB - To understand the time course of action of any small molecule inside a single cell, one would deposit a defined amount inside the cell and initiate its activity at a defined moment. An elegant way to achieve this is to encapsulate the molecule in a micrometer-sized reservoir, introduce it into a cell, remotely open its wall by a laser pulse, and then follow the biological response by microscopy. The validity of this approach is validated here using microcapsules with defined walls that are doped with metallic nanoparticles so as to enable them to be opened with an infrared laser. The capsules are loaded with a fluorescent antigenic peptide and introduced into mammalian cultured cells where, upon laser-induced release, the peptide binds to major histocompatibility complex (MHC) class I proteins and elicits their cell surface transport. The concept of releasing a drug inside a cell and following its action is applicable to many problems in cell biology and medicine. PMID- 19644922 TI - Characterisation of normal and cancer stem cells: one experimental paradigm for two kinds of stem cells. AB - The characterisation of normal stem cells and cancer stem cells uses the same paradigm. These cells are isolated by a fluorescence-activated cell sorting step and their stemness is assayed following implantation into animals. However, differences exist between these two kinds of stem cells. Therefore, the translation of the experimental procedures used for normal stem cell isolation into the research field of cancer stem cells is a potential source of artefacts. In addition, normal stem cell therapy has the objective of regenerating a tissue, while cancer stem cell-centred therapy seeks the destruction of the cancer tissue. Taking these differences into account is critical for anticipating problems that might arise in cancer stem cell-centred therapy and for upgrading the cancer stem cell paradigm accordingly. PMID- 19644930 TI - The metabolic component of cellular refractivity and its importance for optical cytometry. AB - Initially, it has been shown that the phase thickness and refractivity (the latter interpreted as the difference of the refractivity indices of an object and surrounding medium) depend on the functional state of mitochondria. The refractivity of various objects decreased in response to energy depletion. This dependence was then demonstrated for other biological objects such as cyanobacteria, chloroplasts and human cells. This general response brought about the hypothesis of a certain "universal" factor that links the variable (or metabolic) component of refractivity with the object's functional state. However, the origin of this phenomenon remains unknown. Our hypothesis is founded on the dependence of polarization of bound water molecules and the activity of metabolic processes. Here, we show the results of measurements of metabolic component of refractivity different bio-objects (mitochondria, chloroplasts, spores, cancer cells) obtained using the Coherent Phase Microscope "Airyscan". Estimations indicated high (up to n approximately = 1.41-1.45) values for the equivalent refractive index of structured water in cells. PMID- 19644931 TI - Expression of hedgehog signaling molecules in Merkel cell carcinoma. AB - BACKGROUND: The Hedgehog signaling pathway is important for human development and carcinogenesis in various malignancies. METHODS: One tissue microarray with triplets of 28 samples from 25 patients with Merkel cell carcinoma (MCC) was constructed. Six samples of normal skin and 5 samples of normal oral mucosa served as controls. All samples were analyzed immunohistochemically with antibodies directed against Sonic hedgehog, Indian hedgehog, Patched, Smoothened, Gli-1, Gli-2, and Gli-3. RESULTS: All investigated proteins were frequently and intensely overexpressed in MCCs (Sonic hedgehog, 93%; Indian hedgehog, 84%; Patched, 86%; Smoothened, 79%; Gli-1, 79%; Gli-2, 79%; Gli-3, 86%) compared with control samples. High levels of Patched and Indian hedgehog were significantly associated with an increase in patients overall (p = .015) and recurrence-free survival (p = .011), respectively. CONCLUSIONS: Our results indicate that the Hedgehog signaling pathway is strongly activated in MCC and thus may play a role in carcinogenesis. PMID- 19644932 TI - Oral cavity cancer in developed and in developing countries: population-based incidence. AB - BACKGROUND: The incidence of oral cavity cancer (OCC) is not well documented because it is rarely described in accord with the anatomic definition but is usually grouped with oropharyngeal subsites. We studied the incidence of OCC in developed and in developing countries. METHODS: The age-standardized and age specific incidence rates of OCC were calculated for the period 1998-2002, using the topographic definition used by the Union Internationale Contre le Cancer (UICC), based on data from CI5-IX. RESULTS: The highest rates are observed in Pakistan, Brazil, India, and France and were consistent with country-specific risk factors and their prevalence. CONCLUSIONS: In developing countries, people are exposed to a wider range of risk factors, starting at younger ages, and primary prevention measures and policies are needed. Awareness of professionals must be improved to identify people at risk and target them for prevention and to minimize the consequences of OCC. PMID- 19644933 TI - Dynamic and interactive gynecological ultrasound examination. PMID- 19644934 TI - A computationally inspired investigation of the solid forms of (R)-1 phenylethylammonium-(S)-2-phenylbutyrate. AB - Following the computation of a lattice energy landscape which predicted that there should be more stable, denser forms of (R)-1-phenylethylammonium-(S)-2 phenylbutyrate, crystallizations from a range of solvents were performed to search for other polymorphs and investigate the possibility that the known P4(1) structure could be a hydrate. Extensive crystallization experiments from a wide range of solvents gave fine needles or microcrystalline samples. A redetermination of the P4(1) structure by powder X-ray diffraction located all protons, and in conjunction with other experimental and computational evidence showed that the structure was anhydrous. Evidence for two additional forms was found as mixtures with form I. These include an orthorhombic form, possibly a Z' = 3 polymorph, and another as yet unidentified form obtained as a minor component from dichloromethane solution. However, both these forms appear to be metastable with respect to form I (P4(1)), which is therefore probably the most thermodynamically stable form that can be crystallized from solution under ambient conditions. This determination of the solid state behavior of the less readily crystallized member of the diastereomeric salt system (R)-1 phenylethylammonium-(R/S)-2-phenylbutyrate provides a challenge to the theoretical modeling to explain its ideal resolution behavior. PMID- 19644935 TI - On circular dichroism and the separation between chromophore and chiral center: the near carbon K-edge X-ray absorption and circular dichroism spectra of noradrenaline and L-DOPA. AB - The near carbon K-edge X-ray absorption and circular dichroism spectra of noradrenaline (neutral and protonated forms) and L-DOPA (protonated form) have been determined with use of the complex polarization propagator method in conjunction with Kohn-Sham density functional theory. A Coulomb attenuated exchange-correlation functional and London atomic orbitals have been employed to address the issues of hole-electron interactions and gauge-origin dependence of the magnetic-dipole operator, respectively. Results show that the characteristics of the chromophore part of the circular dichroism spectra are shared for all three considered systems, whereas protonation qualitatively alters the part of the spectrum assigned to the chiral side chain. The comparatively larger spatial separation of chromophore and chiral center in L-DOPA inflicts larger differences in spectral intensities between the chromophore and chiral center part of the circular dichroism spectra. PMID- 19644936 TI - Determination of enantiomerization barriers of hypericin and pseudohypericin by dynamic high-performance liquid chromatography on immobilized polysaccharide-type chiral stationary phases and off-column racemization experiments. AB - Direct enantiomer separation of hypericin, pseudohypericin, and protohypericin was accomplished by high-performance liquid chromatography (HPLC) using immobilized polysaccharide-type chiral stationary phases (CSPs). Enantioselectivities up to 1.30 were obtained in the polar-organic elution mode whereby for hypericin and pseudohypericin Chiralpak IC [chiral selector being cellulose tris(3,5-dichlorophenylcarbamate)] and for protohypericin Chiralpak IA (chiral selector being the 3,5-dimethylphenylcarbamate of amylose) gave favorable results. Enantiomers were distinguished by on-line electronic circular dichroism detection. Optimized enantioselective chromatographic conditions were the basis for determining stereodynamic parameters of the enantiomer interconversion process of hypericin and pseudohypericin. Rate constants delivered by computational simulation of dynamic HPLC elution profiles (stochastic model, consideration of peak tailing) were used to calculate averaged enantiomerization barriers (DeltaG(enant)(#)) of 97.6-99.6 kJ/mol for both compounds (investigated temperature range 25-45 degrees C). Complementary variable temperature off-column (i.e., in solution) racemization experiments delivered DeltaG(enant)(#) = 97.1 98.0 kJ/mol (27-45 degrees C) for hypericin and DeltaG(enant)(#) = 98.9-101.4 kJ/mol (25-55 degrees C) for pseudohypericin. An activation enthalpy of DeltaH(#) = 86.0 kJ/mol and an activation entropy of DeltaS(#) = -37.7 J/(K mol) were calculated from hypericin racemization kinetics in solution, whereas for pseudohypericin these figures amounted to 74.1 kJ/mol and -82.6 J/(K mol), respectively. Although the natural phenanthroperylene quinone pigments hypericin and pseudohypericin as well as their biological precursor protohypericin are chiral and can be separated by enantioselective HPLC low enantiomerization barriers seem to prevent the occurrence of an excess of one enantiomer under typical physiological conditions--at least as long as stereoselective intermolecular interactions with other chiral entities are absent. PMID- 19644937 TI - Stereoselective metabolism of propranolol glucuronidation by human UDP glucuronosyltransferases 2B7 and 1A9. AB - Stereoselective metabolism of propranolol side-chain glucuronidation was studied for two recombinant human uridine diphosphate glucuronosyltransferases (UGTs), UGT1A9 and UGT2B7. The S- and R-propranolol side-chain glucuronides produced in the incubation mixtures were assayed simultaneously by RP-HPLC with fluorescent detector. The excitation and emission wavelengths were set at 310 nm and 339 nm, respectively. UGT1A9 prefers catalyzing S-enantiomer to R-enantiomer and the intrinsic clearance (CL(int)) ratios of S-enantiomer to R-enantiomer are 3.8 times and 6.5 times for racemic propranolol and individual enantiomers, respectively. UGT2B7, however, catalyzes slightly less S-enantiomer than R enantiomer and the CL(int) ratio of S-enantiomer to R-enantiomer is 0.8 times. The high concentration of racemic propranolol (>0.57 mmol/l) and individual enantiomers (>0.69 mmol/l) exhibited substrate inhibition of glucuronidation for UGT2B7, but only the S-enantiomer (>0.44 mmol/l) in racemic propranolol exhibited substrate inhibition for UGT1A9. The substrate inhibition constants (K(si)) were all similar (P > 0.05). Drug-drug interactions were also found between S- and R enantiomer glucuronidation metabolisms by UGT1A9 and UGT2B7. PMID- 19644938 TI - The effects of an incentive program on quality of care in diabetes management. AB - An incentive program for general practitioners to encourage systematic and igh quality care in chronic disease management was introduced in Australia in 1999. There is little empirical evidence and ambiguous theoretical guidance on which effects to expect. This paper evaluates the impact of the incentive program on quality of care in diabetes, as measured by the probability of ordering an HbA1c test. The empirical analysis is conducted with a unique data set and a bivariate probit model to control for the self-selection process of practices into the program. The study finds that the incentive program increased the probability of an HbA1c test being ordered by 20 percentage points and that participation in the program is facilitated by the support of Divisions of General Practice. PMID- 19644939 TI - Type 1 deiodinase activity and generation of triiodothyronine (T3) in prostate of sexually active rats. AB - BACKGROUND: Thyroxine (T(4)) and triiodothyronine (T(3)) are involved in the development and function of the male reproductive system. The type 1 deiodinase enzyme (D1) plays a major role in the intracellular conversion of T(4) to the active form, T(3). D1 is expressed in the prostate of pubescent rats, but it is unknown whether locally generated T(3) is involved in the development and function of this gland. METHODS: D1 activity was analyzed in prostates from neonatal to old rats. Local T3 generation (D1 and T3 levels) was evaluated in adult animals with 1-5 months of continuous sexual activity. D1 activity was measured by the radiolabeled-iodide-release method and T(3) concentration by radioimmunoassay. Secretory activity of the prostate was evaluated by a morphological analysis of epithelium (hematoxilin-eosin stain) and by measuring the activity of acid phosphatase as a marker enzyme for secretion. RESULTS: The highest prostate D1 activity was expressed around puberty, and it was almost undetectable during the neonatal period and with aging. Interestingly, 1 and 4 months of sexual activity avoided the decrease of D1 activity associated with aging. Sexual activity provoked a hypertrophy and functional hyperplasia in all lobes, but D1 and acid phosphatase activity increased only in the ventral lobe. D1 activity correlated with an increase in the prostatic T(3) concentration. CONCLUSIONS: The increased local generation of T(3) in prostate might be related to: (1) the differentiation/maturation that occurs at puberty and (2) the energy expenditure associated with maintaining the secretory activity of the glandular epithelium. PMID- 19644942 TI - Placenta previa: the evolving role of ultrasound. PMID- 19644943 TI - Whirlpool sign in the diagnosis of adnexal torsion with atypical clinical presentation. PMID- 19644944 TI - Counseling in isolated mild fetal ventriculomegaly. AB - In this Review we aim to provide up-to-date and evidence-based answers to the common questions regarding the diagnosis of isolated mild fetal ventriculomegaly (VM). A literature search was performed to identify all reports of antenatal VM in the English language literature. In addition, reference lists of articles identified using the search were scrutinized to further identify relevant articles. Fetal mild VM is commonly defined as a ventricular atrial width of 10.0 15.0 mm, and it is considered isolated if there are no associated ultrasound abnormalities. There is no good evidence to suggest that the width of the ventricular atria contributes to the risk of neurodevelopmental outcome in fetuses with mild VM. The most important prognostic factors are the association with other abnormalities that escape early detection and the progression of ventricular dilatation, which are reported to occur in about 13% and 16% of cases, respectively. Most infants with a prenatal diagnosis of isolated mild VM have normal neurological development at least in infancy. The rate of abnormal or delayed neurodevelopment in infancy is about 11%, and it is unclear whether this is higher than in the general population. Furthermore, the number of infants that develop a real handicap is unknown. There are limitations of existing studies of mild VM. Although they address many of the relevant questions regarding the prognosis and management of fetal isolated mild VM, there is a lack of good quality postnatal follow-up studies. The resulting uncertainties make antenatal counseling for this abnormality difficult. PMID- 19644945 TI - Fetal cerebral ventricular measurement and ventriculomegaly: time for procedure standardization. PMID- 19644946 TI - Acute infection with parvovirus B19 in early pregnancy. PMID- 19644947 TI - Hypertensive disorders in pregnancy: screening by uterine artery Doppler at 11-13 weeks. AB - OBJECTIVES: To examine the performance of screening for hypertensive disorders in pregnancy by a combination of the maternal factor-derived a-priori risk with the uterine artery (UtA) pulsatility index (PI) and to determine whether it is best in such screening to use the mean PI of the two arteries, the highest PI or the lowest PI. METHODS: This was a prospective screening study for pre-eclampsia (PE) requiring delivery before 34 weeks (early PE), late PE and gestational hypertension (GH) in women attending their routine first hospital visit in pregnancy at 11 + 0 to 13 + 6 weeks of gestation. Maternal history was recorded and color flow Doppler imaging was used to measure the left and right UtA-PI. The performance of screening for PE and GH by a combination of the maternal factor derived a-priori risks determined in a previous study and the UtA-PI was assessed. RESULTS: There were 8061 (96.4%) cases unaffected by PE or GH, 37 (0.4%) that developed early PE, 128 (1.5%) with late PE and 140 (1.7%) with GH. The lowest, mean and highest UtA-PI were significantly higher in early PE and late PE than in the controls (P < 0.0001) and in early PE than late PE (P < 0.0001). The lowest UtA-PI was higher in GH than in controls (P = 0.014). The best performance in screening was provided by the lowest PI. The detection rate of early PE at a 10% false-positive rate increased from 47% in screening by maternal factors alone to 81% in screening by maternal factors and the lowest UtA PI. The respective detection rates for late PE increased from 41% to 45% and those for GH increased from 31% to 35%. CONCLUSIONS: The patient-specific risk for PE and GH can be derived by combining the disease-specific maternal factor derived a-priori risk with the measurement of the lowest UtA-PI in a multivariate regression model. PMID- 19644948 TI - Placental site trophoblastic tumor diagnosed on transvaginal sonography. PMID- 19644949 TI - Perineural (Tarlov) cysts mimicking adnexal masses: a report of three cases. AB - Perineural (Tarlov) cysts are usually incidental findings during magnetic resonance imaging (MRI) performed for low back pain. However, in a tertiary women's hospital, they may present as incidental findings on gynecological ultrasound imaging. Approximately 40,000 pelvic scans are performed annually in our department. Tarlov cysts were identified in three women between August 2007 and September 2008. In two patients (Cases 1 and 3), these cysts were initially misdiagnosed as hydrosalpinges on ultrasound examination, the latter having a differential diagnosis of an ovarian cyst. Two patients (Cases 1 and 2) were symptomatic, although Case 2 had symptoms that could not entirely be accounted for by the location of the cyst. Although asymptomatic, Case 3 underwent laparoscopy with a view to salpingectomy/cystectomy. In these patients, confirmation of Tarlov cysts was subsequently made on either computed tomography (CT) or MRI. All three patients were managed conservatively. Here we describe their clinical presentation, the appearance of the cysts on ultrasound imaging and on CT or MRI, and their eventual outcomes. PMID- 19644950 TI - Three-dimensional ultrasound features of the polycystic ovary in Chinese women. AB - OBJECTIVES: To quantify the three-dimensional (3D) ultrasound characteristics of ovaries in Chinese women with polycystic ovarian syndrome (PCOS) and to compare these with previous data on a Caucasian cohort with PCOS. METHODS: 3D pelvic ultrasound was performed in 40 Chinese women with PCOS and 40 controls. Ovarian volume, stromal volume and echogenicity, and antral follicle count (AFC) were measured and ovarian blood flow was quantified using both 3D power Doppler and two-dimensional (2D) pulsed wave Doppler. These data were compared with previously published data on a Caucasian cohort with PCOS. RESULTS: Compared with controls, women with PCOS had a higher AFC (median (range), 15 (11-30) vs. 5.5 (1 10) per ovary, P < 0.01), ovarian volume (12.32 (8.10-16.16) mL vs. 5.64 (2.62 8.81) mL, P < 0.01) and stromal volume (9.74 (6.44-13.56) mL vs. 4.07 (1.52-6.67) mL, P < 0.01) but were comparable in stromal echogenicity and ovarian blood flow as measured by 3D power Doppler or 2D pulsed wave Doppler indices. However, in comparison with a previously reported Caucasian cohort with PCOS, the ovaries of Chinese women with PCOS had a significantly smaller stromal volume (median (range), 9.74 (6.44-13.56) mL vs. 10.79 (5.65-17.12) mL, P < 0.05), were less echogenic as reflected in a lower mean gray value (22.43 (13.13-35.50) vs. 32.36 (19.35-53.71), P < 0.01), and had reduced ovarian blood flow as reflected in a lower flow index (30.19 (23.32-44.88) vs. 33.54 (21.88-51.65), P < 0.05). CONCLUSION: Based on 3D ultrasound measurements, Chinese women with PCOS have an increased stromal volume compared with controls. However, their stromal volume, echogenicity and vascularity is significantly lower than that in Caucasian women with PCOS. The possible etiology for these differences is discussed. PMID- 19644951 TI - Reference ranges for middle cerebral artery peak systolic velocity in monochorionic diamniotic twins: a longitudinal study. AB - OBJECTIVES: The role of middle cerebral artery (MCA) peak systolic velocity (PSV) has become established in the management of fetal anemia. To date, singleton reference ranges have also been used in twin pregnancies. However, in monochorionic twin pregnancies, normal ranges for cerebral blood flow may differ from those in singletons owing to intertwin blood exchange. We aimed to establish gestational age-specific reference ranges for MCA-PSV in monochorionic diamniotic (MCDA) twin pregnancies, to compare them with previously reported singleton reference ranges, and to establish terms for calculating conditional reference intervals appropriate for individual serial measurements. METHODS: In a prospective longitudinal study we examined 50 uncomplicated MCDA pregnancies that were recruited between 11 and 14 weeks of gestation. Fetal MCA Doppler waveforms were assessed biweekly from 15 weeks of gestation onwards. Multilevel modeling was used to estimate gestational age-specific reference ranges for MCA-PSV and terms for conditional reference intervals were established. RESULTS: Based on 824 observations in 100 fetuses, normative ranges from 15 to 37 weeks of gestation were constructed. Median MCA-PSV increased with advancing gestational age. Measurements between 18 and 37 weeks were comparable to those in singletons. However, before 18 weeks MCA-PSV values were higher in MCDA twin pregnancies compared with singleton references. CONCLUSIONS: Between 18 and 37 weeks of gestation, reference ranges of singletons can be used to assess fetal anemia in MCDA twin pregnancies. Prior to 18 weeks the application of singleton references may lead to an increased number of false-positive diagnoses of presumed fetal anemia in MCDA twin pregnancies. PMID- 19644953 TI - Descriptive and normative fallacies in presenting detection rates. PMID- 19644954 TI - A novel androgen-dependent prostate cancer xenograft model derived from skin metastasis of a Japanese patient. AB - BACKGROUND: The incidence of, and mortality from, prostate cancer (PCa) has increased in Asian countries over the past decades, partly due to a change in dietary habits. Recent reports have revealed differences in the molecular basis of PCa among people of differing racial or ethnic backgrounds. PCa xenograft models established from Asian patients would be useful for understanding the basis of PCa in Asian populations; we therefore established and characterized a novel PCa xenograft model, JDCaP, from a metastatic skin lesion of a Japanese hormone-refractory prostate cancer (HRPC) patient. METHODS: Skin metastatic tissue derived from poorly differentiated prostatic adenocarcinoma in a 61-year old Japanese male was transplanted to nude mice and JDCaP was established by serial passage. Expression of androgen receptor (AR) and prostate-specific antigen (PSA) was evaluated by immunohistochemistry and the AR sequence was analyzed. Hormone sensitivity of JDCaP was investigated in vivo by orchiectomy followed by administration of steroid hormones, including testosterone, estradiol, progesterone, and hydrocortisone. Therapeutic effects of leuprorelin acetate, bicalutamide, flutamide, diethylstilbestrol (DES), and estradiol were investigated. RESULTS: JDCaP expressed wild-type AR and PSA and showed androgen dependence. Only testosterone administration maintained tumor proliferation after orchiectomy. Administration of leuprorelin acetate, bicalutamide, and flutamide inhibited tumor growth. DES and estradiol also demonstrated significant antitumor effects. CONCLUSIONS: JDCaP expresses wild-type ARs and exhibits androgen dependence despite its origin from a HRPC patient. The model may be useful to elucidate the molecular basis of PCa in Asian populations and to develop prevention and therapeutic strategies. PMID- 19644955 TI - Comparison of ACINUS, caspase-3, and TUNEL as apoptotic markers in determination of tumor growth rates of clinically localized prostate cancer using image analysis. AB - BACKGROUND: The balance between apoptotic and proliferative processes determines the enlargement of a tumor. Accurate measurement of apoptotic and proliferative rates from diagnostic prostate biopsies would allow calculation of tumor growth rates in a population-based prostate cancer (CaP) study. Automated image analysis may be used if proliferation and apoptotic biomarkers provide clearly resolved immunostained images. METHODS: Clinical CaP aggressiveness was assigned as low, intermediate or high using clinical criteria for 46 research subjects with newly diagnosed CaP. Diagnostic biopsy sections from the research subjects were dual labeled for proliferation biomarker, Ki-67 and apoptotic biomarker, apoptotic chromatin condensation inducer in the nucleus (ACINUS). Apoptotic biomarkers, caspase-3 and terminal deoxyribonucleotidyltransferase mediated dUTP-biotin nick end labeling (TUNEL) were labeled separately. Images from immunostained sections were analyzed using automated image analysis and tumor growth rates computed. Association between clinical CaP aggressiveness and tumor growth rates was explored. RESULTS: Sixteen subjects had high, 17 had intermediate, and 13 had low clinical CaP aggressiveness. Positive immunostaining was localized to the nucleus for Ki-67, ACINUS, and TUNEL. A statistically significant linear trend across clinical CaP aggressiveness categories was found when tumor growth rates were calculated using ACINUS (P = 0.046). Logistic regression and ROC plots generated showed ACINUS (AUC = 0.677, P = 0.048) and caspase-3 (AUC = 0.694, P = 0.038) to be better predictors than TUNEL (AUC = 0.669, P = 0.110). CONCLUSIONS: ACINUS met the criteria for automated image analysis and for calculation of apoptotic rate. Tumor growth rates determined using automated image analysis should be evaluated for clinical prediction of CaP aggressiveness, treatment response, recurrence, and mortality. PMID- 19644956 TI - Characterization of LMX-1A as a metastasis suppressor in cervical cancer. AB - DNA methylation is important in cancer development and is a promising biomarker for cancer detection. An epigenomic approach used in our previous work showed that LMX-1A is methylation-silenced in cervical cancer. LMX-1A, a LIM-homeobox gene, is known to participate in developmental events; however, there are at present no data on the role of LMX-1A in cancers. In this study, we characterized the function of this transcription factor by examining cell lines, animal models and human cervical neoplastic tissues, and found that over-expression of LMX-1A does not affect cell proliferation or the cell cycle of cervical cancer cell lines but significantly inhibits colony formation and invasion in vitro. Analysis of changes in epithelial-mesenchymal transition (EMT) markers, such as CDH1, CDH2, VIMENTIN, SNAIL, SLUG and TWIST, revealed involvement of the EMT in LMX-1A mediated cancer invasion; this result was validated in a stable transfectant over expressing LMX-1A with RNA interference. Xenograft studies using immunocompromised mice confirmed the suppressor effects of LMX-1A on tumour formation and distant metastasis in cervical cancer cell lines. LMX-1A immunohistochemical staining of tissue arrays containing the full spectrum of cervical neoplasms, including normal cervix, low-grade cervical intra-epithelial neoplasia (CIN), high-grade CIN, locally invasive and distant metastatic cancers, demonstrated the critical role of LMX-1A in invasion and metastasis. Furthermore, we found by analysing TGFbeta-BMP signalling that BMP4 and BMP6 are down regulated by LMX-1A. The results of this study suggest that LMX-1A suppresses cancer invasion and metastasis in cervical cancer through an incomplete EMT. PMID- 19644957 TI - Over-expression of AEG-1 significantly associates with tumour aggressiveness and poor prognosis in human non-small cell lung cancer. AB - Astrocyte elevated gene 1 (AEG-1), a novel oncoprotein, has been implicated in oncogenesis and cancer progression in various types of human cancers. The clinical significance and biological role of AEG-1 in non-small cell lung cancer (NSCLC), however, remain unclear. In the present study, we found that the expression of AEG-1 was markedly up-regulated in NSCLC cell lines and NSCLC tissues at the level of both transcription and translation. Ectopically expressed AEG-1 enhanced the migratory and invasive abilities of NSCLC cells, whereas knockdown of endogenous AEG-1 by specific shRNAs significantly inhibited these abilities. The function of AEG-1 on metastasis modulation was associated with the activation of the PI3K-Akt and NF-kappaB signalling pathways. Furthermore, we showed high expression of AEG-1 in 99/200 (49.5%) paraffin-embedded archival NSCLC specimens. Moreover, statistical analysis displayed a significant correlation in AEG-1 expression with the clinical stage (p < 0.001), T classification (p = 0.001), N classification (p = 0.015), distant metastasis (p = 0.004) and differentiation (p = 0.027). Patients with higher AEG-1 expression had an overall shorter survival time, whereas patients with lower expression of AEG-1 had a better survival time. Multivariate analysis suggested that AEG-1 expression might be an independent prognostic indicator for the survival of NSCLC patients. Taken together, our results suggest that elevated expression of AEG-1 plays an important role in the aggressiveness of NSCLC, leading to a poor clinical outcome. PMID- 19644958 TI - The pyrolysis of (-)-(S)-nicotine: racemization and decomposition. AB - The pyrolytic behaviour of (-)-(S)-nicotine in methanol was investigated using on line pyrolysis GC/MS to establish whether racemization to the R(+) antipode occurs and to identify other products of pyrolysis. The conditions used included pyrolysing the sample for 15 seconds in an atmosphere of 9% oxygen in nitrogen (275 ml/min total flow) across the temperature range of 200 degrees C-1000 degrees C. A chiral Cyclodex-B analytical column (30 m x 0.25 mm i.d. x 0.25 microm film thickness) was used to separate the enantiomers of nicotine, although the two enantiomer peaks were not baseline resolved. The results of the experiment shows that there is no increase in (+)-(R)-nicotine levels across a wide temperature range. This suggests that the elevated levels of (+)-R-nicotine observed in tobacco smoke (compared to tobacco leaf material) are not due to the pyrolytic auto-racemization of (-)-(S)-nicotine but are a result of more complex interactions between (-)-(S)-nicotine and other smoke components. The pyrolysis of isotopically labelled nicotine established that nicotine undergoes thermal decomposition to beta-nicotyrine which in turn may decompose to other products. PMID- 19644959 TI - Dysfunctional proinflammatory high-density lipoproteins confer increased risk of atherosclerosis in women with systemic lupus erythematosus. AB - OBJECTIVE: Women with systemic lupus erythematosus (SLE) have an increased risk of atherosclerosis. Identification of at-risk patients and the etiology underlying atherosclerosis in SLE remain elusive. The antioxidant capacity of normal high-density lipoproteins (HDLs) is lost during inflammation, and these dysfunctional HDLs might predispose individuals to atherosclerosis. The aim of this study was to determine whether dysfunctional proinflammatory HDL (piHDL) is associated with subclinical atherosclerosis in SLE. METHODS: Carotid artery ultrasound was performed in 276 women with SLE to identify carotid plaques and measure intima-media thickness (IMT). The antioxidant function of HDL was measured as the change in oxidation of low-density lipoprotein after the addition of HDL cholesterol. Two antiinflammatory HDL components, paraoxonase 1 and apolipoprotein A-I, were also measured. RESULTS: Among the SLE patients, 48.2% were determined to have piHDL on carotid ultrasound, while 86.7% of patients with plaque had piHDL compared with 40.7% of those without plaque (P<0.001). Patients with piHDL also had a higher IMT (P<0.001). After multivariate analysis, the only factors found to be significantly associated with plaque were the presence of piHDL (odds ratio [OR] 16.1, P<0.001), older age (OR 1.2, P<0.001), hypertension (OR 3.0, P=0.04), dyslipidemia (OR 3.4, P=0.04), and mixed racial background (OR 8.3, P=0.04). Factors associated with IMT measurements in the highest quartile were the presence of piHDL (OR 2.5, P=0.02), older age (OR 1.1, P<0.001), a higher body mass index (OR 1.07, P=0.04), a cumulative lifetime prednisone dose>or=20 gm (OR 2.9, P=0.04), and African American race (OR 8.3, P=0.001). CONCLUSION: Dysfunctional piHDL greatly increases the risk of developing subclinical atherosclerosis in SLE. The presence of piHDL was associated with an increased prevalence of carotid plaque and with a higher IMT. Therefore, determination of piHDL may help identify patients at risk for atherosclerosis. PMID- 19644960 TI - In vitro propagation and characterization of neoplastic stem/progenitor-like cells from human prostate cancer tissue. AB - BACKGROUND: According to the cancer stem cell hypothesis, tumor growth is sustained by a subpopulation of cancer stem/progenitor-like cells. Self-renewal and high clonogenic potential are characteristics shared by normal stem and neoplastic stem/progenitor-like cells. We investigated whether human prostate cancer specimens contain cells with these properties. METHODS: Self-renewal and clonogenic potential were assessed by serial passaging of spheres and colony formation, respectively. Gene expression was analyzed by real time PCR. Protein expression was detected by immunocytochemistry. The neoplastic nature of the cells was verified by detection of the TMPRSS2/ERG gene fusion expression. RESULTS: The epithelial fraction isolated from surgical specimens generated colonies in 68% (19/28) of the patients. Laminin adhesion selected for cells with high clonogenic potential. The epithelial fraction from 85% (42/49) of the patients generated primary prostaspheres. Serial passaging of prostaspheres demonstrated their self-renewal capacity, which is also supported by their expression of the stem cell markers Oct-4, Nanog, Bmi-1, and Jagged-1 mRNA. Cells derived from prostaspheres were more clonogenic than the parental epithelial fraction. The pattern of mRNA expression in prostaspheres resembled that of the basal compartment of the prostate (CK5(+)/CK14(+)/CK19(high)/CK18(-/low)/c met(+)/AR(-/low)/PSA(-/low)), but also included stem cell markers (CD49b(+)/CD49f(+)/CD44(+)/DeltaNp63(+)/Nestin(+)/CD133(+)). The distribution of marker expression in prostaspheres suggests their heterogeneous cell composition. Prostaspheres expressed significantly higher PSCA mRNA levels than the epithelial fraction. CONCLUSION: Human prostate cancer specimens contain neoplastic cells with self-renewal and clonogenic potential, which can be enriched and perpetuated in prostaspheres. Prostaspheres should prove valuable for the identification of prostate cancer stem/progenitor-like cells. PMID- 19644961 TI - Studies of cell-mediated immune responses to influenza vaccination in systemic lupus erythematosus. AB - OBJECTIVE: Both antibody and cell-mediated responses are involved in the defense against influenza. In patients with systemic lupus erythematosus (SLE), a decreased antibody response to subunit influenza vaccine has been demonstrated, but cell-mediated responses have not yet been assessed. This study was therefore undertaken to assess cell-mediated responses to influenza vaccination in patients with SLE. METHODS: Fifty-four patients with SLE and 54 healthy control subjects received subunit influenza vaccine. Peripheral blood mononuclear cells and sera were obtained before and 1 month after vaccination. Cell-mediated responses to A/H1N1 and A/H3N2 vaccines were evaluated using an interferon-gamma (IFNgamma) enzyme-linked immunospot assay and flow cytometry. Antibody responses were measured using a hemagglutination inhibition test. RESULTS: Prior to vaccination, patients with SLE had fewer IFNgamma spot-forming cells against A/H1N1 compared with control subjects and a lower frequency of IFNgamma-positive CD8+ T cells. After vaccination, the number of IFNgamma spot-forming cells increased in both patients and control subjects, although the number remained lower in patients. In addition, the frequencies of CD4+ T cells producing tumor necrosis factor and interleukin-2 were lower in patients after vaccination compared with healthy control subjects. As expected for a subunit vaccine, vaccination did not induce a CD8+ T cell response. For A/H3N2-specific responses, results were comparable. Diminished cell-mediated responses to influenza vaccination were associated with the use of prednisone and/or azathioprine. The increase in A/H1N1-specific and A/H3N2-specific antibody titers after vaccination was lower in patients compared with control subjects. CONCLUSION: In addition to a decreased antibody response, cell-mediated responses to influenza vaccination are diminished in patients with SLE, which may reflect the effects of the concomitant use of immunosuppressive drugs. This may render these patients more susceptible to (complicated) influenza infections. PMID- 19644963 TI - Association of a variant in the muscarinic acetylcholine receptor 2 gene (CHRM2) with nicotine addiction. AB - Genetic factors contribute to the overall risk of developing nicotine addiction, which is the major cause of preventable deaths in western countries. However, knowledge regarding specific polymorphisms influencing smoking phenotypes remains scarce. In the present study we provide evidence that a common single nucleotide polymorphism (SNP) in the 5' untranslated region of CHRM2, the gene coding for the muscarinic acetylcholine receptor 2 is associated with nicotine addiction. CHRM2 was defined as a candidate gene for nicotine addiction based on previous evidence that linked variations in CHRM2 to alcohol and drug dependence. A total of more than 5,500 subjects representative of the German population were genotyped and assessed regarding their smoking habits. The impact of three SNPs in CHRM2 on smoking behavior/nicotine addiction was investigated using logistic regression models or a quasi-Poisson regression model, respectively. We found the T allele of SNP rs324650 to be associated with an increased risk of smoking/nicotine dependence according to three different models, the recessive models of regular or heavy smokers vs. never-smokers (odds ratio 1.17 in both analyses) and according to the Fagerstrom index of nicotine addiction. In the analysis stratified by gender this association was only found in females. Our data provide further evidence that variations in CHRM2 may be associated with the genetic risk of addiction in general or with certain personality traits that predispose to the development of addiction. Alternatively, variations in CHRM2 could modulate presynaptic auto-regulation in cholinergic systems and may thereby affect an individual's response to nicotine more specifically. PMID- 19644962 TI - European population substructure is associated with mucocutaneous manifestations and autoantibody production in systemic lupus erythematosus. AB - OBJECTIVE: To determine whether genetic substructure in European-derived populations is associated with specific manifestations of systemic lupus erythematosus (SLE), including mucocutaneous phenotypes, autoantibody production, and renal disease. METHODS: SLE patients of European descent (n=1,754) from 8 case collections were genotyped for >1,400 ancestry informative markers that define a north-south gradient of European substructure. Using the Structure program, each SLE patient was characterized in terms of percent Northern (versus percent Southern) European ancestry based on these genetic markers. Nonparametric methods, including tests for trend, were used to identify associations between Northern European ancestry and specific SLE manifestations. RESULTS: In multivariate analyses, increasing levels of Northern European ancestry were significantly associated with photosensitivity (Ptrend=0.0021, odds ratio for highest quartile of Northern European ancestry versus lowest quartile [ORhigh low] 1.64, 95% confidence interval [95% CI] 1.13-2.35) and discoid rash (Ptrend=0.014, ORhigh-low 1.93, 95% CI 0.98-3.83). In contrast, increasing levels of Northern European ancestry had a protective effect against the production of anticardiolipin autoantibodies (Ptrend=1.6x10(-4), ORhigh-low 0.46, 95% CI 0.30 0.69) and anti-double-stranded DNA autoantibodies (Ptrend=0.017, ORhigh-low 0.67, 95% CI 0.46-0.96). CONCLUSION: This study demonstrates that specific SLE manifestations vary according to Northern versus Southern European ancestry. Thus, genetic ancestry may contribute to the clinical heterogeneity and variation in disease outcomes among SLE patients of European descent. Moreover, these results suggest that genetic studies of SLE subphenotypes will need to carefully address issues of population substructure based on genetic ancestry. PMID- 19644964 TI - Inequality of opportunity in health: evidence from a UK cohort study. AB - This paper proposes an empirical implementation of the concept of inequality of opportunity in health and applies this to data from the UK National Child Development Study. Drawing on the distinction between circumstance and effort variables in John Roemer's work on equality of opportunity, circumstances are proxied by parental socio-economic status and childhood health; effort is proxied by health-related lifestyles and educational attainment. Stochastic dominance tests are used to detect inequality of opportunity in the conditional distributions of self-assessed health in adulthood. Two alternative approaches are used to measure inequality of opportunity. Econometric models are estimated to illuminate and quantify the triangular relationship between circumstances, effort and health. The results indicate the existence of a considerable and persistent inequality of opportunity in health. Circumstances affect health in adulthood both directly and through effort factors such as educational attainment. This indicates that, while the influence of some unjust circumstances can only be tackled during childhood, the implementation of complementary educational policies may be of paramount importance. PMID- 19644965 TI - The effect of anterior abdominal wall scars on the vascular anatomy of the abdominal wall: A cadaveric and clinical study with clinical implications. AB - The anterior abdominal wall integument is frequently used in a range of reconstructive flaps. These tissues are supplied by the deep and superficial inferior epigastric arteries (DIEA and SIEAs) and the deep and superficial superior epigastric arteries (DSEA and SSEAs). Previous abdominal wall surgery alters this vascular anatomy and may influence flap design. One hundred and sixty eight patients underwent abdominal wall computed tomographic angiography (CTA) for preoperative imaging. Fifty-eight of these patients had undergone previous abdominal surgery, and were assessed for scar pattern and relationship to the course and distribution of all major axial vessels and perforators. Two cadaveric abdominal wall specimens with midline abdominal scars underwent contrast injection of the DIEAs and DSEAs, with subsequent CTA. The course and distribution of all cutaneous vessels were assessed. In all clinical and cadaveric cases, the vasculature of the abdominal wall had been altered by previous surgery. In the clinical cases, vascular architecture was universally altered in the region of the scar, often modifying the filling patterns of the abdominal wall and occasionally precluding the use of an abdominal wall flap. In both cadaveric specimens, regions of non-filling were evident upon contrast injection, highlighting the angiosomes not supplied by the DIEA or DSEA. Previous abdominal wall surgery necessarily alters the vascular architecture of the abdominal wall, and may alter the source vessels supplying cutaneous tissues. CTA was useful in identifying and delineating these changes, and may be used as a preoperative tool in this role. PMID- 19644966 TI - Shape, height, and location of the lingula for sagittal ramus osteotomy in Thais. AB - This study aims to investigate the shape, height, and location of the lingula in relation to surrounding structures for sagittal ramus osteotomy. Dried Thai mandibles were studied and compared with other races. From both sides of 92 mandibles, the shape of the lingula was classified into triangular, truncated, nodular, or assimilated types. Of 92 mandibles, 146 sides with at least a premolar and a molar on the same side were selected for distance measurement. Height of the lingula was measured from the lingular tip to the mandibular foramen. The location was determined by five distances from the lingular tip to: the anterior and the posterior borders of the mandibular ramus, the mandibular notch, the distal surface of the mandibular second molar, and the occlusal plane. The results showed that truncated lingulae were most frequently found (46.2%) and most appeared to be bilateral (71.7%). Triangular, nodular, and assimilated shapes presented in 29.9%, 19.6%, and 4.3%, respectively. The mean lingular height was 8.2 +/- 2.3 mm. The lingula was located at 20.6 +/- 3.5 mm from the anterior border of the mandibular ramus and 16.6 +/- 2.9 mm from the mandibular notch. In the majority of the mandibles studied, the lingula was located above the occlusal plane. In conclusion, the shape and metric characteristics of the lingula in relation to surrounding structures in Thais vary from other races. All parameters associated with the lingula should be considered for sagittal ramus osteotomy to avoid intraoperative complications. PMID- 19644967 TI - Consideration of the blood supply of the ileocecal segment in valve preserving right hemicolectomy. AB - The ileocecal valve (ICV) is known to control the flow of chyme and to prevent bacterial colonization of the small intestine. Preservation of this segment during right hemicolectomy is likely to prevent loss of its function. This study aimed at evaluating the arterial supply of the ICV to help preserve the valve during right hemicolectomy. Fifty-four fresh human cadavers (37 male, 17 female; median age: 54 years, range: 18-90 years) were studied after relatives gave written, informed consent. At postmortem, 20 cm of terminal ileum with the ileocecal segment and up to 20 cm of ascending colon were removed en bloc with its mesentery and blood supply. The ileocolic artery was cannulated and injected with 10 ml of water-soluble red dye under pressure. The arterial supply was dissected to demonstrate a pattern. In all, the ICV was supplied by the ileocolic artery, a branch of the superior mesenteric, which divided into an anterior and a posterior cecal artery. A marginal branch of the right colic was noted to contribute to ICV blood supply in only two (4%). Furthermore, study of the anastomosis at the ICV showed that the anterior cecal artery was present in all (100%), posterior cecal in 48 (89%), and recurrent ileal artery in 53 (98%). A rich anastomosis between vessels at the ICV; small "windows," short tributaries, were seen in 38 (70%), whereas a poor anastomotic network at the ICV; large "windows," long tributaries, between these vessels were seen in 12 (22%). In four (8%), we were unable to clearly determine between rich and poor anastomotic networks. Other variants included, absent posterior cecal artery in six (11%) and absent recurrent ileal artery in one (2%). The ICV has a predictable blood supply in the majority of patients. Preservation of the anterior cecal artery would ensure a vascularized ICV in right hemicolectomy. PMID- 19644968 TI - Palmaris profundus: one name, several subtypes, and a shared potential for nerve compression. AB - The palmaris profundus is a rare, but known anatomic variation which may lead to compression of the median nerve and/or its branches. Two patients with carpal tunnel syndrome are presented in whom a palmaris profundus was discovered at operation. In these cases, median nerve compression at the wrist was attributed to the course of the extra tendon and its local mass effect on the nerve (i.e., the palmaris profundus and median nerve shared a common sheath); more commonly, the resultant decreased available space for the median nerve within the carpal tunnel due to the presence of an accessory (10th) flexor tendon is thought to be responsible. Postoperative 3 Tesla magnetic resonance imaging (MRI) was performed to demonstrate the full course of the variant muscle; despite variations in the size and longitudinal extent of the accessory musculotendinous unit, an important similarity was noted: the intimate relationship of the median nerve and the palmaris profundus. These two cases and our review of the literature highlight the fact that one name (i.e. palmaris profundus) reflects several anatomic subtypes. However, the close relationship of the palmaris profundus with the median nerve in the forearm and the palm is a common theme which emphasizes the potential pathoanatomic consequences of this relationship: nerve compression. PMID- 19644969 TI - Fetal topohistology of the mesocolon transversum with special reference to fusion with other mesenteries and fasciae. AB - The developing mesocolon transversum was investigated using hematoxylin and eosin stained semiserial sections derived from 17 human fetuses between 12 and 30 weeks of gestation. The mesocolon was attached to the mesoduodenum and greater omentum until 12 weeks. However, the fetal duodenal attachment appeared not to correspond to the right colic flexure in adults. The greater omentum and mesocolon were likely to be irregularly folded at the attachment site possibly because the developing transverse colon "ran into" and pushed up the greater omentum and pancreatic head. Lymphatic vessels invaded the indistinct fusion plane to destroy the primary configuration. Moreover, the mesocolon seemed to "seize" or take-over some parts of the splenic side of the greater omentum, but the thick gastric side containing the right gastroepiploic artery and vein remained along the greater curvature. Until 20 weeks, the left colic flexure was fixed to the pancreatic tail, and near the flexure the mesocolon also fused with the renal fascia. The left splenic end of the greater omentum was folded and fused together to form a thick ligament-like structure, i.e., the gastrocolic ligament. In addition, near the duodenojejunal junction, a peritoneal bridge was often seen containing the inferior mesenteric artery or vein. Although surgeons generally believe that the mesocolon can be gently detached from the greater omentum, the fusion plane in adults appears to be the result of secondary modification and simplification by vascular development. PMID- 19644970 TI - Protective mechanisms of the common fibular nerve in and around the fibular tunnel: a new concept. AB - The most frequent site at which the common fibular nerve is affected by compression, trauma, traction, masses, and surgery is within and around the fibular tunnel. The aim of this study was to determine whether there were protective mechanisms at this site that guard against compression of the nerve. Twenty-six lower limbs of 13 preserved adult cadavers (11 males and two females) were used. Proximal to the entrance of the tunnel, three anatomical configurations seemed to afford the required protection for the nerve: reinforcement of the deep fascia; tethering of the common fibular nerve to both the tendon of the biceps femoris and the reinforced fascia; and the particular arrangement of the deep fascia, fibular head, and soleus and gastrocnemius muscles. At the entrance of the tunnel, contraction of the first segment of fibularis longus muscle could afford the required protection. In the tunnel, contraction of the second and third segments of fibularis longus muscle could guard against compression of the nerve. The tough fascia on the surface of fibularis longus muscle and the fascial band within it, which have long been accused of compression of the nerve, may actually be elements of the protective mechanisms. We conclude that there are innate, anatomical protective mechanisms which should be taken into consideration when decompressing the common fibular nerve. To preserve these mechanisms whenever possible, the technique should be planned and varied according to the underlying etiology. PMID- 19644971 TI - Arterial anatomy of the hallucal sesamoids. AB - The aim of this study was to analyze the arterial supply of the sesamoid bones of the hallux. Twenty-two feet from adult cadavers were injected with epoxide resin or an acrylic polymer in methyl methacrylate (Acrifix) and subsequently processed by two slice plastination methods and the enzyme maceration technique. Afterwards, the arterial supply of the sesamoid bones was studied. The first plantar metatarsal artery provided a medial branch to the medial sesamoid bone. The main branch of the first plantar metatarsal artery continued its course distally along the lateral side of the lateral sesamoid and supplied it. The supplying arteries penetrated the sesamoid bones on the proximal, plantar, and distal sides. The analysis and cataloging of the microvascular anatomy of the sesamoids revealed the first plantar metatarsal artery as the main arterial source to the medial and lateral sesamoid bones. In addition, the first plantar metatarsal artery ran along the lateral plantar side of the lateral sesamoid bone, suggesting that this artery is at increased risk during soft-tissue procedures such as hallux valgus surgery. PMID- 19644972 TI - Follow-up may not be beneficial after treatment of grade 1 breast cancer. AB - BACKGROUND: Identification of women treated for breast cancer who have a low risk of locoregional recurrence or contralateral breast cancer, and who can be discharged safely from follow-up, would lower costs without compromising prognosis. This study investigated the risk of locoregional recurrence and contralateral breast cancer in women treated for grade 1 breast cancer. METHODS: Some 1143 women who had surgery for breast cancer were followed, and the rate of locoregional recurrence or contralateral breast cancer was determined. The risk was compared to the tumour grade. RESULTS: At a mean follow-up of 9.1 years, 10 year estimates of the cumulative risk of locoregional recurrence or contralateral breast cancer for grade 1, 2 and 3 breast cancer were 0.03 (95 per cent confidence interval (c.i.) 0.01 to 0.08), 0.12 (0.09 to 0.15) and 0.16 (0.13 to 0.20) respectively. Grade 1 tumours had a risk of locoregional recurrence or contralateral breast cancer of 285 (95 per cent c.i. 93 to 670) per 100,000 person-years. CONCLUSION: Women treated for grade 1 breast cancer could be discharged from follow-up after completion of the primary treatment, without compromising their quality of care. PMID- 19644973 TI - Randomized clinical trial comparing laparoscopic and open surgery in patients with rectal cancer. AB - BACKGROUND: The laparoscopic treatment of rectal cancer is controversial. This study compared surgical outcomes after laparoscopic and open approaches for mid and low rectal cancers. METHODS: Some 204 patients with mid and low rectal adenocarcinomas were allocated randomly to open (103) or laparoscopic (101) surgery. The surgical team was the same for both procedures. Most patients had stage II or III disease, and received neoadjuvant therapy with oral capecitabine and 50-54 Gy external beam radiotherapy. RESULTS: Sphincter-preserving surgery was performed in 78.6 and 76.2 per cent of patients in the open and laparoscopic groups respectively. Blood loss was significantly greater for open surgery (P < 0.001) and operating time was significantly greater for laparoscopic surgery (P = 0.020), and return to diet and hospital stay were longer for open surgery. Complication rates, and involvement of circumferential and radial margins were similar for both procedures, but the number of isolated lymph nodes was greater in the laparoscopic group (mean 13.63 versus 11.57; P = 0.026). There were no differences in local recurrence, disease-free or overall survival. CONCLUSION: Laparoscopic surgery for rectal cancer has a similar complication rate to open surgery, with less blood loss, rapid intestinal recovery, shorter hospital stay, and no compromise of oncological outcomes. PMID- 19644974 TI - Phase II study of neoadjuvant chemotherapy and extended surgery for locally advanced gastric cancer. AB - BACKGROUND: Locally advanced gastric cancer with extensive lymph node metastasis is usually considered unresectable and so treated by chemotherapy. This trial explored the safety and efficacy of preoperative chemotherapy followed by extended surgery in the management of locally advanced gastric adenocarcinoma. METHODS: Patients with gastric cancer with extensive lymph node metastasis received two or three 28-day cycles of induction chemotherapy with irinotecan (70 mg/m(2) on days 1 and 15) and cisplatin (80 mg/m(2) on day 1), and then underwent gastrectomy with curative intent with D2 plus para-aortic lymphadenectomy. Primary endpoints were 3-year overall survival and incidence of treatment-related death. RESULTS: The study was terminated because of three treatment-related deaths when 55 patients had been enrolled (mortality rate above 5 per cent). Two deaths were due to myelosuppression and one to postoperative complications. Clinical response and R0 resection rates were 55 and 65 per cent respectively. The pathological response rate was 15 per cent. Median overall survival was 14.6 months and the 3-year survival rate 27 per cent. CONCLUSION: This multimodal treatment of locally advanced gastric cancer provides reasonable 3-year survival compared with historical data, but at a considerable cost in terms of morbidity and mortality. PMID- 19644975 TI - Systematic review of endoscopic ultrasonography versus endoscopic retrograde cholangiopancreatography for suspected choledocholithiasis. AB - BACKGROUND: Endoscopic ultrasonography (EUS) has emerged as an accurate diagnostic alternative to endoscopic retrograde cholangiopancreatography (ERCP). The aim of this study was to perform a systematic review of all randomized controlled trials of EUS-guided ERCP versus ERCP alone in patients with suspected choledocholithiasis. METHODS: The search for eligible studies was carried out using the MEDLINE, Cochrane Central Register of Controlled Trials, and Science Citation Index electronic databases. Meta-analysis was conducted using a random effects model. RESULTS: Four trials containing 213 patients randomized to EUS guided ERCP and 210 to ERCP alone were selected. In the EUS-guided ERCP group, ERCP was avoided in 143 patients (67.1 per cent) when EUS did not detect choledocholithiasis. The use of EUS significantly reduced the risk of overall complications (relative risk 0.35 (95 per cent confidence interval (c.i.) 0.20 to 0.62); P < 0.001) and post-ERCP acute pancreatitis (relative risk 0.21 (95 per cent c.i. 0.06 to 0.83); P = 0.030). CONCLUSION: By performing EUS first, ERCP may be safely avoided in two-thirds of patients with common bile duct stones. Application of EUS in the selection of patients for therapeutic ERCP significantly reduces the complication rate. PMID- 19644976 TI - Nonresponse to a population-based postdisaster postal questionnaire study. AB - We examined nonparticipation in a 2-year postdisaster mail survey of Norwegian tourists evacuated from countries affected by the 2004 tsunami. One hundred seventy-one persons out of a random sample of 330 nonparticipants were telephone interviewed concerning disaster exposure, current posttraumatic stress reactions, and reasons for not participating. Fewer nonparticipants than participants had been in a place directly affected by the tsunami. Nonparticipants reported less perceived threat of death and lower levels of posttraumatic stress reactions. Reasons for not participating were "lack of interest or time" (39.2%), "lack of relevant experiences" (32.2%), and "too personal or emotionally disturbing" (15.2%). Our findings suggest that postdisaster studies may be biased in the direction of more severe disaster exposure and pronounced posttraumatic stress reactions. PMID- 19644977 TI - Extremely low frequency pulsed electromagnetic field designed for antinociception does not affect microvascular responsiveness to the vasodilator acetylcholine. AB - A 225 microT, extremely low frequency, pulsed electromagnetic field (PEMF) that was designed for the induction of antinociception, was tested for its effectiveness to influence blood flow within the skeletal microvasculature of a male Sprague-Dawley rat model (n = 103). Acetylcholine (0.1, 1.0, or 10 mM) was used to perturb normal blood flow and to delineate differential effects of the PEMF, based on degree of vessel dilation. After both 30 and 60 min of PEMF exposure, we report no effects on peak perfusion response to acetylcholine (with only 0.2% of the group difference attributed to exposure). Spectral analysis of blood flow data was generated to obtain information related to myogenic activity (0.15-0.40 Hz), respiratory rate (0.4-2.0 Hz), and heart rate (2.0-7.0 Hz), including the peak frequency within each of the three frequency regions identified above, peak power, full width at half maximum (FWHM), and mean within band. No significant effects due to exposure were observed on myogenic activity of examined blood vessels, or on heart rate parameters. Anesthesia-induced respiratory depression was, however, significantly reduced following PEMF exposure compared to shams (although exposure only accounted for 9.4% of the group difference). This set of data suggest that there are no significant acute physiological effects of 225 microT PEMF after 30 and 60 min of exposure on peak blood flow, heart rate, and myogenic activity, but perhaps a small attenuation effect on anesthetic-induced respiratory depression. PMID- 19644978 TI - Mobile telephone use is associated with changes in cognitive function in young adolescents. AB - As part of the Mobile Radiofrequency Phone Exposed Users' Study (MoRPhEUS), a cross-sectional epidemiological study examined cognitive function in secondary school students. We recruited 317, 7th grade students (144 boys, 173 girls, median age 13 years) from 20 schools around Melbourne, Australia. Participants completed an exposure questionnaire based on the Interphone study, a computerised cognitive test battery, and the Stroop colour-word test. The principal exposure metric was the total number of reported mobile phone voice calls per week. Linear regression models were fitted to cognitive test response times and accuracies. Age, gender, ethnicity, socio-economic status and handedness were fitted as covariates and standard errors were adjusted for clustering by school. The accuracy of working memory was poorer, reaction time for a simple learning task shorter, associative learning response time shorter and accuracy poorer in children reporting more mobile phone voice calls. There were no significant relationships between exposure and signal detection, movement monitoring or estimation. The completion time for Stroop word naming tasks was longer for those reporting more mobile phone voice calls. The findings were similar for total short message service (SMS, also known as text) messages per week, suggesting these cognitive changes were unlikely due to radiofrequency (RF) exposure. Overall, mobile phone use was associated with faster and less accurate responding to higher level cognitive tasks. These behaviours may have been learned through frequent use of a mobile phone. PMID- 19644983 TI - PhotoMorphs: a novel light-activated reagent for controlling gene expression in zebrafish. AB - Manipulating gene expression in zebrafish is critical for exploiting the full potential of this vertebrate model organism. Morpholino oligos are the most commonly used antisense technology for knocking down gene expression. However, morpholinos suffer from a lack of control over the timing and location of knockdown. In this report, we describe a novel light- activatable knockdown reagent called PhotoMorph. PhotoMorphs can be generated from existing morpholinos by hybridization with a complementary caging strand containing a photocleavable linkage. The caging strand neutralizes the morpholino activity until irradiation of the PhotoMorph with UV light releases the morpholino. We generated PhotoMorphs to target genes encoding enhanced green fluorescent protein, No tail, and E cadherin to illustrate the utility of this approach. Temporal control of gene expression with PhotoMorphs permitted us to circumvent the early lethal phenotype of E-cadherin knockdown. A splice-blocking PhotoMorph directed to the rheb gene showed light-dependent gene knockdown up to 72 hpf. PhotoMorphs thus offer a new class of laboratory reagents suitable for the spatiotemporal control of gene expression in the zebrafish. PMID- 19644984 TI - Synthesis, characterization, redox properties, and photodynamics of donor acceptor nanohybrids composed of size-controlled cup-shaped nanocarbons and porphyrins. AB - Cup-shaped nanocarbons (CNC) generated by the electron-transfer reduction of cup stacked carbon nanotubes have been functionalized with porphyrins (H(2)P) as light-capturing chromophores. The resulting donor-acceptor nanohybrid has been characterized by thermogravimetric analysis (TGA), Raman and IR spectroscopy, transmission electron microscopy, elemental analysis, and UV/Vis spectroscopy. The weight of the porphyrins attached to the cup-shaped nanocarbons was determined as 20% by TGA and elemental analysis. The UV/Vis absorption spectrum of CNC-(H(2)P)(n) in DMF agrees well with that obtained by the superposition of reference porphyrin (ref-H(2)P) and cup-shaped nanocarbons. The photoexcitation of the CNC-(H(2)P)(n) nanohybrid results in formation of the charge-separated (CS) state to attain the longest CS lifetime (0.64+/-0.01 ms) ever reported for donor-acceptor nanohybrids, which may arise from efficient electron migration following the charge separation. The formation of a radical ion pair was detected directly by electron spin resonance (ESR) measurements under photoirradiation of CNC-(H(2)P)(n) with a high-pressure mercury lamp in frozen DMF at 153 K. The observed ESR signal at g = 2.0044 agrees with that of ref-H(2)P(*+) produced by one-electron oxidation with [Ru(bpy)(3)](3+) in deaerated CHCl(3), indicating the formation of H(2)P(*+). The electron-acceptor ability of the reference CNC compound (ref-CNC) was also examined by the electron-transfer reduction of ref CNC by a series of semiquinone radical anions. PMID- 19644985 TI - Enantioselective synthesis of fluorene derivatives by chiral phosphoric acid catalyzed tandem double Friedel-Crafts reaction. PMID- 19644986 TI - Highly diastereoselective gold- or copper-catalyzed formal [4+3] cycloaddition of 1-(1-alkynyl) cyclopropyl ketones and nitrones. PMID- 19644987 TI - Enantioselective nitroso-Diels-Alder reaction and its application for the synthesis of (-)-peracetylated conduramine A-1. AB - Cu(I)-catalyzed enantioselective nitroso-Diels-Alder reactions (NDA reactions) of 2-nitrosopyridine with various dienes are presented. The [CuPF(6)(MeCN)(4)]/Walphos-CF(3) catalyst system is best suited to catalyze the NDA reaction of various dienes by using 2-nitrosopyridine as a dienophile. In most of the cases studied, cycloadducts are obtained in quantitative yield with very good to excellent enantioselectivities. Based on DFT calculations, a model to explain the stereochemical outcome of the NDA reaction is presented. Finally, an efficient short synthesis of (-)-peracetylated conduramine A-1 by applying the enantioselective NDA reaction as a key step is described. PMID- 19644988 TI - Microfluidic formation of monodisperse, cell-sized, and unilamellar vesicles. PMID- 19644989 TI - Ring-opening polymerization with synergistic co-monomers: access to a boronate functionalized polymeric monolith for the specific capture of cis-diol-containing biomolecules under neutral conditions. PMID- 19644990 TI - Self-replicating amphiphilic beta-sheet peptides. PMID- 19644991 TI - An efficient formal synthesis of the human telomerase inhibitor (+/-)-gamma rubromycin. PMID- 19644992 TI - Tiny tags on RNA. PMID- 19644993 TI - In situ monitoring of backbone thioester exchange by 19F NMR. PMID- 19644994 TI - Disruption of transcriptionally active Stat3 dimers with non-phosphorylated, salicylic acid-based small molecules: potent in vitro and tumor cell activities. PMID- 19644995 TI - Noncompetitive inhibitor of thrombin. PMID- 19644996 TI - Phosphate functional core-shell polymer nanoparticles for the release of vascular endothelial growth factor. PMID- 19644997 TI - Stabilization and large nonlinearity of gold nanoparticles functionalized with a pi-conjugated polymer. AB - Gold nanoparticles protected by a novel pi-conjugated polymer [poly(p-phenylene ethynylene) containing pendent disulfide and bipyridine groups] are synthesized and characterized. The polymer can stabilize the gold nanoparticles effectively. The nonlinear optical properties of the gold nanoparticle colloid solutions in toluene are investigated by using the Z-scan technique at a wavelength of 532 nm and pulse width of 4 ns. The gold-nanoparticle colloid solutions show an exceptional nonlinear absorption effect, which simultaneously contains the saturated absorption resulting from third-order nonlinearity and a large reverse saturated absorption resulting from fifth-order nonlinearity. In addition, asymmetric self-focusing refractive effects are investigated in the colloid solutions. PMID- 19644998 TI - A bistable molecular switch driven by photoinduced hydrogen-atom transfer. AB - The occurrence of photoinduced hydrogen atom transfer between two remote spots of a molecule is experimentally demonstrated. This photoprocess involves the intermediacy of an intramolecular "crane". In an experimental case study, 7 hydroxy-4-methylquinoline-8-carbaldehyde monomers isolated in low-temperature Ar matrices are investigated. On UV (lambda>295 nm) irradiation, a hydrogen atom is transferred from the O(7)H group to the N(1) atom of the quinoline ring. Subsequent irradiation with UV (lambda>360 nm) light reveals that the phototransformation is partially photoreversible. In the studied hydrogen-atom transfer process, the exocyclic carbaldehyde group plays the role of an intramolecular crane. The possible application of systems analogous to 7-hydroxy 4-methylquinoline-8-carbaldehyde as optically driven molecular switches is discussed. PMID- 19644999 TI - Analysis of single-molecule fluorescence spectroscopic data with a Markov modulated Poisson process. AB - We present a photon-by-photon analysis framework for the evaluation of data from single-molecule fluorescence spectroscopy (SMFS) experiments using a Markov modulated Poisson process (MMPP). A MMPP combines a discrete (and hidden) Markov process with an additional Poisson process reflecting the observation of individual photons. The algorithmic framework is used to automatically analyze the dynamics of the complex formation and dissociation of Cu2+ ions with the bidentate ligand 2,2'-bipyridine-4,4'dicarboxylic acid in aqueous media. The process of association and dissociation of Cu2+ ions is monitored with SMFS. The dcbpy-DNA conjugate can exist in two or more distinct states which influence the photon emission rates. The advantage of a photon-by-photon analysis is that no information is lost in preprocessing steps. Different model complexities are investigated in order to best describe the recorded data and to determine transition rates on a photon-by-photon basis. The main strength of the method is that it allows to detect intermittent phenomena which are masked by binning and that are difficult to find using correlation techniques when they are short lived. PMID- 19645000 TI - Evidence for interleaflet slip during spreading of single lipid bilayers at hydrophilic solids. PMID- 19645001 TI - Docking studies of structurally diverse antimalarial drugs targeting PfATP6: no correlation between in silico binding affinity and in vitro antimalarial activity. AB - PfATP6, a calcium-dependent ATPase of Plasmodium falciparum, is considered the putative target of the antimalarial drug artemisinin and its derivatives. Herein, the 3D structure of PfATP6 was modeled on the basis of the crystal structure of SERCA 1a, the mammalian homologue. Model validation was achieved using protein structure checking tools. AutoDock4 was used to predict the binding affinities of artemisinin (and analogues) and various other antimalarial agents for PfATP6, for which in vitro activity is also reported. No correlation was found between the affinity of the compounds for PfATP6 predicted by AutoDock4 and their antimalarial activity. PMID- 19645002 TI - Tungsten-induced protein aggregation: solution behavior. AB - Tungsten has been associated with protein aggregation in prefilled syringes (PFSs). This study probed the relationship between PFSs, tungsten, visible particles, and protein aggregates. Experiments were carried out spiking solutions of two different model proteins with tungsten species obtained from the extraction of tungsten pins typically used in syringe manufacturing processes. These results were compared to those obtained with various soluble tungsten species from commercial sources. Although visible protein particles and aggregates were induced by tungsten from both sources, the extract from tungsten pins was more effective at inducing the formation of the soluble protein aggregates than the tungsten from other sources. Furthermore, our studies showed that the effect of tungsten on protein aggregation is dependent on the pH of the buffer used, the tungsten species, and the tungsten concentration present. The lower pH and increased tungsten concentration induced more protein aggregation. The protein molecules in the tungsten-induced aggregates had mostly nativelike structure, and aggregation was at least partly reversible. The aggregation was dependent on tungsten and protein concentration, and the ratio of these two and appears to arise through electrostatic interaction between protein and tungsten molecules. The level of tungsten required from the various sources was different, but in all cases it was at least an order of magnitude greater than the typical soluble tungsten levels measured in commercial PFS. PMID- 19645003 TI - Differences in the interaction between aryl propionic acid derivatives and poly(vinylpyrrolidone) K30: A multi-methodological approach. AB - The present work aims at the application of several methods to explain differences in the physical interaction of some aryl propionic acid derivatives (ibuprofen [IBP], ketoprofen [KET], flurbiprofen [FLU], naproxen [NAP], fenbufen [FEN]) with poly(vinylpyrrolidone) (PVP) K30, stored together at 298 +/- 0.5 K and 22% RH. X-ray powder diffractometry and (13)C-solid state NMR demonstrated that IBP was able to strongly interact with the polymer, while weak interaction was observed for KET, FLU, NAP, and the least for FEN. The interaction of comelted drug and PVP was studied by differential scanning calorimetry by applying the Gordon-Taylor equation, which revealed that small molar drug volumes may favour the drug diffusion through the PVP amorphous chains increasing the polymer free volume and decreasing the mixture T(g). The molecular docking study revealed that intermolecular energy is mainly due to the contribution of van der Waals energy component, causing the differences among the drugs, and is related to the drug-PVP surface contact area in the complex formed. Solid-state kinetic study demonstrated that IBP molecules are involved in a three-dimensional diffusion mechanism within the polymer favoured by its low molar volume that reduces molecular hindrance, and by the weakness of its crystal lattice, which facilitates crystallinity loss and stabilisation of the amorphous phase. PMID- 19645004 TI - Multivariate modeling of encapsulation and release of an ionizable drug from polymer microspheres. AB - In the formulation of polymer microspheres (MSs) loaded with verapamil hydrochloride (VRP), a low molecular weight ionizable drug, by W/O/W emulsification, the pH of the external aqueous phase proved to be a primary determinant of both IE and drug release behavior. Increasing the pH of the external aqueous phase enhanced IE (approximately 100% at pH 8.4). This was associated with a considerable increase in initial release rate at pH 1.2. Two multivariate methods, factorial analysis (FA) and artificial neural network (ANN), were used to investigate the impact of the combined effect of the external phase pH and other parameters (polymer concentration and initial drug load) on MS characteristics; IE, initial drug release, MS size and yield. FA indicated that the external aqueous phase pH affected all responses, with a particularly strong correlation with IE in addition to a combined synergistic effect with polymer concentration on MS size. ANN showed better internal and external predictive ability of responses compared to FA. The ANN model developed in the study can be successfully used for multivariate modeling of the encapsulation and release of VRP and similar drug salts from hydrophobic polymer MSs prepared by multiple emulsification in addition to other MS characteristics. PMID- 19645005 TI - Metabolic characterization of primary and metastatic ovarian cancer by 1H-MRS in vivo at 3T. AB - (1)H-MRS was performed on 12 women (age range 45-72) with ovarian cancer of FIGO stage 3 or above using a 3T MRI system with an 8-channel cardiac receive coil. Respiratory-triggered PRESS-localized spectra (TE = 144 ms) were obtained separately from an ovarian mass and from metastatic disease. Peak areas were quantified relative to unsuppressed water using LCModel and spectra were discarded if LCModel reported signal-to-noise ratio (SNR) < 3 or if no metabolites were reported with standard deviation (SD) < 30%. The cystic fraction of each voxel was estimated by thresholding T(2)-weighted images, and this was used both to correct the reported metabolite concentrations and to calculate an expected SNR of choline using the measured SNR of water. Choline was detected in 10/12 primary tumors and 5/11 metastatic lesions (range 2.0-16.6 mM). Of the 8/23 failures, 7 had a predicted choline SNR < 2, confirming that the failure to detect choline could be explained by technical problems. Glycine was observed in one benign lesion. (1)H-MRS can be used to quantify choline in primary and metastatic masses in ovarian cancer, but the moderately high rate of failure to detect choline necessitates careful recording of data quality parameters to discriminate true from false negatives. PMID- 19645006 TI - Automatic high-order shimming using parallel columns mapping (PACMAP). AB - This work presents a new automatic high-order shimming method that maps the B(0) field using a group of parallel columns. We found that a pair of four columns in two separate slices could determine an optimal correction field comprising the spherical harmonic terms up to the third-order. The technique of multiple stimulated echoes was incorporated into the method, allowing the use of at least eight shots to accomplish field mapping. The shim currents were first determined in the logic frame by assuming that the slices were in axial planes, and then uniquely converted into the physical frame where the slices could be at any oblique angle, by using a spherical harmonics rotation transformation. This method thus works regardless of slice orientation. It was demonstrated on a 3T scanner equipped with a complete set of second-order harmonic shim coils. Both phantom and in vivo experiments showed that this newly introduced high-order shimming method is an effective and efficient way to reduce field inhomogeneity for a region of imaging slices. PMID- 19645007 TI - Comparison of T1 relaxation times of the neurochemical profile in rat brain at 9.4 tesla and 14.1 tesla. AB - Knowledge of T(1) relaxation times can be important for accurate relative and absolute quantification of brain metabolites, for sensitivity optimizations, for characterizing molecular dynamics, and for studying changes induced by various pathological conditions. (1)H T(1) relaxation times of a series of brain metabolites, including J-coupled ones, were determined using a progressive saturation (PS) technique that was validated with an adiabatic inversion-recovery (IR) method. The (1)H T(1) relaxation times of 16 functional groups of the neurochemical profile were measured at 14.1T and 9.4T. Overall, the T(1) relaxation times found at 14.1T were, within the experimental error, identical to those at 9.4T. The T(1)s of some coupled spin resonances of the neurochemical profile were measured for the first time (e.g., those of gamma-aminobutyrate [GABA], aspartate [Asp], alanine [Ala], phosphoethanolamine [PE], glutathione [GSH], N-acetylaspartylglutamate [NAAG], and glutamine [Gln]). Our results suggest that T(1) does not increase substantially beyond 9.4T. Furthermore, the similarity of T(1) among the metabolites (approximately 1.5 s) suggests that T(1) relaxation time corrections for metabolite quantification are likely to be similar when using rapid pulsing conditions. We therefore conclude that the putative T(1) increase of metabolites has a minimal impact on sensitivity when increasing B(0) beyond 9.4T. PMID- 19645008 TI - Feasibility of T2* mapping for the evaluation of hip joint cartilage at 1.5T using a three-dimensional (3D), gradient-echo (GRE) sequence: a prospective study. AB - This study defines the feasibility of utilizing three-dimensional (3D) gradient echo (GRE) MRI at 1.5T for T(2)* mapping to assess hip joint cartilage degenerative changes using standard morphological MR grading while comparing it to delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). MRI was obtained from 10 asymptomatic young adult volunteers and 33 patients with symptomatic femoroacetabular impingement (FAI). The protocol included T(2)* mapping without gadolinium-enhancement utilizing a 3D-GRE sequence with six echoes, and after gadolinium injection, routine hip sequences, and a dual-flip-angle 3D-GRE sequence for dGEMRIC T(1) mapping. Cartilage was classified as normal, with mild changes, or with severe degenerative changes based on morphological MRI. T(1) and T(2)* findings were subsequently correlated. There were significant differences between volunteers and patients in normally-rated cartilage only for T(1) values. Both T(1) and T(2)* values decreased significantly with the various grades of cartilage damage. There was a statistically significant correlation between standard MRI and T(2)* (T(1)) (P < 0.05). High intraclass correlation was noted for both T(1) and T(2)*. Correlation factor was 0.860 to 0.954 (T(2)*-T(1) intraobserver) and 0.826 to 0.867 (T(2)*-T(1) interobserver). It is feasible to gather further information about cartilage status within the hip joint using GRE T(2)* mapping at 1.5T. PMID- 19645009 TI - High-resolution diffusion tensor imaging of the human pons with a reduced field of-view, multishot, variable-density, spiral acquisition at 3 T. AB - Diffusion tensor imaging of localized anatomic regions, such as brainstem, cervical spinal cord, and optic nerve, is challenging because of the existence of significant susceptibility differences, severe physiologic motion in the surrounding tissues, and the need for high spatial resolution to resolve the underlying complex neuroarchitecture. The aim of the methodology presented here is to achieve high-resolution diffusion tensor imaging in localized regions of the central nervous system that is motion insensitive and immune to susceptibility while acquiring a set of two-dimensional images with more than six diffusion encoding directions within a reasonable total scan time. We accomplish this aim by implementing self-navigated, multishot, variable-density, spiral encoding with outer volume suppression. We establish scan protocols for achieving equal signal-to-noise ratio at 1.2 mm and 0.8 mm in-plane resolution for reduced field-of-view diffusion tensor imaging of the brainstem. In vivo application of the technique on the human pons of three subjects shows a clear delineation of the multiple local neural tracts. By comparing scans acquired with varying in plane resolution but with constant signal-to-noise ratio, we demonstrate that increasing the resolution and reducing the partial volume effect result in higher fractional anisotropy values for the corticospinal tracts. PMID- 19645010 TI - A prospective study on the natural course of low-grade squamous intraepithelial lesions and the presence of HPV16 E2-, E6- and E7-specific T-cell responses. AB - This study investigates the clinical course of low grade squamous intraepithelial lesions (LSIL), HPV status and HPV16-specific immune response in a large prospective study of 125 women with LSIL followed cytologically, virologically and histologically. Women with low-grade abnormal smears were recruited and followed-up for one year. Colposcopy, cervical biopsy for histology and brushings for HPV typing was performed at recruitment, 6 months (no biopsy) and upon completion of the study at one year. HPV16-specific T-cell responses were analysed by interferon-gamma ELISPOT at entry, 6 and 12 months. Infection with multiple HPV types was detected in 70% of all patients, HPV16 was found in 42% of the patients. LSIL lesions progressed to HSIL in 24%, persisted in 60% and regressed to normal in 16% of the patients. No difference was observed in the clearance rate of infections with single or multiple HPV types among the groups with a different histological outcome. HPV16-specific type 1 T-cell responses were detected in only half of the patients with an HPV16+ LSIL, and predominantly reactive to HPV16 E2 and E6. Interestingly, the presence of HPV16 E2-specific T cell responses correlated with absence of progression of HPV16+ lesions (p = 0.005) while the detection of HPV16 E6 specific reactivity was associated with persistence (p = 0.05). This large prospective study showed that the majority of LSIL persisted or progressed within the first year.This was paralleled by immune failure as most of the patients with an HPV16+ LSIL failed to react to peptides of HPV16 E2, E6 or E7. PMID- 19645011 TI - Incident cancer burden attributable to excess body mass index in 30 European countries. AB - Excess adiposity is associated with increased risks of developing adult malignancies. To inform public health policy and guide further research, the incident cancer burden attributable to excess body mass index (BMI >or= 25 kg/m(2)) across 30 European countries were estimated. Population attributable risks (PARs) were calculated using European- and gender-specific risk estimates from a published meta-analysis and gender-specific mean BMI estimates from a World Health Organization Global Infobase. Country-specific numbers of new cancers were derived from Globocan2002. A ten-year lag-period between risk exposure and cancer incidence was assumed and 95% confidence intervals (CI) were estimated in Monte Carlo simulations. In 2002, there were 2,171,351 new all cancer diagnoses in the 30 countries of Europe. Estimated PARs were 2.5% (95% CI 1.5-3.6%) in men and 4.1% (2.3-5.9%) in women. These collectively corresponded to 70,288 (95% CI 40,069-100,668) new cases. Sensitivity analyses revealed estimates were most influenced by the assumed shape of the BMI distribution in the population and cancer-specific risk estimates. In a scenario analysis of a plausible contemporary (2008) population, the estimated PARs increased to 3.2% (2.1-4.3%) and 8.6% (5.6-11.5%), respectively, in men and women. Endometrial, post-menopausal breast and colorectal cancers accounted for 65% of these cancers. This analysis quantifies the burden of incident cancers attributable to excess BMI in Europe. The estimates reported here provide a baseline for future modelling, and underline the need for research into interventions to control weight in the context of endometrial, breast and colorectal cancer. PMID- 19645012 TI - Gefitinib inhibits the proliferation of pancreatic cancer cells via cell cycle arrest. AB - High expression of the epidermal growth factor receptor (EGFR) has been implicated in the development of pancreatic cancer. Gefitinib is an orally active and selective EGFR-TKI (EGFR-tyrosine kinase inhibitor) that blocks signal transduction pathways responsible for the proliferation and survival of cancer cells, and other host-dependent processes promoting cancer growth. This study investigated the anticancer effect of gefitinib on human pancreatic cancer cells and the molecular mechanism involved. We first evaluated the effect of gefitinib on cell proliferation with MTT assay and the results demonstrated that gefitinib significantly inhibited the proliferation of pancreatic cancer cells. Flow cytometric analysis showed that gefitinib induced a delay in cell cycle progression and a G0/G1 arrest together with a G2/M block; these were associated with increased expression of p27(Kip1) cyclin-dependent kinase inhibitor combined with decreased expression of aurora B. Besides, luciferase reporter assay revealed that transcriptional mechanism was responsible for the down-regulation of aurora B protein by gefitinib. Overall, the results suggest a mechanistic connection among these events to provide new insights into the mechanism underlying the antiproliferative effect of gefitinib on pancreatic cancer and supplement a theory basis of gefitinib in clinical treatment of pancreatic cancer. PMID- 19645014 TI - Geometric morphometric methods for bone reconstruction: the mandibular condylar process of Pico della Mirandola. AB - The issue of reconstructing lost or deformed bone presents an equal challenge in the fields of paleoanthropology, bioarchaeology, forensics, and medicine. Particularly, within the disciplines of orthodontics and surgery, the main goal of reconstruction is to restore or create ex novo the proper form and function. The reconstruction of the mandibular condyle requires restoration of articulation, occlusion, and mastication from the functional side as well as the correct shape of the mandible from the esthetic point of view. Meeting all these demands is still problematic for surgeons. It is unfortunate that the collaboration between anthropologists and medical professionals is still limited. Nowadays, geometric morphometric methods (GMM) are routinely applied in shape analysis and increasingly in the reconstruction of missing data in skeletal material in paleoanthropology. Together with methods for three-dimensional (3D) digital model construction and reverse engineering, these methods could prove to be useful in surgical fields for virtual planning of operations and the production of customized biocompatible scaffolds. In this contribution, we have reconstructed the missing left condylar process of the mandible belonging to a famous Italian humanist of the 15th century, Pico della Mirandola (1463-1494) by means of 3D digital models and GMM, having first compared two methods (a simple reflection of the opposite side and the mathematical-statistical GMM approach) in a complete human mandible on which loss of the left condyle was virtually simulated. Finally, stereolithographic models of Pico's skull were prototyped providing the physical assembly of the bony skull structures with a high fitting accuracy. PMID- 19645015 TI - Hydrogen peroxide induces G2 cell cycle arrest and inhibits cell proliferation in osteoblasts. AB - Reactive oxygen species (ROSs) are involved in osteoporosis by inhibiting osteoblastic differentiation and stimulating osteoclastgenesis. Little is known about the role and how ROS controls proliferation of osteoblasts. Mammalian target of rapamycin, mTOR, is a central regulator of cell growth and proliferation. Here, we report for the first time that 5-200 microM hydrogen peroxide (H(2)O(2)) dose- and time-dependently suppressed cell proliferation without affecting cell viability in mouse osteoblast cell line, MC3T3-E1, and in human osteoblast-like cell line, MG63. Further study revealed that protein level of cyclin B1 decreased markedly and the percentage of the cells in G(2)/M phase increased about 2-4 fold by 200 microM H(2)O(2) treatment for 24-72 hr. A total of 0.5-5 mM of H(2)O(2) but not lower concentrations (5-200 microM) of H(2)O(2) inhibited mTOR signaling, as manifested by dephosphorylation of S6K (T389), 4E BP1 (T37/46), and S6(S235/236) in MC3T3-E1 and MG63 cells. Rapamycin, which could inhibit mTOR signaling and cell proliferation, however, did not reduce the protein level of cyclin B1. In a summary, H(2)O(2) prevents cell proliferation of osteoblasts by down-regulating cyclin B1 and inducing G(2) cell cycle arrest. Inhibition of mTOR signaling by H(2)O(2) may not be involved in this process. PMID- 19645016 TI - Expression of KiSS-1 gene and its role in invasion and metastasis of human hepatocellular carcinoma. AB - KiSS-1 has been identified as a putative metastasis-suppressor gene in human melanomas and breast cancer cell lines. Although loss of KiSS-1 expression has been associated with progression and poor prognosis of various cancers, the exact role of KiSS-1 expression in HCC is not well-defined. Our study investigated KiSS 1 expression levels in HCC and its role in invasion and metastasis of human HCC. The expression levels of KiSS-1 and MMP-9 protein were determined by tissue microarray (TMA) serial sections, immunohistochemistry and semi-quantitative image analysis. All clinical and histological data obtained were subjected to statistical analysis. The expression of KiSS-1 protein in HCC and intrahepatic metastasis lesions was significantly lower (P < 0.01) when compared with non tumor liver tissue and normal liver tissue. Multivariate analysis revealed a significant inverse correlation between KiSS-1 expression and o1 TNM stage, (F = 7.113, P < 0.01) and o2 intrahepatic metastasis (t = 2.898, P < 0.01). Loss of KiSS-1 in intrahepatic metastasis versus primary carcinomas was statistically significant (P<0.01). We also found a negative correlation between KiSS-1 and MMP 9 expression in HCC (r = -0.506, P < 0.01). We conclude that loss of KiSS-1 during HCC metastasis, along with a concomitant upregulation of MMP-9 suggests a possible mechanism for cell motility and invasion during HCC metastasis, with KiSS-1 emerging as a possible therapeutic target during HCC metastasis. PMID- 19645017 TI - Effect of hypoxia and aging on PKC delta-mediated SC-35 phosphorylation in rat myocardial tissue. AB - Nuclear speckles, which are sites of pre-mRNA splicing and/or assembly components, are diffusely distributed throughout the nucleoplasm. They are composed of splicing factors (SFs), including SC-35, which are nuclear proteins that remove introns (noncoding sequences in the genes) from precursor mRNA molecules, to form mature RNA, which will be transported to the cytoplasm, site of protein synthesis and activation. In light of such evidences, here we report that hypoxia modulates in vivo SC-35 SF phosphorylation via protein kinase C (PKC) delta in young rat heart. Trichrome Mallory staining and TUNEL analysis along with immunohistochemistry and Western blotting have been performed on left ventricles excised from young and old rats exposed to intermittent hypoxia. Although young hypoxic myocardial cells appear smaller than normoxic cells, connective and endothelial components increase, SC-35 phosphorylation is particularly evident in the endothelium and paralleled by an increased expression of vascular endothelial growth factor (VEGF). In addition, SC-35 and PKC delta coimmunoprecipitation occurs, suggesting that SC-35 phosphorylation could be PKC delta-mediated and that hypoxic young heart needs to counteract the damage through a process of neoangiogenesis involving such SF. Even though the levels of SC-35 and PKC delta are high, the similar response disclosed by normoxic and hypoxic old rat hearts (both showing a fibrotic organization, similar endothelial components and VEGF levels) could be due to the existence of an impaired oxygen sensing mechanism and thus to a low rate of angiogenesis. PMID- 19645019 TI - A reevaluation of the unusual abdominal musculature of squamate reptiles (Reptilia: Squamata). AB - The abdominal muscles of lizards and snakes (Squamata) have been the subject of periodic attention from anatomists, embryologists, and systematists. Until now, the presence of a superficial portion of the m. rectus abdominis, named the m. rectus abdominis lateralis, has been considered a key synapomorphy of the clade Autarchoglossa, which includes all extant squamates save Gekkota and Iguania. However, the precise anatomical relations of the m. rectus abdominis lateralis have never been fully investigated. Here, I show that the m. rectus abdominis lateralis is present in Iguania. Its absence in Gekkota represents rare gross anatomical support for recent molecular-structure-based hypotheses of squamate relationships placing geckoes as sister to the remaining squamates. Where present, it is the most superficial trunk muscle, exterior to the m. obliquus externus. The separation of the m. rectus abdominis lateralis from the m. rectus abdominis occurs as the m. obliquus externus aponeurosis and part of the m. obliquus internus aponeurosis emerge superficially to form the outer portion of the rectus sheath. In Autarchoglossa, the contralateral mm. recti abdomines laterales meet at the midline and are attached to the imbricae of the transverse scale rows characteristic of the clade, suggesting developmental, functional, and evolutionary association. Because the m. rectus abdominis lateralis is sometimes continuous with the pectoralis, its exclusive association with the m. rectus abdominis is questionable. It may be a neomorphic layer that is part of the abaxial developmental system, comprising those muscles whose connective tissue is largely derived from lateral plate as opposed to somatic mesoderm. PMID- 19645018 TI - Blood flow patterns spatially associated with platelet aggregates in murine colitis. AB - In the normal murine mucosal plexus, blood flow is generally smooth and continuous. In inflammatory conditions, such as chemically-induced murine colitis, the mucosal plexus demonstrates markedly abnormal flow patterns. The inflamed mucosal plexus is associated with widely variable blood flow velocity as well as discontinuous and even bidirectional flow. To investigate the mechanisms responsible for these blood flow patterns, we used intravital microscopic examination of blood flow within the murine mucosal plexus during dextran sodium sulphate-and trinitrobenzenesulfonic acid-induced colitis. The blood flow patterns within the mucosal plexus demonstrated flow exclusion in 18% of the vessel segments (P < 0.01). Associated with these segmental exclusions was significant variation in neighboring flow velocities. Intravascular injection of fluorescent platelets demonstrated platelet incorporation into both fixed and rolling platelet aggregates. Rolling platelet aggregates (mean velocity 113 microm/sec; range, 14-186 microm/sec) were associated with reversible occlusions and flow variations within the mucosal plexus. Gene expression profiles of microdissected mucosal plexus demonstrated enhanced expression of genes for CCL3, CXCL1, CCL2, CXCL5, CCL7, CCL8, and Il-1b (P < 0.01), and decreased expression of CCL6 (P < 0.01). These results suggest that platelet aggregation, activated by the inflammatory mileau, contributes to the complex flow dynamics observed in acute murine colitis. PMID- 19645021 TI - The microanatomy of the palatine tonsils of the one-humped camel (Camelus dromedarius). AB - Tonsils form a first line of defense against foreign antigens and are also a route of entry and a replication site for some pathogens. The palatine tonsils are the largest of all the tonsils. Despite their general importance, little is known about the microanatomy of the palatine tonsils of the one-humped camel. Palatine tonsils of 10 clinically healthy male camels were obtained directly after slaughtering for human consumption. The tonsils were examined macroscopically and by light, scanning, and transmission electron microscopy. Palatine tonsils had the unique form of several spherical macroscopic nodules protruding into the pharyngeal lumen. These spherical masses were numerous and close together in the lateral oropharyngeal wall, with a few solitary nodules in the dorsal wall. Each nodule had one or two apical openings to crypts, and was enclosed by an incomplete connective tissue capsule and covered apically with stratified squamous keratinized epithelium. The tonsillar crypt was lined with stratified squamous non keratinized epithelium. Several lymphocytes infiltrated the epithelial layer, forming patches of reticular epithelium. Lymphoid follicles with obvious germinal centers extended under the epithelial surface. Diffusely localized lymphocytes were seen in the interfollicular region. High endothelial venules, dendritic cells, macrophages, and plasma cells were observed among these lymphocytes. The unique arrangement of palatine tonsils in separate units with individual crypts results in a very large surface exposed to antigen and indicates a significant immunological role of palatine tonsils in the camel. PMID- 19645020 TI - The mesencephalic reticular formation as a conduit for primate collicular gaze control: tectal inputs to neurons targeting the spinal cord and medulla. AB - The superior colliculus (SC), which directs orienting movements of both the eyes and head, is reciprocally connected to the mesencephalic reticular formation (MRF), suggesting the latter is involved in gaze control. The MRF has been provisionally subdivided to include a rostral portion, which subserves vertical gaze, and a caudal portion, which subserves horizontal gaze. Both regions contain cells projecting downstream that may provide a conduit for tectal signals targeting the gaze control centers which direct head movements. We determined the distribution of cells targeting the cervical spinal cord and rostral medullary reticular formation (MdRF), and investigated whether these MRF neurons receive input from the SC by the use of dual tracer techniques in Macaca fascicularis monkeys. Either biotinylated dextran amine or Phaseolus vulgaris leucoagglutinin was injected into the SC. Wheat germ agglutinin conjugated horseradish peroxidase was placed into the ipsilateral cervical spinal cord or medial MdRF to retrogradely label MRF neurons. A small number of medially located cells in the rostral and caudal MRF were labeled following spinal cord injections, and greater numbers were labeled in the same region following MdRF injections. In both cases, anterogradely labeled tectoreticular terminals were observed in close association with retrogradely labeled neurons. These close associations between tectoreticular terminals and neurons with descending projections suggest the presence of a trans-MRF pathway that provides a conduit for tectal control over head orienting movements. The medial location of these reticulospinal and reticuloreticular neurons suggests this MRF region may be specialized for head movement control. PMID- 19645023 TI - An embryonic staging table for in ovo development of Eublepharis macularius, the leopard gecko. AB - Squamates constitute a major vertebrate radiation, representing almost one-third of all known amniotes. Although speciose and morphologically diverse, they remain poorly represented in developmental studies. Here, we present an embryonic staging table of in ovo development for the basal gekkotan Eublepharis macularius (the leopard gecko) and advocate this species as a laboratory-appropriate developmental model. E. macularius, is a hardy and tractable species of relatively large body size (with concomitantly relatively large eggs and embryos), that is widely available and easy to maintain and propagate. Additionally, E. macularius displays a body plan appropriate to the study of the plesiomorphic quadrupedal condition of early pentadactylous terrestrial amniotes. Although not unexpected, it is worth noting that the morphological events characterizing limb development in E. macularius are comparable with those described for the avian Gallus gallus. Therefore, E. macularius holds great promise as a model for developmental studies focusing on pentadactyly and the formation of digits. Furthermore, it is also attractive as a developmental model because it demonstrates temperature-dependent sex determination. The staging table presented herein is based on an all-female series and represents the entire 52 day in ovo period. Overall, embryogenesis of E. macularius is similar to that of other squamates in terms of developmental stage attained at the time of oviposition, patterns of limb and pharyngeal arch development, and features of the appearance of scalation and pigmentation, indicative of a conserved developmental program. PMID- 19645022 TI - 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging in the staging and prognosis of inflammatory breast cancer. AB - BACKGROUND: : To prospectively assess fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) staging and prognosis value in patients with suspected inflammatory breast cancer (IBC). METHODS: : Sixty-two women (mean age 50.7 +/- 11.4 years) presenting with unilateral inflammatory breast tumors (59 invasive carcinomas; 3 mastitis) underwent a PET/CT scan before biopsy. RESULTS: : PET/CT scan was positive for the primary malignant tumor in 100% and false positive in 2 of 3 benign mastitis. In 59 IBC patients, FDG nodal foci were detected in axillary (90%; n = 53) and extra-axillary areas (56%; n = 33) ipsilateral to the cancer. Compared with clinical examination, the axillary lymph node status by PET/CT was upstaged and downstaged in 35 and 5 patients, respectively. In 7 of 9 N0 patients, the axillary lymph node positivity on PET/CT was correct, as revealed by pathological postsurgery assessment (not available in the 2 remaining patients). The nodal foci were compared with preoperative fine needle aspiration and/or pathological postchemotherapy findings available in 44 patients and corresponded to 38 true positive, 4 false-negative, and 2 false positive cases. In 18 of 59 IBC patients (31%), distant lesions were found. On the basis of a univariate analysis of the first enrolled patients (n = 42), among 28 patients who showed intense tumoral uptake (standard uptake value(max)>5), the 11 patients with distant lesions had a worse prognosis than the 17 patients without distant lesions (P = .04). CONCLUSIONS: : FDG-PET/CT imaging provides additional invaluable information regarding nodal status or distant metastases in IBC patients and should be considered in the initial staging. It seems also that some prognostic information can be derived from FDG uptake characteristics. Cancer 2009. (c) 2009 American Cancer Society. PMID- 19645024 TI - Proton beam therapy for hepatocellular carcinoma: the University of Tsukuba experience. AB - BACKGROUND: The authors have published a series of studies evaluating the safety and efficacy of proton beam therapy for the treatment of hepatocellular carcinoma in a variety of clinical settings. In the current study, they retrospectively reviewed their entire experience treating hepatocellular carcinoma patients with proton beam therapy at their hospital-based facility at the University of Tsukuba. METHODS: From November 2001 to December 2007, 333 patients with hepatocellular carcinoma were treated with proton beam therapy at the University of Tsukuba. A total of 318 patients were included in this study. Total dose delivered and fractionation scheme were determined by protocols that varied based on location of tumor. Survival rates and prognostic factors were assessed. RESULTS: Overall actuarial survival rates at 1-year, 3-years, and 5-years were 89.5% (95% confidence interval [95% CI], 85.7-93.1%), 64.7% (95% CI, 56.6-72.9%), and 44.6% (95% CI, 29.7-59.5%), respectively. Child-Pugh liver function (hazards ratio [HR], 2.84; P < .01), T stage (HR, 1.94; P < .05), performance status (HR, 2.12; P < .01), and planning target volume (HR, 2.12; P < .05) significantly impacted survival. The 3-year and 5-year survival rates were 69.1% (95% CI, 59.9 78.3%) and 55.9% (95% CI, 41.5-70.3%), respectively, for patients with Child-Pugh A disease and 51.9% (95% CI, 32.3-71.5%) and 44.5% (95% CI, 23.1-65.8%), respectively, for patients with Child-Pugh B disease. The actuarial survival rates of patients with Child-Pugh class A were statistically different between groups of planned target volume 125 mL (P < .05). CONCLUSIONS: The authors have shown proton beam therapy to be both safe and effective for the treatment of patients with hepatocellular carcinoma. They strongly recommend the consideration of proton beam therapy in patients for whom other treatment options are risky or contraindicated. PMID- 19645025 TI - Defining potency: a comparison of the International Index of Erectile Function short version and the Expanded Prostate Cancer Index Composite. PMID- 19645026 TI - ES cell extract-induced expression of pluripotent factors in somatic cells. AB - Reprogramming of somatic cells was induced by ES cell-free extract. The system relied on the transient uptake of regulatory components from a nuclear and cytoplasmic extract derived from ES cells by the nucleus of a reversibly permeabilized NIH3T3 cell. NIH3T3 cells were permeabilized by streptolysin O (SLO). Reprogramming cell-free extracts were prepared by repeatedly freezing and thawing ES cells in liquid nitrogen. After incubation in the extract for 1 hr, permeabilized NIH3T3 cells were resealed by CaCl(2) and continually cultured for weeks to assess expression of ES cell specific markers. As we observed using FACS and fluorescence microscope, the optimal SLO concentration for permeabilizing NIH3T3 cells was 25 U. After 2 weeks of culture, the treated NIH3T3 cells began to express Nanog, c-Myc, Klf4, and 6 weeks later Oct4 was detectable. However, Sox2 was detected only after 8 weeks of culture. Differentiated somatic cells could be reprogrammed in ES extract in vitro, which provides a new approach to decreasing differentiation levels in somatic cells without disturbing the DNA sequences. PMID- 19645027 TI - Gender disparity in the rate of partner abandonment in patients with serious medical illness. AB - BACKGROUND: Life-threatening illness creates severe stress that may result in marital discord, separation, or divorce and may adversely impact treatment, quality of life, and survival. The few studies that are available to date have suggested that the risk of divorce is not higher in cancer patients, but to the authors' knowledge, no data exist to date that have examined the effect of gender on this rate. METHODS: A total of 515 patients were prospectively identified as having either a malignant primary brain tumor (N = 214), a solid tumor with no nervous system involvement (N = 193), or multiple sclerosis (N = 108) who were married at the time of diagnosis. Basic demographic information and data regarding marital status were compiled. Patients were followed prospectively from enrollment until death or study termination. RESULTS: Women composed 53% of the patient population. Divorce or separation occurred at a rate similar to that reported in the literature (11.6%). There was, however, a greater than 6-fold increase in risk after diagnosis when the affected spouse was the woman (20.8% vs 2.9%; P < .001). Female gender was found to be the strongest predictor of separation or divorce in each cohort. Marriage duration at the time of illness was also correlated with separation among brain tumor patients (P = .0001). Patients with brain tumors who were divorced or separated were more likely to be hospitalized, and less likely to participate in a clinical trial, receive multiple treatment regimens, complete cranial irradiation, or die at home (P < .0001). CONCLUSIONS: Female gender was found to be a strong predictor of partner abandonment in patients with serious medical illness. When divorce or separation occurred, quality of care and quality of life were adversely affected. PMID- 19645028 TI - Perioperative chemotherapy for urothelial cancer: how have we made a "sow's ear" out of a chemotherapy-sensitive tumor? PMID- 19645029 TI - Age-specific physical activity and prostate cancer risk among white men and black men. AB - BACKGROUND: : The relation of physical activity across the lifespan to risk of prostate cancer has not been thoroughly investigated, particularly among black men. The authors investigated physical activity, including activity during different age periods and of various intensities, in relation to prostate cancer incidence among white men and black men. METHODS: : In total, 160,006 white men and 3671 black men ages 51 years to 72 years who were enrolled in the National Institutes of Health-AARP Diet and Health Study reported their time spent per week engaging in physical activity during ages 15 to 18 years, 19 years to 29 years, 35 years to 39 years, and during the past 10 years. Cox regression models were used to examine physical activity, categorized by intensity (moderate or vigorous, light, and total), in relation to prostate cancer risk. RESULTS: : During 7 years of follow-up, 9624 white men and 371 black men developed prostate cancer. Among white men, physical activity had no association with prostate cancer regardless of age period or activity intensity. Among black men, engaging in > or =4 hours of moderate/vigorous intensity physical activity versus infrequent activity during ages 19 years to 29 years was related to a 35% lower risk of prostate cancer (relative risk, 0.65; 95% confidence interval [95% CI], 0.43-0.99 [P(trend) = .01]). Frequent moderate/vigorous physical activity at ages 35 years to 39 years also potentially was related to reduced prostate cancer risk (relative risk, 0.59; 95% CI, 0.36-0.96 [P(trend) = .15]). CONCLUSIONS: : Regular physical activity may reduce prostate cancer risk among black men, and activity during young adulthood may yield the greatest benefit. This novel finding needs confirmation in additional studies. Cancer 2009. Published 2009 by the American Cancer Society. PMID- 19645030 TI - Differentiation between microcystin contaminated and uncontaminated fish by determination of unconjugated MCs using an ELISA anti-Adda test based on receiver operating characteristic curves threshold values: application to Tinca tinca from natural ponds. AB - The aim of this study was to evaluate whether the enzyme-linked immunosorbent assay (ELISA) anti-Adda technique could be used to monitor free microcystins (MCs) in biological samples from fish naturally exposed to toxic cyanobacteria by using receiver operating characteristic (ROC) curve software to establish an optimal cut-off value for MCs. The cut-off value determined by ROC curve analysis in tench (Tinca tinca) exposed to MCs under laboratory conditions by ROC curve analysis was 5.90-MUg MCs/kg tissue dry weight (d.w.) with a sensitivity of 93.3%. This value was applied in fish samples from natural ponds (Extremadura, Spain) in order to asses its potential MCs bioaccumulation by classifying samples as either true positive (TP), false positive (FP), true negative (TN), or false negative (FN). In this work, it has been demonstrated that toxic cyanobacteria, mainly Microcystis aeruginosa, Aphanizomenon issatchenkoi, and Anabaena spiroides, were present in two of these ponds, Barruecos de Abajo (BDown) and Barruecos de Arriba (BUp). The MCs levels were detected in waters from both ponds with an anti-MC-LR ELISA immunoassay and were of similar values (between 3.8-6.5 MUg MC-LR equivalent/L in BDown pond and 4.8-6.0-MUg MC-LR equivalent/L in BUp). The MCs cut-off values were applied in livers from fish collected from these two ponds using the ELISA anti-Adda technique. A total of 83% of samples from BDown pond and only 42% from BUp were TP with values of free MCs higher than 8.8-MUg MCs/kg tissue (d.w.). PMID- 19645031 TI - Knowledge, cultural, and attitudinal barriers to mammography screening among nonadherent immigrant Chinese women: ever versus never screened status. AB - BACKGROUND: Chinese-American women have much lower mammography screening rates than the general population. This study examined the collective impact of knowledge, cultural views, and health beliefs on intentions to obtain mammography among Chinese women who had not had a mammogram in the previous year. METHODS: Five hundred sixty-six immigrant Chinese women from the Washington, District of Columbia and New York metropolitan areas completed baseline assessments for a longitudinal intervention study. Validated surveys were used to measure variables of interest. The outcomes were 1) past mammography use (ever vs never) and 2) future screening intention. RESULTS: Only 35% of the participants reported intentions to obtain mammograms, with approximately 19% of the never users reporting intentions (vs 44% ever users). Ever users had higher knowledge (odds ratio [OR], 1.13; 95% confidence interval [CI], 1.03-1.25), less Eastern cultural views (OR, 0.78; 95% CI, 0.70-0.87), and perceived fewer barriers (OR, 0.78; 95% CI, 0.70-0.87) than never users, controlling for covariates. Never users were more likely to be recent immigrants, have low income, have limited English ability, and lack regular sources of care than ever users (all P<.001). Multivariate models showed that ever users who were employed received physician recommendations, had less Eastern views, perceived higher susceptibility, and were more likely to have intentions. Among never users, being 40-49 years of age and perceiving fewer barriers led to increased intention. CONCLUSIONS: Understanding cultural patterns and health beliefs in Chinese women is critical to changing their screening behaviors. Interventions that address their common beliefs and specific group barriers are optimal for promoting mammography adherence. PMID- 19645032 TI - Analysis of factors affecting the ratio of microcystin to chlorophyll-a in cyanobacterial blooms using real-time polymerase chain reaction. AB - Chlorophyll-a concentration has been used as an indicator to estimate microcystin levels in water bodies. This study examined the microcystin to chlorophyll-a ratio in a fishpond in Japan. The ratio varied spatially and temporally during the six-month field survey, which is consistent with reports by other researchers. We investigated the causes of the variability of the ratio by quantifying microcystin synthetase (mcy) A gene with real-time PCR, so as to observe the growth of microcystin-producing cyanobacteria and Microcystis strains in natural cyanobacterial blooms. The application of real-time PCR enabled corroboration of the relationship between the toxigenicity and the toxicity of the blooms. The microcystin to chlorophyll-a ratio was influenced by the combined effects of the durability of the toxic bloom, and the quantity of microcystin producing cyanobacteria carrying the mcy A gene, especially toxic Microcystis strains. Cyanobacterial blooms produced more microcystin when high concentrations of microcystin-producing Microcystis aggregated in a stationary state with low growth rates. The variable toxicity of blooms needs to be reflected in accurate and efficient alert systems for toxic cyanobacteria and cyanotoxins. PMID- 19645033 TI - Predictors of change in walking distance in patients with peripheral arterial disease undergoing endovascular intervention. AB - BACKGROUND: Endovascular treatment of peripheral artery disease is becoming frequent, yet the clinical factors which predict ambulatory outcomes are not known. HYPOTHESIS: To identify predictors of change in walking distance in patients who underwent endovascular intervention for their lower extremity peripheral arterial disease (PAD). METHODS: A total of 134 patients underwent lower extremity peripheral arterial intervention, 52 patients were contacted via phone between 1 and 36 months (a mean of 22 mo) after their initial procedure. The remaining 82 patients were excluded due to the following reasons: death (n = 13), contact information was not available (n = 50), and refusal to participate in the follow-up (n = 19). RESULTS: The patients were 63 +/- 12 years old (mean +/- standard deviation [SD]), 46% were male, 47% were diabetics, 49% had coronary artery disease, of whom 29% had prior revascularization, and 22% had coronary artery bypass grafts (CABG). The disease severity described by Fontaine classification were as follows: 44.2% were in stage II, 15.4% were in stage III, and 40.4% were in stage IV. Walking distance was improved in 21% of patients, worsened in 73% of patients, and unchanged in 6% of patients. Stepwise multiple regression demonstrated that patients who started to walk or exercise (R = 0.372, P < 0.012) and who had a prior history of CABG (R = 0.467, P < 0.006) were the only independent predictors of the change in walking distance at follow-up. Those who started to walk reported worse walking distance at follow-up, while those with a history of CABG reported better walking distance at follow-up. CONCLUSION: CABG prior to endovascular intervention is predictive of favorable change in walking distance in patients with PAD at follow-up. Therefore, post-CABG patients are good candidates for exercise rehabilitation and risk factor modification. PMID- 19645034 TI - Low-density lipoprotein levels are one of the independent determinants of circulating levels of advanced glycation end products in nondiabetic subjects. AB - BACKGROUND: Nonenzymatic modification of proteins by reducing sugars leads to the formation of advanced glycation end products (AGEs), whose process has been reported to progress under diabetes. Recently, diet has been found to be a major environmental source of proinflammatory AGEs in humans. Further, fats or meat derived products processed by high heat such as broiling have been shown to contain more AGEs than carbohydrates boiled for longer periods. Since circulating levels of low-density lipoprotein cholesterol (LDL-C) are also regulated by dietary cholesterol, it is conceivable that intake of cholesterol-rich foods could regulate serum levels of AGEs in humans. In this study, we investigated whether LDL-C levels are one of the independent determinants of circulating AGEs levels in a nondiabetic general population. METHODS: A total of 170 nondiabetic Japanese subjects underwent a complete history, physical examination, determination of blood chemistries, and serum AGEs. RESULTS: Univariate analysis showed that AGEs levels were associated with LDL-C (P < 0.05) and fasting plasma glucose levels (P < 0.05). By the use of multiple stepwise regression analyses, LDL-C (P < 0.01) and fasting plasma glucose levels (P < 0.05) remained significant and were independently related to AGEs levels (R2 = 0.069). CONCLUSIONS: The present study is the first demonstration that LDL-C levels are one of the independent determinants of serum levels of AGEs in a nondiabetic general population. Intake of cholesterol-rich foods may regulate serum levels of AGEs in nondiabetic subjects. PMID- 19645035 TI - C-reactive protein and atrial fibrillation in idiopathic dilated cardiomyopathy. AB - BACKGROUND: Previous studies have found elevated plasma C-reactive protein (CRP) levels in atrial fibrillation (AF) patients. Most of these studies included AF patients with various heart diseases, but few studies were designed to investigate CRP in idiopathic dilated cardiomyopathy (IDCM) patients with AF. METHOD AND RESULTS: CRP levels in 242 IDCM patients with AF were compared with CRP levels in 280 control IDCM patients. Among control patients, 70 had atrial premature beats or atrial tachycardia and 210 had normal sinus rhythm. CRP was higher in the AF group than in the control group (median, 4.59 versus 2.81 mg/L; p < 0.001). The prevalence of AF in IDCM patients increased as plasma CRP levels increased, and the patients with the highest plasma CRP levels had the highest probability of suffering from AF. Outcome of multivariate logistic regression analysis showed body mass index, AF, and white blood cell count significantly correlated with the plasma CRP levels. CONCLUSION: Our data demonstrated that the plasma CRP level in IDCM patients with AF was higher than in IDCM patients without AF, and an increase in plasma CRP levels was associated with an increased prevalence of AF in IDCM patients. Also, body mass index, AF, and white blood cell count correlate with plasma CRP levels in IDCM patients. These data suggest there is presence of inflammation in IDCM patients with AF. PMID- 19645036 TI - Tracheal compression as a result of a double aortic arch: a rare cause of dyspnea. PMID- 19645037 TI - Electrocardiogram showing both tachycardia and prominent J wave. PMID- 19645038 TI - A novel mutation of the beta myosin heavy chain gene responsible for familial hypertrophic cardiomyopathy. AB - BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disorder and shows high variability in genetic heterogeneity and phenotypic characteristics. The genetic etiology responsible for HCM in many individuals remains unclear. OBJECTIVE: This instigation was sought to identify novel genetic determinants for familial hypertrophic cardiomyopathy. METHODS: Six unrelated Chinese families with HCM were studied. For each of the 13 established HCM-susceptibility genes, 3 to 5 microsatellite markers were selected to perform genotyping and haplotype analysis. The linked genes were sequenced. RESULTS: Haplotype analyses on candidate genetic loci revealed cosegregation of the gene beta-myosin heavy chain (MYH7) with HCM in a single family. A novel double heterozygous missense mutation of Ala26Val plus Arg719Trp in MYH7 was subsequently identified by sequencing in this family and was associated with a severe phenotype of HCM. CONCLUSION: The novel double mutation of Ala26Val plus Arg719Trp in MYH7 identified in a Chinese family highlights the remarkable genetic heterogeneity of HCM, which provides important information for genetic counseling, accurate diagnosis, prognostic evaluation, and appropriate clinical management. PMID- 19645039 TI - Efficacy and safety of tirofiban in high-risk patients with non-ST-segment elevation acute coronary syndromes. AB - OBJECTIVE: To evaluate the safety and efficacy of tirofiban in high risk patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS) after percutaneous coronary intervention (PCI). METHODS: A total of 240 patients were randomized to either a tirofiban group or a control group. RESULTS: Compared with the control group, the platelet aggregation rate in the tirofiban group was lower (P < 0.01); the plasma levels of CK-MB and troponin I, cardiac form (cTnI) were lower (P < 0.05); ECG improved significantly (P < 0.05); the incidence of major adverse cardiac events (MACE) was lower (P < 0.05); and there was no difference in bleeding complications between the 2 groups (P = 0.1). CONCLUSIONS: The administration of tirofiban in high risk patients with NSTE-ACS after PCI is safe and effective. PMID- 19645040 TI - Hypercholesterolemia paradox in relation to mortality in acute coronary syndrome. AB - BACKGROUND: Hypercholesterolemia is a risk factor for coronary artery disease, yet is associated with lower risk of adverse outcomes in patients with acute coronary syndromes (ACS). HYPOTHESIS: We explored this paradox in 84,429 patients with non-ST-segment elevation ACS in 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 registry. METHODS: We examined the association between a history of hypercholesterolemia and in-hospital mortality after adjusting for clinical covariates. After excluding patients with previously diagnosed hypercholesterolemia, we repeated the analysis, examining the association between newly diagnosed hypercholesterolemia (in-hospital low-density lipoprotein cholesterol [LDL-C] > or = 100 mg/dL) and mortality. RESULTS: A history of hypercholesterolemia was associated with lower in-hospital mortality (unadjusted odds ratio [OR]: 0.58; 95% confidence interval [CI]: 0.55, 0.62). This protective association persisted after adjusting for baseline characteristics (OR: 0.71; 95% CI: 0.66, 0.76) and prior statin use (OR: 0.74; 95% CI: 0.68, 0.80). Among 22,711 patients with no history of hypercholesterolemia, 12,809 had a new in-hospital diagnosis of hypercholesterolemia. Unadjusted mortality in these patients was lower than among those with normal LDL levels (OR: 0.58; 95% CI: 0.50, 0.67); however, this difference was not significant after multivariable adjustment (OR: 0.86; 95% CI: 0.73, 1.01). CONCLUSIONS: The association of hypercholesterolemia with better outcomes highlights a major challenge in observational analyses. Our results suggest this paradox may result from confounding due to other clinical characteristics, impact of statin treatment, and perhaps most importantly, the fact that previously diagnosed hypercholesterolemia is a marker for patients with more prior medical contact. PMID- 19645041 TI - Decreased high-density lipoprotein cholesterol level is an independent correlate of circulating tumor necrosis factor-alpha in a general population. AB - BACKGROUND: Recent studies implicate a pathophysiological role of tumor necrosis factor-alpha (TNF-alpha) in atherosclerosis, thus suggesting that serum TNF-alpha levels may be one of the biomarkers for future cardiovascular events. However, which anthropometric, metabolic, and inflammatory variables could regulate circulating TNF-alpha levels in humans is not fully understood. In this study, we examined the independent determinants of serum TNF-alpha levels in a Japanese general population. HYPOTHESIS: Anthropometric, metabolic , and inflammatory variables could regulate TNF-alpha. METHODS: A total of 213 Japanese subjects underwent a complete history, physical examination, and determination of blood chemistries, including TNF-alpha levels. Univariate and multivariate analyses were applied for the determinants of TNF-alpha levels. RESULTS: The average TNF alpha levels were 13.4 +/- 0.81 pg/ml in males and 13.9 +/- 4.5 pg/ml in females, respectively. Univariate analysis showed that TNF-alpha levels were associated with age (P = 0.007), body mass index (P = 0.034), waist circumference (<0.001), high-density lipoprotein cholesterol (HDL-C; inversely, P < 0.001), triglycerides (P < 0.001), creatinine (P < 0.001), uric acids (P < 0.001), insulin (P = 0.008), homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.015), high sensitivity C-reactive protein (hs-CRP; P < 0.001), and fibrinogen (P = 0.009). By the use of multiple stepwise regression analyses, HDL-C (inversely, P < 0.001) and hs-CRP (P < 0.001) remained significant and were independently related to TNF alpha levels (R2 = 0.153). CONCLUSIONS: The present study is the first demonstration that besides hs-CRP, a decreased HDL-C level is an independent determinant of circulating TNF-alpha in the Japanese general population. Elevation of TNF-alpha may partly explain the increased risk of cardiovascular events in patients with low HDL-C levels. PMID- 19645042 TI - Clinical outcomes for single stent and multiple stents in contemporary practice. AB - BACKGROUND: Stents had been demonstrated to be safe and effective in the treatment of severe coronary artery disease (CAD); however, the current knowledge on percutaneous coronary intervention (PCI) in treating patients requiring 2 or more stents placements is still limited. HYPOTHESIS: Patients who required 2 or more stents might have worse clinical outcomes. METHODS: A total of 2371 patients who underwent stenting were divided into a single stenting group (n = 1233) and a multiple stenting group (n = 1138). We assessed the cumulative incidence of major adverse cardiac events (death, acute myocardial infarction, and target-vessel revascularization) and stent thrombosis during 1-year follow-up. RESULTS: The 1 year unadjusted cumulative incidence of major adverse cardiac events was 7.7% in the multiple stenting group and 5.4% in the single stenting group (P = 0.02 by log-rank test). After adjustment, there was a trend toward a lower rate of 1-year major adverse cardiac events in the single stenting group than in the multiple stenting group (P = 0.09). A nonsignificant trend was also detected in favor of the single stenting group, as compared with the multiple stenting group, at the rate of acute myocardial infarction (1.3% vs 1.7%, P = 0.89) and at the rate of target-vessel revascularization (4.5% vs 5.4%, P = 0.08). CONCLUSIONS: Although the use of a single stent in coronary artery disease has less incidence of adverse cardiac events at 1 year as compared with the use of multiple stents, the difference was not statistically significant. PMID- 19645043 TI - Preinfarction angina prior to first myocardial infarction does not influence long term prognosis: a retrospective study with subgroup analysis in elderly and diabetic patients. AB - BACKGROUND AND HYPOTHESIS: Although prodromal angina occurring shortly before an acute myocardial infarction (MI) has protective effects against in-hospital complications, this effect has not been well documented after initial hospitalization, especially in older or diabetic patients. We examined whether angina 1 week before a first MI provides protection in these patients. METHODS: A total of 290 consecutive patients, 143 elderly (>64 years of age) and 147 adults (<65 years of age), 68 of whom were diabetic (23.4%) and 222 nondiabetic (76.6%), were examined to assess the effect of preceding angina on long-term prognosis (56 months) after initial hospitalization for a first MI. RESULTS: No significant differences were found in long-term complications after initial hospitalization in these adult and elderly patients according to whether or not they had prodromal angina (44.4% with angina vs 45.4% without in adults; 45.5% vs 58% in elderly, P < 0.2). Nor were differences found according to their diabetic status (61.5% with angina vs 72.7% without in diabetics; 37.3% vs 38.3% in nondiabetics; P = 0.4). CONCLUSION: The occurrence of angina 1 week before a first MI does not confer long-term protection against cardiovascular complications after initial hospitalization in adult or elderly patients, whether or not they have diabetes. PMID- 19645044 TI - Nutrient composition of plants consumed by black and white ruffed lemurs, Varecia variegata, in the Betampona Natural Reserve, Madagascar. AB - The purpose of this study was to quantify the concentrations of crude protein, fat, ash, neutral detergent fiber, acid detergent fiber, lignin, nonstructural carbohydrates, and gross energy in plant foods consumed by wild black and white ruffed lemurs (Varecia variegata). Calcium, phosphorous, magnesium, potassium, sodium, iron, zinc, copper, manganese, molybdenum, and selenium concentrations were also determined. A total of 122 samples from 33 plant families and more than 60 species were collected and analyzed for their nutritional content. The specific nutrient needs of black and white ruffed lemurs are unknown, but quantifying the nutritional composition of the foods they consume in the wild will help nutritionists and veterinarians formulate more appropriate diets for captive ruffed lemurs. This information will also supply information on how man induced habitat changes affect the nutritional composition of foods consumed by free-ranging lemurs. PMID- 19645045 TI - Does reperfusion in the treatment of acute myocardial infarction improve the prognosis of acute myocardial infarction in diabetic patients? AB - BACKGROUND: Diabetic patients have a 6-fold increased mortality in acute coronary syndromes. HYPOTHESIS: Different therapeutic strategies in diabetics with acute coronary syndromes have an impact on in-hospital and long-term prognosis. METHODS: A total of 889 consecutive patients with ST-segment elevation myocardial infarction were included and followed-up for at least 6 months. The study population consisted of 168 (18.9%) diabetic patients and 721 nondiabetics. RESULTS: Invasive therapy and fibrinolysis were less frequently used in diabetic patients (38.7% versus 50.2%; p = 0.0071 and 8.3% versus 15%; p = 0.024, respectively). In-hospital mortality in diabetic individuals was almost twice as high as in nondiabetic subjects (20.2% versus 11.1%; p < 0.0014). In-hospital mortality was slightly higher in diabetic patients undergoing primary percutaneous transluminal coronary angioplasty (PTCA; 8.3% versus 4.8%; p = 0.35), but lower in those treated with fibrinolysis (7.7% versus 16%; p = 0.7) compared with the rest of the patients. At 6-mo follow-up mortality was significantly higher in diabetic subjects as compared with nondiabetic subjects (28.0% versus 15.1%; p < 0.0001). The highest number of deaths was found in individuals receiving conservative treatment with diabetic subjects significantly outnumbering nondiabetic individuals (40.1% versus 27.9%; p = 0.028 at 6 mo). Both in-hospital and 6-mo mortality were similar in diabetics and nondiabetics receiving reperfusion therapy (7.1% versus 8.2%; p < 0.68 and 9.3% versus 15.3%; p < 0.098, respectively). CONCLUSION: Reperfusion therapy, both fibrinolysis and the invasive approach, reduced in-hospital mortality from that observed in nondiabetic individuals. PMID- 19645046 TI - Relationship between integrated backscatter and atrial fibrosis in patients with and without atrial fibrillation who are undergoing coronary bypass surgery. AB - OBJECTIVE: The purpose of this study was to investigate the relationship between the integrated backscatter (IBS) and atrial fibrosis, with and without atrial fibrillation (AF), in patients who are undergoing coronary bypass grafting (CABG). METHODS: A total of 74 patients (18 preoperative AF, 56 sinus rhythm [SR]) with coronary artery disease undergoing CABG were included. The IBS of the left atrium (LA) posterior wall was acquired from transthoracic echocardiographic examination before surgery. Samples from the LA appendage were collected after opening the pericardium and quantitative assessment of atrial fibrosis was performed with collagen volume fraction (CVF). Postoperative AF was monitored with electrocardiographic telemetry in-hospital. RESULTS: There was a positive relationship between age, IBS of the left atrial posterior wall indexed by pericardium (IBS%), and CVF by multivariate linear regression analysis (r = 0.612, p = 0.034; r = 0.887, p < 0.001 respectively). The value of IBS%, LA dimension (LAD), and CVF values were higher in patients with preoperative AF than in patients with preoperative SR (p < 0.001, p < 0.01, p < 0.001, respectively). The value of age, IBS%, and CVF in patients with postoperative AF were higher than in patients without postoperative AF (p = 0.029, p < 0.001, p = 0.001 respectively). CONCLUSIONS: IBS of the LA posterior wall indexed by pericardium provides an objective quantitative measure of atrial fibrosis and correlates with postoperative AF in patients undergoing CABG surgery. PMID- 19645047 TI - Evaluation of three immobilization combinations in the capybara (Hydrochoerus hydrochaeris). AB - Capybaras (Hydrochoerus hydrochaeris) are the world's largest rodent. Owing to its uniqueness, 50 AZA institutions in North America display this species. As shown by a survey, no standard anesthetic protocol has been developed for this species. As a part of an ongoing behavioral study in Venezuela, capybaras were surgically implanted with radio transmitters. Animals were randomly assigned to one of the three immobilization protocols: (1) Tiletamine HCl/Zolazepam HCl, (2) Tiletamine HCl/Zolazepam HCl/Medetomidine HCl, and (3) Tiletamine HCl/Zolazepam HCl/Medetomidine HCl/Butorphanol tartrate. The protocol recommended for minimally invasive procedures when inhalant anesthetics are unavailable is a combination of Tiletamine HCl/Zolazepam HCl/Medetomidine HCl/Butorphanol tartrate. This is based on ease of administration, volume, onset of action, depth of anesthetic achieved, reversibility, safety, and costs. PMID- 19645048 TI - Socioeconomic measures, orofacial clefts, and conotruncal heart defects in California. AB - OBJECTIVE: To examine the association of multiple measures of socioeconomic status (SES) with risks of orofacial clefts and conotruncal heart defects. DESIGN: Data were from a recent population-based case-control study conducted in California that included 608 patients with orofacial clefts, 277 patients with conotruncal heart defects, and 617 nonmalformed controls. RESULTS: The odds ratio for the worst versus best score on a household-level SES index was strongest for cleft lip with or without palate, at 1.7 (95% confidence interval, 0.9-3.4); the odds ratios for this comparison were closer to 1 and less precise for the other defect groups. An index based on neighborhood-level SES was also not associated with increased risk of the studied defects. CONCLUSIONS: This detailed analysis of SES and selected birth defects did not suggest worse SES was associated with increased risk of the studied defects, with the possible exception of cleft lip with or without cleft palate. PMID- 19645049 TI - The effect of thalidomide in chicken embryos. AB - Early in the history of the thalidomide disaster, chick embryos were "eliminated" as useful in the study of thalidomide. One reason for that conclusion was that many of the early experiments were flawed. We employed a number of experiments to expose chick embryos to thalidomide. Our data show that thalidomide does cause limb reduction defects in chick embryos as long as the embryos are directly exposed to the drug. The most useful techniques are implanting thalidomide-soaked beads into the embryo immediately adjacent to the limb territory or soaking presumptive chick limb territories in thalidomide and then grafting the explants to a host embryo celom. Thalidomide affects the chick limb grafted to a host embryo in a dose response fashion. Furthermore, S-thalidomide and S-EM12 are more teratogenic than R-thalidomide and R-EM12. PMID- 19645050 TI - The lifetime prevalence of traumatic events and posttraumatic stress disorder in the Netherlands. AB - Little information exists on the lifetime prevalence of traumatic events and posttraumatic stress disorder (PTSD) in the general population of the Netherlands. A national representative sample of 1087 adults aged 18 to 80 years was selected using random digit dialing and then surveyed by telephone using the Composite International Diagnostic Interview (CIDI) to determine the prevalence of trauma and DSM-IV PTSD. The lifetime prevalence of any potential trauma was 80.7%, and the lifetime prevalence of PTSD was 7.4%. Women and younger persons showed higher risk of PTSD. It was concluded that PTSD is a fairly common disorder and exposure to trauma is high throughout the population. Unexpectedly, prevalence rates resemble those found in the United States and are higher than in several other European countries. PMID- 19645051 TI - Maternal nativity as a risk factor for gastroschisis: a population-based study. AB - BACKGROUND: The prevalence of gastroschisis is increasing in many parts of the world, although the etiology is largely unexplained. Young maternal age has been the only consistently identified, strong risk factor. The objective of this study was to examine the role of maternal nativity in relation to other suspected risk factors for gastroschisis in Florida. METHODS: We conducted a retrospective cohort study of singleton infants born in Florida from 1998-2003. Gastroschisis cases were identified from the Florida Birth Defects Registry. Demographic and perinatal data were obtained from birth records. Multivariable Poisson regression was used to estimate adjusted prevalence ratios (PRs) and 95% confidence intervals (CIs) for each factor of interest. RESULTS: The 6-year birth prevalence of gastroschisis was 3.26 per 10,000 live births, and the annual rate increased 41% during the study period. In addition to maternal age and marital status, maternal race/ethnicity and nativity were significantly associated with the risk of delivering an infant with gastroschisis. Compared with non-Hispanic white women, non-Hispanic black women had the lowest risk of delivering an infant with gastroschisis (PR, 0.19; 95% CI, 0.13-0.26), followed by Hispanic women (PR, 0.60; 95% CI, 0.43-0.83). Women born outside the United States were significantly less likely than U.S.-born women to deliver an infant with gastroschisis (PR, 0.59; 95% CI, 0.41-0.86). CONCLUSIONS: Although young maternal age remains a strong significant risk factor for gastroschisis in Florida, other factors such as maternal race/ethnicity and nativity could be important in explaining the increasing prevalence of gastroschisis. PMID- 19645052 TI - Developmental control of inositol phosphate biosynthesis is altered in the brain of both curly and phenotypically normal straight tail mutant mice. AB - BACKGROUND: Altered levels of inositol phosphate in the central nervous system (CNS) are hypothesized to produce distorted brain signaling and lead to numerous neurologic maladies. Little is known of mechanisms controlling the complex metabolic flux of inositol phosphate. Less is known of controls that regulate inositol-phosphate biosynthesis in the mammalian brain. The expression of 1L-myo inositol-1 phosphate synthase (MIP), the only enzyme known to synthesize inositol phosphate, was studied in the brain of normal (CBA) and curly tail (CT) mutant mice. The CT strain exhibits a neural tube defect, spina bifida, responsive to inositol supplementation, but not to folic acid treatment. METHODS: Utilizing enzyme assays to determine the specific activity of MIP, Western blotting to detect expression, gas chromatography/mass spectrometry to measure inositol concentration, and statistical analyses to evaluate quantitative data, MIP expression was analyzed in newborn, young, and adult brains of CBA and CT (curly tail [ct-CT] and straight tail [st-CT]) mutant mice. RESULTS: Data analyses suggest there is a significant difference in MIP activity in the brain of CBA mice as compared to that of CT mutant mice and that temporal and spatial control of MIP expression and inositol concentrations are altered in the brain of both the ct-CT and phenotypically normal st-CT mutant. Moreover, two differentially expressed forms of MIP were identified in the adult mouse brain. CONCLUSIONS: These findings implicate a role for MIP in the maturation of the CNS and evoke a hypothesis regarding the regulation of inositol phosphate biosynthesis in brain development. PMID- 19645053 TI - Electronic structures of heme a of cytochrome c oxidase in the redox states- charge density migration to the propionate groups of heme a. AB - The electronic structures of heme a of cytochrome c oxidase in the redox states were studied, using hybrid density functional theory with a polarizable continuum model and a point charge model. We found that the most stable electronic configurations of the d electrons of the Fe ion are determined by the orbital interactions of the d orbitals of the Fe ion with the pi orbitals of the porphyrin ring and the His residues. The redox reaction of the Fe ion influences the charge density on the formyl group through the pi conjugation of the porphyrin ring. In addition, we found the charge transfer from the Fe ion to the propionate group of heme a in the redox change despite the lack of the pi conjugation. We elucidated that the charge propagation originates from the heme a structure itself and that the origin of the charge delocalization to the heme propionate is the orbital interactions between the d orbital of the Fe ion and the p orbitals of the carboxylate part of the heme propionate via the pi conjugation of the porphyrin ring and the sigma* orbital of the C-C bond of the propionate group. The electrostatic effect by surrounding proteins enhances the charge transfer from the Fe ion to the propionate group. These results indicate that heme propionate groups serve electron mediators in electron transfer as well as electrostatic anchors, and that proteins surrounding the active site reinforce the congenital abilities of the cofactors. PMID- 19645055 TI - Pena-Shokeir phenotype (fetal akinesia deformation sequence) revisited. AB - BACKGROUND: Pena and Shokeir described the phenotype of two sisters in 1974, and subsequently their features have become recognized as a sequence of deformational changes related to decreased or absent fetal movement (fetal akinesia deformation sequence [FADS]), because of the work of Moessinger (1983). METHODS: Identification of reported cases by searching Online Mendelian Inheritance in Man, Medlines, the London Dysmorphology Database, and the references found in these articles. These case reports were reviewed, tabulated, and summarized. RESULTS: It is now possible to recognize at least 20 familial types of Pena Shokeir phenotype (PSP), based on the differences found in the reports of the natural history and pathology found at fetal and newborn autopsy. In addition, characteristic changes in the central nervous system seen with embryonic/fetal vascular compromise have been recognized in many reported cases. Most of the reported cases of PSP/FADS related to vascular compromise are sporadic, but familial cases have also been reported. CONCLUSION: Lack of fetal movement (fetal akinesia) in humans produces a recognizable sequence of deformations. Many developmental processes must be accomplished for fetal movement to be normal, and for extra-uterine life to be sustainable. Prenatal diagnosis is possible through real-time ultrasound studies as early as 12 weeks. Most reported cases die in utero, at birth, or in the newborn period. Advances in embryo/fetus pathology have led to the recognition of the many familial subtypes, allowing improved genetic counseling and early recognition in subsequent pregnancies. PMID- 19645054 TI - Local effects of the sphingosine 1-phosphate on prostaglandin F2alpha-induced luteolysis in the pregnant rat. AB - Since the regression of the corpus luteum (CL) occurs via a tightly controlled apoptotic process, studies were designed to determine if local administration of the antiapoptotic agent sphingosine 1-phosphate (S1P) effectively blocks the luteolytic action of prostaglandin F-2alpha (PGF-2alpha). On day 19 of pregnancy, 2 hr before systemic PGF-2alpha administration, rats were injected intrabursa with either S1P or vehicle (control). The activity of four caspases, which contribute to the initial (caspase-2, -8, and -9) and final (caspase-3) events in apoptosis was measured in pooled CL from four individual ovaries at 0 and 4 hr after PGF-2alpha injection. The expression of the phosphorylated form of AKT (pAKT) and tumor necrosis factor-alpha (TNF-alpha) was analyzed by ELISA. In addition, cell death was evaluated by electronic microscopy (EM) in CL 4 and 36 hr after PGF-2alpha injection. The activity of caspase-2, -3, and -8 was significantly greater by 4 hr after PGF-2alpha, but not caspase-9 activity. In contrast, expression of pAKT and TNF-alpha decreased significantly. Administration of S1P suppressed (P < 0.05) these effects, decreasing caspase activities and increasing pAKT and TNF-alpha expression. The administration of S1P also significantly decreased the percentage of luteal apoptotic cells induced by PGF-2alpha. PGF-2alpha treatment increased the prevalence of luteal cells with advanced signs of apoptosis (i.e., multiple nuclear fragments, chromatin condensation, or apoptotic bodies). S1P treatment suppressed these changes and increased the blood vessel density. These results suggest that S1P blocks the luteolytic effect of the PGF-2alpha by decreasing caspase-2, -3, and -8 activities and increasing AKT phosphorylation and TNF-alpha expression. PMID- 19645057 TI - Midbrain hyperechogenicity in idiopathic REM sleep behavior disorder. AB - Recent studies have reported an increased risk to develop Parkinson's disease (PD) in patients with idiopathic RBD (iRBD). Midbrain hyperechogenicity is a common transcranial sonography (TCS) finding in PD and has been suggested as a PD risk-marker in nonparkinsonian subjects. The objective of this study is to assess midbrain echogenicity by TCS in patients with iRBD and compare the findings with the healthy controls. TCS was performed in 55 iRBD patients and in 165 age and sex-matched controls. The area of echogenicity in the SN region in the iRBD group was significantly increased compared with the control group (P < 0.001). About 19 (37.3%) of patients with iRBD were found to have SN hyperechogenicity when compared with 16 (10.7%) of the controls (P < 0.001). This is the first case control study assessing midbrain echogenicity in a large iRBD cohort compared to age- and sex-matched healthy individuals. The finding of an increased prevalence of hyperechogenicity in a subgroup of individuals with a priori increased risk for PD supports the potential role of hyperechogenicity as a risk marker for PD. The prospective follow-up of this iRBD cohort is needed to establish if those with midbrain hyperechogenicity will go on to develop clinically defined PD or not. PMID- 19645056 TI - Single nucleotide polymorphism discovery in TBX1 in individuals with and without 22q11.2 deletion syndrome. AB - BACKGROUND: Children with 22q11.2 deletion syndrome (22q11.2DS) have a wide range of clinical features. TBX1 has been proposed as a candidate gene for some of the features in this condition. Polymorphisms in the nondeleted TBX1, which may affect the function of the sole TBX1 gene in individuals with the 22q11.2DS, may be a key to understanding the phenotypic variability among individuals with a shared deletion. Comprehensive single nucleotide polymorphism (SNP) discovery by resequencing candidate genes can identify genetic variants that influence a given phenotype. The purpose of this study was to further characterize the sequence variability in TBX1 by identifying all common SNPs in this gene. METHODS: We resequenced TBX1 in 29 children with a documented 22q11.2 deletion and 95 nondeleted, healthy individuals. We estimated allele frequencies, performed tagSNP selection, and inferred haplotypes. We also compared SNP frequencies between 22q11.2DS and control samples. RESULTS: We identified 355 biallelic markers among the 190 chromosomes resequenced in the control panel. The vast majority of the markers identified were SNPs (n = 331), and the remainder indels (n = 24). We did not identify SNPs or indels in the cis- regulatory element (FOX binding site) upstream of TBX1. In children with 22q11.2DS we detected 187 biallelic markers, six of which were indels. Four of the seven coding SNPs identified in the controls were identified in children with 22q11.2DS. CONCLUSIONS: This comprehensive SNP discovery data can be used to select SNPs to genotype for future association studies assessing the role of TBX1 and phenotypic variability in individuals with 22q11.2DS. PMID- 19645058 TI - Pediatric monomelic amyotrophy: evidence for poliomyelitis in vulnerable populations. AB - Pediatric monomelic amyotrophy may present a diagnostic challenge. This is particularly true for immigrant or adopted children who have little or no available medical history. We present clinical and electrophysiological data from 11 children with monomelic amyotrophy who had electrophysiological evidence of a unilateral or profoundly asymmetric motor neuronopathy. The cause of amyotrophy in each case is most consistent with prior: (1) wildtype poliovirus myelitis; (2) "polio-like" virus myelitis, or (3) vaccine associated paralytic poliomyelitis. PMID- 19645059 TI - Electromyographic sensitivity of peroneus tertius relative to abductor hallucis in assessment of peripheral neuropathy. AB - The objective of this study was to compare the sensitivity of needle electromyography of the abductor hallucis and peroneus tertius muscles in the diagnosis of mild length-dependent peripheral neuropathy (PN). Nerve conduction studies and needle examination were performed on 50 patients with clinical evidence of mild PN. Results demonstrated that the peroneus tertius is as sensitive and is more specific than the abductor hallucis. It is particularly useful when more proximal muscles, such as the tibialis anterior and medial gastrocnemius, are not yet involved. PMID- 19645060 TI - A RYR1 mutation associated with recessive congenital myopathy and dominant malignant hyperthermia in Asian families. AB - In this study we present 3 families with malignant hyperthermia (MH), all of Indian subcontinent descent. One individual from each of these families was fully sequenced for RYR1 and presented with the non-synonymous change c.11315G>A/p.R3772Q. When present in the homozygous state c.11315*A is associated with myopathic symptoms. PMID- 19645061 TI - Effect of the free radical scavenger edaravone on peripheral nerve ischemia reperfusion injury. AB - We investigated the effects of edaravone, a free radical scavenger, on peripheral nerve ischemia-reperfusion injury caused by ligation of vessels supplying the sciatic and tibial nerves in rats. The control group was administered a placebo, the standard-dose group was given 3 mg/kg of edaravone intraperitoneally every 24 hours, and the low-dose group was given 1 mg/kg of edaravone. At 7 days after reperfusion, neurological and electrophysiological parameters were improved in the standard-dose group as compared with the control group. After 14 days, however, these differences were no longer observed. After 21 days, persistent edema and nerve fiber degeneration were noted in the standard-dose group, but not in the control or low-dose groups. Edaravone was effective during the early reperfusion period, but chronic inhibition of reactive oxygen species may be detrimental for nerve regeneration after ischemia-reperfusion injury. Further studies are necessary to confirm the long-term influence of edaravone. PMID- 19645062 TI - Patient with amyloidoma of the ulnar nerve and salivary glands. AB - Amyloidomas of the peripheral nervous system have been reported rarely. We describe a patient with a history of localized amyloidosis of the salivary glands who presented a few years later with paresthesias of her left medial arm, forearm, and fifth digit. A mass affecting the left ulnar nerve was confirmed by MRI studies. It was excised and proven on pathological examination to be an amyloidoma. The benign course of this patient's illness is consistent with localized amyloidosis affecting two different organs. PMID- 19645063 TI - Polyglandular autoimmune syndrome type 3 in a patient with ocular myasthenia gravis. PMID- 19645064 TI - Dopamine receptor D3 (DRD3) genotype and allelic variants and risk for essential tremor. AB - To investigate the possible association between dopamine receptor D3 genotype (DRD3) and allelic variants and the risk for developing essential tremor (ET). Leukocytary DNA from 201 patients with ET and 282 healthy controls was studied for the genotype DRD3 and the occurrence of DRD3 allelic variants by using allele specific PCR amplification and MslI-RFLP's analyses. A meta-analysis of previous studies was performed. The frequencies of the DRD3Ser/Gly genotype and of the allelic variant DRDGly were significantly higher in patients with ET than in controls (P < 0.017 and <0.005, respectively), These findings were especially relevant in women (OR = 1.73, 95% CI: 1.15-2.59, P = 0.008), and in patients with earlier onset of the disease with (P = 0.014). The frequencies of the DRD3Ser/Gly and DRD3Gly/Gly genotypes and of the allelic variant DRD3Gly in patients were significantly higher in patients with voice tremor, but not with head, tongue, or chin tremor, than in controls. The meta-analysis indicated association of variant genotypes with ET risk (OR = 1.18, 95% CI 1.01-1.38). These results suggest that DRD3 genotype and the variant DRD3Gly allelic variant is associated with the risk for and age at onset of ET, and with the risk for voice tremor, in Caucasian Spanish people. PMID- 19645065 TI - Arbitrary visuomotor mapping during object manipulation in Parkinson's disease. AB - The objective of this study is to investigate whether subjects with Parkinson's disease are able to use arbitrary color cues linked to the mass of an object to be lifted allowing for the predictive selection of appropriate grip forces. Fourteen patients with Parkinson's disease used a precision grip to lift two objects of different masses (400 and 600 g) in random order. In a "no cue" condition, a noninformative neutral visual stimulus was presented before each lift, thereby not allowing any judgement about which mass to be lifted. In a "cue" condition an arbitrary color cue provided advance information about which of the two masses patients would have to lift in the subsequent trial. Patients performed the conditions with either hand and by both on and off drugs. In the "no cue" trials patients scaled the predictive grip force output according to the perceived mass of the preceding lift. In the "cue" experiment patients scaled grip force in a predictive manner to mass based on the provided color cues. The ability of arbitrary visuomotor mapping was evident at either hand and not influenced by medication on/off. The precision of arbitrary visuomotor mapping correlated negatively with age, but not with disease duration, severity of motor disability on and off drug, severity of cognitive impairment on and off drug, or the amount of levodopa equivalent daily dosage of dopaminergic drugs. These data imply that Parkinson's disease does not preclude the ability of visuomotor mapping in the grip-lift task. PMID- 19645066 TI - Atypical antipsychotic use and risk of fracture in persons with Parkinsonism. AB - Our objective was to estimate the effect of atypical antipsychotics (AAs) on the rate of fractures in a parkinsonism population. We conducted an age- and state matched nested case-control study in five states (CA, FL, NY, OH, IL) using the Medicaid analytic extract from 2001 to 2002. Eligible participants had a diagnosis of parkinsonism, excluding persons with secondary parkinsonism, bone cancer, bone infections, schizophrenia, schizoaffective disorder, and those who used conventional antipsychotics. The primary outcome was the occurrence of a fracture of the femur, ankle, fibula, tibia, humerus, radius, or ulna (N = 851). Risk-set sampling defined controls (N = 4220). We used conditional-logistic regression to derive adjusted odds ratios (AOR) and 95% confidence intervals of the association between fracture and use of quetiapine, risperidone, or olanzapine in the 60 days before the index date compared to nonuse. After adjustment for confounding, use of quetiapine (AOR 2.4; 95% CI 1.5-3.8), risperidone (AOR 1.2; 95% CI 0.9-1.7), or olanzapine (AOR 1.7; 95% CI 1.2-2.4) was associated with a higher rate of fracture. Use of an AA was associated with a higher rate of fracture in persons with parkinsonism. Prescribers must be cautious when using these agents in elderly persons with parkinsonism. PMID- 19645067 TI - Goal attainment after treatment of parkinsonian camptocormia with botulinum toxin. PMID- 19645068 TI - Amelioration of subacute camptocormia in multiple system atrophy by protirelin tartrate. PMID- 19645069 TI - Head drop in an elder Parkinson's disease after development of myasthenia gravis. PMID- 19645070 TI - Non-therapeutic risk factors for onset of tardive dyskinesia in schizophrenia: a meta-analysis. AB - A meta-analysis of prospective studies with schizophrenia patients was conducted to examine whether the evidence exists for risk factors for the emergence of Tardive Dyskinesia (TD) in schizophrenia. A computer assisted Medline/PubMed and Embase search was conducted in January 2008 for the years 1985-2007. Selected were truly prospective studies of incident cases of TD in a population with at least 80% patients with schizophrenia. Measures of relative risk were collected from the individual studies, either directly or by calculating the relative risk from the cox- or logistic regression coefficient provided in the article. Hazard Ratio's and Odds Ratio's were pooled using fixed and random effect models in case of multiple studies using the same measure of risk and outcome. Only eight studies satisfied the inclusion criteria reporting on 25 different single estimate risk factors. Of 25 risk factors, six concerned replicated estimates suitable for meta-analysis. Of these, non-white ethnic group and early extrapyramidal symptoms qualified as risk factors for the emergence of TD in schizophrenia. The association with older age was suggestive but inconclusive. Despite many reported risk factors for TD in schizophrenia, little conclusive evidence exists to corroborate this. However, the fact that early EPS predicts onset of TD has important clinical and research implications. PMID- 19645071 TI - Suicide following duodenal levodopa infusion for Parkinson's disease. PMID- 19645072 TI - Transient improvement of psychogenic (proprio-)spinal-like myoclonus to electrical nerve stimulation. PMID- 19645073 TI - Remission induction, consolidation and novel agents in development for adults with acute myeloid leukaemia. AB - Chemotherapy regimens used for remission induction in AML have not changed significantly over the last several decades. However the recognition of the prognostic value of cytogenetics and genomics has been a major advance which is helping clarify the most optimal post-remission consolidation strategy among various risk groups. We are not only beginning to realize the pitfalls of a 'one fits-all' approach with intensive, cytarabine-based chemotherapy as the mainstay, but we are finally beginning to reap the rewards of decades of basic, translational, and clinical research. Developing individualized, 'targeted' therapy for each AML patient based on unique molecular features of disease remains a daunting goal yet one that we can now begin to envision. Hypothesis based study designs-from pre-clinical/laboratory experiments to phase-I and subsequent efficacy trials-provide the foundation for advances in the diagnosis, risk stratification, and treatment for patients with AML. Here we critically review the literature for the management of AML, try to give recommendations regarding the appropriate induction and remission strategy, clarify the role of stem cell transplantation and discuss novel agents on the horizon. PMID- 19645075 TI - An exploration of anticipatory grief in advanced cancer patients. AB - BACKGROUND AND OBJECTIVES: Research on anticipatory grief (AG) has been more focused on the experience of relatives than the terminally ill patients. This study will present qualitative 'thick descriptions' of advanced cancer patient's experience of AG and explore how it is experienced in the family context. METHOD: Seven advanced incurable cancer patients (median 58 years) were recruited from the day hospice and five patients comprised the final sample. Participants were invited to attend focus groups and individual interviews to discuss their experience of terminal illness, thoughts and feelings related to AG and how they cope with losses and grief in the family. Qualitative transcripts were analyzed using interpretative phenomenological analysis. RESULT: Two inter-related themes of AG were identified. The first main theme 'subjective experience of AG' comprises confrontations with death and multiple losses; and resistance against death and loss. The second main theme 'experience of AG in the family' explored the patient's role in the family interaction patterns and interpersonal processes. CONCLUSION: An understanding in the subjective experience of AG in terminally ill patients and their experience of AG in the family may contribute to the development of psychotherapeutic interventions. The generative role of the patient in the family grief process is also highlighted. PMID- 19645076 TI - Economic crisis threatens AIDS fight. PMID- 19645077 TI - Detection of epithelial cells by RT-PCR targeting CEA, CK20, and TEM-8 in colorectal carcinoma patients using OncoQuick density gradient centrifugation system. AB - BACKGROUND: The detection of epithelial-specific mRNA correlates well with the presence of cancer cells in the peripheral blood and provides a rational explanation for subsequent metastasis. MATERIAL AND METHODS: Forty-two, patients with colorectal cancer and 14 controls were included in our study. Peripheral blood samples were acquired at 24 h before and 48 h after laparotomy. Tissue samples were also acquired from the primary lesion. All samples were examined for the expression profile of CEA, CK20, and TEM-8. RESULTS: Tissue samples expressed CEA in every specimen, CK20 in 30, and TEM-8 in 41. CEA and CK20 were not identified in the control blood samples while TEM-8 was detected in 4. CEA was detected in 17, CK20 in 28 and TEM-8 in 23, of the preoperative blood samples. CEA mRNA expression in preoperative blood sample and TNM stage were found independently associated with increased tumor size. Positive CEA, CK20, and TEM-8 signals were found in 25, 25, and 23 of the postoperative blood samples respectively. CONCLUSIONS: CK20 and CEA are significantly more frequently detected in colon cancer patients than in healthy controls and can serve as markers. Cancer cell mRNA is commonly detected in the preoperative and postoperative peripheral blood samples. Tumor size was independently associated with the preoperative detection of CEA mRNA. Although TEM-8 mRNA detection in the peripheral blood showed no specificity for cancer patients or correlation with clinical stage, identification and validation of genes and proteins implicated in metastatic process needs to be further investigated. PMID- 19645074 TI - The root of many evils: indolent large granular lymphocyte leukaemia and associated disorders. AB - Large granular lymphocytes (LGL) leukaemia can arise from either natural killer (NK) cells or cytotoxic T lymphocytes (CTL). The T-cell form of LGL leukaemia has significant overlap with other haematological disorders and autoimmune diseases. Here we provide an overview of LGL biology. We also focus discussion on the indolent LGL leukaemia related disorders and their causal relationships. We then discuss the potential relationships and distinctions between indolent LGL leukaemia and non-malignant clonal lymphocyte expansion that occur in otherwise healthy individuals, especially elder people. PMID- 19645078 TI - Relationship between three measures of genetic differentiation G(ST), D(EST) and G'(ST): how wrong have we been? PMID- 19645079 TI - Surgical ventricular reconstruction. PMID- 19645080 TI - Surgical ventricular reconstruction. PMID- 19645081 TI - Surgical ventricular reconstruction. PMID- 19645082 TI - Valsartan and recurrent atrial fibrillation. PMID- 19645083 TI - Telaprevir for chronic HCV infection. PMID- 19645084 TI - Care of war veterans with mild traumatic brain injury. PMID- 19645085 TI - Care of war veterans with mild traumatic brain injury. PMID- 19645086 TI - Recommendations on testing for thrombophilia in venous thromboembolic disease: a French consensus guideline. PMID- 19645087 TI - Practice guidelines for acute bacterial meningitidis (except newborn and nosocomial meningitis). PMID- 19645088 TI - Dealing with China's future population decline: a proposal for replacing low birth rates with sustainable rates. AB - Decreasing population levels due to declining birth rates are becoming a potentially serious social problem in developed and rapidly developing countries. China urgently needed to reduce birth rates so that its population would decline to a sustainable level, and the family planning policy designed to achieve this goal has largely succeeded. However, continuing to pursue this policy is leading to serious, unanticipated problems such as a shift in the country's population distribution towards the elderly and increasing difficulty supporting that elderly population. Social and political changes that promoted low birth rates and the lack of effective policies to encourage higher birth rates suggest that mitigating the consequences of the predicted population decline will depend on a revised approach based on achieving sustainable birth rates. PMID- 19645089 TI - Fertility pattern and family structure in three Alpine settlements in South Tyrol (italy): marriage cohorts from 1750 to 1949. AB - Stelvio, Martello and Curon, three villages of the Venosta Valley, South Tyrol (Italy), were recently included in a large genetic survey because of their isolation. This study focuses on the long-term reproductive behaviour of these villages. Family size, age at marriage and marital fertility were estimated based on a genealogy going back in the 17th century. Marriage behaviour was characterized by an elevated age at marriage and a large proportion of adults never getting married. Marital fertility was among the highest worldwide, because couples tried to use the short time at their disposal to have the largest possible number of children. Together with the already known null population expansion and high geographic endogamy rates, the reduced number of siblings who had the opportunity to get married could have favoured an increased genetic homogeneity. PMID- 19645090 TI - Editorial comment on: Renal angiomyolipoma: long-term results following selective arterial embolization. PMID- 19645091 TI - Words of wisdom. Re: Persistent genital arousal disorder in women: case reports of association with anti-depressant usage and withdrawal. PMID- 19645092 TI - Words of wisdom. Re: FDA public health notification: serious complications associated with transvaginal placement of surgical mesh in repair of pelvic organ prolapse and stress urinary incontinence. PMID- 19645093 TI - Economic stimulus and the environment. PMID- 19645094 TI - The contextual components of ecotoxicology. PMID- 19645095 TI - Duckweed toxicity tests are appropriate for ERA. PMID- 19645096 TI - Is the ECx a legitimate surrogate for a NOEC? PMID- 19645097 TI - Is selenium a global contaminant of potential concern? AB - Selenium is not a new contaminant, but its environmental presence and significance are only now being evaluated. It has been and will continue to be "discovered" in a variety of water bodies generally due to improved analytical chemical detection limits. It has the potential to cause deleterious effects on aquatic life at environmentally relevant concentrations, and there is no definitive regulatory standard for chronic effects. The US Environmental Protection Agency (2004) has recognized the need for a tissue Guideline/criterion, but has not yet finalized such a value. A SETA Pellston Workshop (Pensacola, FL, USA, February 23-28, 2009) has determined the state-of the-science related to ecological assessment of Se in the aquatic environment. The Workshop Executive Summary will shortly be forthcoming followed by a more detailed book published by SETAC Press. However, this workshop was constrained by the areas of the world (see above) where Se has been recognized as a contaminant of potential concern and for which information is available. Thus, by way of this Learned Discourse I solicit information from readers as to whether Se is present at concentrations of concern in other parts of the world than North America, Australia, and New Zealand and, if so, "So what?" (i. e., are there adverse effects to individuals and/or impacts to populations of fish, water birds, and/or amphibians?). PMID- 19645098 TI - Endocrine disrupting effects in fish induced by parasites. PMID- 19645099 TI - [Effect of steroid therapy on the clinical course of bronchial asthma]. AB - Although only some 5% of the asthmatic population develop severe disease, such cases eat up more than half of the spendings for the management of asthma and they are poorly controlled by the currently available therapies. Most of these patients undergo long-term treatment with various steroid formulations that exert selective action in the airways eliminating one cell type and supporting the growth of another. For this reason, inflammation patterns in severe, as opposed to mild, asthma resemble those in COPD, with a high neutrophil count in the sputum, increased oxidative stress, and poor response to corticosteroids. Such differences in asthma pathogenesis may be due to the accumulation of two CD4+ cell subsets (regulatory T cells and Th17 cells) in the lungs. It is believed that the use of alkylating drugs in low (non-cytotoxic) doses selectively inactivating Tregs and Th17 cells is a promising method for the treatment of severe asthma. PMID- 19645100 TI - [Acute and chronic alcoholic intoxication as a cause of modified immunological reactivity in patients with generalized peritonitis]. AB - The importance of assessment of immunological reactivity in patients with generalized peritonitis suffering alcoholic intoxication ensues from the possibility to use it for the prediction of abdominal inflammation dynamics and thereby for the optimization of organ-protective therapy in critical situations. PMID- 19645101 TI - [Dynamics of acoustic properties of skin integument and hydroxyproline content during surgical treatment of congenital limb malformation]. AB - The aim of the work was to examine mechanical and acoustic properties of the skin and collagen metabolism in patients with congenital and developmental malformation (CDM) of extremities. Acoustic tests were performed in 39 patients with forearm CDM and in 30 with leg CDM aged 4-18 years using an ASA-4 apparatus (Russia and Yugoslavia). Mean radial and ulnar lengthening was 6.4 +/- 1.0 (5.5 8) cm, tibial and fibular lengthening 5.0 +/- 1.2 (3-8) cm, and femoral lengthening 6-12 cm. Longitudinalvelocity of sound 1 and 2 months after distraction was 42.3% and 62.9% respectively higher than the preoperative value (p < 0.05). A similar increase (36.8 and 58.4% respectively) was recorded with the ASA-4 sensor in the transverse position. Acoustic inhomogeneity in the thigh skin also increased during distraction. Maximum free to protein-bound hydroxyproline ratio in blood was measured in the end of distraction (0.58 +/- 0.04) and in the beginning of fixation (0.6 +/- 0.01). Its subsequent decrease reflected structural and metabolic changes related to proliferative and biosynthetic processes in the skin, fibrillogenesis, and altered homogeneity patterns. PMID- 19645102 TI - [The radiation environment in the Russian Federation according to the results of radiohygienic certification]. AB - Ensuring nuclear and radiation safety in the use of atomic energy is one of the most important constituents of the Russian Federation's security, which is laid down in the "Foundations of Public Policy in the nuclear and radiation safety of the Russian Federation till 2010 and Further Prospects". The radiation safety in an area is determined by not only the number of radiation objects in it, the grade of their potential radiation hazard, their maintenance, the nature of use, but also by the measures ensuring radiation safety and preventing possible radiation accidents, and the readiness for liquidation of their consequences, and the effective supervision of whether the requirements are carried out. To assure constant and effective control over radiation safety, a uniform system for the information provision of radiation safety has been developed and introduced in the Russian Federation since 1998, which includes radiohygienic certification and the uniform state system for monitoring and considering the radiation doses exposed by the residents of Russia. The 2007 radiohygienic certification covered more than 16000 organizations dealing with the sources of ionizing irradiations. A total of 202.7 million medical diagnostic radiological procedures were performed in Russia in 2007. It should be noted that the dose of medical irradiation is reduced. In general, the radiation environment in the Russian Federation is satisfactory, but in a number of its regions there are reasonably serious problems associated with the population's radiation safety. PMID- 19645103 TI - [The sanitary and epidemiological problems in production and consumption waste handling in the Russian Federation]. AB - At the initiative of the bodies and organizations of the Russian Agency for Consumer Surveillance, the interdepartmental commissions on sanitary purification and on production and consumption waste handling heard more than 2275 items on the subjects of the Russian Federation in 2007. In 2006-2007, in all the subjects of the Russian Federation work was under way with the local authorities to legalize or liquidate unauthorized sites of waste disposal in rural settlements. As compared with 2006, there was a reduction in both the number of unauthorized dumps from 11,062 to 9,069 and the area under them from 33,587.6 to 29,506 ha. According to the administrations of the Russian Agency for Consumer Surveillance, in 2007, the number of enterprises generating waste was 1,092,871, of them 91.2% of the enterprises were under the control of bodies and organizations of the Russian Agency for Consumer Surveillance. The largest number of enterprises (813,233) produces domestic waste and 173,272 enterprises generate factory waste; as for poultry farming and cattle breeding waste, sewage sludge, and agrochemicals, these accounted for less than 10%. As compared with 2006, the number of sludge traps, tailing pits, waste banks, terraces, ash-and-slad burrows, etc. increased and amounted to 2,338. The reduction in the volume of accumulated waste, by involving the latter into the economic turnover, by introducing and improving their processing technologies is urgent. The highest percentage of waste utilization was achieved by building enterprises (91%), followed by agricultural ones (77%). At the same time this index at the enterprising generating the bulk of waste, namely, at the minerals-extracting enterprises, is 39% as that in Russia. In 2007, pesticides and agrochemicals were kept at 5600 storage facilities, of which as many as 2180 have a sanitary-and epidemiological opinion; 60% of the storage facilities have an organized control area. PMID- 19645104 TI - [Impact of the environmental factors on the incidence of thyroid diseases in the population of the Nizhnii Novgorod region]. AB - None of the thyroid diseases is associated with the environment, as thyroid pathology since its structure and function depend on dietary intake of iodine and other trace elements. Iodine deficiency is not the only factor of development of endemic goiter as many authors show the high prevalence of the disease with sufficient dietary intake of iodine. Human thyroid disease may be considered to be a marker of environmental ill-being; therefore, while studying and untangling the mechanisms of development of goiter, thyroiditis, and thyroid tumors, one should keep in mind the environmental factors that have an evident influence on the development of thyroid diseases. PMID- 19645105 TI - [Problems in the monitoring of bromine-containing substances in the drinking water]. AB - The water concentrations of bromide ions at the level of 0.2 mg/dm3 or higher, which are sufficient for redox reaction of humin compounds under the action of potent oxidizing agents present a potential hazard in the hygienic terms of formation of transformation products, which also agrees with the hygienic standards. The concentration of bromide ions below 0.1 mg/dm3 can be considered to be relatively safe in the terms of production of organobromine compounds. PMID- 19645106 TI - [Hygienic assessment of soil pollution on the territory of oil-producing regions in the Republic of Tatarstan]. AB - The paper provides the hygienic characteristics of soil resources on the territory of oil-producing regions in the Republic of Tatarstan (RT). Soil pollution with heavy metals and oil was evaluated. Oil at the detectable concentrations was shown to cause changes in the physiochemical properties of soil, to impair its self-purification, to increase the resistance of soil pollutants, thus deteriorating the ecological-and-hygienic state of soil as a whole. The soils on the territory of oil-producing regions in RT were observed to be characterized by the low levels and poor ratio of essential trace elements, such as copper, zinc, and chromium. Significant soil manganese concentrations, the presence of arsenic and lead may be considered as factors aggravating the problem associated with deficiency of essential trace elements in the body and with the generation of endocrine biopathotype. PMID- 19645107 TI - [Analysis of the late irradiation effects in the population of the north part of the East-Urals radioactive track]. AB - Death records were used to analyze cancer mortality in the rural areas of the Kamensky District, Sverdlovsk Region, within the East-Urals radioactive track area. A study group showed a significant increase in cancer mortality as compared with a control group (65 of the 691 examinees; 90% confidence interval (CI) 18 144; the mean colonic radiation dose was 80 and 3 mGy in the study and control groups, respectively). The additional relative risk per colonic dose was 1.3 Gy( 1) (90% CI 0.36-2.9 Gy(-1)). The association of the additional relative risk with the age-related and time factors was studied and revealed. PMID- 19645108 TI - [Working conditions and occupational morbidity in workers of the Russian Federation]. AB - To create healthy and safe working conditions are constantly in the focus of attention at all governmental levels. To reduce deaths and traumatism from occupational accidents and diseases, by providing safe working conditions is one of the priorities of the demographic policy pursued by the Government of the Russian Federation. In the able-bodied population, the current mortality from natural causes (accidents, poisonings, and traumas, including occupation-related ones) exceeds that by 2.5 and 1.5 times in developed and developing countries, respectively. The worse conditions remain to be those in coal-mining and shipbuilding industries, ferrous and non-ferrous metallurgy, agriculture, tractor building and agricultural engineering, building materials industry, road-building machinery, logging industry, power machine building, and civil engineering. On going checks reveal low sanitary culture and industrial discipline, no package of sanitary-and-prophylactic measures, as well as poor knowledge about sanitary legislation requirements in the heads of small-scale business and private undertakings. In 2006, the Russian Federation notified 357 cases of occupational diseases among medical workers, of which there were 196 cases of pulmonary tuberculosis and 39 cases of viral hepatitis. Despite the fact that the cases of occupational diseases are annually on the decrease, these are being underdetected. PMID- 19645109 TI - [Study of the influence of cellular phones and personal computers on schoolchildren's health: hygienic aspects]. AB - The paper presents the results of studying the impact of using cellular phones and personal computers on the health status of 277 Saratov schoolchildren (mean age 13.2 +/- 2.3 years). About 80% of the adolescents have been ascertained to use cellular phones and computers mainly for game purposes. The active users of cellular phones and computers show a high aggressiveness, anxiety, hostility, and social stress, low stress resistance, and susceptibility to arterial hypotension. The negative influence of cellular phones and computers on the schoolchildren's health increases with the increased duration and frequency of their use. PMID- 19645110 TI - [The physical developmentand the types of constitution in the 7-10-year-old girls and boys of Magadan]. AB - It has been shown that in the 7-10-year-old Magadan girls and boys, there is a reduction in the proportion of mesosomatics and an increase in that of micro- and macrosomatics. The proportion of children with disharmonious physical development substantially increases by age of 10 years, which negatively affects at the level of somatic health. Analysis of body mass index data shows that fewer girls have the average body mass indices with its values being less and higher than the average ones than the boys. PMID- 19645111 TI - [Occurrence of somatic pathology of the gastrointestinal tract: hygienic aspects (a review of literature)]. AB - The paper states the results of modern Russian and foreign scientific literature on the risk factors of human noninfectious gastrointestinal diseases. The major groups of exogenous risk factors of this pathology: social, economic, natural, man-made factors and lifestyle were identified. The paper shows it necessary to reveal priority regional risk factors of gastrointestinal diseases to warrant measures for primary prevention at the population-based level. PMID- 19645112 TI - [Tuberculosis in children and adolescents in the Saratov Region in 2001-2007]. AB - Tuberculosis in children and adolescents is closely associated with the tuberculous infection reservoir existing in the Saratov Region. In this region, the tuberculosis epidemiological situation has improved and stabilized in the past 7 follow-up years, which is undoubtedly associated with the better organization of performed tuberculosis-controlling measures. PMID- 19645113 TI - [Respiratory diseases as a cause of death in schizophrenia]. AB - Eight hundred and thirty autopsy protocols of died patients with schizophrenia from 1952 to 2007 were studied. Respiratory pathology as a cause of death was noted in 29.8% of cases. There are great changes in the study parameters, which have been particularly evident in the past 2 decades: a reduction in the rate of lobar (croupous) and bronchial pneumonia, an increase in the number of cases of active pulmonary tuberculosis and chronic obstructive pulmonary disease, and lung cancer. The higher incidence of the two latter diseases is associated by the author with the side effects of phenothiazine neuroleptics in the long-term treatment of schizophrenia. PMID- 19645114 TI - [Rare localization of tuberculosis in a generalized process in an infant]. PMID- 19645115 TI - [The clinical and diagnostic value of C-reactive protein as a marker of a systematic inflammatory response in pregnancy (a review of literature)]. PMID- 19645116 TI - [Biological functions and biological reactions. Laser correlation spectroscopy in the evaluation of extracellular medium purity--functions of endoecology (lecture)]. PMID- 19645117 TI - [Evaluation of the rate of lipid peroxidation and antioxidant defense in blood during gynecological laparoscopic operations]. AB - The impact of gynecological operations on the rate of lipid peroxidation (LPO) and erythrocytic antioxidant defense (EAOD) was studied in women with uterine myoma. The higher rate of LPO and the decreased level of vitamin E were preoperatively found. A further increase in LPO activity and a reduction in vitamin E concentrations were observed 1-4 days after surgery. Recovery of the study parameters was seen on days 5-7 postoperatively. The enzyme glutathione-S transferase was ascertained to play a pivotal role in the EAOD system. PMID- 19645118 TI - [Maternal serum screening: possibilities of using in the complex diagnosis of fetal malformation]. AB - Along with ultrasonography, maternal serum screening is an initial stage of a diagnostic process of genetically determined fetal malformation. Based on the performed clinical and statistical study, the author estimated the values of alpha-fetoprotein and beta-subunit of chorionic gonadotropin if the fetus has malformations of the central nervous system, heart, anterior abdominal wall, and urinary tract and Down's syndrome. The informative value of alpha-fetoprotein was confirmed in malformations of the anterior abdominal wall (gastroschisis, omphalocele) and the central nervous system (hydrocephalus, spinal hernia) and that of chorionic gonadotropin in Down's syndrome in a fetus of 15 to 24 weeks gestation. PMID- 19645119 TI - [A new procedure for evaluating the severity of childhood celiac disease]. AB - The paper describes a new procedure for evaluating the severity of childhood celiac disease, the basis of which is to determine the salivary activity of the enzyme ornithine decarboxylase (ODC). The salivary ODC activity index of 0.0001 to 0.0080 ncat/ml suggests severe celiac disease; that of 0.0081-0.0145 and 0.0146-0.0410 ncat/ml indicates its moderate and mild forms, respectively. The development of this procedure is urgent since the typical forms of celiac disease, which make the determination of the degree of the disease difficult in most cases. PMID- 19645120 TI - [The rapid method for differentiating bacteria of Listeria strain]. AB - An integrated indicator medium has been designed to differentiate Listeria bacteria from other microorganisms, which may be used at the first stage of diagnosis of the causative agent of listeriosis. The application of this medium makes it possible to simplify and to accelerate the detection of Listeria in the examination of different samples of foodstuffs, environmental objects, clinical material and to extend the range of Russian indicator culture media for the differentiation of this microorganism. PMID- 19645121 TI - Publisher's Note: "The views and preferences of resuscitated and non-resuscitated patients towards family witnessed resuscitation: a qualitative study" [International Journal of Nursing Studies Vol. 46, Issue 1, pages 12-21]. PMID- 19645122 TI - Mergers, acquisitions and partnerships. Lessons from the 1990s. PMID- 19645123 TI - Imaging evaluation of the solitary pulmonary nodule: self-assessment module. AB - The educational objectives for this self-assessment module are for the participant to exercise, self-assess, and improve his or her understanding of the imaging evaluation of the solitary pulmonary nodule. PMID- 19645124 TI - Imaging evaluation of tendon sheath disease: self-assessment module. AB - The educational objectives for this self-assessment module are for the participant to exercise, self-assess, and improve his or her understanding of the imaging evaluation of tendon sheath disease. PMID- 19645126 TI - "Crossed cerebellar diaschisis" in human supratentorial brain infarction. PMID- 19645127 TI - Cholera: global surveillance summary, 2008. PMID- 19645128 TI - Pediculosis pubis and dermoscopy. PMID- 19645129 TI - Incorporating novel treatment strategies into conventional therapy. PMID- 19645130 TI - Clinical trials in adult AML. PMID- 19645131 TI - Molecular characteristics therapy in AML. PMID- 19645132 TI - The new and ever changing PhRMA guidelines are impeding productive relationship. PMID- 19645133 TI - [Pay close attention to standardization of the treatment of primary liver cancer]. PMID- 19645134 TI - [Expert consensus on standardization of the management of primary liver cancer]. PMID- 19645135 TI - [Surgical treatment for hepatocellular carcinoma]. PMID- 19645136 TI - W. Kline Bolton Festschrift. September 13, 2008. Charlottesville, Virginia, USA. PMID- 19645137 TI - Buyer's guide to 3-D imaging/cone beam tomography. Cone beam tomography produces 3-D image ideal for dentists. PMID- 19645138 TI - Buyer's guide to cosmetic imaging systems. Cosmetic imaging creates projection of restorative treatment. PMID- 19645139 TI - [Infections in surgery]. PMID- 19645140 TI - [Intrapancreatic accessory spleen]. AB - BACKGROUND: Intrapancreatic accessory spleen is a rare cause of pancreatic pseudotumors and in about 1-2% located in the pancreatic tail. Accessory spleens itself are found in about 10-15% of the population. Our findings show a case of an intrapancreatic accessory spleen suspected for a malignancy in the pancreatic tail. PATIENT: A 63-year-old man admitted for Cholezystitis was incidencially diagnosed with a tumor at the pancreatic tail. On MRI a hyperintense solid mass of 1.5 cm in diameter in the pancreatic tail was seen, which contrasted hyperdense in T2-weighted imaging. Due to inhomogenous enhancement on the early vascular phase the diagnosis of a endocrine pancreatic tail Carcinoma was suspected. RESULTS: Intraoperative an accessory spleen was found in the pancreatic tail. An oncological left pancreatectomy was performed suspecting a malignant tumor. Histology showed an intrapancreatic accessory spleen in the pancreatic tail excluding presence of cancer. CONCLUSION: Intrapancreatic accessory spleen is a rare cause of unnecessary laparotomy but the absence of reliable diagnostics for this entity make histological ascertainment of a benign tumor indispensable. Therefore we still need an oncological tumor resection. PMID- 19645141 TI - [Antithrombotic prophylaxis in surgery--American College of Chest Physicians recommendations 2008]. AB - A brief content of American College of Chest Physicians Venous thromboembolism prophylaxis guidelines for surgical specialties published in 2008 and selection of significant studies and corresponding references is provided thus a reader has easily accessible review and literature. PMID- 19645143 TI - [The role of surgery in Crohn's disease treatment]. AB - Crohn's disease is a chronic, transmural inflammatory disease of the gastrointestinal tract of unknown origin. Even though surgical therapy may relieve symptoms in patients with complications, it still remains, together with medicamentous therapy, palliative. According to literature, cummulative probability of operation is 78% during 20 years. AIM OF STUDY: Analysis of experiences with surgical therapy of complications of Crohn's disease and search for optimal method of surgical therapy. MATERIAL AND METHODS: Authors present group of patients, that were treated on their clinic for complications of Crohn's disease. In years 2006-2007 group consisted of 21 patients. Most common indications for hospitalisation were signs of perforative peritonitis and ileus, bleeding, fistulas and signs of acute appendicitis. RESULTS: Following recommendations, resections of sick bowel dominated, we performed appendectomy once, bleeding was treated conservatively. Diagnosis was confirmed histologically from resected material or from biopsy. No patient died in the group, all of them were sent for next treatment to gastroenterology. CONCLUSION: Preferred therapy are classical surgical approaches to the acute abdomen, the spectrum of laparoscopical operations is widening, but their advantages may disappear in operations of large inflammatory tumours. It is necessary to consider alternative ways of treatment. PMID- 19645142 TI - [Tolerance of accelerated postoperative rehabilitation following intestinal resections]. AB - INTRODUCTION: Modern procedures in peri-operative care arising from evidence based medicine improve postoperative results. Their acceptance is however not a common clinical practice at most surgical centers. AIM: The aim of our study was to design a protocol and introduce it into the praxis. The subject of announcement is tolerance of protocol in our conditions. PATIENTS AND METHOD: Prospective randomized study included patients who were operated on (open bowel resection) at Department of Surgery in period 4/2005-12/2007. They were randomized in fast track group (n=53) and non-fast track group (n=52). Protocol with accelerated recovery was used in the fast track group (FTG) and we used traditional approach in the not-fast track (non-FTG). Results were statistically evaluated, 2 patients (FTG) were excluded from analysis for protocol failure (protocol was non kept by anesthesiologist in 1 patient and by the nurse in the second patient). Protocol and informed consent form was approved by the Hospital Ethics Committee. RESULTS: Both groups did not differ in age, diagnosis and length of surgery. Analgesia was controlled significantly better in FTG; similarly oral intake tolerance was higher in this group (day of surgery--mean value 634 ml versus 304 ml). Restoration of bowel functions was also faster in interventional group (mean time 2.1 versus 3.9 days). Frequency of postoperative complications was lower and hospital stay was shorter (median 7.0 versus 9.0 days, p < 0.001). CONCLUSION: Designed fast track protocol of postoperative recovery could be introduced in clinical praxis in terms of study. Patients' tolerance was very good. Application of accelerated recovery procedures is possible in our conditions but it means primarily to overcome worse tolerance of attending personnel. PMID- 19645144 TI - [Accidental finding of a malignancy during surgery for unusual intestinal obstruction in a female patient following kidney transplantation]. AB - This case report of 62 year old woman observed and treated in Vascular surgery Dpt. of University Hospital in Pilsen because of small bowel obstruction may be an example of a malignant disease, which can occur after using immunosuppressive drugs. The reason of the obstruction was strangulation of the small bowel in a peritoneal defect, which was made arteficialy as a treatment of posttransplant lymf-collection. We found signs of malignant disease in peritoneal cavity during the operation, that was verified by biopsy. The patient did not suffer from malignant disease before the transplantation. The origin of malignancy was probably ovarian tumor. PMID- 19645145 TI - [Truncus coeliacus stenosis in duodenopancreatectomy]. AB - INTRODUCTION: Patients with celiac axis stenosis are asymptomatic due to the rich collateral blood supply through superior mesenteric artery. Ligating and dividing gastroduodenal artery during pancreatoduodenectomy can cause ischemic threat especially to liver, less frequently stomach and spleen, or failure of anastomoses. CASE REPORT: The authors present a case of 27-year-old female who underwent duodenopancreatectomy for pseudopapillary tumour of the head of pancreas. Celiac axis stenosis was found peroperatively and proven during angiography. Although an attempt of endovascular dilatation of celiac axis was unsuccessful, blood supply to the liver was sufficient and therefore we did not perform any other intervention to improve blood flow to the liver. Postoperative course was uneventful. DISCUSSION: Celiac axis stenosis can be caused by tumour infiltration or lymphadenopathy in malignant disease, atherosclerosis or compression of the median arcuate ligament. The stenosis can be managed by endovascular treatment or arterial reconstruction. In conclusion the authors propose a management algorithm to prevent the consequences of celiac axis stenosis. PMID- 19645146 TI - [Neoplastic thrombosis of the inferior vena cava in kidney carcinoma]. AB - INTRODUCTION: Neoplastic thromboses of the inferior vena cava occur in about 4 15% of patients with conventional, clear-cell renal carcinoma, and significantly increase intraoperative mortality and morbidity rates. AIM: Assessment of outcomes of radical nephrectomies with inferior vena cava thrombectomies, performed in the PlzeN Faculty Hospital from 01-01-1999 to 31-12-2008. PATIENT GROUPS AND METHODS: The study included 16 patients, 12 males and 4 females of 63.6 years of age on average (44-75 y.o.a), suffering from conventional, clear cell renal carcinoma and neoplastic thrombosis of the inferior vena cava. The main symptoms included hematuris in 7 subjects (43.8%), lumbar pressure pain in 4 subjects (25%), leg edema in 2 subjects (12.5%). In 2 patients (12.5%), the finding was accidental and in 1 patient (6.3%), the symptoms were caused by distant metastases. The diagnostic methods included duplex sonography, multidetector computed tomography, magnetic resonance imaging and cavography. In three subjects, the thrombus was located in the renal vein only (grade I), in 9 subjects, the thrombus propagated below the entry of the hepatic veins (grade II), in 3 subjects, the thrombus extended above the entry of the hepatic veins (grade III) and, in 1 patient, it reached the right atrium (grade IV). All the patients underwent transabdominal radical nephrectomy (pT3b,c,pN0-2,pM 0-1) and inferior vena cava thrombectomy. RESULTS: The average duration of IVC closure using vascular clips was 6.3 minutes (3-12 minutes), the average blood loss was 1.7 litres. The intraoperativev mortality rate of the whole study group was 0%. In a single patient, an incompletely removed thrombus resulted in massive pulmonary embolization on day 3, which was urgently managed by cardiosurgery with extracorporeal circulation, when the thrombotic mass was removed from the pulmonary artery. Three subjects (18.8%) died due to generalization of the underlying disease 5-17 months after the primary procedure. Two subjects (12.5%) are currently receiving symptomatic treatment for their generalized underlying disease. 11 subjects (68.8%) show no signs of a relaps of the underlying disease at 3 month-5 years after the procedure. CONCLUSION: Radical nephrectomy combined with complete removal of the neoplastic thrombus provides the best prospects for long-term survival rates of the patients. PMID- 19645147 TI - [Giardiasis as a rare disorder in differential diagnosis of abdominal pain]. AB - The author is submitting a casuistry of the boy with nonspecific tummy ache.The cause of this illness was diagnosed as a paratrophic infection Giardia intestinalis. The author point sout it is necessary to have this seldom occurred children illness in consideration mainly in cases, when the doctor has a patient with nonspecific tummy ache and when these aches do not abate usual therapy or if there is a complication blond all understanding. As far as our patient is concerned it was cholecystitis discovered by ultrasound checkup which was done for nonspecific tummy ache. That is why it is necessary to have this illness in mind and mainly when there is a patient with nonspecific tummy ache and when the usual therapy does not work. In these cases the author recommends ultrasound tummy checkup and stercus checkup for parasites. The diagnostics consist in demonstratio of trophozoits or cystis in stercus. These days imunochromatografic test using ELISA method on the principles of detection with the help of monoclonal antibodies is preferred. The test is high sensitive and specific. The first choice medicine is metronidazol. PMID- 19645148 TI - [Injuries to femoral vessels in fractures of the hip]. AB - Injury to femoral vessels in trochanteric fractures is a rare but a severe complication. Most often it involves the profunda femoris artery, less often the (superficial) femoral artery. This injury may be caused by different mechanisms; most frequently by pressure of a sharp bone fragment (the lesser trochanter), the tip of protruding cortical screws (extramedullary implant) or the distal locking screw (Gamma nail). Less often it is caused by the drill bit or incorrectly placed elevators. Pressure of a sharp bone fragment or contact with protruding tips of screws results in a gradual erosion of vessels and consequently in development of false aneurysm. Sometimes this defect may become evident as late as several weeks or years after operation. Typical of acute bleeding is tachycardia, hypotension, rapid hematocrite decrease, rapid swelling of the thigh with palpable pulsation and pain. It may be associated also with an audible bruit. In the gradually developed false pseudoanerysm, there dominates a slowly growing swelling and increasing pain. Diagnosis and localization of vascular lesion may be performed using duplex ultrasonography, CT, CT contrast angiography, conventional angiography and MRI. Differential diagnosis should be used to eliminate deep venous thrombosis and sarcoma of soft tissues with bleeding into tumour. Treatment of injury to the profunda femoris artery depends on the condition of the (superficialis) femoral artery. If this artery is not blocked, it is possible to perform embolization or ligation of the profunda femoris artery. Where the superficial femoral artery is obstructed, for instance due to arteriosclerosis, the (superficialis) femoral artery or the profunda femoris artery must be reconstructed. Injury to the (superficial) femoral artery is best treated by its reconstruction. PMID- 19645149 TI - [Antimicrobial treatment in complicated intraabdominal infections--current situation]. AB - Compared to other infections, intraabdominal infections include wide spectrum of infections of various severity, have different ethiology, which is frequently polymicrobial, show different microbiological results, which are difficult to interpret. The role of surgical intervention is essential. Intraabdominal infections are common causes of morbidity and mortality. Their prognosis is significantly improved with early and exact diagnosis, appropriate surgical or radiological intervention and timely effective antimicrobial therapy. Practitioners may choose between older or more modern antibiotics, between monotherapy or combination therapy, however, they should also consider clinical condition of the patient, the antibiotic's spectrum of activity, the treatment timing and its duration, the dose and dosing scheme of the particular antimicrobials. Furthermore, antimicrobial therapy should be used with caution, with the aim to prevent development of antimicrobial resistence. Inappropriate choice of antimicrobials in initial empiric therapy results in relapsing infections, surgical intervention and prolongation of hospitalization, and even death rates reflect adequate and timely empiric therapy. PMID- 19645150 TI - The Margaret Haywood case. PMID- 19645151 TI - Ending child poverty in the good times and the bad. AB - It is now 10 years since the present Government pledged to eradicate child poverty by the year 2020. Some progress has been made, for example through increases in child benefit and the tax credit system, increased parental employment rates, and children's centres. However, the charity Child Poverty Action Group (CPAG) argues that progress has been disappointingly slow and that some aspects of policy development have undermined this progress. This article discusses the implications of the current economic recession on child poverty and includes the key points from the CPAG's manifesto, published in 2009 to mark the 10th anniversary of the pledge to end child poverty. PMID- 19645152 TI - Cognitive behavioural therapy and young people: an introduction. AB - Cognitive behavioural therapy (CBT) is a form of psychotherapy or "talking cure" that has been shown to be effective for a wide range of psychological problems and shows promise in many others. Up to now it has been used more with adults but there is a growing body of evidence of its usefulness in children and young people for conditions that include depression, generalised anxiety disorder, obsessive compulsive disorder, school phobia, eating disorders, self-harm and conduct problems. PMID- 19645153 TI - Supporting young carers and their families using a whole family approach. AB - Young carers are children and young people who look after family members with illness, disabilities, mental illness or substance misuse. Many of these young carers help with personal nursing care and administration of medication as well as household tasks and care of younger siblings. Inappropriate levels of caring can impact on a child's own emotional and physical health, educational achievement and life chances. There are many reasons why young carers may remain hidden and unsupported including reluctance among some families to acknowledge children's caring roles or involve agencies because they fear family breakup. It is essential to develop proactive practice that will enable families to feel able to ask for support. Health professionals have a responsibility and are in a key position to identify these vulnerable families and mobilise support services. The key to support is the development of a whole family approach to offering co ordinated assessments and services to support the person with care needs and their family as well as the young carer. The Whole Family Pathway is an online resource directing practitioners to support for young carers and their families. Young carers say that they would like to be listened to, provided with information, supported at school and referred to young carers' projects. The Children's Society Include Project provides training and resources for professionals who work with young carers and their families. PMID- 19645154 TI - Infant atopy and allergic diseases: an introduction to dietary aspects. AB - Allergic diseases including asthma, eczema, hay fever, and food allergies (also referred to as food hypersensitivity) are on the increase. Many factors could play a role in the development of allergic diseases, such as the particular immune response triggered by an allergen and dietary or environmental factors during pregnancy, breast-feeding and early life. However, genotype plays the most important role. In practice, the management of allergic diseases will involve dietary interventions by health care professionals, including the avoidance of food allergens and a number of preventive strategies. PMID- 19645155 TI - Understanding cleft lip and palate. 1: an overview. AB - Cleft lip and/or cleft palate affects about 1:700 babies born in the UK and may occur as a single anomaly or in association with other congenital abnormalities as part of a syndrome. This article, the first in a series, provides a brief overview of the different types of cleft lip and palate and describes the organisation of regional cleft services in England and Wales. PMID- 19645156 TI - Humor can have a place in healthcare leadership. PMID- 19645157 TI - Crossing the miles. The challenges of cancer care in rural America. PMID- 19645158 TI - What challenges do you see when caring for patients in a rural area? Access, health literacy, and health disparities are concerns. PMID- 19645159 TI - Manage toxicities from colorectal cancer treatment. PMID- 19645160 TI - Misuse of social networking may have ethical implications for nurses. PMID- 19645161 TI - ONS testifies to the FDA about opioid regulation. PMID- 19645162 TI - Learn how to manage the loss of a patient. PMID- 19645163 TI - Are you protecting yourself from hazardous drugs? PMID- 19645164 TI - New DNA test for cervical cancer outperforms Pap test. PMID- 19645165 TI - Should I continue or discontinue that medication? PMID- 19645166 TI - Betty Lank: a kind and gentle anesthetist devoted to children. AB - Many noted clinicians and educators led the development of nurse anesthesia as a profession during the first half of the 20th century. Betty E. Lank, CRNA, a nurse anesthetist at Children's Hospital Boston, Massachusetts, for 34 years, devoted her professional life to the delivery and advancement of pediatric anesthesia. She is credited with many contributions including the first use of cyclopropane for infant anesthesia, developing pediatric-sized anesthesia masks and ventilation bags, and instituting standards for specialized postanesthesia recovery areas. Lank recorded her anesthesia experiences in various nursing publications and shared her knowledge with colleagues at professional meetings. Her accomplishments make her a notable figure in the early history of pediatric anesthesia, and her dedication helped forge the foundation for anesthesia at Children's Hospital Boston. PMID- 19645167 TI - A report on the CCNA 2007 professional practice analysis. AB - The purpose of this column is to present the results of the 2007 Professional Practice Analysis (PPA) of the field of nurse anesthesia, conducted by the Council on Certification of Nurse Anesthetists. The PPA used survey and rating scale methodologies to collect data regarding the relative emphasis of various aspects of the nurse anesthesia knowledge domain and competencies. A total of 3,805 survey responses were analyzed using the Rasch rating scale model, which aggregates and transforms ordinal (rating scale) responses into linear measures of relative importance and frequency. Summaries of respondent demographics and educational and professional background are provided, as well as descriptions of how the survey results are used to develop test specifications. The results of this analysis provide evidence for the content outline and test specifications (content percentages) and thus serve as a basis of content validation for the National Certification Examination. PMID- 19645168 TI - Nurse anesthesia program requirements for esophageal/precordial stethoscope earpieces: a survey. AB - Student nurse anesthetists are often required to purchase an auscultatory earpiece device for use in the clinical setting. Although the device is required, students have observed that many anesthesia providers in the clinical setting no longer use this piece of equipment. The purpose of this project was to determine the number of anesthesia programs that required mandatory purchase of the auscultatory earpiece by student nurse anesthetists. A brief survey was developed to collect data from the directors of all 105 accredited nurse anesthesia programs in the United States. The survey was completed by 63 (60%) of the program directors, and 62 completed surveys were used in the analysis. Results revealed that 95% of the responding nurse anesthesia programs (59 of 62) require esophageal/ precordial stethoscope earpieces for their students, but 46% (27) of those programs provide the earpieces. Most (76%) of the programs required the use of the earpieces in the clinical setting, but only 45% thought that they should be used for monitoring every anesthetic delivered. PMID- 19645169 TI - Spinal anesthesia in preterm infant undergoing herniorrhaphy. AB - Inguinal hernias are the most common diagnosis requiring surgical repair in children of all ages. Anesthetic management of premature infants is often difficult due to their comorbidities and propensity for apnea and bradycardia. General anesthesia has been shown to be associated with an increased incidence of postoperative adverse events. The purpose of this review is to determine the benefits and risks of spinal anesthesia in preterm infants undergoing herniorrhaphy. The use of spinal anesthesia in this population has been shown to decrease the incidence of postoperative adverse events. PMID- 19645170 TI - Anesthetic management of acute subcutaneous emphysema and pneumothorax following a Nuss procedure: a case report. AB - The minimally invasive Nuss procedure has become the standard of care for surgical correction of pectus excavatum. Pectus excavatum is the most common congenital deformity of the chest wall. Historically, surgical correction was limited to the Ravitch procedure, an invasive procedure associated with significant drawbacks, where abnormal cartilage was removed and the sternum elevated and stabilized. Patients typically experienced a prolonged recovery period, from 6 to 9 months and significant postoperative pain. The Nuss procedure, invented in 1998, is much less invasive and has a success rate of 90% compared with the Ravitch procedure with a success rate of 70% to 80%. This more recent procedure normally has an exceedingly low complication rate, reported to be 8% to 11%. Postoperative analgesia ranges from patient controlled analgesia to a thoracic epidural depending on the surgeon's preference. This case report details an immediate postoperative complication that occurred with its subsequent anesthetic management. PMID- 19645171 TI - Will the addition of a sciatic nerve block to a femoral nerve block provide better pain control following anterior cruciate ligament repair surgery? AB - Two common forms of postoperative analgesia used in patients following an anterior cruciate ligament repair (ACLR) are the femoral nerve block (FNB) and the combined femoral-sciatic nerve block (FSB). The purpose of this study was to determine if the addition of the sciatic nerve block to the FNB is truly beneficial in ACLR patients requesting regional anesthesia for postoperative pain control. All subjects scheduled for an ACLR, requesting general anesthesia and preoperative placement of a peripheral nerve block (PNB), were randomized to receive an FNB or an FSB. Analgesic requirements, pain scores, and overall postoperative analgesic satisfaction were the primary outcomes measured. The data for 56 subjects (FNB, 27; FSB, 29) were used in analysis. Significantly higher analgesic requirements, pain scores, and lower satisfaction scores were noted in the FNB group compared with the FSB group (P < .05). No other differences were noted between groups in demographic data. Based on this investigation, we concluded that the FSB, compared with FNB alone, provides superior postoperative analgesia in patients receiving an ACLR and should be included in the anesthetic care plan in which a PNB is planned to facilitate postoperative analgesia. PMID- 19645172 TI - An update on sugammadex sodium. AB - Sugammadex sodium is the generic drug name for the novel modified gamma cyclodextrin that terminates neuromuscular blockade induced by aminosteroidal neuromuscular blocking agents. Published phase II and phase III clinical data support preclinical and clinical phase I study findings of fast, safe, and efficacious reversal of all levels of neuromuscular blockade induced by rocuronium and vecuronium. Low levels of neuromuscular blockade induced by pancuronium have also been successfully reversed by sugammadex. This agent does not reverse the bis-isoquinoline neuromuscular blocking agents. Special patient populations, including pediatric, elderly, cardiac, and renal-compromised subjects, have been studied in phase III. This update focuses on the most recent findings of phase II and III clinical studies. PMID- 19645173 TI - Semmelweis revisited: hand hygiene and nosocomial disease transmission in the anesthesia workstation. AB - Hospital-acquired infections occur at an alarmingly high frequency, possibly affecting as many as 1 in 10 patients, resulting in a staggering morbidity and an annual mortality of many tens of thousands of patients. Appropriate hand hygiene is highly effective and represents the simplest approach that we have to preventing nosocomial infections. The Agency for Healthcare Research and Quality has targeted hand-washing compliance as a top research agenda item for patient safety. Recent research has identified inadequate hand washing and contaminated anesthesia workstation issues as likely contributors to nosocomial infections, finding aseptic practices highly variable among providers. It is vital that all healthcare providers, including anesthesia providers, appreciate the role of inadequate hand hygiene in nosocomial infection and meticulously follow the mandates of the American Association of Nurse Anesthetists and other professional healthcare organizations. PMID- 19645174 TI - Facing discrimination issues. PMID- 19645175 TI - The path to quality improvement. PMID- 19645177 TI - The state of cardiology IT. Physician frustration, rapidly advancing technology, and an abundance of sophisticated solutions mean no one is safe from replacement. PMID- 19645176 TI - Documentation myths in litigation. PMID- 19645178 TI - Measure twice, cut once. As hospitals look to qualify for HITECH incentives, proving meaningful use means setting up tools for measurement, now. AB - * Hospitals should not wait for meaningful use to be defined before beginning assessments. * Vendors are one place to turn for assessment assistance. * Anticipate a shortage of trained consultants in this area in the near future. * Outcomes should be measuring process, not just quality. * ClOs may be held accountable for losing HITECH money if they don't plan appropriately. PMID- 19645179 TI - Get out--and stay out. With readmission penalties on the horizon, CIOs are laying the groundwork for post-discharge solutions. AB - * Hospitals will soon face lower reimbursement rates from Medicare for preventable admissions. * Payments may be calculated against a single disease or condition, rather than admission. * There is currently no business model to keep patients out of the hospital, but there will be soon. * The time between discharge and first doctor visit is the most risky. * Home monitoring and follow up through worklists ca help prevent readmissions. PMID- 19645180 TI - Eco-nomics. Despite a tough economy, many CIOs are incorporating eco-friendly initiatives into their strategies. AB - * Several health systems have adopted environmentally friendly practices like computer recycling programs, energy-efficient lighting, carpooling programs, and building design components that limit water usage. * Vendors are offering more energy-efficient products like virtualization software and switching equipment. * ClOs are reducing power usage and costs by consolidating servers, installing more efficient chilling systems, and implementing policies to power down desktops that aren't in use. * Green IT can be a difficult conceptto sell to CEOs and hospital boards unless it goes hand-in-hand with cost savings. PMID- 19645181 TI - One-on-one with IBM research fellow and Johns Hopkins professor Marion Ball, Ed.D. Clinicians need intuitive, mobile technologies that adapt to their needs and provide the right data at the point of care. Interview by Kate Huvane Gamble. PMID- 19645182 TI - Parsing the PACS market. Evaluating a PACS upgrade or replacement decision is all about understanding need. AB - * The current PACS vendor market is particularly unstable right now, because of the global economic recession, much of the industry's attention focusing on EMRs because of the passage of federal healthcare IT stimulus funding for core clinical IT implementation, and vendor downsizing. * In theory, ClOs should be able to obtain particularly good "deals" with vendors at this time; but the complex economic situation makes deal-making more challenging than it might appear at first glance. * ClOs and industry experts agree that CIOs need to strategize carefully with regard to PACS purchasing and especially PACS replacement purchasing, in the current market. PMID- 19645183 TI - High stakes. HITECH's privacy provisions will make costly security breaches even more painful to bear. AB - * The HITECH section of ARRA includes provisions relating to protected health information that could significantly alter the C-suite leader's strategy. * Patients will be entitled to request an accounting of disclosure for up to three years after the date of request. The onus will be on hospital leaders to put in place a process that makes accounting available without disrupting operations or patient care. * Because of the increased risks hospitals now face, it is critical that executives are aware of the new requirements, and are either involved in or have a solid understanding of the organization's breach notification policies. PMID- 19645184 TI - Finding the leverage of adoption. With serious cash at stake, policy wonks struggle to navigate chronic disease management and chart a course on certification. PMID- 19645185 TI - Meet your new best friend. ClOs are realizing that successful clinical IT implementations are almost impossible without strong CMIOs. AB - * CMIO hiring is surging, as the role is now recognized to be critical for IT implementations, especially with regard to EMR, CPOE, etc. * While the need for CMIOs is universally recognized at all but the smallest hospitals, several questions continue to spark debate, including to which position the CMIO should report; whether the CMIO should remain in medical practice part-time; and whether it is preferable to groom a CMIO internally. * Regardless of to whom the CMIO reports, there is a consensus that the CMIO-CIO relationship must be a rock-solid partnership. PMID- 19645186 TI - On-boarding--a personal experience. An employee's first day is a one-time chance to help them hit the ground running. PMID- 19645187 TI - Shady practices still practiced. 20 years ago, Bill Childs called it like he saw it. today, the healthcare IT industry is still seeing some of the same things. PMID- 19645188 TI - [Well tanned and yet not healthy]. PMID- 19645189 TI - [Near death experiences. Attempt at a rational interpretation]. PMID- 19645190 TI - [Can you still afford your office assistants?]. PMID- 19645191 TI - [What should be considered with elderly hypertensive patients?]. PMID- 19645192 TI - [The underestimated catastrophy (interview by Dr. Jochen Aumiller)]. PMID- 19645193 TI - [Why do schizophrenic patients die sooner?]. PMID- 19645194 TI - [Anticoagulation for difficult cases]. PMID- 19645195 TI - [What lets gorgeous hair sprout again?]. PMID- 19645197 TI - [Current state of laser surgery to correct refractive errors]. PMID- 19645196 TI - [Visual impairment and blindness are mostly avoidable today]. PMID- 19645198 TI - [Intraocular lenses: what is important for the family doctor?]. PMID- 19645199 TI - [Early diagnosis of glaucoma]. PMID- 19645200 TI - [Management and therapy of Alzheimer's disease. Recommendations of a general practitioners' guideline]. PMID- 19645201 TI - [Effectiveness of chemical, herbal and dietetic migraine prophylactis. An overview of randomized controlled double-blind studies]. PMID- 19645202 TI - Did Dr. & nurse fail notify pregnant Pt. to D/C Benicar? Mobile OB-GYN, PC. v. Baggett, 2009-AL-0615.006 (6/12/2009)-AL. PMID- 19645203 TI - Did ER nurse's failure to treat Pt. lead to suicide? Case on point: Affinity Hospital, L.L.C. v. Willford, 2009-AL-0420.002 (4/17/2009)-AL. PMID- 19645204 TI - FL: Nurse's notes & records contradict Dr.: court finds for defendants despite nurse's info. St. Joseph's Hospital v. Cox, 2009 FL-0618.068 (6/17/2009)-FL. PMID- 19645205 TI - Failure to order CT scan STAT: Pt. died awaiting scan. Case on point: Bosco v. New York Univ. Hospitals Center, 2009-NY-0624.1790 (6/18/2009)-NY. PMID- 19645206 TI - [The walking test: use in clinical practice]. AB - Exercise Capacity is the expression of the cardiovascular and of metabolic organic efficiency and represents a important prognostic marker. The Six Minute Walking Test is adopted in the practice for exercise capacity evaluation in the normal subject as in pneumologic or cardiac rehabilitation programs, and in both pediatric and elderly ages. The aim of the work is to present a practical summary of the application of the six minutes walking test, according to the American Thoracic Society statement. We reviewed the various experiences of its application, and reported the indications, clinical interpretation parameters, relationship and correlation between functional and clinical parameters (hospitalization, quality of life, therapy and exercise control response and compliance), the basic and advanced protocol, the application modality, the reporting models, and the educational checklist. PMID- 19645207 TI - Carotid artery disease and stroke in patients with peripheral arterial disease. The role of inflammation. AB - Although during the last decade there have been great advances in our knowledge of the epidemiology and pathophysiology of multi-district atherosclerotic disease, little is known about the association between peripheral arterial disease and carotid artery disease. This review was conceived to cast some light on this topic, paying special attention to inflammation which plays a pivotal role in atherosclerosis. An aspect of pathophysiologic and clinical relevance is that the coexistence of carotid disease is more frequent in peripheral arterial disease than in coronary artery disease, not only in terms of carotid stenosis, but also with respect to the presence of hypoechoic unstable plaque. These latter plaques present a large infiltration of macrophages and are associated to high levels of inflammatory markers. In particular, the greater prevalence of hypoechoic carotid plaques in peripheral arterial disease compared to patients with carotid artery disease was poorly related to classic risk factors, but showed an independent association with an increased number of leukocyte and neutrophil cells, which are reliable markers of inflammation. The greater prevalence of hypoechoic unstable carotid plaques could explain why peripheral arterial disease portends higher risk of stroke than coronary artery disease. PMID- 19645208 TI - Additive beneficial effects of beta blockers in the prevention of symptomatic heart failure. AB - The prevention of symptomatic heart failure represents the treatment of patients in the A and B stages of AHA/ACC heart failure classification. Stage A refers to patients without structural heart disease but at risk to develop chronic heart failure. The major risk factors in stage A are hypertension, diabetes, atherosclerosis, family history of coronary artery disease and history of cardiotoxic drug use. In this stage, blockers hypertension is the primary area in which beta blockers may be useful. Beta blockers seem not to be superior to other medication in reducing the development of heart failure due to hypertension. Stage B heart failure refers to structural heart disease but without symptoms of heart failure. This includes patients with asymptomatic valvular disease, asymptomatic left ventricular (LV) dysfunction, previous myocardial infarction with or without LV dysfunction. In asymptomatic valvular disease no data are available on the efficacy of beta blockers to prevent heart failure. In asymptomatic LV dysfunction only few asymptomatic patients have been enrolled in the trials which tested beta blockers. NYHA I patients were barely 228 in the MDC, MERIT and ANZ trials altogether. The REVERT trial was the only trial focusing on NYHA I patients with LV ejection fraction less than 40%. Metoprolol extended release on top of ACE inhibitors ameliorated LV systolic volume and ejection fraction. A post hoc analysis of the SOLVD Prevention trial demonstrated that beta blockers reduced death and development of heart failure. Similar results were reported in post MI patients in a post hoc analysis of the SAVE trial (Asymptomatic LV failure post myocardial infarction). In the CAPRICORN trial about 65% of the patients were not taking diuretics and then could be considered asymptomatic. The study revealed a reduction in mortality and a non significant trend toward reduction of death and hospital admission for heart failure. CONCLUSIONS: beta blockers are not specifically indicated in stage A heart failure. On the contrary, in most of the stage B patients, and particularly after MI, beta blockers are indicated to reduce mortality and, probably, also the progression toward symptomatic heart failure. PMID- 19645209 TI - [The study of left ventricular diastolic function by Doppler echocardiography: the essential for the clinician]. AB - The study of diastolic function by Doppler-echocardiography is complex and demanding. The cardiologist/echocardiographist must have a systematic approach to the study of left ventricular diastolic function, not only based on the Doppler index, but integrating Doppler patterns with other echo-parameters (chamber dimensions, wall thicknesses, systolic function, valve function and morphology) and clinical information. A rational interpretation of clinical and instrumental data can allow a correct diagnosis, which is essential for clinical decision making. PMID- 19645210 TI - Fluctuations in warfarin dose response after heart valve surgery: implications for cardiac rehabilitation. AB - In patients undergoing heart valve surgery (HVS) who require warfarin therapy, the maintenance of low variability in the level of anticoagulation early after operation is generally difficult. Aim of this study was to evaluate the time in therapeutic range (TTR) in HVS patients receiving oral anticoagulation therapy (OAT) during phase I-II of cardiac rehabilitation (CR), and, secondly, to identify clinical variables associated with inadequate anticoagulation. METHODS: Observational study of consecutive in-hospital patients directly tracked from a cardiac surgery unit to a CR facility. OAT was monitored both in terms of administered warfarin doses and resulted INR values, from day 1 to day 15 after operation. Clinical variables were tested in a logistic regression model for the prediction of inadequate anticoagulation, defined as the presence of nontherapeutic INRs for > or = 5 days between day 8 and 15. RESULTS: Eighty-one patients (males 56%, age 62 +/- 19 yrs.), following valvuloplasty (37%), mechanical (17%), and bioprosthetic (45%) valve replacement were considered. The prescribed warfarin dosages were significantly higher from day 1 to day 7 than from day 8 to day 15 (4.6 +/- 3.6 and 3.0 +/- 1.1 mg respectively, p< 0.001). Overall, TTR was 6 +/- 3 days, while time with elevated and lower INRs accounted for 1.3 +/- 1.6 and 8.0 +/- 3.5 days respectively. At day 7, only 25% of patients (n= 20) showed a therapeutic INR value. Inadequate anticoagulation between postoperative day 8 and 15 was displayed in 41 (51%) patients, with hypertension as the only independent predictor (p< 0.001) at multivariate analysis. CONCLUSIONS: Despite intensive monitoring, half of patients have nontherapeutic INR values (mainly subtherapeutic) in the first two weeks after HVS while on warfarin. Giving the high risk of completing the hospitalization phase without a stable OAT in many patients, both cardiac surgeons and cardiologists should not miss the opportunity to improve patients education, and consider a direct track to anticoagulation management services after discharge. PMID- 19645211 TI - Tako-tsubo cardiomyopathy observed in a patient with sepsis and transient hyperthyroidism. AB - A 55-years-old woman, with a history of hypertension and ischemic stroke with residual left hemiparesis, was admitted to our hospital because of dyspnoea with clinical evidence of acute pulmonary edema. She was found to have a sinus tachycardia with ST-elevation in leads D1, aVL and V1-V4 in the electrocardiogram, and akinesis of the left ventricular apex with overall left ventricular systolic function being severely impaired and an ejection fraction of 28% on echocardiography. Orotracheal intubation was performed and mechanical ventilation was immediately started. Emergency cardiac catheterization was performed 2 h after the symptom onset. Coronary angiography showed no significant coronary artery disease. Blood analysis revealed an increase in the creatine kinase MB fraction, a significant positive detection in troponin T, a white blood cell count of 35000 per microliter, C-reactive protein of 59,9 mg/dl, and transient elevation in the concentration of free triiodothyronine, free thyroxine, thyroid globulin antibody, and thyroid peroxidase antibody. The symptoms improved during the next days, and follow-up echocardiography 18 days later showed complete resolution of the left ventricular dysfunction. These data suggest that tako-tsubo cardiomyopathy may be induced in patients with sepsis and transient hyperthyroidism. PMID- 19645212 TI - Anomalous right-sided pulmonary venous connection to the superior vena cava. AB - Over the years, different techniques have been introduced for the repair of sinus venosus atrial septal defect (ASD) with anomalous right-sided pulmonary venous connection to the superior vena cava. We report the case of a 9-year-old girl, who presented with dyspnea and peripheral cyanosis. Preoperative echocardiography and angiography findings suggested a partial anomalous pulmonary venous connection. On cardiopulmonary bypass, the ASD was dilated, and the anomalous pulmonary vein was anastomosed to the right atrium and redirected to the left atrium using an intraatrial baffle and a tube graft. The intraoperative and postoperative periods were uneventful, and the patient is currently in good health at 4.5 years' follow-up. PMID- 19645213 TI - Right atrial mass following transcatheter radiofrequency ablation for recurrent atrial fibrillation: thrombus, endocarditis or mixoma? AB - We report a case of an asymptomatic patient in whom a right atrial mass was fortuitously documented by echocardiography few months after a transcatheter radiofrequency catheter ablation for recurrent AF. No masses were seen in the cardiac chambers before the ablative procedure, raising important diagnostic and decision-making issues. The patient was referred to the surgeon and a diagnosis of right atrial myxoma was made. PMID- 19645214 TI - Transepithelial transport of Cerulenin across Caco-2 cell monolayers. AB - The transepithelial transport of Cerulenin across Caco-2 cell monolayers was examined in this study. The permeated amounts of Cerulenin were measured by HPLC method to calculate the permeation rate and the apparent permeability coefficient (P(app)). The transport of Cerulenin was independent on apical pH and exhibited concentration-dependent and nonsatuable even at 10 mM Cerulenin. The permeation rate at 1 mM Cerulenin in the apical-to-basolateral direction was 0.151 ng/min/mg of protein and the P(app) was 3.76 x 10(-6) cm/second. The permeation rate of Cerulenin was affected by neither metabolic inhibitors nor inhibitors for P glycoprotein, as was the same case in monolayers treated with cytochalasin D. All these data from experiments indicated that transport of Cerulenin across Caco-2 cell monolayers was not mediated by ATP-dependent transport systems nor via paracellular pathway, but via passive diffusion without efflux by P-glycoprotein. PMID- 19645215 TI - Effect of 12-monoketocholic acid on modulation of analgesic action of morphine and tramadol. AB - This work is concerned with the potential promotive action of 12-monoketocholic acid (12-MKC) on the analgesic effect of morphine and tramadol. The investigation was carried out on laboratory Wistar rats divided into five test groups, each treated with either morphine (2 mg/kg), tramadol (9.6 mg/kg), 12-MKC (2 mg/kg), morphine + 12-MKC, or tramadol + 12-MKC, the control group receiving physiological solution (2 mg/kg). The effect of 12-MKC on the analgesic action of morphine and tramadol was determined by radiation heat method. Morphine and tramadol, given in equimolar doses, did not show significant difference in the degree of analgesia. In combination with morphine, 12-MKC increased significantly the analgesic effect compared with the group treated with morphine alone. However, 12-MKC caused no change in the action of tramadol. The 5-day intravenous application of 12-MKC in combination with the two analgesics caused no changes in the biochemical parameters nor pathohistological changes in the liver parenchyma of tested animals. PMID- 19645216 TI - Pharmacokinetics of phillyrin and forsythiaside following iv administration to Beagle dog. AB - The objective of the present study was to firstly investigate the in vivo pharmacokinetics of phillyrin and forsythiaside in beagle dog. On I.V. administration, a rapid distribution was observed and followed by a slower elimination for phillyrin and forsythiaside. The mean t(1/2Z) was 49.99, 34.87 and 43.81 min for 0.19, 0.70 and 1.43 mg/kg of phillyrin, and 60.90, 64.30, 57.99 min for 0.62, 1.39 and 5.52 mg/kg of forsythiaside respectively. And the AUC(o-t) increased linearly from 36.51 to 160.22 microg x min/ml of phillyrin and from 50.63 to 681.08 microg x min/ml after the three dosage administrated. In the range of the dose examined, the pharmacokinetics of phillyrin and forsythiaside in beagle dog was based on first order kinetics. Although both drugs were widely distributed to various tissues in the dog, no concerns about extensive binding to tissues that may be consumed by the public should a dog be exposed to phillyrin and forsythiaside according to the rapid elimination. PMID- 19645217 TI - Evaluation of statistical power function for various diclofenac bioequivalence trials with different subject numbers. AB - This study presents application of statistical power function for the t-test and ANOVA F-test on the evaluation of diclofenac bioequivalence in trials with the wide variations in sample sizes (N = 12, 18 and 24). The power function, together with appropriate equations tables and figures, is used to calculate the power of the ANOVA for crossover design, the number of subjects for a given value of power and the minimum detectable difference in treatment means for different pharmacokinetic parameters of the formulations. The power of the trial with a small, sample size (N = 12) to detect 20% differences between diclofenac formulations is shown to be more than 0.9 and almost the same as the power of the trial with a large sample size (N = 24). In all trials for all pharmacokinetic parameters the power to detect 20% difference is shown to be more than 0.8. For the power of 0.8, the needed subject number to detect 20% difference in treatment means is the same or smaller than used and the minimum detectable difference is smaller than 20% in all our trials. This investigation shows that bioequivalence studies with small number of subjects (N = 12) may be quite adequate for valid conclusions. PMID- 19645218 TI - Lamotrigine and valproate pharmacokinetics interactions in epileptic patients. AB - Lamotrigine (LTG, 3,5-diamino-6- (2,3-dichlorphenyl)-,2,4-triazine) is an antiepileptic drug used mainly for partial and generalized seizures. The efficacy of LTG in treating resistant partial seizures was optimized when it was combined with valproate (VPA). The aim of this study was to investigate the influence of VPA on LTG pharmacokinetics in epileptic patients. METHODS: 38 patients were randomly divided into two groups, one given LTG (n = 18) and the other given LTG + VPA(n = 20). The first group consisted of 10 females (32.50 +/- 12.46 years old, 67.80 +/- 15.18 kg) and 8 males (24.88 +/- 8.92 years old, 69.88 +/- 11.41 kg) and the second group consisted of 9 females (28.33 +/- 6.52 years old, 62.89 +/- 13.28 kg) and 11 males (37.64 +/- 10.43 years old, 85.64 +/- 15.4 kg). Patients were either administered an oral dose of LTG (157 +/- 74 mg/day) or LTG + VPA (150 +/- 83.11 mg/day & 774 +/- 330 mg/day respectively). LTG steady state serum concentrations were determined 1.5-8 h post dose. Analyses were performed by a validated HPLC method. RESULTS: LTG serum concentrations were increased significantly from 4.67 +/- 3.66 and 9.56 +/- 5.27 microg/ml by concomitant administration of VPA. DISCUSSION: The inhibition of LTG metabolism by VPA was shown to have a marked effect on LTG kinetics. This inhibitory effect was complicated further by inter-patients variation in body weight and gender. This emphasizes the importance of continuous monitoring of LTG serum concentrations on an individual basis. Accordingly, if the use of potentially interacting drugs cannot be avoided, adverse reactions can be minimized by dose adjustments guided by careful monitoring of clinical response and measurement of LTG serum concentrations. PMID- 19645219 TI - Pharmacokinetics of forsythoside after intravenous administration in beagle dogs. AB - A high-performance liquid chromatography with ultraviolet detection method was established and validated for quantification of forsythoside concentrations in dog plasma. Following a single-step protein precipitation with perchloric acid, the forsythoside and internal standard were separated on a reversed-phase C18 column with water-glacial acetic acid-methanol as mobile phase at a flow rate of 1 mL/min with ultraviolet detection at 326 and 278 nm for forsythoside and IS, respectively. The calibration curve for forsythoside was linear over a range of 0.052-13.33 microg/mL with correlation coefficient of 0.999. The within- and between-batch precisions of analysis were < 8 % and accuracy was 95-107%. After intravenous administration of forsythoside at the doses of 5, 10, and 20 mg/kg, the C(max) values for forsythoside were estimated to be of 12.33, 22.90 and 54.45 microg/mL, respectively. The AUC increased with the increasing of doses, and the mean AUC(o-t) values were 5.69, 11.80, and 18.66 mg x h/L, respectively. Forsythoside was eliminated quickly and the mean T(1/2) values at doses of 5, 10, and 20 mg/kg were 1.36, 1.49, and 0.71 h, respectively. The pharmacokinetics of forsythoside in beagle dogs complied with linear kinetic course in the dose range. PMID- 19645220 TI - The pharmacokinetics of ceftriaxone based on population pharmacokinetics and the prediction of efficacy in Japanese adults. AB - OBJECTIVE: By using a population pharmacokinetic analysis method, we predicted the efficacy of Ceftriaxone (CTRX) based on the pharmacokinetics of CTRX in Japanese adults and the sensitivity of infective organisms to CTRX in 2004. In addition, we clarified the difference in efficacy between once-a-day administration and twice-a-day administration. METHODS: The population pharmacokinetic analysis was based on the serum concentrations of CTRX already published by NONMEM. The possible effect of body weight and age on the pharmacokinetics of CTRX was examined using a model which incorporated the change of a specific protein-binding ratio of CTRX. A Monte Carlo simulation was conducted based on the population pharmacokinetic parameters obtained by this analysis, and thereby the time above MIC (TAM) was determined from the MIC values of CTRX administered once at 0.5, 1, and 2 g and twice at 1 g. The efficacy ratio was predicted from the TAM thus obtained. RESULTS: Because the time course of serum concentration of CTRX in adult subjects was fitted to a 2-compartment model and both body weight and age were not incorporated as the covariate, the dosing method by which a fixed amount of CTRX is administered to patients has been thought to be adequate. Based on the efficacy ratio estimated from the MIC of CTRX, we have predicted that the once-a-day administration of CTRX even at 0.5g is effective on various infecting organisms. PMID- 19645222 TI - Medication safety. Cocktails to cockpits. PMID- 19645223 TI - Regarding the article "Nurses are not usually associated with anti-government activities". PMID- 19645221 TI - Exploratory population pharmacokinetics (e-PPK) analysis for predicting human PK using exploratory ADME data during early drug discovery research. AB - We have proposed a novel method by population pharmacokinetics analysis for forecasting the drug concentration time-course in humans. This method is based on the non-linear mixed effect model (NONMEM) combined with in vitro-in vivo extrapolation (IVIVE). Eleven clinically tested compounds were selected for retrospective analysis. The in vivo pharmacokinetic (pk) profiles (rats, dogs, monkeys, and humans) and in vitro ADME data [intrinsic clearance (CLint), plasma unbound fraction (fp), and blood-plasma partition ratio (Rb)] for each compound was routinely tested via a screening system to account for inter-compound differences in pk properties. When evaluating the pk parameters, the hepatic plasma flow (Qph) and plasma volume (Vp) were taken into account to compensate for differences in body size among species. All these data were used to conduct population pk (PPK) analyses under the hypothesis that all species constituted one population. The two-compartment model (ADVAN4 TRANS3) and NONMEM software were used for this analysis. The fixed effect model for total body clearance (CL) and central distribution volume (Vd) were constructed as theta(CL)Qph x Eh and theta(Vd) x Vp, respectively, where the hepatic extraction ratio Eh was calculated using the traditional dispersion model. NONMEM generates both fixed and random effects (eta). The key point of this concept was to substitute the eta values of each species (rats, dogs, and monkeys) into the human PPK model to simulate three kinds of pk profiles, compound by compound, for use as a general scaling factor. The NONMEM post hoc option was used to perform the simulation, after which the concentration vs. time courses were compared with actual clinical pk data. The true values were almost within the dynamic range. Thus, the advantage of this concept is that it can generate time-courses without the detail of drug-specific parameters, from which the elimination half time can be determined. This proposed exploratory population pharmacokinetic (e-PPK) approach is a useful and progressive tool that can be applied during the early stages of drug discovery research. PMID- 19645224 TI - Ostomy basics. PMID- 19645226 TI - Informatics: the future of nursing. PMID- 19645225 TI - America's nurses defied economic gloom with solid raises since our 2007 survey. Learn how nurses in your specialty, facility type, or state fared against the national average. PMID- 19645227 TI - You've gotta have heart. PMID- 19645228 TI - [Studies on seed quality evaluation technique and grading rules of Cistanche deserticola]. AB - OBJECTIVE: To establish a seed quality evaluation technique system and quality grading rules for Cistanche deserticola. METHODS: We used stereomicroscope, microphotography and image analysis system, tetrazolium method to measure, analyze and evaluate the size, thousand kernel weight, plumpness, embryo rate and viability of Cistanche deserticola seed. Then we used SPSS 11.0 statistical analysis software to analyze the seed viability and related indexes of another 55 batches. RESULTS: Seed size was significantly correlated with thousand kernel weight, but wasn't correlated with seed viability. However, grain plumpness was negatively correlated with seed viability. Seed quality was not determined by seed size but by seed viability and grain plumpness. CONCLUSION: Seed viability, thousand kernel weight and grain plumpness are significant indicators of seed quality and they can be took in the granding rules of Cistanche deserticola seed. PMID- 19645229 TI - [Genetic diversity of medicinal plant Lonicera confusa populations revealed by random amplified polymorphic DNA]. AB - OBJECTIVE: To analyze the genetic diversity and differentiation degree of five Lonicera confusa populations. METHODS: Random Amplified Polymorphic DNA (RAPD) markers were perfomed to amplify the discernible loci. RESULTS: A total of 100 loci were obtained for all populations using ten primers, 87.00% of which were polymorphic (PPL = 87.00%). Analyzed by POPGENE, the average percentage of polymorphic loci was 58.86%. Nei's genetic diversity (H = 0.2647) and Shannon's information index (I = 0.4022) indicated that Lonicera confusa had a higher level of genetic diversity. The high value of differentiation( G(st) = 0.3839) showed that geographic isolation strongly influenced genetic differentiation among populations and there was a significant correlation between genetic distance and geographic distance (r = 0.8504, P = 96.80%). The clustering analysis was performed using softwares POPGENE and NTSYS-pc. Five populations were divided into 2 clusters, named cluster 1 (LFS, XX and NN) and cluster 2 (XW and HK). CONCLUSION: Management strategies were proposed for species conservation and resource utilization of Lonicera confusa, including the protection from human disturbance to facilitate natural regeneration, construction of germplasm resources and cultivation of plants collected from different populations, in order to select elite lines for good agricultural practice (GAP) of medicinal materials. PMID- 19645230 TI - [Optimization of paper-roast process of Radix Vladimiriae by orthogonal design]. AB - OBJECTIVE: To study the optimum paper-roast conditions of Radix Vladimiriae. METHODS: The contents of naphtha and costunolide and dehydrcostuslactone were used as estimated indexes. The paper-roast process of Radix Vladimiriae was studied by orthogonal design. RESULTS: The optimum condition was adding moderate water and marinates firstly, after getting rid of the water and experimenting 6 hours' closed lay, cutting Radix Vladimiriae into slices with 10 centimeters and drying under natural condition. One layer paper by one layer Radix Vladimiriae slice roasted 2 hours at 120 degrees C. CONCLUSION: The paper-roast process is stable, controllable and can provide referenced foundation for the production of paper-roast Radix Vladimiriae. PMID- 19645231 TI - [Pharmacognostical study on Fructus Hordei germinatus, Fructus Oryzae germinatus and Fructus Setariae germinatus]. AB - OBJECTIVE: To establish the standard for quality control of Fructus Hordei germinatus, Fructus Oryzae germinatus and Fructus Setariae germinatus. METHODS: The digital microscope and infrared spectroscopy were used in the pharmacognostical study. RESULTS: Distinguished differences were found on morphological and microscopical features of these three crude drugs. Whereas, their infrared spectrums were basically all the same. CONCLUSION: The study provides a convenient, effect method for the identification of these three medicinal materials. PMID- 19645232 TI - [Studies on chemical constituents of Daphne genkwa]. AB - OBJECTIVE: To study the chemical constituents of the flower buds of Daphne genkwa. METHODS: The constituents of petroleum ether and ethyl acetate-soluble portions were isolated and purified by means of chromatography, then they were identified by their physico-chemical characteristics and spectral features. RESULTS: Ten compounds were isolated and identified as octacosane (1), dotriacontane (2), beta-sitosterol (3), 4', 7-dimethoxy-5-hydroxyflovone (4), aurantiamide acetate (5), genkwanin (6), luteolin (7), apigenin (8), 3' hydroxygenkwanin (9) and daphnoretin (10). CONCLUSION: Compound 1 and 2 are isolated from this plant for the first time. PMID- 19645233 TI - [Studies on chemical constituents of Swertia mussotii]. AB - OBJECTIVE: To study the chemical constituents of Swertia mussotii. METHODS: The constituents were isolated by various column chromatography methods, and their structures were identified by physico-chemical properties and spectral analysis. RESULTS: Eleven compounds were isolated and identified as 1,3, 8-trihydroxy-7 methoxyxanthone (I), 2,8-dihydroxy-1,6-dimethyoxyxanthone (II), 1,8-dihydroxy-2,6 dimethoxyxanthone (III), 1,2,8-trimethoxyxanthone (IV), 1,3,5,6 tetrohyroxyxanthone (V), 1,8-dihydroxy-3,7-dimethoxyxanthone (VI), beta daucosterol (VII), clerosterol 3beta-O-[6'-o-hydro-benzene-beta-D-glucoside] (VIII), ursolicacid (IX), 3beta,28-dihydroxylup-20 (29) -ene (X), erythrocentaurin (XI). CONCLUSION: Compounds VIII, IX and X are isolated from Swertia mussotii for the first time. PMID- 19645234 TI - [Studies on chemical constituents of rhizome of Buddleia davidii]. AB - OBJECTIVE: To study the chemical constituents of Rhizome of Buddleia davidii. METHODS: The chemical constituents were isolated by repeated column chromatography (Toyopearl HW-40C and HPLC) and their structures were elucidated on the basis of physico-chemical properties and spectroscopic features. RESULTS: From the petroleum ether extract of the material, eight compounds were isolated. Their structures were identified as: Buddlindeterpene B(1), Buddledin B(2), Buddledin C(3), deacetyldihydrobuddledin A(4), dihydrobuddledin C(5), Suberosol B(6), Gadain (7) and Hinokinin (8). CONCLUSION: Compounds 1,4 - 8 are isolated from B. davidii for the first time. PMID- 19645235 TI - [Study on the flavonoids compounds of Thesium chinese]. AB - OBJECTIVE: To study the flavonoids compounds from the effective fraction of Thesium chinese in anti-inflammation. METHODS: The isolation and purification were carried out by many kinds of column chromatographic techniques. The flavonoids were analyzed by HPLC-DAD, and elucidated by 1H-NMR, 13C-NMR and ESI MS. RESULTS: Five compounds were obtained and therir structures were determined as kaempferol-3-O-glucoside (I), rutinoside (II), luteolin-7-O-glucoside (III), kaempferyl 5-methyl ether (IV), apigenin-5-O-neohesperidoside (V). CONCLUSION: Compounds IV and V are isolated from this plant for the first time. PMID- 19645236 TI - [Studies on chemical constituents of root of Millettia speciosa]. AB - OBJECTIVE: To study the chemical constituents from the root of Millettia speciosa. METHODS: To isolate and purify by silica gel, macroporous resin D-101 and Sephadex LH-20. RESULTS: Five compounds were isolated from 95% EtOH extract of Millettia Speciosa and their structures were elucidated by physico-chemical properties and spectroscopic analysis as Isoliquiritigenin (I), Maackiain (II), Pterocarpin (III), Medicarpin (IV) and Homopterocarpin (V). CONCLUSION: Compounds I, III are obtained from this plant for the first time, compounds V is isolated from the genus Millettia for the first time. PMID- 19645237 TI - [Isolation and characterization of polyphenols in seed of Litchi chinensis]. AB - OBJECTIVE: To study the chemical constituents of polyphenols in seed of Litchi chinensis. METHODS: The seeds of Litchi chinensis were extracted by 65% ethanol, then the compounds were separated by repeated silica gel, polyamide and preparative TLC. The structures of polyphones isolated were identified by analysis of their spectral datas and chemical properties. RESULTS: Four polyphones compounds were isolated as protocatechuic aldehyde (I), protocatechuic acid (II), daucosterol (III) and (-) -epicatichin (IV). CONCLUSIONS: Compounds I , III and IV are isolated from this plant for the first time. PMID- 19645238 TI - [Studies on chemical constituents of Ligularia altaica]. AB - OBJECTIVE: To study the chemical constituents of Lighularia altaica. METHODS: Various chromatographic techniques were used to isolate and purify the chemical compounds, their structure were elucidated by means of mass, physico-chemical properties and NMR spectral data. RESULTS: Nine compounds were obtained as: lupeol (1), oleanolic acid (2), 3beta, 16beta-dihydroxy-12-oleanen-28-al (3), ergosterol peroxide (4), stigmasta-7-en-ol (5), 11-hydroxy-10,11-dihydro-euparin (6), 5-hydroxybenzofuran-2(3H) -one- (7), except for beta-sitosterol (8) and daucostrol (9). CONCLUSION: Compounds 3 - 7 are isolated for the first time from this genus, the other compounds are obtained from this plant for the first time. PMID- 19645239 TI - [Study on the chemical constituents of Sarcandra glabra by HPLC-ESI-MS/MS]. AB - OBJECTIVE: To study and compare the main chemical constituents of Sarcandra glabra and qingrexiaoyanning capsules which were extracted by acetic ether. METHODS: The sample solution were analyzed by a Zorbax C18 column with a gradient mobile phase composed of acetonitrile and 0.1% formic acid solution. Both UV and mass spectrometry detector were used simutaneously, full-scan detection mode was evaluated for the identification of all LC peaks. RESULTS: We analyzed the mass spectrum of every LC peak and identified 26 molecular mass from the ion chromatogram of Sarcandra glabra extraction and 16 molecular mass from the extractions of qingrexiaoyanning capsule. 5 compounds were identified. CONCLUSION: High performance liquid chromatography-mass/mass spectrometry has special advantages on analyzing the chemical constituents of traditional Chinese medicine. PMID- 19645240 TI - Breviscapine improves functions of spatial learning and memory of focal cerebral ischemia rats. AB - OBJECTIVE: To investigate the effects of breviscapine on the functions of spatial learning and memory of focal cerebral ischemia rats. METHODS: Rots withl the left middle cerebral artery occluded were made by an intraluminal filament. Then breviscapine (20 mg/kg,40 mg/kg) in experimental group and 10% glucose in control group were administered intraperitoneally once a day for 2 weeks, and the Morris water maze tasks were carried out for 5 days. RESULTS: Compared with sham operation group,the animals of ischemia-control group exhibited seriously impaired spatial learning and memory in both place navigation test and spatial probe test. In the place navigation test, the mean value of escape latency in breviscapine group was significantly shorter than that in ischemia control group (P < 0.01 for lower-dose and P < 0.05 for higher-dose breviscapine group, respectively). In the spatial probe test,compared with sham-operation (P < 0.01) and breviscapine group (P < 0.01), the rats of ischemia-control group spent more time in the no-former platform quadrant, and showed reduced frequency of crossing former platform site significantly. The numbers of neurons with Nissl staining and choline acetyltransferase (ChAT) immunopositive neurons in ipssilateral cortex in the breviscapine group were significantly more than those in the ischemia-control group (P < 0.01). In hippocampus, the numbers of neurons with Nissl staining and ChAT immunopositive neurons in the stratum pyramidale of CA area were similar among the groups. CONCLUSION: These results indicate that breviscapine can improve the functions of spatial learning and memory of focal cerebral ischemia rats and the protection against the loss of ChAT immunopositive neuron in new cortex may be involved in its mechanisms. PMID- 19645241 TI - [The effect of the type II collagen protein from Zaocys on cytokines production by synoviocytes in rats with adjuvant arthritis]. AB - OBJECTIVE: To investigate the effect of the type II collagen (C II) protein from Zaocys on cytokines production by synoviocytes in rats with adjuvant arthritis (AA). METHODS: Type II collagen protein was abstracted and purificated from Zaocys. Adjuvant arthritis (AA) was induced by a single intradermal injection of 0.1 mL of complete Freund's adjuvant into the left hind paw. Synoviocytes' supernatants were harvested and synoviocytes-Peyer's Patches (PP) cells coculture system were developed. Tumor necrosis factor-alpha (TNF-alpha) activity was measured by L929 cytotoxicity bioassay and Interleukin (IL)-1beta activity was measured by MTT dye reduction. The synoviocytes' supernatants cytokines' levels were detected by ELISA. RESULTS: Each concentration of C II from Zaocys had no effect on IL-1beta and TNF-alpha production by synoviocytes in vitro. Middle concentration of C II suppressed the activity of IL-1beta and TNF-alpha production by synoviocytes-PP cells coculture system (P < 0.05). Treating with low and high dose of C II suppressed the activity of TNF-alpha and IL-1beta producing by synoviocyte (P < 0.05), significantly suppressed in the group of AA rats treated with middle dose of C II (P < 0.01). Treating with middle and high dose of C II decreased the level of synoviocytes' supernatants TNF-alpha (P < 0.05), the level of synoviocytes' supernatants IL-1beta decreased in all treating groups (P < 0.05). Treating with middle dose of C II increased the level of serum TGF-beta (P < 0.05). Middle concentration of C II suppressed the activity of IL-1 and TNF production by synoviocytes-PP cells coculture system (P < 0.05). CONCLUSIONS: C II from Zaocys has no direct effect on the activity of IL-1beta and TNF production by synoviocytes in vitro. Oral administration of type II collagen protein from Zaocys can effectively suppressed the activity and level of the cytokines production by synoviocytes in rats with adjuvant arthritis (AA). PMID- 19645242 TI - [Effect of Flammulina velutipes polysaccharides on production of cytokines by murine immunocytes and serum levels of cytokines in tumor-bearing mice]. AB - OBJECTIVE: To study the effect of Flammulina velutipes polysaccharides (FVP) on the production of tumor necrosis factor alpha (TNF-alpha), interferon-gamma (INF gamma) and interleukin 2 (IL-2) by murine immunocytes. METHODS: The cell's metabolic activity was determined with methylthiazolyl tetrazolium (MTT) colorimetry assay and the amounts of TNF-alpha, INF-gamma and IL-2 were measured by ELISA. RESULTS: FVP (200, 100, 50 microg/mL) could promote the metabolic activity of murine splenocytes and peritoneal exudate cells (PEC) and increase the amounts of TNF-alpha, INF-gamma and IL-2 in the supernatants of splenocyte cultures, and the amount of TNF-alpha in PEC cultures, with the most marked increase on TNF-alpha level. FVP (100, 50, 25 mg/kg) could raise the serum levels of TNF-alpha and INF-gamma in S180 tumor-bearing mice. CONCLUSION: FVP may regulate murine immune function through promoting the production of TNF-alpha, INF-gamma and IL-2. PMID- 19645243 TI - [Effect of paeonol on protecting endothelial cells of diabetic rats]. AB - OBJECTIVE: To study the effect of paeonol on protecting endothelial cells of diabetic rats. METHODS: Streptozocin was used on rats to make diabetic models. Different dosages of paeonol were fed on all the model rats. PGI, TXA2, ET, CRP, ICAM-1, VCAM-1 and NO were tested after 30 day's therapy. RESULTS: Compared with control group PGI increased from 89.75 +/- 2.75, 89.97 +/- 7.28, 89.97 +/- 11.36 to 120.03 +/- 13.85, 108.34 +/- 11.25, 105.32 +/- 8.85, respectively. TXA2 decreased from 157.64 +/- 10.36, 156.64 +/- 11.35, 153.33 +/- 19.40 to 124.46 +/- 18.67, 136.40 +/- 18.15, 138.40 +/- 22.20, respectively. ET decreased from 181.68 +/- 5.10, 181.27 +/- 4.76, 181.04 +/- 4.19 to 140.55 +/- 3.01, 150.51 +/- 2.22, 161.02 +/- 3.76, respectively. CRP decreased from 41.63 +/- 7.37, 44.83 +/- 7.80, 42.06 +/- 7.21 to 28.62 +/- 5.45, 30.00 +/- 10.73, 37.09 +/- 4.94, respectively. ICAM-1 decreased from 225.77 +/- 11.96, 222.78 +/- 14.46, 225.17 +/- 10.03 to 190.93 +/- 12.67, 197.42 +/- 14.56, 200.64 +/- 15.36, respectively. VCAM-1 decreased from 566.72 +/- 24.46, 560.61 +/- 25.67, 359.61 +/- 42.75 to 506.26 +/- 37.26, 516.83 +/- 28.17, 527.02 +/- 43.47, respectively. NO had no change. CONCLUSIONS: Paeonol can protect the endothelial cells of diabetic rats. PMID- 19645244 TI - [Inhibitory effects of Scutellaria barbate extracts on diethylnitrosamine-induced hepatocarcinoma in rats]. AB - OBJECTIVE: To investigate the inhibitory effects of Scutellaria barbate extracts on diethylnitrosamine-induced hepatocarcinoma in rats. METHODS: Hepatocarcinoma model rats were induced by diethylnitrosamine (DEN). Sixty SD male rats were randomly divided into 4 groups: normal control group, hepatocarcinoma model group, ESB of high dose group and ESB of low dose group. All rats were killed in the 18th week, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), alkaline phosphatase (ALP), gamma glutamyltransferase (gamma-GT) and alpha-L-fucosidase (AFU) in serum were measured by biochemical examinations; Hematoxy and eosin (HE) methods were used to examine the changes of liver pathology. RESULTS: The levels of ALT, AST, TBIL, ALP, gamma-GT, AFU in hepatocarcinoma model group and ESB groups were higher than that of control group (P < 0.05). ESB could relieve hepatic injures. The levels of liver function indexes in ESB groups were lower than that of model group. Histological examination demonstrated that the number of liver cancer nodus in ESB groups were lower than that of model group. Furthermore, ESB could attenuate the grade of cancer cell differentiation. CONCLUSION: ESB could inhibit experimental hepatocarcinoma and relieve hepatic injures in rats. PMID- 19645245 TI - [Study on the antitussive and antiasthmatic effects of Radix Fici Hirtae]. AB - OBJECTIVE: To observe the antitussive and antiasthmatic effects of Radix Fici Hirtae (RFH). METHODS: Antitussive effects were observed by ammonia water steaming test in mice and by citric acid test in guinea pigs. Antiasthmatic actions in guinea pigs were observed by histamine and acetylcholine ultrasonic atomization test, involved isolated guinea pig tracheal smoth muscle experiment and anaphylactic shock of guinea pigs. RESULTS: RFH decreased the frequency of cough induced by ammonia in mice and by citric acid in guinea pig, prolonged the latent period of cough and inhibited the experimental asthma by histamine and acetylcholine solution in conscious guinea pigs, antagonisted the contraction of tracheal smooth muscle by histamine phosphate in guinea pigs and could compete anaphylactic shock in guinea pigs. CONCLUSION: RFH has obvious antitussive and antiasthmatic effects. PMID- 19645246 TI - [Study on the tissue distribution of berberine from Rhizoma Coptidis and compatibility with Rhizoma Coptidis and Cortex Cinnamomi in rats]. AB - OBJECTIVE: To study the effects of Rhizoma Coptidis extracts and Rhizoma Coptidis and Cortex Cinnamomi extracts on the distribution of terberine in rats' tissues. METHODS: The rats were intragastrically given the two different extracts. HPLC was used to determine the concentration of berberine in rats' tissues and the sample was extracted by liquid-liquid extraction method. RESULTS: At the same time, with the same gavage of the three extracts, the trend of the berberine in rats was: the concentration of Rhizoma Coptidis and Cortex Cinnamomi extracts > the concentration of Rhizoma Coptidis extracts. CONCLUSION: Berberine can be detected in intestinal, stomach, colon, pancreatic, heart, kidney, liver, spleen, lung, testicular, uterus, especially the gastrointestinal system with higher concentration, so berberine has a wide range of distribution in vivo. PMID- 19645247 TI - [Study on the inhibitory effect of Reduqing Oral Liquid on respiratory syncytial virus in vitro]. AB - OBJECTIVE: To explore the antiviral effect of Reduqing Oral Liquid on respiratory syncytial virus (RSV). METHODS: The anti-RSV effect of Reduqing Oral Liquid in Hep-2 cell culture was investigated by the cytopathic effect (CPE) inhibition assay and MTT assay, with ribavirin as the positive control drug. RESULTS: Reduqing Oral Liquid was effectively antiviral agent for RSV in a concentration dependent manner in vitro. The median toxic concentration (TC50) was 9182.4 mg/L, the median effective concentration (EC50) was 559.8 mg/L and the treatment index (TI) was 16.4. CONCLUSION: Reduqing Oral Liquid has obvious inhibitory effect on RSV in vitro. PMID- 19645249 TI - [Study on the enrichment and purification of total flavonoids in Microcos paniculata by macroporous adsorption resin]. AB - OBJECTIVE: To establish an optimum enrichment and purification process of total flavonoids in Microcos paniculata by macroporous resins. METHODS: Five kinds of resins were compared and the best one was chosen. Then the parameters of the process were optimized by single factor tests, uniform design and statistical methods. RESULTS: DI01 was selected for its excellent adsorption and desorption properties, 70% ethanol was found to be the best elution solution. As far as the yield was considered, the best result was based on the followings: feed rate-1.0 BV/h, elution flow rate-2.0 BV/h, sample concentration-7.88 mg/mL, eluting agent amount-2.0 BV, pH value 4.8; then the yield reached 90.18% and the purity was 54.37%. If the purity was considered, the best parameters wereas follows: feed rate-1.0 BV/h, elution flow rate-2.0 BV/h, sample concentration-2.0 mg/mL, eluting agent amount-2.8 BV, pH value 7.8; then the purity reached 61.77% and the yield was 80.25%. CONCLUSION: The total flavonoids of Microcos paniculata can be effectively purificated and separated by D101 macroporous resin. PMID- 19645250 TI - [Preparation and characterization of hydroxycamptothecin nanoparticles of amphiphilic block copolymer]. AB - OBJECTIVE: To prepare hydroxycamptothecin nanoparticles of amphiphilic block copolymer and study its characterization initially. METHODS: Polyethyleneglycol polycaprolactone (PEG-PCL) was synthesized and its structure was characterized by 1H-NMR. The HCPT-PEG-PCL-NPs were prepared by solvent-diffusion method using PEG PCL block copolymer as a matrix and HCPT as an antitumor agent. Then the obtained NPs were evaluated and the physical stabilities of both suspl and freeze drying powder were investigated. RESULTS: The mean particle size of the prepared NPs was 164.5 nm, polydispersity index (PI) was 0.14, drug loading (DL) was 5.49%, entrapment efficiency (EE) was 83.2%, zeta potential was -26.1 mV. The physical stability of freeze drying powder was better and hot environment seemed to be bad for the stability. CONCLUSION: The HCPT-PEG-PCL-NPs increase the solubility of HCPT in water and are valuable for the development of the novel dosage form of HCPT. PMID- 19645248 TI - [Extraction and purification of Atractylodes macrocephala monosaccharide composition]. AB - OBJECTIVE: To study the method of Atractylodes macrocephala monosaccharide composition (AMMC)'s extraction, purification and analysis. METHODS: To extract AMMC with water extraction method and purify it with neutro-alumina and resin adsorption method, to observe removal impurity effect of several methods and determine the technology parameters. To detect monosaccharide's content in AMMC with hydrochloric acid-ultraviolet spectrophotometric determination and Evaporative light scattering detector (ELSD). RESULTS: After purificated with neutro-alumina, the yield and purity of AMMC were 23% - 25.5% and 56% - 60%, respectively. According to the static decoloring curve of D900, D201 and AB-8 resins, their decolorization effect's rank was D900 > AB-8 > D201. The yield of AMMC purificated with D900 ion exchange resin was above 17%, and the purity of monosaccharide was above 76%. CONCLUSION: The effect of AMMC purificated with D900 ion exchange resin after water extration is much better, the ideal method for the quantitative analysis of monosaccharide is hydrochloric acid-ultraviolet spectrophotometric determination. PMID- 19645251 TI - [Study on extraction of quercetin in guava leaf by microemulsion]. AB - OBJECTIVE: To study the extraction of quercetin in guava leaf by microemulsion. METHODS: The optimal component proportion was obtained by investigating the ratio of oil, water, surfactant and cosurfactant. The extraction of quercetin in microemulsion was determined by HPLC which compared with the traditional method. RESULTS: The traditional solvent extraction methods were used to extract quercetin in guava leaf, and the content of quercetin extracted with methanol was the highest (4.72 microg/mL). But the contents of quercetin extracted by 72 percent of the microemulsions were higher than methanol, and the extraction by the optimum formulation of microemulsion which consisted of acetoacetate (oil phase) -30% avantin solution (water phase) -RH60 (surfactant) was 2 times as much as that was extracted by methanol (10.43 microg/mL). CONCLUSION: Compared with traditional solvent extraction methods, microemulsion method can effectively improve the extraction rate of quercetin in guava leaf. PMID- 19645253 TI - [Pulmonary problems in dogs in the Netherlands with alarming cause (angiostrongylus vasorum)]. AB - Two 9 month old dogs, that were presented with a history of increasing dyspnoea, are discussed. Examination of blood and lung lavage material gave indications for a parasitic cause. Using the Baermann method of fresh feces, larvae of the French heartworm Angiostrongylus vasorum were found. This worm is transferred via snakes and to a lesser extent by other (paratenic) hosts and has been reported regularly as autochthonous infection in The Netherlands during the last two years. Treatment with a licensed product with a combination of the active ingredients moxidectin and imidacloprid was effective. PMID- 19645252 TI - [Botulism in dairy cattle in 2008: symptoms, diagnosis, pathogenesis, therapy, and prevention]. AB - Botulism affects about 20 dairy herds a year in the Netherlands. This article describes the dramatic outcome of botulism in a dairy herd. The main clinical symptoms in this herd were increased lying down, slight ataxia of the hind legs, and a high mortality (98%). The diagnosis is difficult to establish in adult cattle, and for this reason the clinical and laboratory findings, differential diagnosis, therapy, and preventive measures are discussed. On the basis of this outbreak, previous experience with botulism, and cases described in literature, it is suggested that presence of 'free-range" poultry could contaminate grazing pastures with botulism neurotoxins, causing clinical problems in cattle. If there is an increased risk of contamination of the pasture and/or silage with botulinum neurotoxins, vaccination should be considered to prevent substantial economic and emotional damage. PMID- 19645254 TI - [The consequences of temporarily bottle feeding in terms of biological availability of animal feed and growth of piglets]. PMID- 19645255 TI - [Veterinary suspension to practice withdrawn]. PMID- 19645256 TI - [Ethics in practice: an injured pig]. PMID- 19645257 TI - [Instruments, books and other objects memorable to (almost) forgotten opinions, therapies, buildings, etc. Etazon Celsius]. PMID- 19645258 TI - [Operation crisis!?]. PMID- 19645259 TI - [Pension]. PMID- 19645260 TI - [Veterinarians can help with abuse identification]. PMID- 19645261 TI - [Chairman column: "Look in the mirror yourself"]. PMID- 19645262 TI - Surface-level fine particle mass concentrations: from hemispheric distributions to megacity sources. AB - Since 1990, basic knowledge of the "chemical climate" of fine particles, has greatly improved from Junge's compilation from the 1960s. A worldwide baseline distribution of fine particle concentrations on a synoptic scale of approximately 1000 km can be estimated at least qualitatively from measurements. A geographical distribution of fine particle characteristics is deduced from a synthesis of a variety of disparate data collected at ground level on all continents, especially in the northern hemisphere. On the average, the regional mass concentrations range from 1 to 80 microg/m3, with the highest concentrations in regions of high population density and industrialization. Fine particles by mass on a continental and hemispheric spatial scale are generally dominated by non-sea salt sulfate (0.2 to approximately 20 microg/m3, or approximately 25%) and organic carbon (0.2 > 10 microg/m3, or approximately 25%), with lesser contributions of ammonium, nitrate, elemental carbon, and elements found in sea salt or soil dust. The crustal and trace metal elements contribute a varied amount to fine particle mass depending on location, with a larger contribution in marine conditions or during certain events such as dust storms or volcanic disturbances. The average distribution of mass concentration and major components depends on the proximity to areal aggregations of sources, most of which are continental in origin, with contributions from sea salt emissions in the marine environment. The highest concentrations generally are within or near very large population and industrial centers, especially in Asia, including parts of China and India, as well as North America and Europe. Natural sources of blowing dust, sea salt, and wildfires contribute to large, intermittent spatial-scale particle loadings beyond these ranges. A sampling of 10 megacities illustrates a range of characteristic particle composition, dependent on local and regional sources. Long-range transport of pollution from spatially aggregated sources over hundreds of kilometers creates persistent regional- and continental-scale gradients of mass concentration, sulfate, and carbon species especially in the northern hemisphere. Data are sparse in the southern hemisphere, especially beyond 45 degrees S, but are generally very low in mass concentrations. PMID- 19645263 TI - Evaluating environmental parameters for minimum ammonium losses during composting of trimming residues. AB - A neural fuzzy system was used to investigate the influence of environmental variables (time, aeration, moisture, and particle size) on composting parameters (pH, organic matter [OM], nitrogen [N], ammonium nitrogen [NH4(+)-N] and nitrate nitrogen [NO3(-)-N]). This was to determine the best composting conditions to ensure the maximum quality on the composts obtained with the minimum ammonium losses. A central composite experimental design was used to obtain the neural fuzzy model for each dependent variable. These models, consisting of the four independent process variables, were found to accurately describe the composting process (the differences between the experimental values and those estimated by using the equations never exceeded 5-10% of the former). Results of the modeling showed that creating a product with acceptable chemical properties (pH, NH4(+)-N and NO3(-)-N) entails operating at medium moisture content (55%) and medium to high particle size (3-5 cm). Moderate to low aeration (0.2 L air/min m kg) would be the best compromise to compost this residue because of the scant statistical influence of this independent variable. PMID- 19645264 TI - Development of colorimetric ozone detection papers with high ultraviolet resistance using ultraviolet absorbers. AB - Two types of colorimetric ozone detection paper with high resistance to ultraviolet (UV) light have been developed for outdoor ozone detection. These detection papers incorporate indigo carmine and UV absorbers (UVAs). When exposed to ozone, the papers change color from blue to white, and the ozone concentration can be determined by measuring the reflectance of the papers. However, indigo carmine is strongly affected by UV light, thus making the papers unsuitable for outdoor ozone detection. The authors succeeded in sufficiently improving the resistance of the papers to UV light for them to be used outdoors. This was achieved by using hydrophilic UVAs, namely sodium 2-hydroxy-4-methoxybenzophenone 5-sulfonate and ferulic acid. Without a UVA, the maximum measurement error of the papers derived from UV effect is approximately 290 parts per billion (ppb) x hr when one assumes 8 hr of UV exposure at low- to mid-latitudes (approximately 60 Wh/m2), and this error is too great for accurate ozone measurement. In contrast, the measurement errors of the papers with UVAs are only approximately 60-70 ppb x hr under the same conditions. Ozone measurement accuracies of these detection papers with UVAs are +/- 4.3-4.5% (coefficient of variation [CV]) at 25 degrees C and 60% relative humidity without UV effect. As a result, the improved ozone detection paper with high resistance to UV rays is suitable for outdoor ozone measurements (e.g., for detecting photochemical oxidants). PMID- 19645265 TI - Analysis of traffic and meteorology on airborne particulate matter in Munster, northwest Germany. AB - The importance of street traffic and meteorological conditions on the concentrations of particulate matter (PM) with an aerodynamic diameter smaller than 10 microm (PM10) was studied in the city of Munster in northwest Germany. The database consisted of meteorological data, data of PM10 mass concentrations and fine particle number (6-225 nm diameter) concentrations, and traffic intensity data as counted with tally hand counters at a four- to six-lane road. On working days, a significant correlation could be found between the diurnal mean PM10 mass concentration and vehicle number. The lower number of heavy-duty vehicles compared with passenger cars contributed more to the particle number concentration on working days than on weekend days. On weekends, when the vehicle number was very low, the correlation between PM10 mass concentration and vehicle number changed completely. Other sources of PM and the meteorology dominated the PM concentration. Independent of the weekday, by decreasing the traffic by approximately 99% during late-night hours, the PM10 concentration was reduced by 12% of the daily mean value. A correlation between PM10 and the particle number concentration was found for each weekday. In this study, meteorological parameters, including the atmospheric stability of the boundary layer, were also accounted for. The authors deployed artificial neural networks to achieve more information on the influence of various meteorological parameters, traffic, and the day of the week. A multilayer perceptron network showed the best results for predicting the PM10 concentration, with the correlation coefficient being 0.72. The influence of relative humidity, temperature, and wind was strong, whereas the influence of atmospheric stability and the traffic parameters was weak. Although traffic contributes a constant amount of particles in a daily and weekly cycle, it is the meteorology that drives most of the variability. PMID- 19645266 TI - A new method for determining the initial mobile formaldehyde concentrations, partition coefficients, and diffusion coefficients of dry building materials. AB - The initial mobile formaldehyde concentration, C(m,0); the partition coefficient, K; and the diffusion coefficient, D, of a dry building material are key parameters to characterize formaldehyde emissions from the building material. The solvent extraction method and direct thermal desorption method can overestimate C(m,0) because of high temperature. A new method has been developed to determine C(m,0) under similar conditions to common indoor environment, together with K and D. In the proposed method, the tested materials are placed in an airtight environmental chamber for which the temperature can be controlled by a water bath, then the materials undergo a multisorption/emission process and the instantaneous formaldehyde concentration in the chamber is recorded. The K and C(m,0) are determined from the equilibrium concentrations after every sorption by means of the linear least-square regression, and D is obtained by fitting the concentration at the emission stage into a mass-transfer-based model in the literature. Four kinds of wooden medium-density boards are tested. The C(m,0) measured using this method is the mobile formaldehyde concentration in the material, which differs significantly from the total formaldehyde concentration in the material measured by using the traditional method recommended by the Chinese standard (GB/T 17657-1999) extraction method. This means that the mobile formaldehyde takes only a small portion of the total quantity in the tested material. The K, D, and C(m,0) values measured using this new method are used to predict formaldehyde concentrations for sorption processes. The results agree well with experimental data. In addition, some factors influencing the accuracy are analyzed. PMID- 19645267 TI - Characterization of the sunset semi-continuous carbon aerosol analyzer. AB - The field-deployable Sunset Semi-Continuous Organic Carbon/Elemental Carbon (Sunset OCEC) aerosol analyzer utilizes the modified National Institute for Occupational Safety and Health thermal-optical method to determine total carbon (TC), organic carbon (OC), and elemental carbon (EC) at near real-time. Two sets of OC and EC are available: thermal OC and EC, and optical OC and EC. The former is obtained by the thermal-optical approach, and the latter is obtained by directly determining EC optically and deriving optical OC from TC. However, the performance of the Sunset OCEC is not yet fully characterized. Two collocated Sunset OCEC analyzers, Unit A and Unit B, were used to determine the pooled relative standard deviation (RSD) and limit of detection (LOD) between September 18 and November 6, 2007 in Richland, WA. The LOD of Unit A was approximately 0.2 microgC/m3 (0.1 microgC/cm2) for TC, optical OC, and thermal OC, and 0.01 microgC/m3 (0.01 microgC/cm2) for optical EC. Similarly, Unit B had an LOD of approximately 0.3 microgC/m3 (0.2 microgC/cm2) for TC, optical OC, and thermal OC, and 0.02 microgC/m3 (0.01 microgC/cm2) for optical EC. The LOD for thermal EC is estimated to be 0.2 microgC/m3 (0.1 microgC/cm2) for both units. The pooled RSDs were 4.9% for TC (carbon mass loadings 0.6-6.0 microgC/cm2), 5.6% for optical OC (carbon mass loadings 0.6-5.4 microgC/cm2), 5.3% for thermal OC (carbon mass loadings 0.6-5.3 microgC/ cm2), and 9.6% for optical EC (carbon mass loadings 0-1.4 microgC/cm2), which indicates good precision between the instruments. The RSD for thermal EC is higher at 24.3% (carbon mass loadings 0 1.2 microgC/cm2). Low EC mass loadings in Richland contributed to the poor RSD of EC. The authors found that excessive noise from the nondispersive infrared (NDIR) laser in the Sunset OCEC analyzer could result in a worsened determination of OC and EC. It is recommended that a "quieter" NDIR laser and detector be used in the Sunset OCEC analyzer to improve quantification. Future work should re-evaluate the precision of the EC parameters in an environment favorable for EC collection. Investigation among quantification differences using various thermal-optical protocols to determine OC and EC is also in need. PMID- 19645268 TI - Analysis of biofilters using synthetic macroporous foam media. AB - The removal efficiency of a pollutant being treated in a biofilter packed with macroporous units as biofilm media carriers can be maximized provided that more fouled air flows inside of the unit pieces of the media rather than around it, because the internal specific area of the carrier is several orders of magnitude higher than outside of it. A new model that accounts for the hydrodynamic distribution of a gas stream flowing inside of a macroporous packed bed, more specifically open-pore foams, is proposed. The model allows for the design of the carrier (pore size, media internal porosity, bed porosity, and external bed resistance coefficient) in the presence or absence of outer layers such as a biofilm and a liquid film so that a given pollutant removal efficiency can be attained or increased based on the amount of fouled gas flowing inside of the media rather than around it, whereas the clogging effects typically observed in the field can be avoided. The model can also be used for the special case in which the bed is packed with a monolithic open-pore carrier. Predicted values for the biofilter performance for a monolithic bed and a open-pore packed bed are in good agreement with experimental results obtained in systems treating toluene and hydrogen sulfide under a wide range (4-120 sec) of empty bed residence times and inlet concentrations (10-200 parts per million by volume). PMID- 19645269 TI - A compilation and development of spatial and temporal profiles of high-resolution emissions inventory over Thailand. AB - Thailand, located in Southeast Asia, has both anthropogenic and natural emission sources. It is important to develop an emission information system to provide fundamental data to support emission control strategies and air quality studies. In this research, emissions were compiled for the year 2005. Emission sources cover key anthropogenic and natural emission sources. The methodology to calculate emissions is based on the bottom-up approach using local specific data. For gaseous species, annual emission estimation is found as follows: 9465.9 Gg of carbon monoxide, 2583.1 Gg of nonmethane volatile organic compounds, 886.0 Gg of sulfur dioxide, 790.3 Gg of oxides of nitrogen, and 439.2 Gg of ammonia. For aerosol species, annual emission estimations are 1277.4 Gg of particulate matter smaller than or equal to 10 p.m in aerodynamic diameter, 325.5 Gg of organic carbon, and 136.4 Gg of black carbon. The intercomparison with literature shows an acceptable agreement of annual estimation. Emissions are projected until the year 2027 based on a Business-as-Usual scenario from governmental trends. Spatial allocations with 1- by 1-km resolution and temporal (i.e., monthly, weekly, and diurnal) allocation profiles are also developed to investigate the variation of emissions. PMID- 19645270 TI - Real-world energy use and emission rates for idling long-haul trucks and selected idle reduction technologies. AB - Long-haul freight trucks typically idle for 2000 or more hours per year, motivating interest in reducing idle fuel use and emissions using auxiliary power units (APUs) and shore-power (SP). Fuel-use rates are estimated based on electronic control unit (ECU) data for truck engines and measurements for APU engines. Engine emission factors were measured using a portable emission measurement system. Indirect emissions from SP were based on average utility grid emission factors. Base engine fuel use and APU and SP electrical load were analyzed for 20 trucks monitored for more than 1 yr during 2.76 million mi of activity within 42 U.S. states. The average base engine fuel use varied from 0.46 to 0.65 gal/hr. The average APU fuel use varied from 0.24 to 0.41 gal/hr. Fuel use rates are typically lowest in mild weather, highest in hot or cold weather, and depend on engine speed (revolutions per minute [RPM]). Compared with the base engine, APU fuel use and emissions of carbon dioxide (CO2) and sulfur dioxide (SO2) are lower by 36-47%. Oxides of nitrogen (NO(x)) emissions are lower by 80 90%. Reductions in particulate matter (PM), carbon monoxide (CO), and hydrocarbon emissions vary from approximately 10 to over 50%. SP leads to more substantial reductions, except for SO2. The actual achievable reductions will be lower because only a fraction of base engine usage will be replaced by APUs, SP, or both. Recommendations are made for reducing base engine fuel use and emissions, accounting for variability in fuel use and emissions reductions, and further work to quantify real-world avoided fuel use and emissions. PMID- 19645271 TI - Methods for characterizing fine particulate matter using ground observations and remotely sensed data: potential use for environmental public health surveillance. AB - This study describes and demonstrates different techniques for surface fitting daily environmental hazards data of particulate matter with aerodynamic diameter less than or equal to 2.5 microm (PM2.5) for the purpose of integrating respiratory health and environmental data for the Centers for Disease Control and Prevention (CDC) pilot study of Health and Environment Linked for Information Exchange (HELIX)-Atlanta. It presents a methodology for estimating daily spatial surfaces of ground-level PM2.5 concentrations using the B-Spline and inverse distance weighting (IDW) surface-fitting techniques, leveraging National Aeronautics and Space Administration (NASA) Moderate Resolution Imaging Spectrometer (MODIS) data to complement U.S. Environmental Protection Agency (EPA) ground observation data. The study used measurements of ambient PM2.5 from the EPA database for the year 2003 as well as PM2.5 estimates derived from NASA's satellite data. Hazard data have been processed to derive the surrogate PM2.5 exposure estimates. This paper shows that merging MODIS remote sensing data with surface observations of PM,2. not only provides a more complete daily representation of PM,2. than either dataset alone would allow, but it also reduces the errors in the PM2.5-estimated surfaces. The results of this study also show that although the IDW technique can introduce some numerical artifacts that could be due to its interpolating nature, which assumes that the maxima and minima can occur only at the observation points, the daily IDW PM2.5 surfaces had smaller errors in general, with respect to observations, than those of the B Spline surfaces. Finally, the methods discussed in this paper establish a foundation for environmental public health linkage and association studies for which determining the concentrations of an environmental hazard such as PM2.5 with high accuracy is critical. PMID- 19645272 TI - Investigation of the treatability of the primary indoor volatile organic compounds on activated carbon fiber cloths at typical indoor concentrations. AB - Volatile organic compounds (VOCs) are a major concern for indoor air pollution because of the impacts on human health. In recent years, interest has increased in the development and design of activated carbon filters for removing VOCs from indoor air. Although extensive information is available on sources, concentrations, and types of indoor VOCs, there is little or no information on the performance of indoor air adsorption systems for removing low concentrations of primary VOCs. Filter designs need to consider various factors such as empty bed contact time, humidity effects, competitive adsorption, and feed concentration variations, whereas adsorption capacities of the indoor VOCs at the indoor concentration levels are important parameters for filter design. A preliminary assessment of the feasibility of using adsorption filters to remove low concentrations of primary VOCs can be performed. This work relates the information (including VOC classes in indoor air, the typical indoor concentrations, and the adsorption isotherms) with the design of a particular adsorbent/adsorbates system. As groundwork for filter design and development, this study selects the primary VOCs in indoor air of residences, schools, and offices in different geographical areas (North America, Europe, and Asia) on the basis of occurrence, concentrations, and health effects. Activated carbon fiber cloths (ACFCs) are chosen as the adsorbents of interest. It is demonstrated that the isotherm of a VOC (e.g., toluene on the ACFC) at typical indoor concentrations-parts per billion by volume (ppbv) level-is different than the isotherm at parts per million by volume (ppmv) levels reported in the publications. The isotherms at the typical indoor concentrations for the selected primary VOCs are estimated using the Dubinin-Radushkevitch equation. The maximum specific throughput for an indoor VOC removal system to remove benzene is calculated as a worst-case scenario. It is shown that VOC adsorption capacity is an important indicator of a filter's lifetime and needs to be studied at the appropriate concentration range. Future work requires better understanding of the realistic VOC concentrations and isotherms in indoor environments to efficiently utilize adsorbents. PMID- 19645273 TI - Importance of the "what," "when," and "where" of mosquito collection events. AB - There is increasing need to apply established standards for recording data on mosquito collection events, because of the diversity of potential data providers, and the growth and interoperability of online databases designed to host these collection records. In particular, adequate taxonomic and georeference data are needed for geodatabases such as Mosquitomap (http://www. mosquitomap.org/) that map and compare these collection points with other spatial information in a geographical information system (GIS) setting. Accurately georeferenced collection data are crucial for understanding mosquito biogeography, ecology, and the impact of environmental changes, as well as for species distribution modeling, planning mosquito surveys, and for determining disease risk. We sampled representative published reports of new mosquito species records from 1980 in North America to the present to ascertain the quality of georeference information. Our results show that authors have increased the frequency of reporting georeferences but that they vary in the precision of the georeference, and some information, such as the source, date, and datum of the georeference, are usually not given. We discuss recently established standards for recording collection events, some relevant online resources available to researchers to assist them in their georeferencing, and the data input schema developed for the Mosquitomap database. We propose that the mosquito research community adopt data standards for recording and reporting the results of mosquito collection events to increase the value of these data. In particular, we recommend authors lodge voucher specimens and use a GPS set to the WGS84 datum. PMID- 19645274 TI - Ecology of Rickettsia felis: a review. AB - It has been two decades since the first description of Rickettsia felis, and although a nearly cosmopolitan distribution is now apparent, much of the ecology of this unique microorganism remains unresolved. The cat flea, Ctenocephalides felis, is currently the only known biological vector of R. felis; however, molecular evidence of R. felis in other species of fleas as well as in ticks and mites suggests a variety of arthropod hosts. Studies examining the transmission of R. felis using colonized cat fleas have shown stable vertical transmission but not horizontal transmission. Likewise, serological and molecular tools have been used to detect R. felis in a number of vertebrate hosts, including humans, in the absence of a clear mechanism of horizontal transmission. Considered an emerging flea-borne rickettsiosis, clinical manifestation of R. felis infection in humans, including, fever, rash, and headache is similar to other rickettsial diseases. Recent advances toward further understanding the ecology of R. felis have been facilitated by stable R. felis-infected cat flea colonies, several primary flea isolates and sustained maintenance of R. felis in cell culture systems, and highly sensitive quantitative molecular assays. Here, we provide a synopsis of R. felis including the known distribution and arthropods infected; transmission mechanisms; current understanding of vertebrate infection and human disease; and the tools available to further examine R. felis. PMID- 19645275 TI - Studies of vector competency and efficiency of North American fleas for Yersinia pestis: state of the field and future research needs. AB - The etiological agent of plague, Yersinia pestis, is most commonly transmitted by the bite of infectious fleas. To date, at least 28 flea species occurring in North America have been experimentally confirmed as vectors of Y. pestis. Transmission efficiency differs among species and also between different studies of a single species. These differences may, however, in large part reflect nonstandardized experimental conditions used during the first half of the 20th century when such studies were conducted in response to the rapid spread of Y. pestis across the western United States after its introduction at the beginning of this century. The majority of these early transmission studies focused on the blocked flea mechanism of transmission, which typically does not occur until > 2 3 wk after the flea becomes infected. Recent studies have challenged the paradigm that Y. pestis is usually spread by blocked fleas by demonstrating that numerous flea species, including the oriental rat flea Xenopsylla cheopis, which was the focus of the early classical studies on blocked flea transmission, are capable of"early-phase" transmission during the first few days after becoming infected and before a complete blockage can form. The aims of this review are to 1) summarize Y. pestis vector competency and efficiency studies for fleas occurring in North America, 2) discuss the implications of the results of these studies for our understanding of the dynamics of plague epizootics, 3) demonstrate why older transmission studies need to be repeated using a standardized experimental system, and 4) outline future directions for studies of fleas as vectors of Y. pestis. PMID- 19645276 TI - Identification of Culex (Melanoconion) species of the United States using female cibarial armature (Diptera: Culicidae). AB - Species within the subgenus Culex (Melanoconion) Theobald are the primary enzootic vectors of viruses in the Venezuelan equine encephalitis complex including Everglades virus, and probable enzootic vectors of eastern equine encephalitis and West Nile viruses. Adult females of this subgenus are often difficult or impossible to identify to species based on external morphological characters. The use of female cibarial armature allows for the identification of field-collected adult female specimens of Culex (Melanoconion). The cibarial armatures are described and illustrated for all species from the United States and a key to species using this character is presented. PMID- 19645277 TI - Chigger mites (Acari: Trombiculidae) from Makalu region in Nepal Himalaya, with a description of three new species. AB - Three new species of chigger mites, Neotrombicula kounickyi sp. n., Leptotrombidium angkamii sp. n., and Doloisia vlastae sp. n., are described from two species of small mammals collected in the Barun Glacier Valley, Makalu region, Nepal Himalaya. Two species, Trombiculindus mehtai Fernandes et Kulkarni, 2003 and Cheladonta ikaoensis (Sasa et al., 1951) are recorded for the first time in Nepal. Data on altitude distribution of chiggers and their host preferences are given. PMID- 19645278 TI - Hatch plasticity in response to varied inundation frequency in Aedes albopictus. AB - Eggs of container-breeding mosquitoes are able to withstand drought conditions as an egg and hatch when submerged. Frequent rainfall can be simulated by frequent submersion, and drought conditions can be simulated by infrequent submersion. We examined the hatch response of Aedes albopictus (Skuse) eggs to simulated drought conditions. Ae. albopictus eggs from a strain originating outside Kobe, Japan, were subjected to one of three treatments; high-frequency hatch stimulation consisting of submerging the eggs in a nutrient broth mixture every 3 d, low frequency hatch stimulation consisting of submerging the eggs every 7 d, and delayed high-frequency hatch stimulation. Eggs that were subjected to lower frequency stimulation showed a significant decrease in hatch delay, which was the opposite of the predicted response. This decrease in hatch delay may be an example of hatch plasticity in response to drought conditions. This response could not be explained as a result of the difference in the ages of the eggs on any given stimulus. A decreased hatch delay response to potential drought conditions combined with rapid larval development may enable Ae. albopictus, whose eggs are not as desiccation resistant as some other container-breeding mosquitoes, to survive extended drought. PMID- 19645279 TI - No evolutionary response to four generations of laboratory selection on antipredator behavior of Aedes albopictus: potential implications for biotic resistance to invasion. AB - Aedes albopictus (Skuse) is an invasive container-dwelling mosquito and an important disease vector that co-occurs with the native mosquito, Aedes triseriatus (Say), and the predatory midge, Corethrella appendiculata (Grabham). Larval Ae. triseriatus show significantly greater antipredatory responses when compared to larval Ae. albopictus in the presence of predation cues from C. appendiculata. The potential for evolution of antipredatory behavioral responses to C. appendiculata in Ae. albopictus is unknown. We used a controlled laboratory selection experiment to test whether Ae. albopictus could evolve antipredatory behavioral responses to C. appendiculata predation. We subjected replicate Ae. albopictus populations to four generations of predation by C. appendiculata or a predator-free control treatment and compared the behavior and life history of Ae. albopictus in the two treatments in each generation. There were no differences in Ae. albopictus behavioral responses between predation and control lines in any of the four generations. There was also no evidence of differences in life histories between predation and control lines. Ae. albopictus is superior as a competitor compared with Ae. triseriatus, which it has replaced in areas where C. appendiculata are rare. Our results suggest limited potential for Ae. albopictus to evolve stronger antipredatory behavioral responses to C. appendiculata predation and imply that C. appendiculata will continue to act as an impediment to invasion by Ae. albopictus and replacement of Ae. triseriatus and to promote coexistence of these competitors. PMID- 19645280 TI - Reducing honey bee defensive responses and social wasp colonization with methyl anthranilate. AB - Human victims of a massive number of stings have been steadily increasing since the invasion of Africanized honey bees (Apis mellifera) to the United States in 1990. Multiple honey bee stings may result in venom toxicity, leading to renal failure and even death. Here we tested the efficacy of methyl anthranilate as a honey bee repellent during a massive defensive response by Africanized honey bees. An aerosolized solution of 10% methyl anthranilate reduced the number of defensive bee hits to a retreating victim by 95% compared with a water control. One hundred fifty milliliters of the 10% methyl anthranilate solution sprayed onto stationary foam balls covered with black suede leather located 2 m from provoked Africanized colonies received 80% fewer stings than targets treated with water. Methyl anthranilate (100%) delivered through a UV blocking 3 mil polyethylene pouch was 100% effective in preventing Polistes colonization in wildlife observation huts and from the roof overhang of home patios. Although methyl anthranilate was not 100% effective in preventing honey bee stinging, it seemed to reduce number of stings below the average human LD50, indicative of a promising tool for preventing honey bee venom toxicity and wasp colonization. PMID- 19645281 TI - Copulation and mate guarding behavior in Triatoma brasiliensis (Hemiptera: Reduviidae). AB - The hematophagous bug Triatoma brasiliensis (Neiva) is an important vector of Chagas disease in Brazil. We describe the mating behavior of this species in a comparative manner and analyze the effect of time elapsed since the first imaginal bloodmeal on motivation of males to mate, on female mate-rejections, and on overall mating frequency. We also evaluate whether females of this species copulate with several males in short time intervals, and we examine whether the duration of copulation may vary in the presence of other males compared with what is observed with isolated pairs. Age affected the motivation of males to perform mating attempts, whereas nutritional status affected the receptivity of females. Results showed that 70% of the females tested accepted copulating with three males over a period of 90 min, whereas the remaining 30% mated with at least two males. Mating duration in T. brasiliensis was prolonged in the presence of other males compared with observations of isolated pairs, and males of this species performed long postcopulatory associations only in the presence of other males, apparently as a mate guarding response to the presence of potential competitors. PMID- 19645283 TI - Permethrin induces overexpression of cytochrome c oxidase subunit 3 in Aedes aegypti. AB - Using quantitative polymerase chain reaction (QPCR), the relative transcriptional levels of cytochrome c oxidase subunit 3 (CO3) were studied in Aedes aegypti in response to treatment with acetone, permethrin, and fipronil. The transcriptional levels of CO3 were significantly (P < 0.05) higher in acetone-treated Ae. aegypti compared with that in untreated samples. Using ribosomal L24, heat shock protein (HSP), and actin as reference genes, relative transcription levels of CO3 in acetone-treated Ae. aegypti were 2.88 +/- 0.38-, 2.60 +/- 0.60-, and 3.24 +/- 0.70-fold higher, respectively, compared with that in untreated mosquitoes. Transcriptional levels of CO3 were induced significantly higher (6.54 +/- 1.22-, 4.62 +/- 0.74-, and 9.47 +/- 3.71-fold, respectively) by permethrin at LD10 compared with acetone (P < 0.05). Taken together, our results suggest that overexpression of CO3 is tightly regulated in Ae. aegypti in response to xenobiotic treatment. PMID- 19645282 TI - Molecular population genetics and phylogeography of the Chagas disease vector Triatoma infestans in South America. AB - Knowledge of the genetic variability, population structure, and evolutionary history of Triatoma infestans may be useful for developing rational vector control strategies. A 661-bp fragment of the mitochondrial gene cytochrome oxidase I (COI) was sequenced and analyzed in bugs from Argentina, Uruguay, Peru, and Bolivia, including peridomestic, domestic, Andean, and Chaco sylvatic bugs. A total of 48 polymorphic sites among 37 haplotypes were described. Nucleotide variation fluctuated among samples, with the highest nucleotide diversity observed in seven Argentinean provinces. Within this group, some populations showed patterns of variability compatible with population expansions and/or fine scale population structure, whereas others suggested population bottlenecks and/or population admixture processes. A maximum parsimony analysis of the haplotypes showed the presence of a Bolivian/Peruvian and an Argentinean/Uruguayan clade. Bolivian sequences were further divided in Chaco sylvatic and Andean domestic and sylvatic. Two different nested clades were found within the Argentinean/Uruguayan cluster. Analysis of molecular variance (AMOVA) and K(ST)* analysis supported a strong population structure in Argentina, where genetic differentiation was correlated with geographic distance. Departures from neutrality expectations and a nested cladistic analysis suggest a recent population expansion of T. infestans in Argentina, followed by restricted gene flow and patterns of isolation by distance. This expansion could have taken place as a two-wave process, as was shown by the phylogenetic analysis and signatures of population admixture in the southern most Argentinean populations. PMID- 19645284 TI - Control of phlebotomine sand flies with vertical fine-mesh nets. AB - Insecticide-treated vertical net barriers were used to intercept foraging sand flies. Two different nets were draped on fenced enclosures (10 by 10 m; 2 m high) in the central Jordan Valley. One enclosure was draped with a deltamethrin impregnated net (PermaNet, 225 holes/in2). The holes of this net are sufficiently large to allow sand flies to pass through but not without coming in close contact with the mesh. The other enclosure was covered with SpiderNet+ (1,240 holes/in2) and sprayed with beta-cyfluthrin. Sand flies were captured inside and outside the enclosures before and after draping with the nets using CO2-baited CDC traps or CDC light traps. Both barrier types exhibited > 90% efficacy in blocking sand flies from entering the enclosures (P < 0.01). The Spider-Net+ exhibited high efficiency even before being sprayed with insecticide because the small mesh size physically prevented flies from passing through. In Ma'ale Adumim, a 60-m-long, 2 m-high PermaNet barrier was erected to intercept sand flies approaching houses from their natural habitats. Sand flies were monitored on all sides of the barrier using CO2-baited CDC traps or CDC light traps. Results showed a 60% reduction in the mean number of sand flies trapped behind the net compared with the untreated areas adjacent to it (P < 0.05). Integrated vector control campaigns for reducing the burden of sand fly bites should consider vertical fine mesh nets to reduce the numbers of sand flies arriving at inhabited areas. PMID- 19645285 TI - Dihydronepetalactones deter feeding activity by mosquitoes, stable flies, and deer ticks. AB - The essential oil of catmint, Nepeta cataria L., contains nepetalactones, that, on hydrogenation, yield the corresponding dihydronepetalactone (DHN) diastereomers. The DHN diastereomer (4R,4aR,7S,7aS)-4,7 dimethylhexahydrocyclopenta[c]pyran-1(3H)-one, DHN 1) was evaluated as mosquito repellent, as was the mixture of diastereomers {mostly (4S,4aR,7S,7aR)-4,7 dimethylhexahydrocyclopenta[c]pyran-1(3H)-one, DHN 2} present after hydrogenation of catmint oil itself. The repellency of these materials to Aedes aegypti L. and Anopheles albimanus Wiedemann mosquitoes was tested in vitro and found to be comparable to that obtained with the well-known insect repellent active ingredient N,N-diethyl-3-methylbenzamide (DEET). DHN 1 and DHN 2 also repelled the stable fly, Stomoxys calcitrans L., in this study. DHN 1, DHN 2, and p menthane-3,8-diol (PMD), another natural monoterpenoid repellent, gave comparable levels of repellency against An. albimanus and S. calcitrans. Laboratory testing of DHN 1 and DHN 2 using human subjects with An. albimanus mosquitoes was carried out. Both DHN 1 and DHN 2 at 10% (wt:vol) conferred complete protection from bites for significant periods of time (3.5 and 5 h, respectively), with DHN2 conferring protection statistically equivalent to DEET. The DHN 1 and DHN 2 diastereomers were also efficaceous against black-legged tick (Ixodes scapularis Say) nymphs. PMID- 19645286 TI - Survival of larvivorous fish used for biological control of Aedes aegypti larvae in domestic containers with different chlorine concentrations. AB - The two fish species Betta splendens (Regan) and Poecilia reticulata (Peters) are known predators of Aedes aegypti (L., 1762) larvae. Both species have been used for biological control in northeastern Brazil. However, the feasibility of these fish for the control of Ae. aegypti larvae in domestic containers may be limited by their survival in chlorinated water, as supplied by the public water system. We exposed fish to three different concentrations of chlorine: 1, 1.5, and 2.0 mg/liter. All B. splendens survived at 1.0 mg/liter chlorine concentration; 72.5 and 39.3% of B. splendens survived chlorine concentrations of 1.5 and 2.0 mg/liter, respectively. In contrast, only 4.4% of P. reticulata survived at a chlorine concentration of 1.0 mg/liter. We conclude that B. splendens may be an appropriate species for biological control of Ae. aegypti in domestic water tanks. PMID- 19645288 TI - Survival of avian H5N1 influenza A viruses in Calliphora nigribarbis (Diptera: Calliphoridae). AB - In a previous study, the highly pathogenic avian influenza (HPAI) H5N1 viruses were isolated from blow flies collected at the Tamba Town of Kyoto prefecture during the outbreak period in March 2004. In this study, we carried out virus exposure experiments to investigate whether the H5N1 virus would survive in a blow fly, Calliphora nigribarbis. The virus exposure experiments showed that the H5N1 influenza virus was isolated from the crop and intestine of C. nigribarbis for at least 24 h, and the viruses remained viable with titers ranging from 0.5 to 4.63 TCID50. This result suggests that C. nigribarbis could possibly transport the H5N1 virus over a distance of 2 km, which is the distance they can migrate within 24 h. PMID- 19645287 TI - Extracts of Sarcoptes scabiei De Geer downmodulate secretion of IL-8 by skin keratinocytes and fibroblasts and of GM-CSF by fibroblasts in the presence of proinflammatory cytokines. AB - Previous in vitro studies showed that molecules in an extract of the mite Sarcoptes scabiei variety canis De Geer could modulate the secretion of cytokines from cultured normal human epidermal keratinocytes and dermal fibroblasts in the absence of proinflammatory cytokines in the cell culture media. The purpose of this study was to investigate whether scabies extract could also modulate cytokine and chemokine secretion from epidermal keratinocytes and dermal fibroblasts in the presence of proinflammatory cytokines that are likely present in the scabietic lesion in vivo. In particular, could the downmodulating properties of this ectoparasitic mite on skin cells be maintained in the presence of proinflammatory cytokines? We found that even in the presence of the proinflammatory cytokines interleukin (IL)-1alpha, IL-beta, and a mixture of tumor necrosis factor (TNF)alpha + IL-17, scabies extract still downregulated the levels of IL-8 secretion from keratinocytes and fibroblasts and of granulocyte/macrophage-colony stimulating factor (GM-CSF) secretion from fibroblasts that were induced by stimulation of the cells with proinflammatory cytokines alone. This study also showed that scabies molecules induced secretions of growth-related oncogene alpha (GROalpha), transforming growth factor alpha (TGFalpha), and cutaneous T-cell attracting chemokine (CTACK) from keratinocytes and IL-6 and granulocyte-colony stimulating factor (G-CSF) from fibroblasts. These findings, coupled with the previous findings that molecules in scabies extract could downregulate expression of intracellular adhesion molecule-1 (ICAM 1) and E-selectin by normal dermal microvascular endothelial cells and secretion of IL-1alpha from keratinocytes, suggest that multiple factors from scabies mites play a role in the characteristic delayed inflammatory response to a primary infestation with S. scabiei. These are adaptations that favor invasion of the host by the parasite. PMID- 19645289 TI - Detection and identification of rickettsial agents in ticks from domestic mammals in eastern Panama. AB - Several outbreaks of Rocky Mountain spotted fever have occurred in recent years in Colombian communities close to the border with Panama. However, little is known about rickettsiae and rickettsial diseases in eastern Panamanian provinces, the Darien Province and the Kuna Yala, located north of the endemic area in Colombia. In 2007, 289 ticks were collected in several towns from dogs, horses, mules, cows, and pigs. DNA was extracted from 124 Dermacentor nitens, 64 Rhipicephalus sanguineus, 43 Amblyomma ovale, 35 A. cajennense, 10 Boophilus microplus, 4 A. oblongoguttatum, and 9 A. cajennense nymphs. SYBR-Green polymerase chain reaction assays targeting a fragment of the OmpA and 16S rRNA genes were used for detection of DNA of the spotted fever group rickettsiae (SFGR) and Anaplasmataceae (Anaplasma and Ehrlichia), respectively. In total, 37.4% ticks were positive for SFGR, including 20.3% R. sanguineus, 27.9% A. ovale, 25.8% D. nitens, 50% B. microplus, 50% A. oblongoguttatum, and 100% A. cajennense. The presence of Rickettsia amblyommii DNA was confirmed by sequencing in A. cajennense, A. oblongoguttatum, A. ovale, B. microplus, and R. sanguineus. DNA of R. rickettsii was only detected in one D. nitens collected from a horse in Santa Fe, Darien Province. Prevalence of Anaplasmataceae varied from 6.3% in R. sanguineus to 26.5% in A. cajennense. DNA of Ehrlichia chaffensis was found in three D. nitens and three A. cajennense from horses. This is the first study providing molecular characterization and prevalence information on SFGR in ticks from these areas and thus will be helpful for future evaluations of the risk of rickettsial diseases for individuals living in this region. PMID- 19645290 TI - Use of hamster-baited no. 17 Trinidad mosquito traps at an eastern equine encephalomyelitis focus in Tennessee. AB - We set out no. 17 Trinidad traps baited with hamsters at a swamp in Tennessee, where recent eastern equine encephalomyelitis (EEE) equine outbreaks had occurred, to determine which mosquito species at this site were attracted to these traps. We also set out CO2-baited CDC light traps for comparison. Of 11 species present in CO2-baited CDC light traps, only Culex (Melanoconion) erraticus (Dyar and Knab) blood fed on hamsters in the Trinidad traps. Significantly less Cx. erraticus mosquitoes entered Trinidad traps per trap night (mean = 17.6, median = 6.0) compared with CDC traps (mean = 38.7, median = 35.0). Advantages and disadvantages in using hamster-baited no. 17 Trinidad traps compared with CO2-baited CDC light traps to capture Cx. erraticus mosquitoes are discussed. Further understanding of the feeding behavior and ecology of this potential vector is warranted. PMID- 19645291 TI - Experimental transmission of vesicular stomatitis New Jersey virus from Simulium vittatum to cattle: clinical outcome is influenced by site of insect feeding. AB - Vesicular stomatitis New Jersey virus (VSNJV) is an insect-transmitted Rhabdovirus causing vesicular disease in domestic livestock including cattle, horses, and pigs. Natural transmission during epidemics remains poorly understood, particularly in cattle, one of the most affected species during outbreaks. This study reports the first successful transmission of VSNJV to cattle by insect bite resulting in clinical disease. When infected black flies (Simulium vittatum Zetterstedt) fed at sites where VS lesions are usually observed (mouth, nostrils, and foot coronary band), infection occurred, characterized by local viral replication, vesicular lesions, and high neutralizing antibody titers (> 1: 256). Viral RNA was detected up to 9 d postinfection in tissues collected during necropsy from lesion sites and lymph nodes draining those sites. Interestingly, when flies were allowed to feed on flank or neck skin, viral replication was poor, lesions were not observed, and low levels of neutralizing antibodies (range, 1:8-1:32) developed. Viremia was never observed in any of the animals and infectious virus was not recovered from tissues on necropsies performed between 8 and 27 d postinfection. Demonstration that VSNJV transmission to cattle by infected black flies can result in clinical disease contributes to a better understanding of the epidemiology and potential prevention and control methods for this important disease. PMID- 19645292 TI - Ecological meta-analysis of density-dependent processes in the transmission of lymphatic filariasis: survival of infected vectors. AB - The survival rate of infected vectors represents one of the fundamental components that influence the transmission dynamics of mosquito-borne diseases. Despite the occurrence of a number of studies investigating mosquito survival after infection with filarial worms, there remains conflicting evidence from both laboratory and field experiments as to the existence and mechanism for parasite induced mortality among filarial mosquitoes. Here, we used a mixed effects meta analytical framework to combine the data from all available vector-human host blood feeding experiments to evaluate the evidence for the impact of parasite load on the mortality rates of the three major lymphatic filariasis transmitting mosquito genera, Culex, Aedes, and Anopheles mosquitoes, over the extrinsic incubation period of parasitic infection. The results show that, despite the application of this approach, or in the case of Anopheles using a convention fixed effects logistic regression analysis supplemented with additional survival analysis of longitudinal data, no strong association between mortality rate and microfilariae (mf) uptake for either of the three mosquito genera is apparent in the combined data. Instead, a key finding is that study effects played a more crucial role in determining the levels of mortality observed in these experimental studies. This was most revealing in the case of Culex, given that the largest single study in terms of both the number of data points and range of mf intensities, in contrast to smaller studies, showed a significant positive association between mf intensity and mortality, indicating that in this genus at least, the detrimental effect of infection may be manifested only at the highest mf intakes. Although no density dependence in vector mortality was also observed for Aedes, possibly because of the use of restricted human mf intensity range in previous studies, an intriguing finding was that a significantly higher overall mortality was observed for this genus over mfintake ranges that produced much less corresponding mortality in Culex and Anopheles. The results also indicate that currently very little can be said about the survival rate of Anopheles mosquitoes infected with filarial worms because of the striking paucity of data for this genus. Further studies, using standardized methods and covering an appropriate range of mf uptake intensities and using study frameworks that allow the design and comparison of data from both experimental and field experiments, are clearly indicated if we are to reliably quantify the likely effect of filarial infection on vector survival. PMID- 19645293 TI - Susceptibility of Culex pipiens (Diptera: Culicidae) field populations in Cyprus to conventional organic insecticides, Bacillus thuringiensis subsp. israelensis, and methoprene. AB - Culex pipiens pipiens L. populations on Cyprus were sampled over a 6-yr period from 2002 to 2008 to evaluate the status of insecticide resistance toward the insecticides temephos, chlorpyrifos, and permethrin and to study susceptibility levels toward the recently introduced bacterial insecticide Bacillus thuringiensis subsp. israelensis De Barjac and the juvenile hormone analog, methoprene. Susceptibility to the three conventional chemical insecticides varied between different collections, with most collections showing moderate or low resistance. The 2004 Akrotiri collection had the highest temephos resistance ratio, 167-fold at the LC95, although later sampling showed that the population returned to susceptibility after treatments stopped. Chlorpyrifos resistance was generally higher than temephos resistance. Four collections showed high resistance, and the resistance ratios of two collections were notably high with resistance ratios of 110- and 248-fold at the LC95. Three collections showed high permethrin resistance (22.5-, 23.9-, and 86.3-fold). The frequency of elevated esterase activity in populations was estimated using a filter paper test, and frequencies varied from 0.9 to 65% among collections. The levels of temephos resistance and the frequency of elevated esterases in this survey were generally lower than in earlier reports, suggesting a decline in temephos resistance. Dose response values for B. thuringiensis subsp. israelensis covered an approximate eight-fold range, but no resistance was detected. Methoprene values showed a 4.7 fold and 16-fold range at the LC50 and LC95, respectively. Two populations showed significant resistance ratios at the LC95. These data are discussed in relation to the changes in larval control practices underway in Cyprus. PMID- 19645294 TI - Quantification of Theileria parva in Rhipicephalus appendiculatus (Acari: Ixodidae) confirms differences in infection between selected tick strains. AB - Theileria parva is the etiologic agent of East Coast fever, an economically important disease of cattle in sub-Saharan Africa. This protozoan parasite is biologically transmitted by Rhipicephalus appendiculatus (Neumann) (Acari: Ixodidae). An understanding of the vector-parasite interaction may aid the development of improved methods for controlling transmission. We developed quantitative polymerase chain reaction (qPCR) and nested PCR (nPCR) assays targeting the T. parva-specific p104 gene to study T. parva pathogenesis in two strains of R. appendiculatus that had previously been selected to be relatively more (Kiambu) or less (Muguga) susceptible to infection. Nymphs from both strains were fed simultaneously to repletion on acutely infected calves. Nymphs from the Kiambu strain showed significantly higher engorgement weights compared with Muguga strain nymphs. Immediately after engorgement qPCR confirmed that nymphal Kiambu ticks had significantly higher parasite loads at repletion than Muguga nymphs. By 12 d postengorgement, parasites were below quantifiable levels but could be detected by nPCR in 83-87% (Muguga and Kiambu, respectively) of nymphs. After the molt, adult feeding on naive cattle stimulated parasite replication in the salivary glands. PCR detected significantly more infected ticks than microscopy, and there was a significant difference between the two tick strains both in the proportion of ticks that develop salivary gland infections, and in the number of parasites within infected salivary glands. These data confirm that although both tick strains were competent vectors, Kiambu is both a significantly more susceptible and a more efficient host for T. parva than Muguga. The mechanisms that contribute to the levels of susceptibility and efficiency are unknown; however, this study lays the groundwork for a comparison of the transcriptome of these tick strains, the next step toward discovering the genes involved in the tick-parasite interaction. PMID- 19645295 TI - Ants (Hymenoptera: Formicidae) as carriers of fungi in hospital environments: an emphasis on the genera Tapinoma and Pheidole. AB - The aim of this study was to evaluate the presence of filamentous fungi and yeasts on the external surface of ants at hospitals. From March 2007 to February 2008, 2,899 ants were evaluated in two public hospitals in the city of Fortaleza, Ceara, in northeastern Brazil. The ants were attracted by nontoxic baits, distributed within critical and semicritical hospital areas. The fungi were identified through macro- and micromorphological analysis, biochemical profile, and growth in chromogenic medium. From this study, 5 genera and 13 species of ants were identified, from critical (8% of the collected ants) and semicritical (92%) areas, during the daytime (48%) and nighttime (52%) periods. In the mycological analysis, 75% of the ants were fungi carriers, with the species Tapinoma melanocephalum and species from the genus Pheidole having the most potential as carriers of airborne fungi (75 and 18%, respectively) and yeasts (6 and 1%, respectively). In summary, ants act as carriers of airborne fungi and yeasts, including some pathogenic species. PMID- 19645296 TI - Host-seeking height preferences of Aedes albopictus (Diptera: Culicidae) in north central Florida suburban and sylvatic locales. AB - The response of Aedes albopictus to the BG-Sentinel, Omni-directional-Fay-Prince, and Mosquito MagnetX traps was evaluated in four suburban and four sylvatic habitats in north-central Florida to ascertain potential height preference of this species. These traps, which are primarily designed to attract diurnal mosquitoes, were set at 1 and 6 m and were evaluated during 40 trapping periods over 4 mo. We collected 45,640 mosquitoes, representing 26 species from 10 genera, the most common being Aedes albopictus, Ae. vexans, Coquilletidia perturbans, Culex nigripalpus, Aedes infirmatus, Ae. triseriatus, and Psorophora ferox. Although significantly more Ae. albopictus were captured at 1 m above ground than at 6 m, fewer were captured in sylvatic habitats than suburban habitats. Although not statistically different, the BG-Sentinel caught more Ae. albopictus compared with the other two traps regardless of locale. These results suggest that, although Ae. albopictus was captured as high as 6 m, the majority seek hosts at or below 1-m heights. This further supports prior research that, although Ae. albopictus has been shown to disseminate West Nile virus, it has not been implicated as a major vector for the virus, which is likely because of its propensity to feed on ground-dwelling hosts. The study also shows how trap type, trap heights, and environments influence sampling estimates when determining species abundance. PMID- 19645297 TI - Aedes aegypti densonucleosis virus amplifies, spreads, and reduces host populations in laboratory cage studies. AB - Aedes densonucleosis virus (family Parcoviridae, genus Brevidensovirus, AeDNV) is a mosquito pathogen that increases Aedes aegypti larval mortality and reduces adult life span. We conducted three laboratory population cage trials, each lasting 16-25 wk. We tested two broad hypotheses. First, Ae. aegypti raised in containers seeded with 10(8) AeDNV genome equivalents/ml (geq/ ml), a concentration feasible for field application, increase AeDNV to concentrations that cause significant adult and larval mortality. Second, infected female mosquitoes disperse AeDNV to uninfected larval habitats. In hypothesis 1, we addressed the rate at which infected larvae secrete virus, how AeDNV titers change in seeded containers over time, whether AeDNV decays over time, and whether AeDNV exposed populations are reduced. In hypothesis 2, we monitored AeDNV concentrations in novel containers after oviposition by infected females. Both hypotheses were supported. Larvae increased AeDNV, secreting virus at a rate of 2.14 x 10(6) geq/larva/d when exposed to 10(8) geq/ml. AeDNV titers reached an asymptote of 10(10) geq/ml by week 10 in seeded containers. AeDNV decayed by 1 log every 4 d as indicated by a reduction in larval mortality. Adult population size was reduced in treated populations. Infected females dispersed AeDNV to novel containers, with titers reaching 10(8) geq/ml. The parameters were used in a Leslie-Lewis matrix model. This model predicted that AeDNV negatively affects Ae. aegypti densities and population structure and thus vectorial capacity. PMID- 19645298 TI - Field efficacy of BG-Sentinel and industry-standard traps for Aedes albopictus (Diptera: Culicidae) and West Nile virus surveillance. AB - Standard surveillance traps in North America for adult Aedes albopictus (Skuse) (Diptera: Culicidae), an invasive mosquito with public health implications, are currently ineffective. We compared the efficacy of the BG-Sentinel trap (BGS) with and without lures (BG-lure, octenol, and CO2), the Centers for Disease Control and Prevention light trap (CDC) with and without lures, and the gravid trap (GT) for Ae. albopictus collection in two urban sites in New Jersey. The BGS with or without lures collected more Ae. albopictus compared with other trap configurations and was more specific for Ae. albopictus. In Camden County, the BGS with lures collected three times more Ae. albopictus than the CDC (with CO2 only) and five times more than the GT. In Mercer County, BGS with lures collected the most mosquitoes, with 3 times more Ae. albopictus than the CDC with all lures and 50 times more than the GT. The BGS collected more male Ae. albopictus than other traps in both counties, providing further population monitoring. The GT and BGS provided a relative measure of the enzootic activity of West Nile virus in Culex spp. and the potential epidemic activity of WNV in Ae. albopictus. The BGS provides effective chemical and visual cues for host-seeking Ae. albopictus and should be used as a part of existing surveillance programs and new initiatives targeting this mosquito. PMID- 19645299 TI - Evidence for the presence of Francisella and spotted fever group rickettsia DNA in the tick Amblyomma fimbriatum (Acari: Ixodidae), Northern Territory, Australia. AB - Ticks (n = 252) were collected from five wild-caught reptile species during routine trapping in the Djukbinj National Park and Fogg Dam Reserve, Northern Territory, Australia. Pooling of ticks (one to four ticks per pool), according to sex or host animal, resulted in 187 samples used for screening for the presence of Rickettsia species via molecular methods. Rickettsia DNA was detected via the amplification of the gltA, ompA, and ompB genes in 57 (34%) of the 187 tick samples, all of which contained only the tick Amblyomma fimbriatum Koch (Acari: Ixodidae). Further amplification and sequencing of nine of the positive samples (4.8%) for the gltA, ompA, ompB, 17-kDa, and 16S rRNA genes identified a Rickettsia species sharing closest identity to Rickettsia tamurae. In addition, amplification and sequencing of the 16S rRNA gene detected in the same tick samples the presence of a Francisella species closely related to other tick-borne Francisellae identified in ticks from the Northern Hemisphere. PMID- 19645300 TI - Genomic sequence and phylogenetic analysis of Culex flavivirus, an insect specific flavivirus, isolated from Culex pipiens (Diptera: Culicidae) in Iowa. AB - Adult mosquitoes (Diptera: Culicidae) were collected in 2007 and tested for specific viruses, including West Nile virus, as part of the ongoing arbovirus surveillance efforts in the state of Iowa. A subset of these mosquitoes (6,061 individuals in 340 pools) was further tested by reverse transcription-polymerase chain reaction (RT-PCR) using flavivirus universal primers. Of the 211 pools of Culex pipiens (L.) tested, 50 were positive. One of 51 pools of Culex tarsalis Coquillet was also positive. The flavivirus minimum infection rates (expressed as the number of positive mosquito pools per 1,000 mosquitoes tested) for Cx. pipiens and Cx. tarsalis were 10.3 and 1.2, respectively. Flavivirus RNA was not detected in Aedes triseriatus (Say) (52 pools), Culex erraticus (Dyar & Knab) (25 pools), or Culex territans Walker (one pool). Sequence analysis of all RT-PCR products revealed that the mosquitoes had been infected with Culex flavivirus (CxFV), an insect-specific virus previously isolated in Japan, Indonesia, Texas, Mexico, Guatemala and Trinidad. The complete genome of one isolate was sequenced, as were the envelope protein genes of eight other isolates. Phylogenetic analysis revealed that CxFV isolates from the United States (Iowa and Texas) are more closely related to CxFV isolates from Asia than those from Mexico, Guatemala, and Trinidad. PMID- 19645301 TI - New approaches to detection and identification of Rickettsia africae and Ehrlichia ruminantium in Amblyomma variegatum (Acari: Ixodidae) ticks from the Caribbean. AB - Imported from Africa in the 1700s and despite frequent modern eradication efforts, Amblyomma variegatum (F.) spread through the Caribbean by cattle transport, small ruminants, and migrating birds. A. variegatum is a vector for Rickettsia africae, the causative agent of African tick bite fever, and Ehrlichia ruminantium, the causative agent of heartwater. We examined 95 A. variegatum and six Rhipicephalus (Boophilus) microplus (Canestrini) collected from cattle at an abattoir in Antigua. Engorged tick extracts adsorbed on Nobotu filter paper strips and new nested polymerase chain reaction (PCR) assays for E. ruminantium and Dermatophilus congolensis were used to evaluate these ticks for the presence of these pathogenic bacteria. Amblyomma ticks (62.4%) contained R. africae DNA by PCR/restriction fragment length polymorphism analysis and DNA sequencing of the OmpA and 17-kDa antigen genes. Twenty Amblyomma and two Rh. microplus contained E. ruminantium DNA. No E. chaffeensis, Anaplasma phagocytophilum, Coxiella burnetii, or D. congolensis DNA was detected in these ticks. The continued presence of Am. variegatum in the Caribbean poses a significant risk of infection in cattle with E. ruminantium and in humans by R. africae. Eradication efforts are essential to prevent the further spread of Am. variegatum. PMID- 19645302 TI - Predicting the potential geographical distribution of Rhodnius neglectus (Hemiptera, Reduviidae) based on ecological niche modeling. AB - Rhodnius neglectus is frequently found in palm trees and bird nests in sylvatic environments. However, adult specimens infected by Trypanosoma cruzi have been invading houses in central Brazil. Analyzing and predicting the geographical distribution of this species may improve vector surveillance strategies for Chagas disease. Ecological niche modeling using the genetic algorithm for rule set production (GARP) was applied to predict the geographical distribution of R. neglectus from occurrence records and a set of 23 predictor variables (e.g., temperature, precipitation, altitude, and vegetation). Additionally, the geographical distribution of R. neglectus was compared with the geographical distribution of four species of palm trees and two species of birds from the study region. The models were able to predict, with high probability, the occurrence of R. neglectus as a regular (although nonendemic) species of the Cerrado biome in central Brazil. Caatinga, Amazonian savanna, Pantanal, and the Bolivian Chaco appear as areas with lower probabilities of potential occurrence for the species. A great overlap was observed between the distribution of R. neglectus, palm trees (Acrocomia aculeata and Syagrus oleracea), and birds (Phacellodomus ruber and Pseudoseisura cristata). By including new records for R. neglectus (from both sylvatic and domestic environments), our study showed a distribution increase toward the west and northeast areas of Brazil in the "diagonal of open/dry ecoregions of South America". These results should aid Chagas disease vector surveillance programs, given that household invasion by Rhodnius species maintains the risk of disease transmission and limits control strategies. PMID- 19645303 TI - New state records for Lutzomyia shannoni and Lutzomyia vexator. AB - Two species of phlebotomine sand flies, Lutzomyia shannoni (Dyar) and Lutzomyia vexator (Coquillett), are reported for the first time from Kentucky and Ohio. L. vexator also is reported for the first time from Tennessee. These insects were found in a northeasterly band extending from southwestern Kentucky to southwestern Ohio. Both species were consistently captured from mid-July through September in 2006 and 2007 by using CO2-baited Center for Disease Control light traps. Weekly sampling revealed that these flies are more abundant in the southern part of this band than in the northern part, but increasing densities throughout this new range indicate that the flies are currently expanding their range. Although both species have been reported further north along the Atlantic coast, and L. vexator along the Pacific coast, neither of them had been reported this far north along the Mississippi Valley. Previous reports established L. shannoni as far north as west central Tennessee and L. vexator in a similar spatial pattern in the eastern part of its range, extending as far north as northern Alabama. Whether the new records reported herein represent a northerly expansion of the geographic range of these species or are reflective of sampling changes is inconclusive. However, the former scenario could presage an increased prevalence of the diseases associated with this group of insects. PMID- 19645304 TI - Biomechanical methods applied in dentistry: a comparative overview of photoelastic examinations, strain gauge measurements, finite element analysis and three-dimensional deformation analysis. AB - The aim of this article is to illustrate and discuss current methods applied in the analysis of biomechanical components in dental applications. For illustration purposes, the strain development of a non-passively fitting implant supported fixed restoration was evaluated using the four techniques: photoelastic examination, strain gauge measurements, finite element analysis, and three dimensional deformation analysis. Photoelastic analysis only allowed for a raw estimation of the strains evoked by superstructure fixation. Quantitative results could be derived from both strain gauge measurements and three-dimensional deformation analysis which could then be used to simulate the loading situation around the supporting implants. PMID- 19645305 TI - Effect of curing cycles on the mechanical properties of heat cured acrylic resins. AB - Traditionally long curing cycles have been recommended for heat cured acrylic resin denture base materials. Recently manufacturers have produced materials for which they recommend short curing cycles. Specimens conforming to British Standards Specification were made using three different brands of heat cured acrylic resin denture base material. Each material was processed in three batches using either the manufacturer's recommended short curing cycle, an arbitrary medium curing cycle or a traditional long cycle. Specimens were subjected to a three point bending test. With one exception using the arbitrary medium curing cycle, all specimens achieved the British Standard suggesting that the manufacturers' recommended cycles should be followed. PMID- 19645306 TI - A questionnaire based study to investigate the variations in the management of tooth wear by UK and prosthodontists from other countries. AB - The aim of this research project was to compare how the management of toothwear differs between specialist prosthodontists in the United Kingdom and other countries' specialist prosthodontists. A questionnaire on the management of toothwear was sent to two groups of 100 specialist prosthodontists randomly selected in the United Kingdom and overseas. The response rate was 64% for UK and 54% for overseas respondents. Similarities existed in the management of bruxism and the prevention of erosion, but there were significant differences between the two groups regarding treatment of palatal erosion, short clinical crowns and wear on the lower incisors. UK prosthodontists more often use resin-based materials and a showed a more conservative approach to treatment of tooth wear compared to their overseas colleagues. PMID- 19645307 TI - Determining the dimensional stability, fracture toughness and flexural strength of light-cured acrylic resin custom tray material. AB - Light-cured acrylic resin custom tray material is used in commercial dental laboratories but little evidence-based scientific information on its physical properties is available. OBJECTIVES: This study investigates the dimensional stability of light-cured acrylic resin custom tray material and compares its fracture toughness and flexural strength to a chemically-cured acrylic material. METHOD: For dimensional stability, 20 light-cured specimens were fabricated and measured 3 times at regular time intervals over 48 hours. Mean shrinkage was calculated for each time interval and the mean values were compared to the standard using the Wilcoxon Rank Sum test. A p-value of <0.05 was considered significant. For fracture toughness, 2 groups of 20 light-cured and chemically cured acrylic materials with a single-edge notch were subjected to a compressive load using the 3-point bending technique. For flexural strength, 1 group (n=20) of each material was subjected to a compressive load using 3-point bending. The highest load before failure was used to calculate the fracture toughness and flexural strength. Differences in fracture toughness and flexural strength values between the 2 groups were compared using ANOVA testing. A p-value of <0.05 was considered significant. The chemically-cured group was accepted as the control group. RESULTS: Compared to the standard, shrinkage was significant for all time intervals (p<0.05). The difference in shrinkage among time intervals was not significant (p>0.05). The fracture toughness and flexural strength were significantly higher for the light-cured material. CONCLUSIONS: Trays made from light-cured acrylic resin can be used immediately following polymerization. The light-cured material is more resistant to bending and crack propagation than the chemically-cured type. PMID- 19645308 TI - The reproducibility and accuracy of internal fit of Cerec 3D CAD/CAM all ceramic crowns. AB - The objective of this study was to evaluate the reproducibility and accuracy of internal fit using Cerec 3D CAD/CAM (computer aided design/computer aided manufacturing) all-ceramic crowns and to investigate the proximal contact point areas between the crowns and neighbouring teeth, in terms of location and the presence or absence of contact. A total of 48 crowns were milled and divided into two groups of twenty-four each. One group consisted of testing a Control die and the other group consisted of testing single Replica stone die duplicates of the Control die. The Internal Marginal Gap, Axio-Occlusal Transition Gap and Occlusal Gap were measured on each crown in both groups. No significant differences were identified between the mean thickness of the Marginal Gap, the Axio-Occlusal Transition Gap and the Occlusal Gap of the Control die when compared with the Replica dies indicating uniformity and consistency of the accuracy of fit and therefore die replication. PMID- 19645309 TI - Three-dimensional finite element analysis of posterior fiber reinforced composite fixed partial denture: framework design for pontic. AB - This study investigated the effects of two types of loading conditions on mechanical behavior of the pontic of composite fixed partial denture (C-FPD) and fiber reinforced composite fixed partial denture (FRC-FPD). Two types of FE model of posterior bridge were developed. Two types of loading conditions, i.e. vertical 629 N, and lateral of 250 N, were used. In lateral load, displacement was showed a similar behaviours. However in vertical load, displacement of FRC FPD was less than C-FPD. These results clarified the magnitude, distribution of stress and displacement generated in C-FPD and FRC-FPD of pontic caused by two different loading conditions. PMID- 19645310 TI - Prosthetic status and treatment needs among patients attending the prosthodontic department in a dental institute in India. AB - This cross-sectional study was planned to evaluate the prosthetic status and treatment needs among patients who reported to the department of prosthodontics in Institute of Dental Sciences, Belgaum. A proforma was designed consisting of questions on sociodemographic factors like age, sex, socioeconomic status and a clinical examination was carried out according to the dentition status and treatment needs using a mouth mirror and a Community Periodontal Index Probe (CPI probe). All the patients who reported to the department of prosthodontics in Institute of Dental Sciences, Belgaum in a period of 2 months, with at least one missing tooth (excluding third molars) were included in the study. There was a statistically highly significant difference between gender and age according to reasons for tooth loss, while there was no statistically significant difference between reasons for tooth loss and socioeconomic status. 58.3% of males and 59.5% of females required complete removable dental prosthesis. A statistically highly significant difference was obtained between age and type of prosthesis required by the patient. There was no statistically significant difference between socioeconomic status and the type of prosthesis required by the patient. The prosthetic status of the population was low with 65.8% of the patients needing prostheses. PMID- 19645311 TI - Effects of vertical interarch space and abutment height on stress distributions: a 3D finite element analysis. AB - This three dimensional Finite Element Analysis study investigated stress distribution and intensity in implants restored with cemented or screwed crown. Two parameters varied: interarch space and abutment height. Highest stresses occurred at the cervical area in all models. Stresses increased mainly with vertical interarch space highness, and secondarily with abutments shortness. From a mechanical point of view, bone and prosthetics components supporting cemented crowns were not as solicited as with screwed crowns. PMID- 19645312 TI - EB7 now in your hands. PMID- 19645313 TI - Labour Day recognises importance of unions. PMID- 19645314 TI - Value added in nursing. PMID- 19645315 TI - Your NEW rights at work. PMID- 19645316 TI - QNU calls for renewed focus on aged care. PMID- 19645317 TI - QNU member wins appeal against "discreditable conduct" finding by nursing tribunal. PMID- 19645318 TI - Power in our ranks. PMID- 19645319 TI - Summary health statistics for U.S. adults: National Health Interview Survey, 2007. AB - OBJECTIVES: This report presents health statistics from the 2007 National Health Interview Survey (NHIS) for the civilian noninstitutionalized adult population, classified by sex, age, race and ethnicity, education, family income, poverty status, health insurance coverage, marital status, and place and region of residence. Estimates are presented for selected chronic conditions and mental health characteristics, functional limitations, health status, health behaviors, health care access and utilization, and human immunodeficiency virus testing. Percentages and percent distributions are presented in both age adjusted and unadjusted versions. SOURCE OF DATA: NHIS is a household, multistage probability sample survey conducted annually by interviewers of the U.S. Census Bureau for the Centers for Disease Control and Prevention's National Center for Health Statistics. In 2007, data were collected on 23,393 adults in the Sample Adult questionnaire. The conditional response rate was 78.3%, and the final response rate was 67.8%. The health information for adults in this report was obtained from one randomly selected adult per family. In very rare instances where the sample adult was not able to respond for him- or herself, a proxy was used. HIGHLIGHTS: In 2007, 61% of adults 18 years of age or over reported excellent or very good health. Sixty-one percent of adults never participated in any type of vigorous leisure-time physical activity, and 15% of adults did not have a usual place of health care. Eleven percent of adults had been told by a doctor or health professional that they had heart disease, and 23% had been told on two or more visits that they had hypertension. Twenty percent of all adults were current smokers and 21% were former smokers. Based on estimates of body mass index, 35% of adults were overweight and 26% were obese. PMID- 19645320 TI - Validation of a high-performance liquid chromatography method for pharmacokinetic evaluation of pentoxifylline and lisofylline in rat serum and tissues. AB - The aim of this paper was to validate an analytical method for the simultaneous determination of PTX and its active metabolite (-)-(R)-M1 in rat serum and some tissues using a high-performance liquid chromatography method with ultraviolet detection (HPLC-UV). The specificity, linearity, precision, accuracy, recovery, lower limit of detection, lower limit of quantification and stability study were successively conducted according to GLP procedures. HPLC separation of all compounds was carried out on a normal-phase ChiralPak AD column (250 mm x 4.6 mm i.d., 5 mm), using, as a mobile phase, a mixture of hexane and 2-propanol (84:16, v/v) containing 0.01% of diethylamine with a flow rate of 1.5 mL x min(-1). The calibration curves from all studied matrices were linear across the concentration range from 0.01 to 100 mg x mL(-1) with a lower limit of quantification of 0.01 microg x mL(-1) for all analytes. The application of the assay to a pilot pharmacokinetic study and tissue distribution of the compounds in rats after intraperitoneal dosing of 50 mg x kg(-1) of PTX was described. Significant (p<0.05) differences between serum and tissue levels of PTX, (-)-(R)-M1 and (+) (S)-M1 were observed. PMID- 19645321 TI - Ameliorative effects of ginger extract on paraben-induced lipid peroxidation in the liver of mice. AB - We have evaluated the ameliorative effect of ginger extract on paraben (p hydroxybenzoic acid)-induced lipid peroxidation in the liver of mice. Adult female albino mice were orally administered with 2.25 or 4.50 mg of paraben in 0.2 mL olive/animal/day (67.5 and 135 mg/kg of body weight) for 30 days. The results revealed significantly higher (p < or = 0.05) lipid peroxidation in the liver of paraben-treated mice than that of controls. As compared with the controls, the levels of non-enzymatic antioxidants: glutathione and ascorbic acid, as well as the enzymatic antioxidants: superoxide dismutase, glutathione peroxidase and catalase were significantly (p < or = 0.05) lowered in the liver of paraben-treated mice. Oral administration of aqueous extract of Zinziber officinale (3 mg/animal/day) along with paraben for 30 days (Groups 6 and 7) caused significant (p < or = 0.05) amelioration in paraben-induced lipid peroxidation and increased significantly (p < or = 0.05) the activities of enzymatic (superoxide dismutase, glutathione peroxidase, catalase) and contents of non-enzymatic (glutathione and ascorbic acid) antioxidants in the liver of mice, as compared with those given paraben alone (Groups 4, 5). Thus, oral administration of aqueous extract of Zinziber officinale along with paraben significantly (p < or = 0.05) ameliorates paraben-induced lipid peroxidation in the liver of mice. PMID- 19645322 TI - The mechanism of butyrate-induced collagen biosynthesis in cultured fibroblasts. AB - The data showing that butyrate may play an important role in cellular metabolism led us to study its effect on collagen biosynthesis in cultured fibroblasts. Since insulin-like growth factor-I (IGF-I) is the most potent stimulator of collagen biosynthesis in fibroblasts, the effect of butyrate on IGF-I receptor (IGF-IR) expression was evaluated. Confluent human dermal fibroblasts were treated with millimolar concentrations of sodium butyrate (NaB) for 48 hours. It was found that butyrate induced collagen biosynthesis and prolidase activity. It was found that the exposure of the cells to 4 mM butyrate contributed to a distinct increase in IGF-IR. It was accompanied by a parallel increase in the expression of Sos protein and MAP-kinases (ERK1, ERK2). It was found that the MEK inhibitor decreased collagen biosynthesis and expression of MAP-kinases (ERK1, ERK2), while NaB counteracted the process. The data suggests that butyrate dependent stimulation of collagen biosynthesis in cultured human skin fibroblasts undergoes through IGF-IR signaling. PMID- 19645324 TI - Synthesis and biological screening of di- and trisubstituted imidazoles. AB - Disubstituted imidazoles were prepared by reacting appropriate phenylglyoxal with different aryl aldehydes in the presence of ammonium acetate. Trisubstituted imidazoles were prepared by reacting disubstituted imidazoles with chlorobenzene in the presence of catalytic amount of triethylamine (TEA). The synthesized compounds were characterized on the basis of IR, 1H-NMR and mass spectral data and elemental analysis results. They were tested for their antiinflammatory and antimicrobial actions. Two compounds showed good antiinflammatory activity in carrageenan induced rat paw edema test with very low ulcerogenic activity. Fair number of compounds were found to have significant antimicrobial activity especially against fungal species. PMID- 19645323 TI - The in vitro effect of eptifibatide, a glycoprotein IIb/IIIa antagonist, on various responses of porcine blood platelets. AB - The current study systematically evaluates the in vitro effect of eptifibatide, a GPIIb/IIIa blocker, on various responses of porcine platelets evoked by principal physiological stimulators. Eptifibatide at concentrations up to 40 mg/mL did not affect the calcium signal produced by thrombin, partly reduced the procoagulant response evoked by collagen, and strongly inhibited (IC50 approximately 11 mg/mL) adhesion of these cells to fibrinogen coated surfaces. Eptifibatide in a concentration-dependent manner reduced ADP, collagen, and thrombin-induced platelet aggregation (IC50 = 16-27 mg/mL), dense granule secretion (IC50 = 22-31 mg/mL) and lysosome secretion (IC50 = 25-50 mg/mL). Substantial (up to 30-40%) collagen or thrombin-evoked platelet aggregation still occurred at high (52 mg/mL) eptifibatide concentrations. Direct comparison of the susceptibility of platelet aggregation and dense granule secretion to the inhibitory action of eptifibatide indicates that aggregation is appreciably more sensitive than secretion. Eptifibatide (8 mg/mL) added together with a low (70 ng/mL) concentration of bivalirudin (a direct thrombin inhibitor) effectively (approximately 90%) reduced platelet aggregation induced by thrombin (0.2 U/mL). Based on these results, eptifibatide is not expected to reduce efficiently thrombus formation initiated by rapid local production of large amounts of thrombin. One practical consequence of our in vitro studies is the suggestion that the anti-thrombotic efficacy of eptifibatide, especially in preventing acute thrombotic events, may be largely improved by its combination with direct thrombin inhibitors. PMID- 19645325 TI - Synthesis and anticonvulsant evaluation of some N-substituted phthalimides. AB - Two series of phthalimides--one possessing an N-phenoxyalkyl moiety substituted at position 3 or 4 of the phenyl ring (1-9) and the other of N-alkenyl or alkinyl phthalimides (10-18)--were synthesized, evaluated for anticonvulsant activity and had their in silico lipophilicity estimated using computer programs. The anticonvulsant activity of phthalimides containing an unsaturated substituent at the phthalimide nitrogen was superior to that of the N-phenoxyalkyl phthalimides. Alkinyl derivative 10 emerged as the most active (in MES and ScMet tests) of all the compounds tested. A correlation between anticonvulsant activity and in silico estimated lipophilicity was not observed. PMID- 19645326 TI - Synthesis of novel tetrahydronaphthalen-2-yl heterocycles for analgesic, anti inflammatory and antipyretic evaluation. AB - Condensation of 2-acetyltetralin with ethylcyanoacetate and/or malononitrile and some aldehydes in the presence of excess of ammonium acetate afforded the respective hydroxycyanopyridines or aminocyanopyridines 1a-f and 2a-f. Treatment of 2-acetyltetralin with some sulfonylhydrazides yielded the hydrazone derivatives 3a-d, respectively, which upon treatment with thioglycolic acid gave the corresponding thiazole derivatives 4a-d, respectively. Compounds 4a-d underwent cyclocondensation with different arylidene derivatives to give the corresponding pyrane derivatives 5a-d. Upon the reaction of compounds 4a-d with some secondary amines and paraformaldehyde the corresponding Mannich bases 6a,c, 7b,d and 8a,d were obtained. Compounds 1c, 1d, 1e, 2e, 3a and 3d were evaluated as analgesic, anti-iflammatory and antipyretic agents. PMID- 19645327 TI - Synthesis, spectral and biological studies on some mixed ligand Ni(II) complexes. AB - Mixed ligand Ni(II) complexes of the type [M(Q)(L) x 2H2O] have been synthesized by using 8-hydroxyquinoline (HQ) as a primary ligand and N- and/or O- donor amino acids (HL) such as L-serine, L-isoleucine, L-proline, 4-hydroxy-L-proline and L threonine as secondary ligands. The metal complexes have been characterized on the basis of elemental analysis, electrical conductance, room temperature magnetic susceptibility measurements, spectral and thermal studies. The electrical conductance studies of the complexes in methanol at 10(-3) M concentration indicate their non-electrolytic nature. Room temperature magnetic susceptibility measurements revealed paramagnetic nature of the complexes. Electronic absorption spectra of the complexes show intra-ligand, charge transfer and d-d transitions, respectively. The thermal analysis data of the complexes indicate the presence of coordinated water molecules. Tube dilution method has been used to study the antibacterial activity of the complexes against the pathogenic bacteria C. diphtheriae, S. aureus and C. albicans. The results have been compared with those of control tetracycline, which was screened simultaneously and indicated mild antibacterial activity of the complexes. PMID- 19645328 TI - Synthesis and anticancer activity of novel tetralin-6-ylpyridine and tetralin-6 ylpyrimidine derivatives. AB - A series of tetralin-6-ylpyridines and tetralin-6-ylpyrimidines was newly synthesized starting from 1-(1,2,3,4-tetrahydronaphthalen-6-yl)ethanone (1). The two groups of derivatives incorporated also different five membered nitrogen containing heterocycles. The anticancer activity of some of the prepared compounds was evaluated using two human tumor cell lines, representing liver and breast. The compounds tested were, in most of cases, selective towards liver cancer, where the most potent compound showed IC50 = 1.01 microg/mL. PMID- 19645329 TI - Evaluation of tocolytic activity of ethanol extract of the stem bark of Ficus capensis Thunb. (Moraceae). AB - Ficus capensis, a wild fig tree is used in herbal medicines to treat pregnancy related ailment and most especially as a remedy for threatened abortion. The purpose of this study was to investigate this claim with view to validating scientifically the ethno-medicinal usage. The ethanolic extract obtained by maceration technique was subjected to pharmacological testing in vitro on a piece of isolated rat uterus previously pretreated with stilbestrol, suspended in De Jalon at 37 degrees C. Concentrations used were 40 mg/mL and 80 mg/mL. The higher concentration (80 mg/mL) significantly (p < 0.05) exerted smooth muscle relaxant activity on the uterus (a reduction of oxytocin, ergometrin and acetylcholine induced contractions as well as an increase of the EC50 was observed for all the agonists tested in the presence of the extract). Evaluation of the data also indicated that the effect of the 40 mg/mL concentration was statistically insignificant, although a lowering of the dose response curve was observed for oxytocin, acetylcholine and ergometrin. Its relaxant activity at 80 mg/mL was 40 and 50% of the inhibitory effects produced by salbutamol (0.002 microg/mL) and atropine (0.02 microg/mL) on oxytocin and acetylcholine induced contractions, respectively. The results indicate the presence of active principles in the bark extract of Ficus capensis which may be responsible for some of the applications in traditional medicines as an anti-abortifacient and as a remedy against threatened abortion. PMID- 19645330 TI - Isoflavonoids from Flemingia strobilifera (L) R. Br. roots. AB - A new isoflavone (1) isolated from the roots of Flemingia strobilifera (L) R. Br. was identified as 5,7,4'-trihydroxy 8,2',5'-tri(3-methylbut-2-enyl)isoflavone along with the known phytoconstituents: 5,7,2',4'-tetrahydroxyisoflavone (2), 5,7,4'-trihydroxyisoflavone (3) and beta-sitosterol (4). Structure assignments were performed on the basis of spectroscopic data including homo- and heteronuclear 1D and 2D NMR (COSY, HMBC and DEPT) and MS studies. The compounds were tested in vitro for antimicrobial activity and antioxidant activity and compounds (1-3) proved to be moderately active. PMID- 19645331 TI - The effects of Urtica dioica L. leaf extract on aniline 4-hydroxylase in mice. AB - The effects of hydroalcoholic (80% ethanol-20% water) extract of Urtica dioica L. on microsomal aniline 4-hydroxylase (A4H) were investigated in the liver of Swiss albino mice (8- 10-weeks-old) treated with two doses (50 and 100 mg/kg body weight, given orally for 14 days ). The activities of A4H showed a significant increase in the liver at both dose levels of extract treatment. The hydroalcoholic extract of Urtica dioica induced the activities of A4H that had been increased by treatment of metal ions (Mg2+ and Ca2+) and the mixture of cofactors (NADH and NADPH). At saturated concentration of cofactor, microsomal A4H exhibited significantly even higher activities in the presence of the mixture of cofactors than NADPH and NADH. Mg2+ and Ca2+ ions acted as stimulants in vitro. The present results suggest that the hydroalcoholic extract of Urtica dioica may have modalatory effect on aniline hydroxylase at least in part and enhance the activity of A4H adding metals ions and cofactors. PMID- 19645332 TI - Influence of starch steeping period on dimensionless disintegration values of a paracetamol tablet formulation. AB - In this study, tapioca starches obtained after different steeping periods, i.e. TS 24, TS 48 and TS 72, were used as disintegrants with corn starch BP as the standard disintegrant in a paracetamol tablet formulation. Two dimensionless disintegration quantities, T(N) and T(C) were used in the determination of the influence that steeping period of starch disintegrant would have on the crushing strength friability-disintegration time ratio (CSFR/DT). These quantities were used to assess the influence of steeping period, relative density and disintegrant concentration on CSFR/DT as well as to compare disintegrant efficiency. The results suggest that the CSFR/DT is more dependent on the disintegrant concentration than on steeping period and relative density. The study further showed that TS 72 is a more reliable disintegrant because its activity would not be influenced by changes in relative density of tablets. This work concludes that the T(N) would be more useful for quantitative assessment while T(C) is more relevant for qualitative assessment. PMID- 19645333 TI - Stability of extemporaneous enalapril maleate suspensions for pediatric use prepared from commercially available tablets. AB - In this paper, the stability of enalapril maleate in oral formulations prepared from commercially available tablets was investigated. Extemporaneously compounded, 0.1 mg/mL and 1.0 mg/mL, oral suspensions of enalapril maleate in sugar-containing and sugar-free vehicles were stored in the absence of light at 4 degrees and 25 degrees C for 30 days. Enalapril maleate stability was quantified after 7, 14, 21, and 30 days using HPLC method. Viscosities and pH of prepared suspensions were measured on each study day and no appreciable changes from the initial pH and initial viscosities occurred in any of the samples both at 25 degrees and 4 degrees C. It was shown that all the formulations retain minimum 98% of the initial enalapril maleate concentration after 30 days of storage at 25 degrees and 4 degrees C and they may provide an option in situations where the marketed suspension is unavailable. PMID- 19645334 TI - Evaluation of antidepressant like property of amisulpride per se and its comparison with fluoxetine and olanzapine using forced swimming test in albino mice. AB - Amisulpride, an atypical antipsychotic was evaluated for antidepressant like activity in forced swimming test in Swiss albino mice. The effect of amisulpride was compared with that of fluoxetine, the standard antidepressant and olanzapine, another atypical antipsychotic claimed to have antidepressant like activity. Both acute and chronic studies were carried out. In both the studies, animals were divided into four groups (n = 8 each) and subjected to oral drug interventions as follows -- Group 1- control (distilled water, 1 mL/kg); Group 2- fluoxetine in a dose of 10 mg/kg 23.5, 5 and 1 h before the test; Group 3-amisulpride in a dose of 70 mg/kg 23.5, 5 and 1 h before the test; Group 4- olanzapine in a dose of 2 mg/kg 23.5, 5 and 1 h before the study. In the chronic study, the treatment was given daily for 28 days with last dose being given 2 h prior to the test. A time sampling method was used to score the behavioral activity in each group. Results of both the studies indicated that animals given amisulpride displayed significant improvement in swimming behavior (p < 0.01), while markedly reducing immobility as compared to control group (p <0.01). Fluoxetine also showed significant difference in activity as compared to amisulpride and olanzapine (p < 0.01). There was no statistically significant difference between amisulpride and olanzapine in terms of effect on immobility and swimming phases in albino mice (p > 0.05). We conclude that amisulpride per se has an antidepressant like activity comparable to that of olanzapine though the activity was significantly less than that of fluoxetine. PMID- 19645335 TI - A cyclohexanecarboxamide derivative with inhibitory effects on Schistosoma mansoni cercarial serine protease and penetration of mice skin by the parasite. AB - A cyclohexanecarboxamide derivative, N-phenyl-N-[1-(piperidine-1 carbonyl)cyclohexyl] benzamide (MNRC-5), was evaluated for its inhibitory effects on Schistosoma mansoni cercarial serine protease activity and cercarial penetration. MNRC-5 exerted an inhibitory effect on S. mansoni cercarial serine protease at serial concentrations of the specific chromogenic substrate Boc-Val Leu-Gly-Arg-PNA for such enzyme family and the inhibitory coefficient (Ki) value was deduced. Moreover, topical treatment of mice tails with the most potent inhibitory concentration of MNRC-5 formulated in jojoba oil successfully blocked cercarial penetration as demonstrated by a significant reduction (75%; p < 0.05) in the recovered S. mansoni worms from treated mice in comparison to control ones whose tails were painted with jojoba oil base containing no MNRC-5. In addition, the IgM and IgG reactivities to crude S. mansoni cercarial, worm and egg antigens were generally lower in sera from treated infected mice than untreated infected mice. In conclusion, we report on a new serine protease inhibitor capable for blocking penetration of host skin by S. mansoni cercariae as measured by lowering worm burden and decrease in the levels of both IgM and IgG towards different bilharzial antigens upon topical treatment. PMID- 19645336 TI - [Advantages and disadvantages in medicine--IQWIG Symposium 2008]. PMID- 19645337 TI - [Effectiveness, benefit and necessity: making an attempt at a scientific definition]. AB - Effectiveness does not always mean benefit but there is no benefit without effectiveness. Benefit does not always involve necessity but there is no necessity without benefit. In spite of this simple relationship these three important terms of the social security regulations are not well-defined. The array of the terms "effectiveness", "benefit" and "necessity" exhibits a decreasing accuracy of definition, a diminishing popularity in the context of scientific discourse, a rising importance for cost compensation, an increase of context dependencies and growing judgement dependence. PMID- 19645338 TI - [Are there differences in the assessment of medical and non-medical interventions?]. AB - Usually medical and/or non-medical interventions are applied to treat both acute and chronic disease. The non-medical measures include a broad range of heterogeneous principles, among them surgical, physical, technical and psychological ones. Not uncommonly, these measures derive from particular theoretical concepts. They frequently involve complex interventions, that is, programmes with varying combinations of different interacting measures. It has been postulated by advocates of the so called complementary medicine that 'different treatment concepts and hence different assessment methods' not only do, but must exist. This claim will be examined in a four-step procedure, and it will be demonstrated that this claim cannot be maintained: 1) in the face of the German Social Code, Book V Para. 35b Sect. 1, 2) with respect to the required and available knowledge base, 3) against the background of professionally approved international standards of EbM and 4) the requirements of scientific acceptance of psychotherapeutic methods and procedures. PMID- 19645339 TI - [Integrative assessment of evidence in healthcare: the GRADE system]. AB - Decisions are a double-edged sword: they always and inevitably come with positive and negative consequences. Decisions in healthcare--from a systems level to the individual patient--are not different. This approach acknowledges that for all recommendations and decisions all the important consequences need to be considered. Along these lines, one must evaluate the certainty that estimates of effects and decisions are likely to be correct. Thus, as institutions, professional societies, organisations and individuals, we should follow approaches focusing on systematic and integrative assessment of available best evidence. Longstanding and broad experience with the development of recommendations, including systematically developed guidelines, led a group of methodologists, health officers, clinicians and guideline developers to form the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group. The GRADE approach differentiates the assessment of the quality of evidence from the strength of a recommendation in healthcare. For a step-by-step evaluation of the quality of evidence, one must consider all patient relevant endpoints. It is common that many relevant and acceptable studies provide evidence for single outcomes. Therefore, integrating summaries and assessments beyond meta-analyses are required. The explicit and transparent description of the single steps in these assessments and the consideration of all currently known criteria for the assessment of the quality of evidence are among the most important advantages and innovations of the GRADE system and are described here briefly. The overall quality of evidence of all outcomes that are critical for decision-making are summarized on the basis of the lowest quality of evidence. If, for example, the evidence for six of seven critical outcomes is of low quality while moderate quality evidence is available for the other critical outcome, the overall quality of evidence is considered low to avoid a false sense of certainty with the assessment of the evidence for a given topic. A recommendation according to GRADE also requires a considerate judgement about the magnitude of the expected balance of benefits and downsides for the important outcomes, the relative values and preferences associated with these outcomes and considerations about the required resources. The international collaboration and acceptance by many organisations is an indicator of GRADE's innovative nature and advances in the assessment of evidence and development of recommendations in the context of healthcare. PMID- 19645340 TI - [Novel therapeutics risk management]. AB - The identification and assessment of risks, in particular, of new or innovative medicines, as well as risk mitigation are the most important tasks of pharmacovigilance. Pharmacovigilance activities should abide by the 'precautionary principle'. Risk management plans are a new tool for achieving this goal. The key elements of risk management plans include a drug-specific risk specification, a pharmacovigilance plan as well as appropriate risk communication procedures. PMID- 19645341 TI - [Evidence-based health policy or scientifically cloaked lobbyism--the utilization of research findings in health politics]. AB - Like no other political field health politics has become the target of well connected lobbyists. On the other hand, there is hardly any other area with so many different methodological and institutional consulting approaches. Since the emergence of concepts like evidence-based medicine and evidence-based healthcare now evidence-based policy seems to be cropping up at conferences and in publications. The author has been working at the various interfaces of research and politics. In this article he takes health politics as an example to look at the actual utilisation of scientific knowledge in politics. Following a brief introduction to the particularities of the healthcare sector the tense relationship between research and politics will be highlighted and specific examples will be given using both the genesis of the SHI Competition Act and the competencies and responsibilities of the Federal Joint Committee. PMID- 19645342 TI - [How much knowledge do health insurance companies need to make reimbursement decisions?]. AB - Health insurance companies play a very significant role in the sociopolitical context. It is their responsibility to meet the demands of modern health services delivery, while at the same time limited financial resources need to be considered. Difficult decisions have to be made which must take into account the needs of the insured party as well as the healthcare situation and oncoming possibilities. Health insurance companies rely on secure knowledge with a high level of evidence to justify their decisions in a collectively funded healthcare system. Where the elimination of knowledge gaps is not related to the expectation of profit on the part of potential providers of medical services, procedures or products the funding of high-quality studies should be considered. PMID- 19645343 TI - [The right to self-determination versus the obligation to protect one's health]. AB - "Individual responsibility" and the abidance by any "health-related obligations" are key words of the present political and legal German healthcare debate. In the process of adjusting the German welfare state by focussing the ideal allocation of common health resources patients who do not meet their "health-related obligations" are thus expected to accept cutbacks in medical care services. However, from the perspective of constitutional law there is no "health-related obligation" deriving from the German constitution - the right to self determination guaranteed in Art. 2 Sect. 2 Sent. 1 of the German constitution has not been amended to impose a corresponding duty. Hence, health-related obligations may only refer to indirect ways of exercising individual responsibility, no more and no less. The present article highlights the few possibilities which the German constitution provides for the implementation of "health-related obligations" and reminds us of the conceptual aspects which have to be considered by the legislator. PMID- 19645344 TI - Retrograde transfer of 125I-radiolabelled activin and inhibin in the periovarian vascular complex in the sow. AB - This study investigated whether activin A and an inhibin-alpha subunit fragment (INHalpha) could permeate in a periovarian vascular complex from ovarian effluent into the ovarian artery and be retrograde transferred into the ovary. Radiolabelled activin A (125I-activin A) and INHalpha (125I-INHalpha) were injected (2.7 x 10(7) dpm) into follicles or corpora lutea (CL). It was demonstrated that 125I-activin A and 125I-INHalpha were released into the ovarian effluent and permeated into the arterial blood supplying the ovary in both phases of the cycle. The concentration of 125I-activin A in ovarian arterial blood was higher in the luteal phase (LP) than in the follicular phase (FP) (P<0.0001) in contrast to 125I-INHalpha which was higher in the FP (P<0.0001). The concentration of 125I-activin A in uterine tissues generally did not differ between the phases of the estrous cycle, but the concentration of 125I-INHalpha was higher (P<0.05) in the FP than in the LP. The concentration of 125I-activin A was higher in the LP in samples of endometrium and myometrium (P<0.05), as well as mesometrium (P<0.01), and higher in the FP in samples of mesometrium (P<0.05) close to the ovary than in the samples adjoining the uterine body. In the FP, the concentration of 125I-INHalpha was higher in endometrium and mesometrium close to the ovary than in samples adjoining the uterine body (P<0.05). In conclusion, the study demonstrated that it was possible for INHalpha and activin A to be retrograde transferred to the ovary. Thus this transfer could elevate their concentration in arterial blood supplied to the ovarian follicles or CL and may influence production of these peptides in the ovary, modulating ovarian function. PMID- 19645345 TI - Serum homocysteine and oxidative stress evaluation during exercise in horse. AB - The aim of the present work was to evaluate the influence of exercise on serum homocysteine and oxidative stress in Thoroughbreds during official races. For our study, ten Thoroughbred mares, 5 years old and clinically healthy, were used. The horses were trained to take part in an official 2100 meter race. Reactive oxygen species (dROMs), antioxidant barrier (Oxy-adsorbent), thiol antioxidant barrier (SHp) and homocysteine (sHcy) were investigated. Blood samples, collected from each horse at rest, immediately after the race, and 30 and 180 min after the end of the race, were collected by jugular venipuncture using vacutainer tubes with no additive for the assessment of dROMs, Oxy-adsorbent and SHp by means of a UV spectrophotometer, while serum total Hcy values were determined by high performance liquid chromatography with fluorimetric detection and isocratic elution. Statistical analysis, one way repeated measures analysis of variance (ANOVA), followed by Bonferroni's test, showed statistical differences (P<0.05 was considered statistically significant) for all parameters studied. Moreover, a coefficient of linear correlation (r) was computed for values of dROMs and sHcy for all sampling times but a significant linear regression (r = 0.94) was found only after the race. The variations of sHcy, dROMs, Oxy-adsorbent and SHp during the experimental period considered suggest the important role of oxidative status in the athletic horse. The systematic analysis of oxidative stress and its influence on homocysteine levels contribute to the clinical evaluation and assessment of the athletic performance of the horse. PMID- 19645346 TI - Effect of platelet-activating factor on motility, plasmalemma integrity, the process of capacitation and acrosome reaction of fresh and cryopreserved boar spermatozoa. AB - The aim of the present study was to establish the effects of platelet-activating factor (PAF) on selected movement parameters, plasmalemma integrity, capacitation process and acrosome reaction in cryopreserved boar spermatozoa. A positive effect of PAF addition to cryopreserved semen on sperm motility was demonstrated, particularly with the application of phospholipid concentration of 1 x 10(-6)M-1 x 10(-5)M. A moderate induction of plasmalemma damage of cryopreserved spermatozoa was observed when PAF was used at a low concentration (1 x 10(-8)M-1 x 10(-7)M). The rate at which PAF induced the process of capacitation was inversely proportional to its concentration in the sample (the highest for the concentration of 1 x 10(-8)M, and the lowest at 1 x 10(-5)M). In turn, the strongest induction of acrosome reaction of spermatozoa was observed in samples with the addition of PAF at a concentration of 1 x 10(-7)M. The results obtained suggest that the application of PAF supplement to post-thawed boar semen can be used as a laboratory test of the ability of spermatozoa to induce the acrosome reaction. PMID- 19645347 TI - Isolation and characterization of caprine arthritis encephalitis virus in goats from Poland. AB - The caprine arthritis-encephalitis virus (CAEV) was isolated from monocyte derived macrophages (M/M), but not from PBMC of seropositive goats by co cultivation with goat synovial membrane cells. Out of eight M/M co-cultures, CAEV was evidenced by the syncytia formation and presence of proviral DNA in two and four cultures, respectively. Two virus isolates from co-cultures showing cytopathic effects were further confirmed as CAEV by western blotting, PCR, and sequence analysis. The nucleotide sequence of gag gene showed 92.0% and 90.3% homology to the prototype CAEV-Co strain. Supernatants harvested from these cultures induced syncytia when cultured with uninfected cells and the resultant titer was 10(3.5) and 10(2.5) TCID50 per ml. New CAEV isolates are suitable candidates for further analysis of their genetic and biological properties. PMID- 19645349 TI - Endoscopy and histopathology in the examination of the nasal cavity in dogs. AB - Nasal diseases of chronic nature are a common clinical complaint in canine practice. However, precise diagnosis in these cases is often difficult and require the use of various, additional diagnostic methods. The aim of this study was to estimate the occurrence of diseases of the upper respiratory tracts in dogs, and to evaluate the usefulness of endoscopy in the diagnostic process as a method of obtaining a final diagnosis. In the group of dogs in which rhinoscopy was performed, the most common final diagnoses were nonspecific chronic rhinitis, followed by neoplasms and infectious rhinitis. It can be concluded that rhinoscopy should be considered mainly as a preliminary method of inspection of the nasal cavity, helpful in obtaining the most representative tissue specimen/specimens for histopathology. In some cases, especially foreign objects and congenital abnormalities rhinoscopy can give the possibility of obtaining a final diagnosis. However, even in these situations and also when any macroscopic lesion is found during endoscopy, microscopic examination of the mucosa specimen should be performed. PMID- 19645348 TI - Isolation of Yersinia enterocolitica from aborted fetuses and sows in pig farms with reproductive disturbances. AB - The purpose of the study was to determine the occurrence of Yersinia enterocolitica in tissues of aborted fetuses, placentas, vaginal and rectal swabs of aborting sows from pig farms where reproductive disturbances were found and to determine and analyze the biotype and serotype affinity of the strains isolated. Altogether 97 fetuses aborted in various stages of pregnancy, 25 placentas and swabs from 231 sows were taken. All sows originated from farms where reproductive disorders appeared. In general, 1069 samples were collected. Two enrichment methods were used in this study; fast enrichment techniques in ITC broth, then plating onto CIN agar (ITC/CIN), and cold enrichment in phosphate buffered saline followed by plating onto CIN agar (PBS/CIN). From all samples examined, 96 Y. enterocolitica strains were isolated including 57 (59.4%) from rectal swabs of sows, followed by 6 (6.3%) from vaginal swabs and 2 (2.1%) from placentas. The bacteria were isolated from tissues of 18 out of 97 aborted fetuses. A total of 60 strains were selected for further examination--29 strains originated from aborting sows and 31 from aborted fetuses. Among strains examined 54 isolates (90%) belonged to the biotype 1A of Y. enterocolitica and to the different serotypes O:3, O:5, O:6, O:7/13, O:8 and NT (not typable). Only 6 strains belonged to serotype O:3, biotype 4 Y. enterocolitica. Our study has revealed the possibility of Y enterocolitica isolation from internal organs of aborted swine fetuses and sows from farms with reproductive disturbances. The results suggest the connection between fetal death, pregnancy course disorders and Y. enterocolitica infection. PMID- 19645350 TI - The influence of methisoprinol applied in ovo upon hatchability and health status of turkeys. AB - A study was undertaken to determine the effect of a synthetic immunomodulator, i.e. methisoprinol applied in ovo, upon the hatchability of turkey poults under conditions of a standard hatchery as well as on their health status evaluated based on analyses of selected biochemical indices in their blood serum. Experiments were conducted on 5 groups of BUT 9 turkeys at the age of 5 days (35 birds in each group) hatched from eggs to which methisoprinol (VetAgro, Lublin, Poland) was applied in ovo at a dose of 5 mg (group I), 10 mg (group II) or 20 mg per egg (group III) on the 26th day of incubation. Turkeys hatched from eggs to which a physiological solution of NaCl was applied on the same day at a dose of 0.1 ml per egg (group IV) as well as those hatched from eggs without in ovo injection (group V) served as controls. Five hundreds eggs were used in each group. Hatchability was evaluated based on the number of hatched poults in respect of the number of eggs with live embryos transferred from the setting compartment to the hatching compartment, that were subjected to in ovo administration of the preparations according to the experimental design. Blood serum of the 5-day-old turkey poults was analyzed for activities of AST, ALP, LDH L, CK, lysozyme and ceruloplasmine as well as for total protein and albumin contents. Analyses were also conducted for the immune system organ index - percentage contribution of organs of the immune system (spleen, thymus and the bursa of Fabricius) in the body weight of turkeys. The study demonstrated that methisoprinol administered to turkey embryos in ovo on day 26 of incubation at doses of 5, 10 or 20 mg per embryo did not induce any disturbances in the hatching process or affect its final result. In addition, it was shown not to exert any negative effect on the health status of the reared turkey poults. PMID- 19645351 TI - Evaluation of medetomidine-midazolam-atropine (MeMiA) anesthesia maintained with propofol infusion in New Zealand White rabbits. AB - An anesthetic combination of medetomidine-midazolam-atropine and propofol was investigated in twenty New Zealand White rabbits. Each rabbit received combined medetomidine at a dosage of 0.2 mg/kg (b.w.), midazolam (0.5 mg/kg b.w.) and atropine (0.5 mg/kg b.w.) intramuscularly for induction of anesthesia. Propofol was administered intravenously - given to effect, and after that by an infusion pump to maintain anesthesia. The influence of the anesthetic combination on the cardiopulmonary system was evaluated by monitoring respiratory and heart rates, blood pressure, and arterial blood gas tensions. The results obtained showed that propofol infusion at a rate of 0.5 mg/kg b.w./min maintained general anesthesia effectively with few side effects on the cardiopulmonary system during 30 minutes. However, slight hypotension, hypercapnia, and respiratory acidosis were associated with infusion of this anesthetic. The recovery of the rabbits from the anesthesia was smooth. Two rabbits died 20 to 24 hours after anesthesia. In conclusion, an anesthetic combination with medetomidine-midazolam-atropine and propofol at the investigated doses was shown to be a safe method to induce and maintain general anesthesia enabling short-term surgical procedures in healthy animals. PMID- 19645352 TI - Macroscopic and histopathological examination of the gastric mucosa in dogs with inflammatory bowel disease (IBD) treated with mesalazine. AB - The objective of this study was to carry out a macroscopic and histopathological examination of the gastric mucosa in dogs with inflammatory bowel disease and to evaluate the effect of mesalazine therapy on histopathological changes in the gastric mucosa. The treatment was performed on 18 dogs with histopathologically confirmed inflammation of the duodenum and the jejunum. The animals were administered mesalazine at 12.5 mg/kg b.w. bid over a six-week period. The dogs investigated were diagnosed with chronic catarrhal gastritis with intense lymphocytic/plasmocytic infiltration. In 83% of the dogs, intestinal metaplasia had been noted in bioptates before examination. The results of macroscopic and microscopic examinations revealed that the applied treatment had a positive effect on gastric mucosal morphology. Cellular infiltration of the gastric mucosa was significantly inhibited, most probably, due to the anti-inflammatory effect of mesalazine. PMID- 19645353 TI - Occurrence of strongyles (Strongylidae) in horses from small farms on the basis of necropsy. AB - Three parts of the large intestine, i.e. the dorsal and ventral colon, and caecum in 41 working horses from small farms in southern Poland were examined. Five species of large strongyles (3 migratory species from genus Strongylus and 2 non migratory from genus Triodontophorus) and as well as 17 species of cyathostomes were revealed. The prevalence of large strongyles was observed, accordingly: Strongylus vulgaris--80.5%, S. equinus--9.8%, S. edentatus--4.9%, Triodontophorus serratus--19.5% and T. brevicauda--7.3%. Among cyathostomes, 5 most prevalent species were Cyathostomum catinatum--31.7%, Coronocyclus coronatus--31.7%, Cylicostephanus calicatus--24.4%, Cylicocyclus nassatus--24.4% and C. ashworthi- 19.5%. The highest prevalence of S. vulgaris among all Strongylidae isolated specimens suggests that the infection with this parasite should be taken into account in the diagnosis of colics in working horses kept in the small farming system. PMID- 19645354 TI - Influence of Dermanyssus gallinae (poultry red mite) invasion on the plasma levels of corticosterone, catecholamines and proteins in layer hens. AB - The results of studies conducted in 2006 revealed that mass red mite (Dermanyssus gallinae) invasions cause somatic stress which may be responsible for the pathophysiological mechanism of decreased egg production, lower humoral immunity and higher mortality in layer hens. The aim of this study was to validate the above research results, to investigate whether in addition to somatic stress, red mite invasions cause psychogenic stress due to the activation of the sympatho adrenomedullar system, and to determine the level of stress resulting from red mite infestations in comparison with a short, 1.5 h period of acute immobilisation stress. The study investigated 36 HY-Line Brown layer hens divided into three groups: a non-infested control group, an experimental group infested with red mites and a non-infested experimental group subjected to acute immobilisation stress for 1.5 h. Blood samples were taken from all hens for the determination of the levels of corticosterone, adrenaline, noradrenaline, albumin, and alpha-, beta- and gamma-globulins. The results validated the previous reports on the occurrence of somatic stress and on a significant decrease in y-globulin levels (p < or = 0.01) in the group of birds infested with red mites, in comparison with the control group. Adrenaline levels in infested hens were indicative of psychogenic stress. Based on a comparison of hormonal indicators in all hen groups, the level of somatic stress resulting from red mite infestation can be classified as moderate, while the level of psychogenic stress can be interpreted as high. A significant drop in y-globulin levels in the blood of birds infested with red mites also shows that the invasion induces chronic stress which lowers the humoral immunity of hens. PMID- 19645355 TI - Slaughter value and pork quality traits in primiparous sows nursing a different number of piglets. AB - The study involved 70 sows slaughtered after the first farrowing. The carcass dressing percentage and the percentage content of primal cuts in the carcass were evaluated. Samples of m. longissimus dorsi were taken to determine the chemical composition and the physicochemical and sensory properties of the pork. Primiparous sows were divided into five groups, based on the number of piglets they had nursed, i.e. from 11 to 13 piglets, 10 piglets, 9 piglets, 8 piglets, and from 4 to 7 piglets. It was found that among sows culled after the first farrowing a higher carcass dressing percentage and a higher percentage content of neck and loin in the carcass can be expected in those nursing a lower number of piglets (up to 8). An analysis of the pork quality revealed a similar content of chemical components. Only the mineral content of the carcass was lower in the group of sows that had nursed the fewest piglets. Meat from sows that had nursed fewer piglets was characterized by a higher water-holding capacity, a brighter color and a lower aroma intensity, and it received higher scores for juiciness and palatability. PMID- 19645356 TI - Hygienic and technological value of meat of turkey raw meat originating from flocks with green muscle disease. AB - Breeding selection of slaughter poultry aimed at assuring fast body weight gains of birds has resulted in the occurrence of various forms of chronic diseases, including deep pectoral myopathy, also known as green muscle disease. The objective of the study was to determine the hygienic and technological value of meat of turkeys originating from flocks with diagnosed green muscle disease. The experimental material comprised 376 samples of the major and minor pectoral muscle from post-production turkey hens. The samples were subjected to microbiological analyses as well as determinations of pH, water binding capacity, color and chemical composition (fat, protein, water). The results obtained enabled concluding that, in terms of microbiological assessment, the meat originating from turkeys affected by the green muscle disease may be acknowledged as suitable for consumption. In turn, due to negligibly diminished technological value, resulting from deviations in pH value, water binding capacity, color and chemical composition, the authors postulate considering the advisability of stipulating separate qualitative standards for meat originating from post production turkey hens. PMID- 19645357 TI - Morphometric analysis of occipital bone in the domestic cat in comparison with selected skull size parameters and with special regard to skull morphotype. AB - The aim of this study was to elaborate criteria defining the morphotype and to perform a morphological and morphometric analysis of the squamous part of the occipital bone and of the foramen magnum in the European cat. The study material comprised 50 corpses of European cats of both sexes and of bodyweight from 1.35 to 7.7 kg, aged from 1 year to 17 years. The study material underwent detailed preparation and morphometries of the skull, squamous part of the occipital bone and the foramen magnum were performed. The skull index (IC) data obtained indicate that the European cat represents a mesaticephalic morphotype. In the morphometrical analysis of the foramen magnum the following were included: the foramen magnum index (IFM), the occipital index (IOF), and the index of the squamous part of the occipital bone (ISO). In the morphology of the squamous part of the occipital bone two categories were distinguished: the first was characterized by a form close to an isosceles triangle with its base directed to the bottom. In none of the specimens studied was a dorsal notch in the form of a "keyhole" observed, nor was there any other deformation in the foramen magnum, which takes the form of a slightly crosswise elongated regular oval. The results of this study indicate that in the European cat the foramen magnum is free from any pathology and its shape, in the individual development, is conservative. PMID- 19645358 TI - Contamination of turkey carcasses by thermotolerant species of Campylobacter during postslaughter processing. AB - Ample literature data indicate explicitly that the major source of alimentary infections induced by Campylobacter spp. is poultry meat and its products. The undertaken research was aimed at determining the level of contamination of turkey carcasses during selected stages of postslaughter processing. Analyses were conducted on 200 turkey carcasses that were examined in 10 experimental series. In each series, 5 carcasses were analyzed at the selected stages of processing, i.e.: after defeathering, evisceration, washing and chilling. Swabs were collected from each carcass from 20 cm2 skin surface at the area of neck, steak and wall of the body cavity. Out of 550 samples of swabs from the skin surface and wall of the body cavity, 385 isolates were classified as Campylobacter- positive, which constituted 70% of the samples. Out of 100 analyzed swabs collected from the carcasses after defeathering, 73 (73%) were found to contain Campylobacter species. In turn, the presence of this pathogen was confirmed in 122 (81.33%) out of 150 swabs collected from carcasses after evisceration, in 106 (70.66%) swabs collected after washing and in 84 (56%) swabs collected after chilling. PMID- 19645359 TI - Lymphadenomegaly in dogs--cytological study. AB - Lymphadenomegaly is the enlargement of the lymph node/nodes, due to various nonneoplastic or neoplastic processes, observed mainly in dogs, rarely in other animal species. The first step of a diagnostic procedure in cases of lymph nodes enlargement, apart from physical examination and morphological blood analysis, should be a cytological examination of an enlarged lymph node/nodes. The aim of the present study was to determine the character and the cause of the lymph node/nodes enlargement in dogs and to evaluate the usefulness of fine-needle cytology in a diagnosis of lymphadenomegaly. The study was performed on dogs submitted to consultation in the Small Animal Clinic of Department of Clinical Sciences, Warsaw University of Life Sciences, due to generalized or local lymphadenomegaly, and in which fine-needle biopsy was made. A signalement, general state of dog, the presence and duration of clinical signs, the character (generalized vs. localized) and intensity (mild, moderate or severe) of lympadenomegaly were recorded during physical examination. The average age of dogs examined was 8 years, 64 were males and 36 were females of various breeds; however the majority of them were greater than 25 kg in weight. The cytological diagnosis including most often lymphoma and reactive hyperplasia, more seldom metastatic neoplasm and lymphadenitis were recognized, some of the samples were considered nondiagnostic/nondefined. On the basis of the present results it can be concluded that cytological examination of good quality samples allows to obtain final diagnosis in over 90% of lymphadenomegaly. Higher incidence of canine lymphomas in males is suggested. PMID- 19645360 TI - Susceptibility of Campylobacter jejuni and Campylobacter coli isolated from animals and humans to ciprofloxacin. AB - Fifty five thermophilic Campylobacter spp. strains were isolated from the caecum of broilers, cecum and colon of pigs and from human faeces. The strains were identified as Campylobacter jejuni and Campylobacter coli. The more prevalent species in humans and broilers was Campylobacter jejuni, and in pigs Campylobacter coli. In the framework of this study, sensitivity to ciprofloxacin in isolated strains of Campylobacter jejuni and Campylobacter coli was tested by E-test. Resistant to ciprofloxacin were 50.0% of 24 thermophilic Campylobacter strains isolated from humans. In 16 tested strains isolated from broilers, 56.2% were resistant to ciprofloxacin. More resistant species was Campylobacter coli (83.3%). In 15 strains of thermophilic Campylobacter spp. isolated from pigs, the percentage of resistant strains was 26.7%, a relatively high percentage considering the quinolones have not been extensively used in swine farming compared to poultry farming. PMID- 19645361 TI - Comminuted tibial fracture treatment with type II frame external fixators with Maynard clamps and Schanz pins. AB - The management of comminuted tibial fractures is a challenging problem in small animal orthopedics. External skeletal fixators with Maynard clamps and Schanz pins are commonly used for the osteosynthesis of such fractures. The aim of this study was to perform a clinical assessment of Schanz pins with type II frame external fixators in the treatment of comminuted tibial fractures, and the possibility of pin changing when osteolysis and pins loosening appear using Maynard clamps. Schanz pins and external fixators were applied in five dogs. The healing of the treated tibia bones was noted in all cases. Radiological signs of osteolysis, pin loosening and pin tract discharge were observed in two dogs. The results obtained indicate that Schanz pins with type II frame external fixators are reliable and easily manageable. It was also ascertained that Maynard clamps are especially useful for quick pin changing. PMID- 19645362 TI - Prospects for the use of probiotic bacteria in the treatment of gastrointestinal diseases in dogs. AB - Probiotic bacteria have been known for over a century. Probiotics are defined as direct feed microbials or microbial cell preparations with a beneficial effect on the health and well-being of the host. Lactobacillus, Bifidobacterium and Enterococcus strains are used most frequently as probiotics. In recent years, their use has increased significantly in both human and veterinary medicine. These bacteria play a significant role in the prevention and treatment of many diseases. Lactobacillus and Enterococcus are capable of colonizing the alimentary tract in dogs. As a result, probiotic bacteria take an important part in the treatment of chronic inflammatory bowel disease. PMID- 19645363 TI - Campylobacter spp.--a significant microbiological hazard in food. II. Lesions and infection development, pathogenic mechanisms and complications. AB - Infections with Campylobacter spp. occur as a result of consumption of live cells with food. In developing countries those infections are immensely common, particularly during early childhood and 5 to 10 cases can appear during the initial two years of life. The symptoms appear usually after 1-7 days from infection depending on the number of ingested cells and individual sensitivity. Characteristic symptoms of infections caused by Campylobacter spp. infrequently occurring jointly in the clinical form of the disease include: diarrhea, abdominal pain and increased temperature. In the majority of cases the disease is mild and lasts from 2 to 7 days. Usually Campylobacter are excreted with feces during a period of 7-21 days, sometimes even longer. Occasionally in the increased risk group dangerous complications may occur. They include: bacteremia, meningo-myelitis, neurological disturbances and reactive arthritis. PMID- 19645364 TI - The biotransformation of chosen mycotoxins. AB - Despite the unfavourable influence of mycotoxins on human and animal health and few toxicological aspects that have been documented, about these biologically active substances has not been explored. Aiming at more knowledge and a better understanding of the effects and mechanism of mycotoxin action in mammals would provide the basics for developing strategies to restrain different mycotoxicoses. One of the processes not fully understood is biotransformation, to which mycotoxins are subjected the animal organism. Biotransformation is the conversion of mycotoxins to non-toxic metabolites and occurs mostly in the intestinal mucosal membrane and liver, although other tissues and systems also take part in this process. Mycotoxin biotransformation reactions can be considered bioinactivation or detoxication, but mycotoxin biotransformation processes could also result in products more toxic than the mycotoxin. It can be concluded from research studies that our knowledge of mycotoxin biotransformation is scarce. PMID- 19645365 TI - Faculty application of the American Psychological Association style. AB - This article explores current faculty methods with the application and evaluation of the American Psychological Association (APA) style. Specific aims were to determine concerns related to APA style, review faculty grading practices, identify institutional resources, and report potential solutions for improving application of APA style. A survey with an exploratory descriptive research design was developed and distributed online to academic chairs and deans, requesting their support in distributing the survey to their faculty. Responses (N = 704) were grouped into five categories: departmental and personal concerns; faculty grading practices; institutional resources; format, writing style, and grammar; and suggestions and potential solutions. Sixty percent reported that application and evaluation of APA style is a concern in their department. Content analysis identified four categories as proposed solutions: consistency, education, resources, and dialogue. On the basis of the feedback of the participants, the CRED program is proposed for the issues that were identified. PMID- 19645366 TI - Assuring ethical treatment of students as research participants. AB - Nurse educators are obligated to design protocols that include ethical sensitivity when conducting education research using students as participants. Because students are vulnerable to the power differential between them and faculty, the principles of autonomy, nonmaleficence, beneficence, veracity, and justice can help researchers make choices that are intended to preserve the trust and respect formed during this collegial relationship. This article presents the basic assumptions and examples of how these principles have been applied to nursing education research. PMID- 19645367 TI - Teaching transcultural nursing through literature. AB - One of the biggest challenges in nursing education is to develop culturally sensitive graduates. Although theory and lecture are appropriate to introduce cultural issues, the application of those skills is limited by the kinds of clinical experiences and patient populations students may treat. Literary works are a rich source of information for nursing. This assignment was created to sensitize the students to the influence of cultural diversity. Students were assigned to read one novel from an approved list and answer the questions posed on the Cultural Discovery worksheet. The only direction that was given regarding novel selection was that the novel had to represent a culture other than the student's own. The focus was to expose students to a different culture. Classroom discussion, based on worksheet answers, followed. The assignment's good, bad, and ugly outcomes are discussed. Suggestions for adaptation of this assignment to an online format are also provided. PMID- 19645368 TI - Partnering with community agencies to provide nursing students with cultural awareness experiences and refugee health promotion access. AB - Refugees' cultural beliefs, communication barriers, and low health literacy may lead to health disparities within the Western health care system. This article describes a teaching-learning strategy emphasizing the community partnership between a baccalaureate school of nursing, an immigrant-refugee program, and a community literacy program in a rural state. Senior community health nursing students partnered with an immigrant-refugee program and a community literacy program to provide health promotion and prevention services to recently immigrated Hmong and Russian refugees. Priority health needs were identified and culturally appropriate health promotion and prevention education modules were designed and implemented by students. Students collaborated with community agencies and businesses to increase access to health resources for these vulnerable populations. Outcomes were the provision of cultural awareness experiences for nursing students and access to health care with increased knowledge of Western health care practices and beliefs for refugees. PMID- 19645369 TI - Communicating with Latino patients. AB - This article describes the efforts of the University of California, San Francisco, School of Nursing to develop the Spanish language and cultural competency skills of advanced practice nursing students by establishing an elective course, Communicating with the Latino Patient. The need for this training is reflected in the literature, which has shown that language barriers decrease patient satisfaction and quality of care and increase the likelihood of medical error. Fifty-seven first-year master's students participated in this course. The effectiveness of the training was monitored during and after each course by self-assessment surveys of the participants' language acquisition. The data suggest that the most successful outcomes result from limiting class size, emphasizing high interactivity, and incorporating clinical experiences in the instruction, as well as focusing exclusively on intermediate-level speakers when resources are limited. Training can be time consuming and costly, yet graduates agreed that the training was imperative and valuable. PMID- 19645370 TI - Hispanic nursing students' journey to success: a metasynthesis. AB - With the Hispanic population considered the largest and fastest growing minority population, Hispanic health care needs will continue to place significant demands on our current system. Increasing the number of Hispanic nurses has become a priority. However, Latinos continue to account for only a small percentage of those enrolled in nursing programs. High attrition rates also negatively affect the number of Hispanic graduates. A more in-depth investigation of this complex issue may lead to increased awareness and understanding of the obstacles. This meta-synthesis aims to identify facilitators and barriers for Hispanic nursing students along their journey to success. PMID- 19645371 TI - Development of a multidisciplinary course in cultural competence for nursing and human service professions. AB - A multidisciplinary teaching model was used to develop a pilot course for students in the human service professions of nursing, education, and social work to gain additional knowledge and skills in providing diverse clients with culturally appropriate services during field and clinical experiences. This article focuses on the process of developing a multidisciplinary course in cultural competence that is consistent with a university mission to prepare students for leadership and service in an increasingly diverse society. Using the theoretical framework of Campinha-Bacote's process of cultural competence and the six developmental stages of intercultural competence in Bennett's developmental model of intercultural sensitivity, the course content covered the five components of cultural awareness, cultural knowledge, cultural skills, cultural encounters, and cultural desire. Students' written reflections indicated growth in acquisition of cultural knowledge, skills, and desire. Faculty collaboration across disciplines included the benefits of an enriched knowledge base and shared scholarship. PMID- 19645372 TI - Process and outcomes evaluation of retention strategies within a nursing workforce diversity project. AB - A commitment to enhancing the diversity of the nursing workforce is reflected in the recruitment and retention strategies designed by Stony Brook University with support of a grant received from the Department of Health and Human Services, Health Resources and Services Administration. Three specific student retention strategies are evaluated in terms of their influence on student inclusion and promotion of student success. A review of the cultural competence of teaching and learning strategies and the promotion of cultural self-awareness underpinned these strategies. A mentorship program designed to provide individual support for students, particularly for those engaged in distance learning, proved to be challenging to implement and underused by students. Students found other means of support in their workplace and through individual connections with the faculty. Instructional programs that enhanced individual skills in the use of computer hardware and software were particularly effective in promoting student success. PMID- 19645373 TI - Nursing education challenges: students with English as an additional language. AB - Nurse educators are challenged by students who did not learn Standard American English as a primary language. It is not only language that makes these students stand out-cultural beliefs, values and practices need to be appreciated as well. The purpose of this article is to synthesize the current qualitative literature on challenges faced in nursing education for students with English as an additional language. Ten qualitative studies regarding educational issues of nursing students with EAL were included in the synthesis. The study was conducted using the ethnographic metasynthesis model of Noblit and Hare. Two major reciprocal translations of educational issues emerged: challenges and reinforcements. Challenges included language, academics, resources, and culture. Reinforcements included resources, academics, and culture. The results may be used by nurse educators for developing interventions to help culturally diverse students succeed. Interventions are directed toward issues surrounding language and culture. PMID- 19645375 TI - Orbital Dermoid Cyst Presenting with a Discharging Sinus Tract. AB - This report describes a case of orbital dermoid cyst presenting with a discharging sinus tract. The embryologic basis for orbital dermoids in general is discussed, as well as their typical presentation and management. In the current case, patient presentation and management were somewhat different because of signs of infection and a communicating sinus tract, both highly unusual for orbital dermoids. However, after complete excision of the dermoid and sinus tract, the patient showed complete recovery. PMID- 19645377 TI - Appearance and Spontaneous Resolution of Macular Pucker After Triple Freeze-Thaw Cryotherapy for Retinoblastoma. AB - This report describes a case of macular pucker after triple freeze-thaw cryotherapy for retinoblastoma. Seven months after cryotherapy, the macular pucker resolved spontaneously. PMID- 19645376 TI - Self-limiting fourth and sixth cranial nerve palsy after Lyme disease. AB - Lyme disease, or borreliosis, is caused by a bacteria (Borrelia burgdorferi sensu lato) and is transmitted to humans by the bite of ticks of the Ixodes genus. The authors describe a 16-year-old girl who presented with extraocular muscle palsies and had serology positive for Lyme disease. The muscle palsies resolved after antibiotic treatment with no residual limitation of ocular movements. PMID- 19645378 TI - Intramuscular Bupivacaine Injection for the Treatment of Oculomotor Paresis. AB - The main goal of this study is to examine the effect of intramuscular bupivacaine in oculomotor paresis, analyzing whether it is possible to obtain a stronger muscle contraction due to the muscle hypertrophy caused by the drug. An injection of 4.5 mL of a 0.50% solution of bupivacaine was administered in the paretic muscle of three patients. Magnetic resonance imaging was performed before and 3 months after injection to compare muscle cross-sectional areas. The symptoms of two patients improved and an increase of muscle cross-sectional area was observed. However, it is necessary to be prudent when employing intramuscular bupivacaine in oculomotor paresis treatment until there are more and larger studies. PMID- 19645379 TI - Unique Ocular Findings in an Infant with Pierson (Microcoria-Congenital Nephrosis) Syndrome. AB - Pierson syndrome is a recently described autosomal recessive genetic disorder that presents in the neonatal period with bilateral microcoria and congenital nephrotic syndrome. This report describes a case of Pierson syndrome with an emphasis on the ocular findings. PMID- 19645381 TI - Carbon Monoxide Poisoning: A Patient with Bilateral Internuclear Ophthalmoplegia and Exotropia. AB - Carbon monoxide poisoning, which occurs in poorly ventilated areas, is associated with different symptoms and signs. This report describes an 8-year-old girl with severe carbon monoxide intoxication, scattered retinal nerve fiber layer and subhyaloid hemorrhages, and exotropia with bilateral internuclear ophthalmoplegia. PMID- 19645382 TI - Diffuse corneoscleral limbal neuromas with prominent corneal nerves in multiple endocrine neoplasia syndrome type IIB. AB - This report describes a 7-year-old boy with multiple endocrine neoplasia type 2B who presented to the ophthalmology department because of peripheral corneal changes. In addition to prominent corneal nerves and eyelid neuromas, the patient was found to have substantial corneoscleral limbal thickening with corneal neovascularization. PMID- 19645383 TI - Congenital dacryocystocele with significant enlargement of the nasolacrimal duct diagnosed with computed tomography dacryocystography. AB - The authors successfully assessed the lacrimal systems of two patients with dacryocystocele based on dacryocystographic observations using computed tomographic scanning. The results showed that both the lacrimal sac and the nasolacrimal duct were largely distended, and the duct terminated in a closed cyst in the nasal cavity. PMID- 19645384 TI - Congenital Anterior Staphyloma. AB - Staphyloma in the anterior segment of the eye is a rare abnormality of development. Histopathologic and electron microscopic studies suggest that the alteration occurs during embryogenesis. This report describes a 1-year-old girl with protrusion of the cornea between the eyelids in the left eye. Surgical removal of the staphyloma was performed, with reconstruction of the eyeball and total corneoscleral transplant. The clinical and histopathologic findings were typical of congenital anterior staphyloma. Although most affected patients are treated with enucleation, corneoscleral transplant provides a good cosmetic option in these cases. PMID- 19645385 TI - Presumed atypical HDR syndrome associated with Band Keratopathy and pigmentary retinopathy. AB - This report describes presumed atypical hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome associated with unexpected ocular findings. The patient had exotropia, bilateral band keratopathy, and pigmentary retinopathy, including attenuated retinal vessels and atrophy of the retinal pigment epithelium. Even though the calcific plaques were successfully removed, visual acuity in both eyes gradually decreased and electroretinography was extinguished. PMID- 19645386 TI - Progression of an Anterior Polar Cataract to a Complete White Cataract in the Setting of Overlying Focal Capsular Disruption. AB - A 10-month-old child with unilateral visually insignificant anterior polar lens opacity was examined 6 years after initial presentation and found to have complete white cataract and apparent focal disruption of the anterior capsule in the affected eye. Although anterior lens opacities are generally static and visually insignificant, progression can occur. PMID- 19645387 TI - Relapse of Acute Lymphoblastic Leukemia as a Conjunctival Mass in a 9-Year-Old Girl. AB - A 9-year-old girl with a history of acute lymphoblastic leukemia in remission presented with a right subconjunctival mass and ipsilateral preauricular lymphadenopathy despite normal findings on blood cell profile. Excisional biopsy of the lesion was performed to exclude extramedullary relapse of acute lymphoblastic leukemia. Histopathologic examination showed infiltration of leukemic cells at the conjunctival substantia propria. The patient was referred to her oncologist, and bone marrow aspiration showed medullary relapse of acute lymphoblastic leukemia for which systemic and intrathecal chemotherapy was administered. Leukemic infiltration of the conjunctiva in the presence of normal findings on blood cell profile can be a rare manifestation of relapsed acute lymphoblastic leukemia. PMID- 19645388 TI - Retinal Vasoproliferative Tumor in Association with Neurofibromatosis Type 1. AB - Retinal vasoproliferative tumor is an uncommon benign vascular tumor that most often occurs sporadically. Vision loss can occur secondary to retinal fibrosis, subretinal exudation, and neovascular glaucoma. This report describes a functionally monocular patient with neurofibromatosis type 1 who had a vasoproliferative tumor with neovascularization of the iris that was successfully treated with intravitreal bevacizumab and cryotherapy. PMID- 19645389 TI - Cholesterolosis Bulbi of the Anterior Chamber in Coats Disease. AB - Coats disease is characterized by the presence of cholesterol crystals and lipid laden macrophages in the subretinal space. These cholesterol crystals may rarely be found in the anterior chamber in Coats disease, a phenomenon known as cholesterolosis bulbi. This report describes a patient with advanced Coats disease who presented with anterior chamber cholesterolosis. PMID- 19645390 TI - Molluscum Contagiosum-Induced Periocular Toxic Dermatitis. AB - This report describes an unusual case of a 9-year-old boy with a 6-month history of right lower eyelid lesion and excoriation of the adjoining skin that had not responded to topical treatment. The umbilicated lesion was electively excised and the base of the lesion was cauterized under general anesthesia, which resulted in complete resolution of the periocular dermatitis without additional treatment. It is important to consider molluscum contagiosum in the differential diagnosis in patients with periocular dermatitis, especially in the presence of an umbilicated vesicle, although it is classically taught that these lesions present with toxic conjunctivitis. PMID- 19645391 TI - Bilateral Optic Nerve Aplasia in a Child. AB - An 3-month-old female infant was admitted to the authors' clinic because of abnormal gaze position. On examination, the eyes were in the down gaze position. The left eye had a partial iris and lens coloboma. On funduscopic examination, the optic nerve and retinal vessels could not be detected. Optic nerve and optic chiasm were not observed on magnetic resonance imaging. PMID- 19645392 TI - Multiple Evanescent White Dot Syndrome After Vaccination for Human Papilloma Virus and Meningococcus. AB - Multiple evanescent white dot syndrome is a rare chorioretinopathy causing transitory vision loss, usually in females and generally in one eye. In 2007, widespread vaccination of older children against human papilloma virus and meningococcus was recommended by the Centers for Disease Control and Prevention. A 17-year-old girl presented with multiple evanescent white dot syndrome 1 month after receiving these two vaccinations. PMID- 19645393 TI - Secondary implantation of intraocular lenses in children. PMID- 19645394 TI - Chronic newborn primary congenital glaucoma with secondary lens subluxation. PMID- 19645395 TI - Pediatric eye trauma in the summer. PMID- 19645396 TI - Outcome and prognosis of pediatric patients with delayed diagnosis of open-globe injuries. AB - PURPOSE: Open-globe injuries in children can present in a delayed fashion, potentially increasing the risk of endophthalmitis and delaying surgical intervention. This article presents the outcome of pediatric patients with delayed diagnosis of open-globe injuries for 24 hours or more. METHODS: The study was a retrospective observational case series of patients who presented with open globe injuries diagnosed 24 hours or more after the injury between July 2002 and March 2007. RESULTS: Thirteen patients were included in the study. The average age at presentation was 5.8 +/- 2.8 years; average follow-up was 11.5 +/- 14.5 months. Mean time of presentation after injury was 9.2 +/- 16.0 days. The most common chief complaints were chronic red eye (7 of 13 patients), eye pain (5 of 13 patients), and decreased vision (4 of 13 patients). All patients had self sealing corneal wounds; 8 of 13 patients had a visually significant traumatic cataract. One patient had sympathetic ophthalmia. Initial visual acuity was 20/200 or worse in 10 patients, and final visual acuity was 20/40 or better in 6 patients. No patient had endophthalmitis. CONCLUSION: Open-globe injuries, especially self-sealing corneal wounds, can present in a delayed fashion in children or may be missed if obvious findings, such as subconjunctival hemorrhage or prolapsed iris tissue, are not present. Pediatricians should be educated that they should maintain a high level of suspicion in the setting of chronic unilateral red eye, decreased visual acuity, or abnormal red reflex. PMID- 19645398 TI - Nationwide trends in hospitalization and surgical treatment of congenital and infantile cataract among italian children 4 years and younger. AB - PURPOSE: To determine the number of patients 4 years and younger who were hospitalized and operated on for congenital or infantile cataracts in Italy from 1999 through 2004. METHODS: A retrospective review was performed of the Ministry of Health database on hospital admissions in Italy from 1999 through 2004. RESULTS: In patients younger than 1 year, the mean number of admissions for congenital or infantile cataract was 3.78 and the mean number of admissions involving cataract surgery per 10,000 live births was 2.61. During the study period, an intraocular lens was implanted during 8.6% of the cataract extraction procedures performed in patients younger than 1 year and during 25.4% of those performed in older children (1 to 4 years old). Primary intraocular lens implantations were performed in 43 infants younger than 1 year (6-year mean: 5.9%) and in 77 children 1 to 4 years old (6-year mean: 11.6%). CONCLUSION: The percentage of pediatric hospital admissions with discharge diagnoses of congenital or infantile cataract remained fairly stable from 1999 through 2004; rates were higher in children 1 to 4 years old than in children younger than 1 year. The percentage of hospitalizations for cataract that involved surgical extraction was higher in children 1 to 4 years old. It decreased over time in both age groups. Ophthalmologists in Italy use intraocular lens implantation in children who are at least 1 year old, although this procedure is not common. PMID- 19645399 TI - Balloon catheter dilation for complex congenital nasolacrimal duct obstruction in older children. AB - PURPOSE: To evaluate the effectiveness of lacrimal balloon catheter dilation in the treatment of complex congenital nasolacrimal duct obstruction in older children. METHODS: In a retrospective study, the case records of 65 eyes of 59 children 2 to 6 years (mean: 37 months) who underwent probing for congenital nasolacrimal duct obstruction were evaluated. Complex obstruction was noted in 21 (32.3%) of the 65 children older than 2 years who underwent probing. Secondary balloon dacryoplasty was performed in 8 (38.09%) of these 21 lacrimal systems. Patient age ranged from 3 to 6 years (mean: 47 months). Balloon catheter dilation was performed according to a standard protocol. Clinical patency of the nasolacrimal system was the main outcome measure and was defined as complete resolution of signs and symptoms (crusting, discharge, and watering) on follow up. The procedures were performed under general anesthesia. All dilations were performed by the same lacrimal surgeon. RESULTS: Secondary balloon dacryoplasty was successful in seven of the eight lacrimal systems (87.5%). Complex obstruction at the distal end of the nasolacrimal duct was noted in all children. All children were older than 3 years (mean: 37 months), and all underwent secondary procedures because previous probing was unsuccessful. CONCLUSION: Balloon catheter dilation is an effective procedure for complex nasolacrimal duct obstruction in older children. It can be an alternative to silicone intubation and dacryocystorhinostomy in children after unsuccessful probing. PMID- 19645400 TI - Topical anesthesia in strabismus surgery: a review of 101 cases. AB - PURPOSE: To analyze the results over a 10-year period with a different type of strabismus surgery performed with topical anesthesia, to describe the differences in technique compared with surgery performed with general anesthesia, and to detail current indications and technical changes made according to the experience accrued during these years. METHODS: A total of 101 patients undergoing strabismus surgery with topical anesthesia in a single hospital were analyzed. These patients were randomly selected from a total of 567 patients who had undergone extra-ocular muscle surgery in the past 10 years. RESULTS: A good result was obtained (squint angle < 10 prism diopters and absence of diplopia) in 95% of patients immediately after surgery and in 85% at final follow-up (mean follow-up: 3.1 years). The mean operating time for each muscle was 29 minutes. Surgery was well tolerated in every patient. Conversion to general anesthesia was not necessary in any case. Atropine was used in three patients (3%) because of induction of the vagal reflex. CONCLUSION: Topical anesthesia in strabismus surgery is a useful technique in the treatment of extraocular muscle pathology, with few limitations. Appropriate monitoring by an anesthetist is vital to ensure adequate control of pain and possible side effects and to enable conversion to general anesthesia. The oculocardiac reflex is infrequent. For experienced strabismus surgeons, the total surgical time is comparable with topical and general anesthesia. PMID- 19645401 TI - Lateral orbitotomy in the management of challenging exotropia. AB - The authors present an unorthodox surgical approach to reach the posterior segment of the lateral rectus muscle through a lateral orbitotomy and to manage difficult cases of recurrent exotropia. A review of the records of two patients with recurrent exotropia was done. After an anterior approach had been demonstrated to be inadequate due to shortening or fibrosis of the anterior part of this muscle following repeated surgeries, both patients underwent a lateral orbitotomy to reach the posterior segment of the lateral rectus muscle. Both patients achieved satisfactory ocular alignment following surgery with stable results, showing that this approach is a safe and effective surgical procedure. PMID- 19645402 TI - Retinopathy of prematurity in twin-twin transfusion syndrome. AB - The authors present the first reported case of retinopathy of prematurity in twin twin transfusion syndrome. A 31-year-old woman gave birth to twins at 31 weeks' gestation. The pregnancy had been complicated by twin-twin transfusion syndrome and had been managed with two amnioreductions and laser ablation of the interplacental blood vessels. The donor twin, born at 1,310 g, had threshold retinopathy of prematurity and underwent argon laser retinal photocoagulation treatment. The recipient twin (1,775 g) did not show any evidence of retinopathy of prematurity. PMID- 19645404 TI - Cavernous sinus syndrome as the initial presentation of childhood non-hodgkin lymphoma. AB - A 10-year-old boy with unilateral ophthalmoplegia, ptosis, and proptosis underwent diagnostic examination. Symptoms of headache, nausea, dyspnea, fatigue, weakness, and loss of appetite began 14 days after the onset of ocular manifestations and 7 days before he was examined. Complete blood count showed an increased white blood cell count with 64% blast cells, anemia, and thrombocytopenia. The patient was transferred to a pediatric hematology unit, where he underwent bone marrow aspiration biopsy. Bilateral ocular inflammatory findings and left-sided mild proptosis became evident. He was diagnosed as having B-cell non-Hodgkin lymphoma infiltrating the bilateral cavernous and sphenoid sinuses. PMID- 19645403 TI - Benign hamartoma masquerading as a deep orbital hemangioma. AB - A 3-month-old infant with a digital hemangioma had relative proptosis of the left eye. Ultrasound, computed tomography, and magnetic resonance imaging showed a retro-orbital mass with features consistent with a capillary hemangioma. Despite the radiographic appearance, however, biopsy findings showed histologically benign tissues of a hamartomatous nature, inconsistent with a capillary hemangioma. PMID- 19645405 TI - Acute v pattern esotropia without abduction deficit, secondary to a posterior fossa pilocytic astrocytoma. AB - A case of acute esotropia with bilateral inferior oblique muscle overaction in a 4-year-old boy with a posterior fossa pilocytic astrocytoma is reported. After tumor excision, the esotropia and oblique dysfunction resolved. Acute esotropia with bilateral inferior oblique muscle overaction without abducens palsy is an unusual sign of brain stem mass. PMID- 19645406 TI - Optic nerve head drusen and idiopathic intracranial hypertension in a 14-year-old girl. AB - A 14-year-old girl had a 3-month history of headache and blurred vision. Funduscopy showed bilateral optic disc edema. Findings on brain imaging were normal, and a diagnosis of idiopathic intracranial hypertension was confirmed after lumbar puncture showed an elevated opening pressure of 32 cm H(2)O. Optic nerve head drusen were noted on computed tomography scan and confirmed with B scan ultrasound. After 2 years, resolution of symptoms coincided with variable compliance to treatment with acetazolamide and concomitant papilledema. In general, optic disc edema poses a clinical conundrum due to the more common occurrence of optic nerve head drusen, potentially resulting in delayed diagnosis and treatment of idiopathic intracranial hypertension. PMID- 19645407 TI - Corneal anomalies in newborn primary congenital glaucoma. AB - This report describes the corneal pathology in an infant with newborn primary congenital glaucoma and discusses whether these findings could be due to a developmental anomaly. The corneal specimen of a 4-month-old infant with newborn primary congenital glaucoma and cloudy corneas who had undergone penetrating keratoplasty was evaluated by light and electron microscopy. Light microscopy showed a thinned epithelium, areas of thickened Bowman's layer (approximately 27 mum thick) interspersed with nuclei, and a thickened and disorganized stroma. Descemet's membrane was intact, and the endothelium was mildly attenuated. The corneal changes seen in this patient may be specific to primary congenital glaucoma and may contribute to the corneal clouding seen so frequently in these patients. PMID- 19645408 TI - Presumed early-onset sarcoidosis: a case of devastating ocular inflammation in an infant. AB - Involvement of the orbit and posterior segment of the eye in early-onset sarcoidosis may necessitate prompt and aggressive immunosuppressive treatment to prevent a poor visual outcome. PMID- 19645409 TI - Congenital cytomegalovirus infection: progressive postnatal chorioretinitis. AB - Immunocompetent children with congenital cytomegalovirus rarely have postnatal progression of chorioretinitis. Optimal treatment of this disease is not well established. The authors describe an infant who had congenital cytomegalovirus infection with postnatal progression of chorioretinitis and required an extended course of ganciclovir therapy. PMID- 19645410 TI - Frequent ROP Associated with Hypoxic Protocol. PMID- 19645411 TI - Bilateral papillomacular retinal folds. PMID- 19645414 TI - In silico study of full-length amyloid beta 1-42 tri- and penta-oligomers in solution. AB - Amyloid oligomers are considered to play causal roles in the pathogenesis of amyloid-related degenerative diseases including Alzheimer's disease. Using MD simulation techniques, we explored the contributions of the different structural elements of trimeric and pentameric full-length Abeta1-42 aggregates in solution to their stability and conformational dynamics. We found that our models are stable at a temperature of 310 K, and converge toward an interdigitated side chain packing for intermolecular contacts within the two beta-sheet regions of the aggregates: beta1 (residues 18-26) and beta2 (residues 31-42). MD simulations reveal that the beta-strand twist is a characteristic element of Abeta aggregates, permitting a compact, interdigitated packing of side chains from neighboring beta-sheets. The beta2 portion formed a tightly organized beta-helix, whereas the beta1 portion did not show such a firm structural organization, although it maintained its beta-sheet conformation. Our simulations indicate that the hydrophobic core comprising the beta2 portion of the aggregate is a crucial stabilizing element in the Abeta aggregation process. On the basis of these structure-stability findings, the beta2 portion emerges as an optimal target for further antiamyloid drug design. PMID- 19645417 TI - Old drugs, new tricks: the effect of molecule-ion interactions on the precipitation-dissolution equilibrium of lithium carbonate in aqueous solution and on the chiral recognition of cyclodextrins to D-,L-tryptophan. AB - In the present work, the influence of molecule-ion interactions on the precipitation-dissolution equilibrium of a typical inorganic drug, lithium carbonate (Li2CO3), in water and on the chiral recognition behaviors and binding abilities of alpha-, beta-, gamma-, and heptakis(2,6-di-O-methyl)-beta cyclodextrin (CD) to D- and L-tryptophan (Trp) was investigated. Our results revealed that the solubility of Li2CO3 was increased to a large extent and the phase solubility diagram of Li2CO3 belonged to the AN type. This finding provided a new insight into the link between molecule-ion interactions and precipitation dissolution equilibriums of poorly dissolving inorganic salts. Furthermore, despite having a negative effect on the isomer recognition behaviors, the molecule-ion interaction between CDs and Li2CO3 effectively increased the binding abilities of these CDs to both D- and L-Trp synchronously. The observation gave an important implication that buffer solutions consisting of inorganic salts are used with caution in molecular recognition fields between host and guest or between acceptor and donor. Further analyses confirmed the interaction among Li2CO3, beta-CD, and L-Trp using an electrospray ionization mass spectrum. PMID- 19645416 TI - Disulfide bond formation in yeast NAD+-specific isocitrate dehydrogenase. AB - The tricarboxylic acid cycle NAD+-specific isocitrate dehydrogenase (IDH) of Saccharomyces cerevisiae is an octameric enzyme composed of four heterodimers of regulatory IDH1 and catalytic IDH2 subunits. Recent structural analyses revealed the close proximity of Cys-150 residues from IDH2 in adjacent heterodimers, and features of the structure for the ligand-free enzyme suggested that formation of a disulfide bond between these residues might stabilize an inactive form of the enzyme. We constructed two mutant forms of IDH, one containing a C150S substitution in IDH2 and the other containing C56S/C242S substitutions in IDH2 leaving Cys-150 as the sole cysteine residue. Treatment of the affinity-purified enzymes with diamide resulted in the formation of disulfide bonds and in decreased activities for the wild-type and C56S/C242S enzymes. Both effects were reversible by the addition of dithiothreitol. Diamide had no effect on the C150S mutant enzyme, suggesting that Cys-150 is essential for the formation of a disulfide bond that inhibits IDH activity. Diamide-induced formation of the Cys 150 disulfide bond was also observed in vivo for yeast transformants expressing the wild-type or C56S/C242S enzymes but not for a transformant expressing the C150S enzyme. Finally, natural formation of the Cys-150 disulfide bond with a concomitant decrease in cellular IDH activity was observed during the stationary phase for the parental strain and for transformants expressing wild-type or C56S/C242S enzymes but not for a transformant expressing the C150S enzyme. A reduction in viability for the latter strain suggests that a decrease in IDH activity is important for metabolic changes in stationary phase cells. PMID- 19645418 TI - New variable selection method using interval segmentation purity with application to blockwise kernel transform support vector machine classification of high dimensional microarray data. AB - One problem with discriminant analysis of microarray data is representation of each sample by a large number of genes that are possibly irrelevant, insignificant, or redundant. Methods of variable selection are, therefore, of great significance in microarray data analysis. A new method for key gene selection has been proposed on the basis of interval segmentation purity that is defined as the purity of samples belonging to a certain class in intervals segmented by a mode search algorithm. This method identifies key variables most discriminative for each class, which offers possibility of unraveling the biological implication of selected genes. A salient advantage of the new strategy over existing methods is the capability of selecting genes that, though possibly exhibit a multimodal distribution, are the most discriminative for the classes of interest, considering that the expression levels of some genes may reflect systematic difference in within-class samples derived from different pathogenic mechanisms. On the basis of the key genes selected for individual classes, a support vector machine with block-wise kernel transform is developed for the classification of different classes. The combination of the proposed gene mining approach with support vector machine is demonstrated in cancer classification using two public data sets. The results reveal that significant genes have been identified for each class, and the classification model shows satisfactory performance in training and prediction for both data sets. PMID- 19645415 TI - Selection of peptides that target the aminoacyl-tRNA site of bacterial 16S ribosomal RNA. AB - For almost five decades, antibiotics have been used successfully to control infectious diseases caused by bacterial pathogens. More recently, however, two thirds of bacterial pathogens exhibit resistance and are continually evolving new resistance mechanisms against almost every clinically used antibiotic. Novel efforts are required for the development of new drugs or drug leads to combat these infectious diseases. A number of antibiotics target the bacterial aminoacyl tRNA site (A site) of 16S rRNA (rRNA). Mutations in the A-site region are known to cause antibiotic resistance. In this study, a bacterial (Escherichia coli) A site rRNA model was chosen as a target to screen for peptide binders. Two heptapeptides, HPVHHYQ and LPLTPLP, were selected through M13 phage display. Both peptides display selective binding to the A-site 16S rRNA with on-bead fluorescence assays. Dissociation constants (Kd's) of the amidated peptide HPVHHYQ-NH2 to various A-site RNA constructs were determined by using enzymatic footprinting, electrospray ionization mass spectrometry (ESI-MS), and isothermal titration calorimetry (ITC) under a variety of buffer and solution conditions. HPVHHYQ-NH2 exhibits moderate affinity for the A-site RNA, with an average Kd value of 16 microM. In addition, enzymatic footprinting assays and competition ESI-MS with a known A-site binder (paromomycin) revealed that peptide binding occurs near the asymmetric bulge at positions U1495 and G1494 and leads to increased exposure of residues A1492 and A1493. PMID- 19645420 TI - Stability of a ferryl-peptide conjugate is controlled by a remote substituent. AB - The formation of a synthetic ferryl-peptide conjugate and mechanistic studies that elucidate its mode of decomposition are presented. A ferryl species is generated from a ligand-dipeptide conjugate 4. The ferryl species [Fe(IV)(4)(O)](2+), noted as compound 5, was characterized by UV-vis spectroscopy and by high-resolution electrospray mass spectrometry. The ferryl-peptide conjugate 5 is stable for over 1 h at room temperature. Ester derivatives of 5 decay at different rates, consistent with the remote ester group controlling the stability of the ferryl. The kinetic isotope effect value (4.5) and rho = -1.3 observed with ester derivatives suggest that the mechanism for decomposition of 5 follows a hydrogen-atom-transfer pathway. The formation and decay of 5 was fit to a two-step process, with the decay being unimolecular with respect to the ferryl 5. PMID- 19645419 TI - The partial substrate dethiaacetyl-coenzyme A mimics all critical carbon acid reactions in the condensation half-reaction catalyzed by Thermoplasma acidophilum citrate synthase. AB - Citrate synthase (CS) performs two half-reactions: the mechanistically intriguing condensation of acetyl-CoA with oxaloacetate (OAA) to form citryl-CoA and the subsequent, slower hydrolysis of citryl-CoA that generally dominates steady-state kinetics. The condensation reaction requires the abstraction of a proton from the methyl carbon of acetyl-CoA to generate a reactive enolate intermediate. The carbanion of that intermediate then attacks the OAA carbonyl to furnish citryl CoA, the initial product. Using stopped-flow and steady-state fluorescence methods, kinetic substrate isotope effects, and mutagenesis of active site residues, we show that all of the processes that occur in the condensation half reaction performed by Thermoplasma acidophilum citrate synthase (TpCS) with the natural thioester substrate, acetyl-CoA, also occur with the ketone inhibitor dethiaacetyl-CoA. Free energy profiles demonstrate that the nonhydrolyzable product of the condensation reaction, dethiacitryl-CoA, forms a particularly stable complex with TpCS but not pig heart CS. PMID- 19645421 TI - Effect of stacking order on the electric-field induced carrier modulation in graphene bilayers. AB - When planar graphene sheets are stacked on top of each other, the electronic structure of the system varies with the position of the subsequent sublattice atoms. Here, we employ scanning photocurrent microscopy to study the disparity in the behavior of charge carriers for two different stacking configurations. It has been found that deviation from the regular Bernal stacking decouples the sheets from each other, which imparts effective electrostatic screening of the farther layer from the underlying backgate. Electrochemical top-gating is demonstrated as a means to selectively tune the charge carrier density in the decoupled upper layer. PMID- 19645422 TI - Tuning nanoelectromechanical resonators with mass migration. AB - We demonstrate tuning of nanoelectromechanical resonators via mass migration. Indium nanoparticles can be reversibly migrated to different locations along cantilevered multiwalled carbon nanotube resonators using electrical currents as the control parameter. Nonvolatile mass redistributions result in stable resonant frequency shifts as large as 20%. The tuning method is robust and can be utilized for nanoelectromechanical resonators operating at frequencies from audio to microwave. PMID- 19645423 TI - Electrochemical charging of individual single-walled carbon nanotubes. AB - The influence of the electrode potential on the electronic structure of individual single-walled carbon nanotubes is studied using Raman spectroscopy. By analyzing the radial breathing mode intensity versus electrode potential profiles in the Raman spectra at many different laser excitation energies, we show that the charging of individual carbon nanotubes causes a broadening of the resonant Raman profiles (resonance window). This effect is observed for both a semiconducting and a metallic tube. The broadening of the resonance Raman profiles already begins at potentials where the first electronic states of a particular tube are filled or depleted. The important consequence of this effect is a striking difference between the Raman intensity versus potential profiles of metallic and semiconducting tubes. While for a metallic tube the intensity of the Raman signal is attenuated at potentials which deviate slightly from 0 V, for a semiconducting tube, the Raman intensity is significantly attenuated only after the electrode potential reaches the first van Hove singularity. Furthermore, for the metallic tube, a strong asymmetry is found in the bleaching of the Raman signal with respect to positive and negative potentials, which results from the different energy bandwidth for the pi* band and the pi band. PMID- 19645424 TI - Magnesium-based 3D metal-organic framework exhibiting hydrogen-sorption hysteresis. AB - A new magnesium metal-organic framework (MOF) based on an asymmetrical ligand, biphenyl-3,4',5-tricarboxylate (H(3)BPT), has been synthesized and structurally characterized. MOF Mg(3)(BPT)(2)(H(2)O)(4) (1) consists of 1D hexagonal nanotube like channels and exhibits pronounced hydrogen-sorption hysteresis at medium pressure. PMID- 19645425 TI - Agarose-assisted dip-pen nanolithography of oligonucleotides and proteins. AB - This paper describes a method for the direct transfer of biomolecules encapsulated within a viscous fluid matrix by dip-pen nanolithography (DPN). The method relies on the use of agarose as a "universal" carrier that is compatible with many types of biomolecules including proteins and oligonucleotides. Agarose assisted DPN allows one to generate nanoarrays of such materials on activated glass substrates with the same deposition rates for different biomolecules, which will greatly expand future capabilities for parallel, multiplexed biomolecule deposition. The fluidity of the matrix may be systematically varied to control the deposition process, resulting in an additional parameter affecting deposition rates besides tip-substrate contact-time and humidity. Agarose-assisted DPN results in extremely fast biomolecule patterning with typical contact times less than 1 s. Feature sizes as small as 50 nm are demonstrated. The biorecognition properties of both protein and oligonucleotide structures are characterized by studying their reactivity with fluorophore-labeled antibody and complementary oligonucleotide sequences, respectively. PMID- 19645426 TI - An asymmetric hetero-claisen approach to 3-alkyl-3-aryloxindoles. AB - The reaction of a chiral N-phenylnitrone derived from Garner's aldehyde with alkylarylketenes generates 3-alkyl-3-aryloxindoles directly in excellent yields and with good to excellent levels of enantioselectivity (up to 90% ee). PMID- 19645427 TI - Impact of solvent polarity on N-heterocyclic carbene-catalyzed beta-protonations of homoenolate equivalents. AB - N-Heterocyclic carbenes have been demonstrated to react through divergent pathways under the same conditions. Experimental and computational evidence demonstrates that the ability to favor generation of homoenolate equivalents from alpha,beta-unsaturated aldehydes versus the oxidation of aldehydes to esters is highly dependent upon the choice of solvent. The solvation environment plays an important role due to the mechanistic differences in these processes, with polar protic solvent favoring the oxidation process due to solvation of intermediates with greater charge separation. PMID- 19645429 TI - Testing assumptions and hypotheses for rescoring success in protein-ligand docking. AB - In protein-ligand docking, the scoring function is responsible for identifying the correct pose of a particular ligand as well as separating ligands from nonligands. Recently there has been considerable interest in schemes that combine results from several scoring functions in an effort to achieve improved performance in virtual screens. One such scheme is consensus scoring, which involves combining the results from several rescoring experiments. Although there have been a number of studies that have investigated factors affecting success in consensus scoring, these studies have not addressed the question of why a rescoring strategy works in the first place. Here we propose and test two alternative hypotheses for why rescoring has the potential to improve results, using GOLD 4.0. The "consensus" hypothesis is that rescoring is a way of combining results from two scoring functions such that only true positives are likely to score highly. The "complementary" hypothesis is that the two scoring functions used in rescoring have complementary strengths; one is better at ranking actives with respect to inactives while the other is better at ranking poses of actives. We find that in general it is this hypothesis that explains success in a rescoring experiment. We also test an assumption of any rescoring method, which is that the scores obtained are representative of the fitness of the docked pose. We find that although rescored poses tended to have slightly higher clash values than their docked equivalents, in general the scores were representative. PMID- 19645428 TI - Flexible alignment of small molecules using the penalty method. AB - An efficient flexible alignment method using the penalty method, called FAP, is described. FAP is a pairwise alignment algorithm that matches a flexible sample to a rigid template. It is a pure atom-based 3D method that utilizes the modified SEAL similarity index combined with an energy penalty term. The penalty term, defined as the third power of the ratio of the local strain energy to its target value, enables effective control of energy increase during alignment. The alignment procedure consists of the seed conformer generation, rigid-body alignment, and flexible optimization steps. Both conformation and alignment spaces are efficiently explored by the sparse, random sampling schemes. FAP has been tested with benchmark sets of seven different classes of ligands taken from the literature. In terms of the ability to produce the bioactive overlays, FAP is comparable to, or in some cases better than, other alignment methods. FAP is accurate, objective, fully automated, and fast enough to be used as a tool for virtual screening. PMID- 19645430 TI - Determination of binding strengths of a host-guest complex using resonance Raman scattering. AB - The detection of analyte-binding events by receptors is drawing together the fields of Raman spectroscopy and supramolecular chemistry. This study is intended to facilitate this cohering by examining a model in the solution phase. The resonance Raman scattering (RRS) spectra of the complexation between tetrathiafulvalene (TTF) and cyclobis(paraquat-p-phenylene) (CBPQT(4+)) has been used as the model system to characterize the binding event of a host-guest system. RRS spectra are generated by excitation (lambda(exc) = 785 nm) within the lowest-energy charge-transfer (CT) transition (lambda(max) = 865 nm) of the TTF subsetCBPQT(4+) complex. The paired binding curves from the RRS and UV-vis-NIR titration data agrees with prior work, and a DeltaG of -5.7 +/- 0.6 kcal mol(-1) (MeCN, 298 K) was obtained for the complexation of TTF with CBPQT(4+). Computations on the complex and its components reproduce the energy shifts and resonance enhancements of the Raman band intensities, providing a basis to identify the structural and vibrational changes occurring upon complexation. The changes in bond lengths coincide with partial depopulation of a TTF-based HOMO and population of a CBPQT(4+)-based LUMO through CT mixing in the ground state of 0.46e(-). The structural changes upon complexation generally lead to lower wavenumber vibrations and to changes in the normal mode descriptions. PMID- 19645431 TI - Synthesis and characterization of one-dimensional and molecular M(tren)InAsS4 (M = Mn, Co, and Zn) compounds with a noncondensed AsS3(3-) unit. AB - Four transition-metal-amine complexes incorporating indium thioarsenates with the general formula M(tren)InAsS(4) (M = Mn, Co, and Zn) and a noncondensed AsS(3)(3 ) unit have been prepared and characterized. Single-crystal X-ray diffraction analyses show that compound 1 (M = Mn) crystallizes in the triclinic crystal system (space group: P1) and consists of a one-dimensional (1D) inorganic (1)(infinity){[InAsS(4)](2-)} chain and [Mn(tren)](2+) groups bonded to the opposite sides of an eight-membered In(2)As(2)S(4) ring along the backbone of the infinite inorganic chains. Compounds 2 (M = Mn), 3 (M = Zn), and 4 (M = Co) are isomorphous molecular compounds. They all crystallize in the monoclinic crystal system (space group: P2(1)/c). The Mn(2+) cation of [Mn(tren)](2+) in 1 has a distorted octahedral environment, while the transition-metal cations of [M(tren)](2+) in the other three compounds locate in trigonal-bipyramidal environments. This difference results in different bonding modes of [M(tren)](2+) to indium thioarsenates between compound 1 and the other three compounds. PMID- 19645432 TI - Lanthanide (Eu3+, Tb3+)/beta-diketone modified mesoporous SBA-15/organic polymer hybrids: chemically bonded construction, physical characterization, and photophysical properties. AB - Novel organic-inorganic mesoporous luminescent polymeric hybrid materials containing lanthanide (Eu(3+), Tb(3+)) complexes covalently bonded to mesoporous silica SBA-15 have been successfully prepared by co-condensation of the modified 2-thenoyltrifluoroacetone (TTA-Si) and tetraethoxysilane (TEOS) in the presence of Pluronic P123 surfactant as a template. 2Z-Thenoyltrifluoroacetone (TTA) was grafted onto the coupling agent 3-(triethoxysilyl)-propyl isocyanate (TEPIC) and used as the first precursor, and the other precursor PMMA was synthesized through the addition polymerization reaction of the monomer methyl methacrylate. Then these precursors coordinated to rare earth ions, and the final mesoporous polymeric hybrid materials Ln(TTA-SBA-15)(3)PMMA (Ln = Eu, Tb) were obtained after hydrolysis and copolycondensation with the tetraethoxysilane (TEOS) via a sol-gel process. In addition, for comparison, SBA-15 covalently bonded with the binary Ln(3+) complexes with TTA ligand were also synthesized, denoted as Ln(TTA SBA-15)(3) (Ln = Eu, Tb). All of these hybrid materials have high surface area, uniformity in the mesostructure, and good crystallinity. The detailed luminescence studies on all the materials showed that the ternary rare-earth mesoporous polymeric hybrid materials present stronger luminescent intensities, longer lifetimes, and higher luminescent quantum efficiencies than the binary rare-earth mesoporous hybrid materials, indicating that the introduction of the organic polymer chain is a benefit for the luminescence properties of the overall hybrid system. PMID- 19645433 TI - Novel flufenamic acid analogues as inhibitors of androgen receptor mediated transcription. AB - The androgen receptor (AR), which mediates the signals of androgens, plays a crucial role in prostate-related diseases. Although widely used, currently marketed anti-androgenic drugs have significant side effects. Several studies have revealed that non-steroidal anti-inflammatory drugs, such as flufenamic acid, block AR transcriptional activity. Herein we describe the development of small molecule analogues of flufenamic acid that antagonize AR. This novel class of AR inhibitors binds to the hormone binding site, blocks AR transcription activity, and acts on AR target genes. PMID- 19645435 TI - Sub-Doppler stark spectroscopy in the A-X (1,0) band of CN. AB - The effect of external electric fields has been measured in hyperfine-resolved sub-Doppler transitions in the A (2)Pi-X (2)Sigma (1,0) band of the CN radical near 10,900 cm(-1). Static electric fields less than 1 kV/cm are sufficient to mix the most closely spaced Lambda-dpublets in the A state, leading to Stark spectra with both new and shifted resonances. Simulations of the saturation-dip Stark spectral line profiles allow extraction of the A-state permanent electric dipole moment with a magnitude of 0.06 +/- 0.02 D. PMID- 19645434 TI - Electronic and magnetic properties of ultrathin Au/Pt nanowires. AB - We have reported the synthesis of Au(25)Pt(75) and Au(48)Pt(52) alloyed ultrathin nanowires with average widths of less than 3 nm via a wet chemistry approach at room temperature. Using a combination of techniques, including scanning transmission electron microscopy equipped with X-ray energy dispersive spectroscopy, ultraviolet-visible spectroscopy, and X-ray absorption near-edge structure and extended X-ray absorption fine structure spectroscopies, we identified the stoichiometry-dependent heterogeneous crystalline structures, as well as electronic structures with respect to the charge transfer between Pt and Au within both nanowires. In particular, we observed d-charge depletion at the Au site and the d-charge gain at the Pt site in Au(48)Pt(52) nanowires, which accounted for its ferromagnetic magnetic behavior, in contrast to the paramagnetism and diamagnetism appearing respectively in bulk Pt and Au. PMID- 19645436 TI - Novel regulation of Smad3 oligomerization and DNA binding by its linker domain. AB - Smad proteins are key effectors of the transforming growth factor beta (TGFbeta) signaling pathway in mammalian cells. Smads are composed of two highly structured and conserved domains called Mad homology 1 (MH1) and 2 (MH2), which are linked together by a nonconserved linker region. The recent identification of phosphorylation sites and binding sites for ubiquitin ligases in the linker regions of TGFbeta and bone morphogenetic protein (BMP) receptor-regulated Smads suggested that the linker may contribute to the regulation of Smad function by facilitating cross-talks with other signaling pathways. In the present study, we have generated and characterized novel Smad3 mutants bearing individual substitutions of conserved and nonconserved amino acid residues within a previously described transcriptionally active linker fragment. Our analysis showed that the conserved linker amino acids glutamine 222 and proline 229 play important roles in Smad functions such as homo- and hetero-oligomerization, nuclear accumulation in response to TGFbeta stimulation, and DNA binding. Furthermore, a Smad3 mutant bearing a substitution of the nonconserved amino acid asparagine 218 to alanine displayed enhanced transactivation potential relative to wild type Smad3. Finally, Smad3 P229A inhibited TGFbeta signaling when overexpressed in mammalian cells. In conclusion, our data are in line with previous studies supporting an important regulatory role of the linker region of Smads in their function as key transducers of TGFbeta signaling. PMID- 19645437 TI - Optimization and basis-set dependence of a restricted-open-shell form of B2-PLYP double-hybrid density functional theory. AB - The performance of the restricted-open-shell form of the double-hybrid density functional theory (DHDFT) B2-PLYP procedure has been compared with that of its unrestricted counterpart using the G3/05 test set. Additionally, the influence of basis set on the parametrization and performance of ROB2-PLYP, and the further improvement of ROB2-PLYP through augmentation with a long-range dispersion function, have been investigated. We find that, after optimization of the two empirical DHDFT parameters, the ROB2-PLYP method (HF exchange = 59% and MP2 correlation = 28%) performs slightly better than the corresponding UB2-PLYP method (HF exchange = 62% and MP2 correlation = 35%), with mean absolute deviations (MADs) from the experimental energies in the G3/05 test set of 9.1 and 9.9 kJ mol(-1), respectively, when the cc-pVQZ basis set is employed. Separate optimizations of the parameters for the RO and U procedures are crucial for a fair comparison. For example, for the G2/97 test set, ROB2-PLYP(53,27) and ROB2 PLYP(62,35) show MADs of 12.2 and 13.5 kJ mol(-1), respectively, compared with the 6.6 kJ mol(-1) for (the optimized) ROB2-PLYP(59,28). The performance of ROB2 PLYP deteriorates significantly as the basis-set size is decreased, reflecting the enhanced basis-set dependence of the MP2 contribution compared with standard DFT. We find that this deficiency can be partly overcome through reparametrization. However, when the basis set drops below triple-zeta, the improvements made on reoptimizing the ROB2-PLYP parameters are not sufficient to warrant their general use. We find that the dispersion- and BSSE-corrected ROB2 PLYP(59,28)-D HCP procedure performs significantly better than ROB2-PLYP(59,28) for the S22 test set of interaction energies in which dispersion interactions are particularly important, with the MAD falling from 6.1 to 1.6 kJ mol(-1). However, when the same D correction is applied to the G3/05 test set, the performance of ROB2-PLYP(59,28)-D deteriorates slightly compared with ROB2-PLYP(59,28), with the MAD increasing from 9.1 to 9.5 kJ mol(-1). PMID- 19645438 TI - Electrides: early examples of quantum confinement. AB - Electrides are ionic solids with cavity-trapped electrons, which serve as the anions. Localization of electrons in well-defined trapping sites and their mutual interactions provide early examples of quantum confinement, a subject of intense current interest. We synthesized the first crystalline electride, Cs(+)(18-crown 6)(2)e(-), in 1983 and determined its structure in 1986; seven others have been made since. This Account describes progress in the synthesis of both organic and inorganic electrides and points to their promise as new electronic materials. Combined studies of solvated electrons in alkali metal solutions and the complexation of alkali cations by crown ethers and cryptands made electride synthesis possible. After our synthesis of crystalline alkalides, in which alkali metal anions and encapsulated alkali cations are present, we managed to grow crystalline electrides from solutions that contained complexed alkali cations and solvated electrons. Electride research is complicated by thermal instability. Above approximately -30 degrees C, trapped electrons react with the ether groups of crown ethers and cryptands. Aza-cryptands replace ether oxygens with less reactive tertiary amine groups, and using those compounds, we recently synthesized the first room-temperature-stable organic electride. The magnetic and electronic properties of electrides depend on the geometry of the trapping sites and the size of the open channels that connect them. Two extremes are Cs(+)(15 crown-5)(2)e(-) with nearly isolated trapped electrons and K(+)(cryptand 2.2.2)e( ), in which spin-pairing of electrons in adjacent cavities predominates below 400 K. These two electrides also differ in their electrical conductivity by nearly 10 orders of magnitude. The pronounced effect of defects on conductivity and on thermonic electron emission suggests that holes as well as electrons play important roles. Now that thermally stable organic electrides can be made, it should be possible to control the electron-hole ratio by incorporation of neutral complexant molecules. We expect that in further syntheses researchers will elaborate the parent aza-cryptands to produce new organic electrides. The promise of electrides as new electronic materials with low work functions led us and others to search for inorganic electrides. The body of extensive research studies of alkali metal inclusion in the pores of alumino-silicate zeolites provided the background for our studies of pure silica zeolites as hosts for M(+) and e(-) and our later use of nanoporous silica gel as a carrier of high concentrations of alkali metals. Both systems have some of the characteristics of inorganic electrides, but the electrons and cations share the same space. In 2003, researchers at the Tokyo Institute of Technology synthesized an inorganic electride that has separated electrons and countercations. This thermally stable electride has a number of potentially useful properties, such as air-stability, low work function, and metallic conductivity. Now that both organic and inorganic electrides have been synthesized, we expect that experimental and theoretical research on this interesting class of materials will accelerate. PMID- 19645439 TI - In situ fabrication of inorganic nanowire arrays grown from and aligned on metal substrates. AB - The full potential of nanotechnology can be unleashed only when one is able not only to synthesize a rich variety of nanoscale building blocks but also assemble them into various patterns at the supramolecular and supracluster levels. In particular, the application of nanoparticle and nanowire materials often requires their assembly in the form of thin films, preferably on conductive surfaces for electrical addressing, control, and detection. Although a dazzling array of nanostructures has been fabricated by bottom-up approaches, one of the contemporary challenges is to assemble these nanostructures so that they introduce and realize functionalities. An alluring avenue is to simultaneously accomplish both the nanostructure synthesis and assembly on a useful substrate in a parallel fashion, affording the advantages of simplicity, low cost, and high throughput. In this Account, we review our recent work on growing inorganic nanowires (for example, metal sulfides, metal oxides, and so forth) directly from and on metal substrates in arrays without using templates and catalysts. This method of engineering nanowire arrays on metal substrates integrates the nanowire synthesis and assembly into a parallel process, both in time and in space, by exploiting in situ chemistry on the metal substrates. Both gas-phase and solution phase approaches have been developed to synthesize the aligned nanowires; here, full advantage is taken of interfacial kinetics of restricted diffusion and surface-specific reactions, often accompanied by new interfacial growth mechanisms. The setting of nanowire arrays on metal substrates has allowed exploration of their application potentials in areas such as field electron emission and chemical sensing. The approaches described here are general, and we predict that they will be extended to more inorganic materials, such as metal halides. Moreover, as more control is achieved with synthetic methods, inorganic nanowire arrays should provide unusual magnetic, optical, and electronic properties for nanostructural engineers willing to confront the attendant challenges. Accordingly, applications for which there is a current impetus for progress, such as solar cells or lithium ion secondary batteries, might well be addressed with this methodology. PMID- 19645440 TI - Polyanion hydrophobicity and protein basicity affect protein stability in protein polyanion complexes. AB - Stability of four dissimilar basic proteins (chymotrypsinogen A, ribonuclease A, cytochrome c, lysozyme) in the complex with four polyanions (heparin, poly(vinylsulfate), poly(4-styrene-sulfonate), Nafion) has been studied by differential scanning calorimetry. The polyanions were chosen because of their different charge density and hydrophobicity. Relative hydrophobicity of polyanions have been compared by three different parameters: (i) partition coefficient determined in octanol/water system, (ii) electrocapillary curves obtained by the method of controlled convection, and (iii) change in absorbance of small cationic amphiphilic molecule, aminoacridine, due to interaction with polyanion. Our results suggest that stability of proteins in the complex with polyanions negatively correlate with charge-related properties of the proteins such as isoelectric point and surface charge density and hydrophobicity of the polyanions. PMID- 19645441 TI - Elastic modulus of single cellulose microfibrils from tunicate measured by atomic force microscopy. AB - The elastic modulus of single microfibrils from tunicate ( Halocynthia papillosa ) cellulose was measured by atomic force microscopy (AFM). Microfibrils with cross-sectional dimensions 8 x 20 nm and several micrometers in length were obtained by oxidation of cellulose with 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO) as a catalyst and subsequent mechanical disintegration in water and by sulfuric acid hydrolysis. The nanocellulosic materials were deposited on a specially designed silicon wafer with grooves 227 nm in width, and a three-point bending test was applied to determine the elastic modulus using an AFM cantilever. The elastic moduli of single microfibrils prepared by TEMPO-oxidation and acid hydrolysis were 145.2 +/- 31.3 and 150.7 +/- 28.8 GPa, respectively. The result showed that the experimentally determined modulus of the highly crystalline tunicate microfibrils was in agreement with the elastic modulus of native cellulose crystals. PMID- 19645442 TI - Effect of double-tailed surfactant architecture on the conformation, self assembly, and processing in polypeptide-surfactant complexes. AB - This work describes the solid-state conformational and structural properties of self-assembled polypeptide-surfactant complexes with double-tailed surfactants. Poly(L-lysine) was complexed with three dialkyl esters of phosphoric acid (i.e., phosphodiester surfactants), where the surfactant tail branching and length was varied to tune the supramolecular architecture in a facile way. After complexation with the branched surfactant bis(2-ethylhexyl) phosphate in an aqueous solution, the polypeptide chains adopted an alpha-helical conformation. These rod-like helices self-assembled into cylindrical phases with the amorphous alkyl tails pointing outward. In complexes with dioctyl phosphate and didodecyl phosphate, which have two linear n-octyl or n-dodecyl tails, respectively, the polypeptide formed antiparallel beta-sheets separated by alkyl layers, resulting in well-ordered lamellar self-assemblies. By heating, it was possible to trigger a partial opening of the beta-sheets and disruption of the lamellar phase. After repeated heating/cooling, all of these complexes also showed a glass transition between 37 and 50 degrees C. Organic solvent treatment and plasticization by overstoichiometric amount of surfactant led to structure modification in poly(L lysine)-dioctyl phosphate complexes, PLL(diC8)(x) (x = 1.0-3.0). Here, the alpha helical PLL is surrounded by the surfactants and these bottle-brush-like chains self-assemble in a hexagonal cylindrical morphology. As x is increased, the materials are clearly plasticized and the degree of ordering is improved: The stiff alpha-helical backbones in a softened surfactant matrix give rise to thermotropic liquid-crystalline phases. The complexes were examined by Fourier transform infrared spectroscopy, small- and wide-angle X-ray scattering, transmission electron microscopy, differential scanning calorimetry, polarized optical microscopy, and circular dichroism. PMID- 19645444 TI - Bio-oxidation of terpenes: an approach for the flavor industry. PMID- 19645443 TI - Impact of polymer-bound iodine on fibronectin adsorption and osteoblast cell morphology in radiopaque medical polymers: tyrosine-derived polycarbonate blends as a model system. AB - Imaging of polymer implants during surgical implantations is challenging in that most materials lack sufficient X-ray contrast. Synthetic derivatization with iodine serves to increase the scattering contrast but results in distinct physicochemical properties in the material which influence subsequent protein adsorption and cell morphology behavior. Herein we report the impact of increasing iodine inclusion on the cell morphology (cell area and shape) of MC3T3 E1 osteoblasts on a series of homopolymers and discrete blend thin films of poly(desaminotyrosyl tyrosine ethyl ester carbonate), poly(DTE carbonate), and an iodinated analogue poly(I(2)-DTE carbonate). Cell morphology is correlated to film chemical composition via measuring fibronectin (FN) adhesion protein adsorption profile on these films. FN exhibits up to 2-fold greater adsorption affinity for poly(I(2)-DTE carbonate) than (poly(DTE carbonate)). A correlation was established between cell area, roundness, and the measured FN adsorption profile on the blend films up to 75% by mass poly(I(2)-DTE carbonate). Data suggest that incorporation of iodine within the polymer backbone has a distinct impact on the way FN proteins adsorb to the surface and within the studied blend systems; the effect is composition dependent. PMID- 19645445 TI - Development of molecular electrocatalysts for CO2 reduction and H2 production/oxidation. AB - The conversion of solar energy to fuels in both natural and artificial photosynthesis requires components for both light-harvesting and catalysis. The light-harvesting component generates the electrochemical potentials required to drive fuel-generating reactions that would otherwise be thermodynamically uphill. This Account focuses on work from our laboratories on developing molecular electrocatalysts for CO(2) reduction and for hydrogen production. A true analog of natural photosynthesis will require the ability to capture CO(2) from the atmosphere and reduce it to a useful fuel. Work in our laboratories has focused on both aspects of this problem. Organic compounds such as quinones and inorganic metal complexes can serve as redox-active CO(2) carriers for concentrating CO(2). We have developed catalysts for CO(2) reduction to form CO based on a [Pd(triphosphine)(solvent)](2+) platform. Catalytic activity requires the presence of a weakly coordinating solvent molecule that can dissociate during the catalytic cycle and provide a vacant coordination site for binding water and assisting C-O bond cleavage. Structures of [NiFe] CO dehydrogenase enzymes and the results of studies on complexes containing two [Pd(triphosphine)(solvent)](2+) units suggest that participation of a second metal in CO(2) binding may also be required for achieving very active catalysts. We also describe molecular electrocatalysts for H(2) production and oxidation based on [Ni(diphosphine)(2)](2+) complexes. Similar to palladium CO(2) reduction catalysts, these species require the optimization of both first and second coordination spheres. In this case, we use structural features of the first coordination sphere to optimize the hydride acceptor ability of nickel needed to achieve heterolytic cleavage of H(2). We use the second coordination sphere to incorporate pendant bases that assist in a number of important functions including H(2) binding, H(2) cleavage, and the transfer of protons between nickel and solution. These pendant bases, or proton relays, are likely to be important in the design of catalysts for a wide range of fuel production and fuel utilization reactions involving multiple electron and proton transfer steps. The generation of fuels from abundant substrates such as CO(2) and water remains a daunting research challenge, requiring significant advances in new inexpensive materials for light harvesting and the development of fast, stable, and efficient electrocatalysts. Although we describe progress in the development of redox active carriers capable of concentrating CO(2) and molecular electrocatalysts for CO(2) reduction, hydrogen production, and hydrogen oxidation, much more remains to be done. PMID- 19645446 TI - Steering electrons on moving pathways. AB - Electron transfer (ET) reactions provide a nexus among chemistry, biochemistry, and physics. These reactions underpin the "power plants" and "power grids" of bioenergetics, and they challenge us to understand how evolution manipulates structure to control ET kinetics. Ball-and-stick models for the machinery of electron transfer, however, fail to capture the rich electronic and nuclear dynamics of ET molecules: these static representations disguise, for example, the range of thermally accessible molecular conformations. The influence of structural fluctuations on electron-transfer kinetics is amplified by the exponential decay of electron tunneling probabilities with distance, as well as the delicate interference among coupling pathways. Fluctuations in the surrounding medium can also switch transport between coherent and incoherent ET mechanisms--and may gate ET so that its kinetics is limited by conformational interconversion times, rather than by the intrinsic ET time scale. Moreover, preparation of a charge-polarized donor state or of a donor state with linear or angular momentum can have profound dynamical and kinetic consequences. In this Account, we establish a vocabulary to describe how the conformational ensemble and the prepared donor state influence ET kinetics in macromolecules. This framework is helping to unravel the richness of functional biological ET pathways, which have evolved within fluctuating macromolecular structures. The conceptual framework for describing nonadiabatic ET seems disarmingly simple: compute the ensemble-averaged (mean-squared) donor-acceptor (DA) tunneling interaction, , and the Franck-Condon weighted density of states, rho(FC), to describe the rate, (2pi/variant Planck's over 2pi)rho(FC). Modern descriptions of the thermally averaged electronic coupling and of the Franck-Condon factor establish a useful predictive framework in biology, chemistry, and nanoscience. Describing the influence of geometric and energetic fluctuations on ET allows us to address a rich array of mechanistic and kinetic puzzles. How strongly is a protein's fold imprinted on the ET kinetics, and might thermal fluctuations "wash out" signatures of structure? What is the influence of thermal fluctuations on ET kinetics beyond averaging of the tunneling barrier structure? Do electronic coupling mechanisms change as donor and acceptor reposition in a protein, and what are the consequences for the ET kinetics? Do fluctuations access minority species that dominate tunneling? Can energy exchanges between the electron and bridge vibrations generate vibronic signatures that label some of the D-to-A pathways traversed by the electron, thus eliminating unmarked pathways that would otherwise contribute to the DA coupling (as in other "which way" or double-slit experiments)? Might medium fluctuations drive tunneling-hopping mechanistic transitions? How does the donor-state preparation, in particular, its polarization toward the acceptor and its momentum characteristics (which may introduce complex rather than pure real relationships among donor orbital amplitudes), influence the electronic dynamics? In this Account, we describe our recent studies that address puzzling questions of how conformational distributions, excited-state polarization, and electronic and nuclear dynamical effects influence ET in macromolecules. Indeed, conformational and dynamical effects arise in all transport regimes, including the tunneling, resonant transport, and hopping regimes. Importantly, these effects can induce switching among ET mechanisms. PMID- 19645447 TI - Antitumor agents 268. Design, synthesis, and mechanistic studies of new 9 substituted phenanthrene-based tylophorine analogues as potent cytotoxic agents. AB - Nineteen new phenanthrene-based tylophorine analogues with various functional groups on the piperidine moiety were designed, synthesized, and evaluated for in vitro anticancer activity against four human tumor cell lines. Analogues 15 and 21 showed approximately 2-fold enhanced inhibitory activity as compared with our prior lead compound (PBT-1). Analogues 23 and 24 with S- and R-configured substituents, respectively, at the piperidine 3'-position exhibited comparable cytotoxicity to that of PBT-1. Furthermore, mechanistic studies to investigate the effects of the new compounds on Akt protein in lung cancer cells and the NF kB signaling pathway suggested that the compounds may exert their inhibitory activity on tumor cells through inhibition of activation of both Akt and NF-kB signaling pathway. PMID- 19645448 TI - ATP-competitive inhibitors of the mammalian target of rapamycin: design and synthesis of highly potent and selective pyrazolopyrimidines. AB - The mammalian target of rapamycin (mTOR), a central regulator of growth, survival, and metabolism, is a validated target for cancer therapy. Rapamycin and its analogues, allosteric inhibitors of mTOR, only partially inhibit one mTOR protein complex. ATP-competitive, global inhibitors of mTOR that have the potential for enhanced anticancer efficacy are described. Structural features leading to potency and selectivity were identified and refined leading to compounds with in vivo efficacy in tumor xenograft models. PMID- 19645449 TI - Gold-catalyzed [3+3]-annulation of azomethine imines with propargyl esters. AB - The gold-catalyzed [3+3]-cycloaddition reaction of propargyl esters and azomethine imines has been developed. The reaction provides a rapid entry into a wide range of substituted tetrahydropyridazine derivatives from simple starting materials. A stepwise mechanism involving addition of the 1,3-dipole to a gold carbenoid intermediate is proposed. PMID- 19645451 TI - Exocyclic delocalization at the expense of aromaticity in 3,5-bis(pi-donor) substituted pyrazolium ions and corresponding cyclic bent allenes. AB - Small ring allenes are usually highly strained and highly reactive species, and for a long time considered only as transient intermediates. The recent isolation of a five membered heterocyclic allene 1f has raised questions and debate regarding the factors responsible for its stability. Since 1f has been derived by deprotonation of a pyrazolium ion 2f, it has been suggested that the stability of 1f comes from its aromatic character. Here we report computational evidence, including HOMA and NICS aromaticity indices, that allenes derived from 3,5-bis(pi donor) substituted pyrazolium salts are weakly aromatic to nonaromatic, and that even their pyrazolium ion precursors have dramatically reduced aromaticity. Exocyclic delocalization, involving the pi-donor substituents, occurs at the expense of aromaticity and increases with the strength of the donor. Experimental support for these conclusions is found in the crystallographically determined structure of 3,5-bis(dimethlamino)pyrazolium ion 2g, which exhibits highly pyramidalized endocyclic nitrogen centers but planarized exocyclic ones, and from the facile C4 protonation to give a stable pyrazole-1,2-diium salt 3g, which has also been crystallographically characterized. PMID- 19645450 TI - Palladium-catalyzed regio-, diastereo-, and enantioselective benzylic allylation of 2-substituted pyridines. AB - We report a new method for the highly regio-, diastereo-, and enantioselective palladium-catalyzed allylic alkylation of 2-substituted pyridines that allows for the formation of homoallylic stereocenters containing alkyl, aryl, heteroaryl, and nitrogen substituents. When the reaction is conducted with asymmetric acyclic electrophiles, both linear and branched products may be obtained exclusively by selecting the appropriate regioisomeric starting material and ligand, an example of the "memory effect." Deuterium-labeling studies reveal that though no such phenomenon occurs with racemic cyclic electrophiles, the chiral ligand employed reacts kinetically faster with the enantiomer of the substrate for which it is "matched" and yet eventually converts all "mismatched" substrate to product. PMID- 19645452 TI - Toward the synthesis of high boron content polyanionic multicluster macromolecules. AB - Reported are further consequences of the dioxane ring opening in [3,3'-Co(8 (CH(2)CH(2)O)(2)-1,2-C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))], [1], with 12-vertex carborane mono- and dianions. The removal of one BH vertex from the 1,2-closo C(2)B(9)H(12) part of the double-cluster monoanions of type [1''-X-2''-R-closo 1'',2''-C(2)B(10)H(11)](-), [2](-) (where X = [3,3'-Co(8-(CH(2)CH(2)O)(2)-1,2 C(2)B(9)H(10))(1',2'-C(2)B(9)H(11))](-) and R = H, [2](-); CH(3), [8](-) and C(6)H(5), [9](-)), via heating with ethanolic KOH or CsF led to the isolation of a series of orange dianions having the general formula [7''-X-8''-R-7'',8''-nido C(2)B(9)H(11)](2-) (R = H, [11](2-); CH(3), [12](2-); and C(6)H(5), [13](2-)). The same procedure applied to the dianionic triple-cluster compound [1'',2''-X(2) 1'',2''-closo-C(2)B(10)H(10)](2-), [5](2-), yielded the trianionic species [7'',8''-X(2)-7'',8''-nido -C(2)B(9)H(10)](3-), [14](3-). Boron degradation of the related 1,7-carborane anion [1''-X-1'',7''-closo-C(2)B(10)H(11)](-), [3](-), was achieved upon heating with CsF in ethylene glycol to generate the [7''-X 7'',9''-nido-C(2)B(9)H(11)](2-), [15](2-), dianion. However, the degradation of the corresponding [1'',7''-X(2)-1'',7''-closo-C(2)B(10)H(10)](2-), [6](2-), dianion under the same conditions led only to the cleavage of the ether chain with no possible isolation of the expected [7'',9''-X(2)-7'',9''-nido C(2)B(9)H(10)](3-) trianion. The study has been complemented by experimental procedures leading to the still not fully reported starting monoanionic compounds [2](-), [3](-), [8](-) and [9](-) and to the starting dianions [5](2-) and [6](2 ). The anions containing the eleven-vertex moiety can be isolated as either Cs(+) or [N(CH(3))(4)](+) salts and can be converted into other salts via metathesis with suitable countercations. The structures of all compounds isolated in this study have been suggested on the basis of NMR and mass spectrometry methods. The disarticulation of complex (11)B NMR spectra has been successfully achieved in this work and has been proven to be a powerful tool for the characterization of multicluster boron-containing molecules. PMID- 19645453 TI - Temporary anion states of ferrocene and dibenzene chromium using stabilization method in density functional theory. AB - The Koopmans-based (KB) approximation is used to investigate the ionization potentials of ferrocene and dibenzene chromium in density functional theory. As to the energies of low-lying temporary anion states of these transition metal complexes, the stabilization method coupled with KB approximation (S-KB) is adopted. Here, the stabilization is accomplished by varying the exponents of appropriate diffuse functions. Results indicate that the S-KB method is much more successful than other methods in predicting absolute and relative energies of temporary anion states. Furthermore, the ionization potentials via KB approach are very close to the experimental values. PMID- 19645455 TI - Half-life mapping of nitroxyl radicals with three-dimensional electron paramagnetic resonance imaging at an interval of 3.6 seconds. AB - This technical note reports a continuous-wave electron paramagnetic resonance (CW EPR) imager that can visualize the distribution of free radicals with a half-life of subminutes in three-dimensional (3D) space. A total of 46 EPR spectra under magnetic field gradients, called projections, were obtained for image reconstruction at an interval of 3.6 s. A shortened data-acquisition time was achieved with the use of analog signals that drove field gradient coils in the imager. 3D mapping of the half-lives of nitroxyl radicals (4-hydroxyl-2,2,6,6 tetramethyl-piperidinyl-1-oxyl) was demonstrated in their reduction reaction with ascorbic acid. Inhomogeneous half-lives were clearly mapped pixel-by-pixel in a sample tube. PMID- 19645456 TI - Interaction forces between asphaltene surfaces in organic solvents. AB - The colloidal interactions between asphaltene surfaces in heptol, a mixture of n heptane and toluene, were studied for the first time by colloidal force measurements using an atomic force microscope (AFM). Asphaltenes were deposited on silica wafers and silica spheres using the Langmuir-Blodgett upstroke technique. The results showed that the ratio of toluene to heptane can significantly change solvent quality in terms of the ability to solubilize asphaltenes and hence the nature and the magnitude of the interaction forces between asphaltene surfaces. In pure toluene, there is a steric long-range repulsion which can be well fitted by the scaling theory of polymer brushes. As toluene volume fraction in heptol (Phi(T)) is gradually decreased from Phi(T) = 1 (pure toluene) to Phi(T) = 0 (pure n-heptane), the steric repulsion reduced and changed to weak attraction when Phi(T) < 0.2. The attraction in heptane can be fitted by van der Waals forces alone which are thus believed to promote asphaltene aggregation, leading to asphaltene precipitation. The results obtained in this study provide an insight into interactions that determine asphaltene behavior in an organic medium and hence in crude oils. PMID- 19645457 TI - Organic depth profiling of a binary system: the compositional effect on secondary ion yield and a model for charge transfer during secondary ion emission. AB - In recent years, it has been demonstrated that cluster ion beams may be used to sputter some materials, particularly organic materials, without the significant accumulation of damage. It is therefore possible to use cluster ion beam sputtering in conjunction with a surface analytical technique, such as SIMS, to obtain depth profiles and three-dimensional images of the distribution of organic species in the near-surface region. For SIMS organic depth profiling to be useful as an analytical tool, it is important that it is able to measure physically meaningful quantities, such as the local concentration of a species within a blend. In this paper, we investigate a model system of a miscible binary mixture of codeine and poly(lactide). We show that there is a strong surface enrichment of poly(lactide), which provides a reference signal and permits the direct comparison of different samples in terms of secondary ion yield behavior. We demonstrate that it is possible to relate secondary ion intensities to local concentrations for a binary system and that there is a direct correspondence between the yield enhancement of one component and the yield suppression of the other. The dependence of secondary ion yield on composition is described using a model of the kinetically limited transfer of charge between secondary ions and secondary neutrals. Application of the model to pure materials under the assumption that only highly fragmented secondary ions are initially produced and interact with unfragmented secondary neutrals leads to the prediction that high molecular mass quasi-molecular ions have intensities proportional to the square of the total secondary ion yield. This relationship has been independently observed in other work (Seah, M. P. Surf. Interface Anal. 2007, 39, 634.). PMID- 19645454 TI - Kinetic and structural investigations of the allosteric site in human epithelial 15-lipoxygenase-2. AB - Allosteric regulation of human lipoxygenase (hLO) activity has recently been implicated in the cellular biology of prostate cancer. In the current work, we present isotope effect, pH, and substrate inhibitor data of epithelial 15-hLO-2, which probe the allosteric effects on its mechanistic behavior. The Dk(cat)/KM for 15-hLO-2, with AA and LA as substrate, is large indicating hydrogen atom abstraction is the principle rate-determining step, involving a tunneling mechanism for both substrates. For AA, there are multiple rate determining steps (RDS) at both high and low temperatures, with both diffusion and hydrogen bonding rearrangements contributing at high temperature, but only hydrogen bonding rearrangements contributing at low temperature. The observed kinetic dependency on the hydrogen bonding rearrangement is eliminated upon addition of the allosteric effector, 13-(S)-hydroxyoctadecadienoic acid (13-HODE), and no allosteric effects were seen on diffusion or hydrogen atom abstraction. The (k(cat)/KM)AA/(k(cat)/KM)LA ratio was observed to have a pH dependence, which was fit with a titration curve (pKa = 7.7), suggesting the protonation of a histidine residue, which could hydrogen bond with the carboxylate of 13-HODE. Assuming this interaction, 13-HODE was docked to the solvent exposed histidines of a 15-hLO-2 homology model and found to bind well with H627, suggesting a potential location for the allosteric site. Utilizing d31-LA as an inhibitor, it was demonstrated that the binding of d31-LA to the allosteric site changes the conformation of 15 hLO-2 such that the affinity for substrate increases. This result suggests that allosteric binding locks the enzyme into a catalytically competent state, which facilitates binding of LA and decreases the (k(cat)/KM)AA/(k(cat)/KM)LA ratio. Finally, the magnitude of the 13-HODE KD for 15-hLO-2 is over 200-fold lower than that of 13-HODE for 15-hLO-1, changing the substrate specificity of 15-hLO-2 to 1.9. This would alter the LO product distribution and increase the production of the pro-tumorigenic, 13-HODE, possibly representing a pro-tumorigenic feedback loop for 13-HODE and 15-hLO-2. PMID- 19645458 TI - Catalysis effects of water molecules and of charge on intramolecular proton transfer of uracil. AB - In this work, the three most stable uracil isomers (U1, U2, and U3) and their neutral, positive, and negative charged multihydrates are chosen as research objects to investigate the tautomeric process between the most stable uracil, U1, and its two minor stable isomers, U2 and U3. By the study, deeper insight can be obtained regarding point mutations induced by uracil deformation. Toward the target, the activation energies of the intramolecular proton transfer (tautomeric process) as well as the catalysis effects of water molecules and of charges attached are investigated using density functional theory (DFT) calculations by means of the B3LYP exchange and correlation functions. Results reveal that water molecules hold a stronger catalysis effect on the proton transfer in these negative charged uracil hydrates than in the neutral counterparts. The optimal number of water molecules needed to catalyze the proton transfer is determined as two in the neutral hydrated systems, whereas it is three in the negative charged systems. Positive charge attachment, however, hinders the intramolecualr proton transfer of uracil, and the charge and the proton of uracil will transfer to the water clusters if water molecules are attached. Then the positive charged hydrates look more like U1a/b+[(H2O)n+H+] species in structure. Analysis reveals that it is the acceptance process of the last proton to determine the impossibility of proton transfer and result in the failure of tautomeric processes from cat-U1a-nw to cat-U2-nw and from cat-U1b-nw to cat-U3-nw. Detailed structural parameters and energy changes are discussed for the above different processes. PMID- 19645459 TI - Charge sensing and controllable tunnel coupling in a Si/SiGe double quantum dot. AB - We report integrated charge sensing measurements on a Si/SiGe double quantum dot. The quantum dot is shown to be tunable from a single, large dot to a well isolated double dot. Charge sensing measurements enable the extraction of the tunnel coupling t between the quantum dots as a function of the voltage on the top gates defining the device. Control of the voltage on a single such gate tunes the barrier separating the two dots. The measured tunnel coupling is an exponential function of the gate voltage. The ability to control t is an important step toward controlling spin qubits in silicon quantum dots. PMID- 19645460 TI - High-yield organic dispersions of unfunctionalized graphene. AB - We report a simple, high-yield, method of producing homogeneous dispersions of unfunctionalized and nonoxidized graphene nanosheets in ortho-dichlorobenzene (ODCB). Sonication/centrifugation of various graphite materials results in stable homogeneous dispersions. ODCB dispersions of graphene avert the need for harsh oxidation chemistry and allow for chemical functionalization of graphene materials by a range of methods. Additionally, films produced from ODCB-graphene have high conductivity. PMID- 19645461 TI - Fast-switching photovoltachromic cells with tunable transmittance. AB - In this study, we demonstrate a photovoltachromic cell (PVCC) which is a solar cell and able to take solar energy to stimulate chromic behavior with the characteristic of tunable transmittance. The cell is composed of a patterned WO(3)/Pt electrochromic electrode and a dye-sensitized TiO(2) nanoparticle photoanode. Compared to reported photoelectrochromic cells (PECC) with nonpatterned WO(3) electrochromic electrodes, PVCC achieves a much faster bleaching time of only 60 s by blocking the light at short circuit. When PVCC is bleached under illumination at open circuit, an exceedingly short bleaching time of 4 s is achieved. Furthermore, PVCC has photovoltaic characteristics comparable to those of dye-sensitized solar cells (with Pt as the counter-electrode). In contrast to conventional photochromic devices, the transmittance of PVCC under a constant illumination can be adjusted by the resistance of a load in series with the cell. These characteristics are a result of the patterned WO(3)/Pt electrode, which provides effective charge transfer pathways to facilitate the charging/discharging of Li ions and electrons via the photovoltaic potential and the Pt-electrolyte catalytic route, respectively. PMID- 19645462 TI - Re-evaluation of recombination losses in dye-sensitized cells: the failure of dynamic relaxation methods to correctly predict diffusion length in nanoporous photoelectrodes. AB - Photocurrents generated by thick, strongly absorbing, dye-sensitized cells were reduced when the electrolyte iodine concentration was increased. Electron diffusion lengths measured using common transient techniques (L(n)) were at least two times higher than diffusion lengths measured at steady state (L(IPCE)). Charge collection efficiency calculated using L(n) seriously overpredicted photocurrent, while L(IPCE) correctly predicted photocurrent. This has implications for optimizing cell design. PMID- 19645463 TI - Steroidal glycosides from Agave utahensis and their cytotoxic activity. AB - Eight new spirostanol saponins (1-8) and three new furostanol saponins (9-11) were isolated from the whole plants of Agave utahensis. The structures of 1-11 were determined by analysis of extensive spectroscopic data. The saponins were evaluated for their cytotoxic activity against HL-60 human promyelocytic leukemia cells. Compound 1 showed cytotoxicity against HL-60 cells with an IC(50) value of 4.9 microg/mL, induced apoptosis in HL-60 cells, and markedly activated caspase 3. PMID- 19645465 TI - Nitric oxide switches on the photoluminescence of molecularly engineered quantum dots. AB - The photoluminescence of nonfluorescent molecularly engineered quantum dots (QDs) with iron(III) dithiocarbamates was selectively switched on by nitric oxide. Such functional QDs consisted of CdSe-ZnS nanocrystals as fluorophores and surface bound tris(N-(dithiocarboxy)sarcosine)iron(III) as reactive centers for nitric oxide. The fluorescence of the QDs was quenched by energy transfer between the excited QD cores and the surface bound iron(III) dithiocarbamates due to their optical energy overlapping. Nitric oxide restored the fluorescence of the QDs through reduction of the surface bound iron(III) complexes to iron(I)-NO adducts and thus shutting down the energy transfer pathway. The fluorescence of the iron(III) complex engineered QDs was selectively and quantitatively restored by nitric oxide but not by other reactive oxygen species. Such a property of the functional QDs could be used for sensing nitric oxide based on the fluorescence "turn on" mechanism. PMID- 19645464 TI - Dynamic imaging of molecular assemblies in live cells based on nanoparticle plasmon resonance coupling. AB - We used molecular-specific gold nanoparticles to monitor epidermal growth factor receptors (EGFR) in live A431 cells over time. Dark-field hyperspectral imaging, electron microscopy, and electrodynamic modeling were used to correlate optical properties of EGFR-bound plasmonic nanoparticles with receptor regulation state. We showed that receptor trafficking resulted in a progressive red shift of greater than 100 nm in the nanoparticle plasmon resonance wavelength over a time period of 60 min. Furthermore, we demonstrated that changes in peak scattering wavelengths of gold nanoparticles from 546 +/- 15 to 574 +/- 20, and to 597 +/- 44 nm are associated with EGFR trafficking from the cell membrane, to early endosomes, and to late endosomes/multivesicular bodies, respectively. Finally, we used the changes in scattering spectra of EGFR-bound nanoparticles and a straightforward statistical analysis of RGB-channel color images of labeled cells to create near real-time maps of EGFR regulatory states in living cells. PMID- 19645466 TI - Decarboxylation via addition of water to a carboxyl group: acid catalysis of pyrrole-2-carboxylic acid. AB - The decarboxylation of pyrrole-2-carboxylic acid is subject to acid catalysis in strongly acidic solutions. Protonation of the pyrrole ring at C2 produces a potentially low-energy carbanion leaving group. Carbon dioxide formation is suppressed by the requisite formation of its high-energy conjugate acid. As a result, decarboxylation must proceed via an associative mechanism through the addition of water to the carboxyl group of the protonated reactant, leading to the formation of pyrrole and protonated carbonic acid, which rapidly dissociates into H(3)O(+) and carbon dioxide. PMID- 19645467 TI - Spatial control of crystal nucleation in agarose gel. AB - Spatial and temporal control of crystal nucleation is demonstrated by nonphotochemical laser-induced nucleation of an aqueous agarose gel prepared with supersaturated potassium chloride. The location of nucleation was controlled by means of an optical mask; crystals were only observed in the area exposed to near infrared laser radiation. The dependence of nucleation on laser power was measured, and the results suggest that the agarose gel reduces the effective supersaturation of the aqueous potassium chloride. PMID- 19645468 TI - Total synthesis of etnangien. AB - The first total synthesis of the potent RNA-polymerase inhibitor etnangien is described, which establishes unequivocally the relative and absolute configuration of this sensitive macrolide antibiotic. Key features of the expedient and modular synthesis include stereoselective substrate-controlled boron- and tin-mediated aldol couplings to set the characteristic sequences of methyl and hydroxyl bearing stereogenic centers with high degrees of stereoselectivity and yield, an efficient Heck macrocyclization of a conformationally restricted substrate, and a late-stage introduction of the labile side chain. The convergent approach should be amenable to designed analogues. PMID- 19645469 TI - Template-directed synthesis of a covalent organic capsule based on a 3 nm-sized metallocapsule. AB - A 4 nm-sized covalent organic capsule having 24 pyridyl groups was synthesized in extremely high yield (43% in three steps) using an octahedron-shaped metallocapsule as a template molecule. The entity was fully characterized by NMR and MALDI-TOF MS measurements. N-Methylation of the 24 pyridyl groups of the organic capsule produced a 5 nm-sized polycationic capsule, which is larger than the neutral precursory capsule because of the electrostatic repulsion between the positive charges on the pyridinium groups of the capsule. PMID- 19645470 TI - Site-specific two-color protein labeling for FRET studies using split inteins. AB - Fluorescence resonance energy transfer (FRET) is an ideal tool for studying protein conformational changes and dynamics. Strategies to specifically label proteins with multiple colors at structurally important sites, a prerequisite for such studies, however, need to be devised on a protein-by-protein basis. Here we describe a simple yet widely applicable two-color site-specific protein labeling method utilizing Npu DnaE split intein. PMID- 19645471 TI - 31P MAS refocused INADEQUATE spin-echo (REINE) NMR spectroscopy: revealing J coupling and chemical shift two-dimensional correlations in disordered solids. AB - Two-dimensional (2D) variations in (2)J(P(1),P(1)), (2)J(P(1),P(2)), and (2)J(P(2),P(2)) are obtained--using the REINE (REfocused INADEQUATE spin-Echo) pulse sequence presented by Cadars et al. (Phys. Chem. Chem. Phys. 2007, 9, 92 103)--from pixel-by-pixel fittings of the spin-echo modulation for the 2D correlation peaks due to linked phosphate tetrahedra (P(1)-P(1), P(1)-P(2), P(2) P(1), and P(2)-P(2)) in a (31)P refocused INADEQUATE solid-state MAS NMR spectrum of a cadmium phosphate glass, 0.575CdO-0.425P(2)O(5). In particular, separate variations for each 2D (31)P REINE peak are obtained which reveal correlations between the J couplings and the (31)P chemical shifts of the coupled nuclei that are much clearer than those evident in previously presented 2D z-filtered (31)P spin-echo spectra. Notably, such correlations between the J couplings and the (31)P chemical shifts are observed even though the conditional probability distributions extracted using the protocol of Cadars et al. (J. Am. Chem. Soc. 2005, 127, 4466-4476) indicate that there is no marked correlation between the (31)P chemical shifts of neighboring phosphate tetrahedra. For 2D peaks at the P(2) (31)P chemical shift in the direct dimension, there can be contributions from chains of three units (P(1)-P(2)-P(1)), chains of four units (P(1)-P(2)-P(2) P(1)), or longer chains or rings (-P(2)-P(2)-P(2)-): for the representative glass considered here, best fits are obtained assuming a glass comprised predominantly of chains of four units. The following variations are found: (2)J(P(1),P(1)) = 13.4 +/- 0.3 to 14.8 +/- 0.5 Hz, (2)J(P(1),P(2)) = 15.0 +/- 0.3 to 18.2 +/- 0.3 Hz, and (2)J(P(2),P(2)) = 5.9 +/- 0.6 to 9.1 +/- 0.9 Hz from the fits to the P(1) P(1), P(1)-P(2), and P(2)-P(2) peaks, respectively. The correlation of a particular J coupling with the (31)P chemical shifts of the considered nucleus and the coupled nucleus is quantified by the coefficients C(F(2)) and C(F(1)) that correspond to the average pixel-by-pixel change in the J coupling with respect to the chemical shift of the observed (F(2)) and neighboring (F(1)) (31)P nuclei, respectively. PMID- 19645472 TI - Identification of a radical intermediate in the enzymatic reduction of oxygen by a small laccase. AB - The enzyme mechanism of the Cu-containing small laccase (SLAC) from Streptomyces coelicolor has been investigated by optical and electron paramagnetic resonance spectroscopy. A new intermediate was identified after the reaction of molecular oxygen with the reduced trinuclear site of the type-1-depleted (T1D) form of the enzyme. It has the fingerprint of a biradical with a triplet ground state. One of the spins resides on a Cu in the trinuclear site, tentatively identified as the type-2 site, while the other spin derives from a protein-based radical. The latter is tentatively identified as a tyrosyl radical on the basis of the similarity of the optical characteristics with those observed for a Cu tyrosyl radical pair. The spin-spin distance was found to be 5.0 +/- 0.2 A. PMID- 19645473 TI - Direct interaction between amphotericin B and ergosterol in lipid bilayers as revealed by 2H NMR spectroscopy. AB - Although amphotericin B (AmB) is thought to exert its antifungal activity by forming transmembrane ion-permeable self-assemblies together with ergosterol, no previous study has directly proven AmB-ergosterol interaction. To establish the interaction, we measured (2)H NMR using deuterium-labeled sterols and AmB. The (2)H NMR spectra of deuterated ergosterol in palmitoyloleoylphosphatidylcholine (POPC) bilayers showed that fast axial diffusion of erogosterol was almost completely inhibited by the coexistence of AmB. Conversely, cholesterol mobility in POPC membrane was essentially unchanged with or without AmB. These results unequivocally demonstrate that ergosterol has significant interaction with AmB in POPC bilayers. In addition, we examined the mobility of AmB using deuterium labeled AmB, and found that, although AmB is almost immobilized in sterol-free and cholesterol-containing POPC membranes, a certain ratio of AmB molecules acquires mobility in the presence of ergosterol. The similar mobility of AmB and ergosterol in POPC bilayers confirmed the idea of the direct intermolecular interaction between ergosterol and AmB. PMID- 19645474 TI - Interface engineering: an effective approach toward high-performance organic field-effect transistors. AB - By virtue of their excellent solution processibility and flexibility, organic field-effect transistors (OFETs) are considered outstanding candidates for application in low-cost, flexible electronics. Not only does the performance of OFETs depend on the molecular properties of the organic semiconductors involved, but it is also dramatically affected by the nature of the interfaces present. Therefore, interface engineering, a novel approach towards high-performance OFETs, has attracted considerable attention. In this Account, we focus on recent advances in the study of OFET interfaces--including electrode/organic layer interfaces, dielectric/organic layer interfaces, and organic/organic layer interfaces--that have resulted in improved device performance, enhanced stability, and the realization of organic light-emitting transistors. The electrode/organic layer interface, one of the most important interfaces in OFETs, usually determines the carrier injection characteristics. Focusing on OFETs with copper and silver electrodes, we describe effective modification approaches of the electrode/organic layer interfaces. Furthermore, the influence of electrode morphology on device performance is demonstrated. These results provide novel approaches towards high-performance, low-cost OFETs. The dielectric/organic layer interface is a vital interface that dominates carrier transport; modification of this interface therefore offers a general way to improve carrier transport accordingly. The dielectric layer also affects the device stability of OFETs. For example, high-performance pentacene OFETs with excellent stability are obtained by the selection of a dielectric layer with an appropriate surface energy. The organic/organic layer interface is a newly investigated topic in OFETs. Introduction of organic/organic layer interfaces, such as heterojunctions, can improve device performance and afford ambipolar OFETs. By designing laterally arranged heterojunctions made of organic field-effect materials and light emitting materials, we realized both light emission and field effects simultaneously in a single OFET. The preceding decade has seen great progress in OFETs. Interface engineering provides a simple but effective approach toward creating high-performance OFETs and will continue to make essential contributions in the development of useful OFET-based devices. The exploration of novel interface engineering applications also merits further attention; the design of gas sensors through a more complete understanding of interface phenomena serves as just one example. PMID- 19645475 TI - Comb-shaped copolymers composed of hydroxypropyl cellulose backbones and cationic poly((2-dimethyl amino)ethyl methacrylate) side chains for gene delivery. AB - Cationic polymers have been of interest and importance as nonviral gene delivery carriers. Herein, well-defined comb-shaped cationic copolymers (HPDs) composed of long biocompatible hydroxypropyl cellulose (or HPC) backbones and short poly((2 dimethyl amino)ethyl methacrylate) (or P(DMAEMA)) side chains were prepared as gene vectors via atom transfer radical polymerization (ATRP) from the bromoisobutyryl-terminated HPC biopolymers. The P(DMAEMA) side chains of HPDs can be further partially quaternized to produce the quaternary ammonium HPDs (QHPDs). HPDs and QHPDs were assessed in vitro for nonviral gene delivery. HPDs exhibit much lower cytotoxicity and better gene transfection yield than high-molecular weight P(DMAEMA) homopolymers. QHPDs exhibit a stronger ability to complex pDNA, due to increased surface cationic charges. Thus, the approach to well-defined comb-shaped cationic copolymers provides a versatile means for tailoring the functional structure of nonviral gene vectors to meet the requirements of strong DNA-condensing ability and high transfection capability. PMID- 19645476 TI - Synthesis and characterization of accessible metal surfaces in calixarene-bound gold nanoparticles. AB - Use of organic ligands to partially passivate nanoparticles against sintering yet retain a degree of small molecule accessibility to the metal surface has been a lofty goal in functional materials synthesis, which in principle also enables the design of preferred electronic and steric environments on a nanoparticle surface. Catalysis using gold in particular requires donor ligands that facilitate an electron-rich metal surface and generalizable strategies for dealing with deactivation due to sintering. Here, synthesis and characterization of gold nanoparticles postsynthetically modified with the chelating ligand cone 5,11,17,23,29,35-hexa(tert-butyl)-37,39,41-tris(diphenylphosphinomethoxy) 38,40,42-trimethoxycalix[6]arene (1) is reported. In solution as well as when supported on the surface of TiO2, nanoparticles modified with tripodal calix[6]arene phosphine ligand 1 demonstrate enhanced protection against sintering relative to unmodified, tetraoctylammonium bromide-surfactant stabilized gold nanoparticles. In between adsorbed calixarene ligands, there is accessible gold surface area in these nanoparticles, and this is measured quantitatively for the first time for a calixarene-modified nanoparticle, using a newly developed fluorescence methodology involving 2-naphthalenethiol as a relevant chemisorption probe molecule. Ligand steric bulk critically influences amount of accessible surface on the metal nanoparticle since the use of a smaller calix[4]arene ligand (MBC) results in a 7-fold lower accessible surface area relative to using 1 under otherwise similar conditions. In addition, surface coverage of 1 controls accessible surface area in an unintuitive fashion: a 4 fold increase in accessible metal surface area is observed upon increasing the surface coverage of 1 to be 1.5-fold higher than the minimum required for surface saturation. This is presumably the result of a more open ligand packing of 1 at higher surface coverages, which allows greater accessibility to 2 napthalenethiol. PMID- 19645477 TI - DNA strands from denatured duplexes are translocated through engineered protein nanopores at alkaline pH. AB - Nanopores are under development for the detection of a variety of analytes and the investigation of chemical reactions at the single molecule level. In particular, the analysis of nucleic acid molecules is under intense investigation, including the development of systems for rapid, low-cost DNA sequencing. Here, we show that DNA can be translocated through an engineered alphaHL protein pore at pH 11.7, a value at which dsDNA is denatured. Therefore, the alphaHL pore is sufficiently stable to entertain the possibility of direct nanopore sequencing of genomic dsDNA samples, which are more readily obtained and handled than ssDNA. PMID- 19645479 TI - Differential absorption of metals from soil to diverse vine varieties from the Valley of Tulum (Argentina): consequences to evaluate wine provenance. AB - We report the effect of vine variety on the absorption of metals from soil and follow the variety from wine through juice, verifying which metals could be used to assess wine provenance. Eleven metals were determined by atomic absorption spectroscopy in 32 soils, 16 grapes juices, and 18 wines sampled from a single vineyard having four red grape varieties (Cabernet Sauvignon, Bonarda, Malbec, and Syrah). The K nearest neighbor method allows us to distinguish among different soils, juices, and wines. Linear discriminant analysis affords descriptors to point out differences, mainly Mg, Mn, Ca, K, and Na. Data analysis evidenced that some elements have equivalent concentrations in soil, juice, and wine, while others did not. Canonical analysis shows good correlation between grape juice and wine with their provenance soil. We suggest using Mg as a marker of wine provenance, while Mn could be used to evaluate differences between wine varieties associated with plant physiology. PMID- 19645478 TI - Aptamer nano-flares for molecular detection in living cells. AB - We demonstrate a composite nanomaterial, termed an aptamer nano-flare, that can directly quantify an intracellular analyte in a living cell. Aptamer nano-flares consist of a gold nanoparticle core functionalized with a dense monolayer of nucleic acid aptamers with a high affinity for adenosine triphosphate (ATP). The probes bind selectively to target molecules and release fluorescent reporters which indicate the presence of the analyte. Additionally, these nanoconjugates are readily taken up by cells where their signal intensity can be used to quantify intracellular analyte concentration. These nanoconjugates are a promising approach for the intracellular quantification of other small molecules or proteins, or as agents that use aptamer binding to elicit a biological response in living systems. PMID- 19645481 TI - Discovery of small peptides derived from embryonic lethal abnormal vision proteins structure showing RNA-stabilizing properties. AB - Four peptides corresponding to highly conserved motives within the first two RNA recognition motif-type domains of ELAV proteins were prepared, and their effect on the stability of NOVA-1 and VEGF ELAV-target mRNAs was evaluated. Biological results show that in the presence of phorbol 12-myristate 13-acetate (a PKC activator triggering the ELAV pathway), an equimolar mixture of peptides induces a statistically significant stabilization of the selected transcripts, suggesting a synergic effect of the two stimuli. PMID- 19645480 TI - Structure-based design, synthesis, and biological evaluation of a series of novel and reversible inhibitors for the severe acute respiratory syndrome-coronavirus papain-like protease. AB - We describe here the design, synthesis, molecular modeling, and biological evaluation of a series of small molecule, nonpeptide inhibitors of SARS-CoV PLpro. Our initial lead compound was identified via high-throughput screening of a diverse chemical library. We subsequently carried out structure-activity relationship studies and optimized the lead structure to potent inhibitors that have shown antiviral activity against SARS-CoV infected Vero E6 cells. Upon the basis of the X-ray crystal structure of inhibitor 24-bound to SARS-CoV PLpro, a drug design template was created. Our structure-based modification led to the design of a more potent inhibitor, 2 (enzyme IC(50) = 0.46 microM; antiviral EC(50) = 6 microM). Interestingly, its methylamine derivative, 49, displayed good enzyme inhibitory potency (IC(50) = 1.3 microM) and the most potent SARS antiviral activity (EC(50) = 5.2 microM) in the series. We have carried out computational docking studies and generated a predictive 3D-QSAR model for SARS CoV PLpro inhibitors. PMID- 19645483 TI - Synthesis and biological evaluation of C-5 methyl substituted 4-arylthio and 4 aryloxy-3-Iodopyridin-2(1H)-one type anti-HIV agents. AB - A series of C-5 methyl substituted 4-arylthio- and 4-aryloxy-3-iodopyridin-2(1H) ones has been synthesized as new pyridinone analogues for their evaluation as anti-HIV inhibitors. The optimization at the 5-position was developed through an efficient use of the key intermediates 5-ethoxycarbonyl- and 5-cyano-pyridin 2(1H)-ones (14 and 15). Biological studies revealed that several compounds show potent HIV-1 reverse transcriptase inhibitory properties, for example, compounds 93 and 99 are active at 0.6-50 nM against wild type HIV-1 and a panel of major simple/double HIV mutant strains. PMID- 19645482 TI - Discovery of a highly potent, selective, and bioavailable soluble epoxide hydrolase inhibitor with excellent ex vivo target engagement. AB - 4-Substituted piperidine-derived trisubstituted ureas are reported as highly potent and selective inhibitors for sEH. The SAR outlines approaches to improve activity against sEH and reduce ion channel and CYP liability. With minimal off target activity and a good PK profile, the benchmark 2d exhibited remarkable in vitro and ex vivo target engagement. The eutomer entA-2d also elicited vasodilation effect in rat mesenteric artery. PMID- 19645485 TI - Quantitative analysis of an aberrant glycoform of TIMP1 from colon cancer serum by L-PHA-enrichment and SISCAPA with MRM mass spectrometry. AB - Variations in glycosylation levels or in the glycoprofile of a certain glycoprotein in tumor-related sera have been widely reported and can be used as a means of differentiation. However, quantitative mass analysis of glycoproteins is difficult because of their high structural complexity and low mass sensitivity of glycopeptides. Therefore, more powerful technologies are required for the discovery of these potential biomarkers. Tissue inhibitor of metalloproteinase 1 (TIMP1), a glycoprotein typically present at a low concentration in serum, is known to be aberrantly glycosylated in colorectal cancer cell lines as a result of the terminal addition of beta-1,6-N-acetylglucosamine (beta-1,6-GlcNAc) by N acetylglucosaminyltransferase-V (GnT-V), which is reportedly up-regulated in invasive/metastatic cancer cells. In this report, a highly sensitive method is presented for the quantitative analysis of aberrant GlcNAcylated TIMP1 in the serum of colorectal cancer (CRC) patients. Glycoproteins having an N-linked glycan terminating with beta-1,6-GlcNAc were enriched by phytohemagglutinin-L(4) (L-PHA), a lectin that specifically recognizes the beta-1,6-GlcNAc moiety of N linked glycan. The L-PHA-enriched glycoproteins were digested in solution with trypsin. With the use of a monoclonal anti-peptide TIMP1 antibody linked covalently to magnetic beads, a unique target peptide (antigen) of TIMP1 was immuno-enriched from the L-PHA-enriched tryptic digests and analyzed quantitatively by multiple reaction monitoring (MRM) mass analysis. The systematic coupling of L-PHA lectin enrichment followed by stable isotope standards and capture by anti-peptide antibodies (SISCAPA) with MRM mass analysis afforded quantitation of TIMP1 at attomolar (10(-18)) concentrations. An aberrantly GlcNAcylated substoichiometric TIMP1 isoform was quantified at approximately 0.8 ng/mL serum, using sample equivalent to only 1.7 microL of serum from a CRC patient. This approach provides a useful tool for the quantitation of a specific aberrant glycoform from human serum containing a variety of protein isoforms and may be helpful in studies of biological function as it pertains to protein glycan heterogeneity. PMID- 19645486 TI - Structure control of polysaccharide derivatives for efficient separation of enantiomers by chromatography. PMID- 19645484 TI - The application of phosphoramidate protide technology to acyclovir confers anti HIV inhibition. AB - Recently, it has been reported that phosphorylated acyclovir (ACV) inhibits human immunodeficiency virus type 1 (HIV-1) reverse transcriptase in a cell-free system. To deliver phosphorylated ACV inside cells, we designed ACV monophosphorylated derivatives using ProTide technology. We found that the L alanine derived ProTides show anti-HIV activity at noncytotoxic concentrations; ester and aryl variation was tolerated. ACV ProTides with other amino acids, other than L-phenylalanine, showed no detectable activity against HIV in cell culture. The inhibitory activity of the prodrugs against herpes simplex virus (HSV) types -1 and -2 and thymidine kinase-deficient HSV-1 revealed different structure-activity relationships but was again consistent with successful nucleoside kinase bypass. Enzymatic and molecular modeling studies have been performed in order to better understand the antiviral behavior of these compounds. ProTides showing diminished carboxypeptidase lability translated to poor anti-HIV agents and vice versa, so the assay became predictive. PMID- 19645487 TI - Experimental equilibrium structures: application of molecular dynamics simulations to vibrational corrections for gas electron diffraction. AB - A general method is described that allows experimental equilibrium structures to be determined from gas electron diffraction (GED) data. Distance corrections, starting values for amplitudes of vibration and anharmonic "Morse" constants (all required for a GED refinement) have been extracted from molecular dynamics (MD) simulations. For this purpose MD methods have significant advantages over traditional force-field methods, as they can more easily be performed for large molecules, and, as they do not rely on extrapolation from equilibrium geometries, they are highly suitable for molecules with large-amplitude and anharmonic modes of vibration. For the test case Si(8)O(12)Me(8), where the methyl groups rotate and large deformations of the Si(8)O(12) cage are observed, the MD simulations produced results markedly superior to those obtained using force-field methods. The experimental equilibrium structure of Si(8)O(12)H(8) has also been determined, demonstrating the use of empirical potentials rather than DFT methods when such potentials exist. We highlight the one major deficiency associated with classical MD--the absence of quantum effects--which causes some light-atom bonded pair amplitudes of vibration to be significantly underestimated. However, using C(3)N(3)Cl(3) and C(3)N(3)H(3) as examples, we show that path-integral MD simulations can overcome these problems. The distance corrections and amplitudes of vibration obtained for C(3)N(3)Cl(3) are almost identical to those obtained from force-field methods, as we would expect for such a rigid molecule. In the case of C(3)N(3)H(3), for which an accurate experimental structure exists, the use of path-integral methods more than doubles the C-H amplitude of vibration. PMID- 19645488 TI - Bioconjugation of rod-shaped fluorescent nanocrystals for efficient targeted cell labeling. AB - In the present work, we report a three-step approach for the functionalization of CdSe/CdS core/shell and CdSe/CdS/ZnS double-shell quantum rods (QRs) with either biotin or folic acid. We carried out an in vitro study on cultured cells and fixed tissue sections in which the biofunctionalized QRs were compared with the more traditional CdSe/ZnS quantum dots (QDs), which were also functionalized with either biotin or folic acid. The QR and the QD samples exhibited the same specificity toward the targeting cells. In addition, due to the enhanced photoluminescence of the QRs with respect to QDs, a lower amount of rods was required to image cells. In immuno-localization experiments on rat brain tissue sections, biotin-functionalized QRs have shown the typical protein localization patterns expected both for neuronal enolase NSE and actin, confirming the specificity of the interaction of QRs with avidin, and the feasibility of these materials as fluorescent probes in tissue staining. In this specific targeting study, we could assess via the MTT test, a cell viability assay, the lower toxicity of the CdSe/CdS/ZnS QRs with respect to CdSe/CdS QRs. PMID- 19645490 TI - Substrate binding mechanism of HIV-1 protease from explicit-solvent atomistic simulations. AB - The binding mechanism of a peptide substrate (Thr-Ile-Met-Met-Gln-Arg, cleavage site p2-NC of the viral polyprotein) to wild-type HIV-1 protease has been investigated by 1.6 micros biased all-atom molecular dynamics simulations in explicit water. The configuration space has been explored biasing seven reaction coordinates by the bias-exchange metadynamics technique. The structure of the Michaelis complex is obtained starting from the substrate outside the enzyme within a backbone rmsd of 0.9 A. The calculated free energy of binding is -6 kcal/mol, and the kinetic constants for association and dissociation are 1.3 x 10(6) M(-1) s(-1) and 57 s(-1), respectively, consistent with experiments. In the main binding pathway, the flaps of the protease do not open sizably. The substrate slides inside the enzyme cavity from the tight lateral channel. This may contrast with the natural polyprotein substrate which is expected to bind by opening the flaps. Thus, mutations might influence differently the binding kinetics of peptidomimetic ligands and of the natural substrate. PMID- 19645489 TI - Allylic C-H amination for the preparation of syn-1,3-amino alcohol motifs. AB - A highly selective and general Pd/sulfoxide-catalyzed allylic C-H amination reaction en route to syn-1,3-amino alcohol motifs is reported. Key to achieving this reactivity under mild conditions is the use of electron-deficient N-nosyl carbamate nucleophiles that are thought to promote functionalization by furnishing higher concentrations of anionic species in situ. The reaction is shown to be orthogonal to classical C-C bond-forming/-reduction sequences as well as nitrene-based C-H amination methods. PMID- 19645491 TI - Tuning polymer thickness: synthesis and scaling theory of homologous series of dendronized polymers. AB - The thickness of dendronized polymers can be tuned by varying their generation g and the dendron functionality X. Systematic studies of this effect require (i) synthetic ability to produce large samples of high quality polymers with systematic variation of g, X and of the backbone polymerization degree N, (ii) a theoretical model relating the solvent swollen polymer diameter, r, and persistence length, lambda, to g and X. This article presents an optimized synthetic method and a simple theoretical model. Our theory approach, based on the Boris-Rubinstein model of dendrimers predicts r approximately n(1/4)g(1/2) and lambda approximately n(2) where n = [(X - 1)(g) - 1]/(X - 2) is the number of monomers in a dendron. The average monomer concentration in the branched side chains of a dendronized polymer increases with g in qualitative contrast to bottle brushes whose side chains are linear. The stepwise, attach-to, synthesis of X = 3 dendronized polymers yielded gram amounts of g = 1-4 polymers with N approximately = 1000 and N approximately = 7000 as compared to earlier maxima of 0.1 g amounts and of N approximately = 1000. The method can be modified to dendrons of different X. The conversion fraction at each attach-to step, as quantified by converting unreacted groups with UV labels, was 99.3% to 99.8%. Atomic force microscopy on mixed polymer samples allows to distinguish between chains of different g and suggests an apparent height difference of 0.85 nm per generation as well as an increase of persistence length with g. We suggest synthetic directions to allow confrontation with theory. PMID- 19645493 TI - Photoinitiated charge transport through pi-stacked electron conduits in supramolecular ordered assemblies of donor-acceptor triads. AB - Photochemical electron donor-acceptor triads having an aminopyrene primary donor (APy) and a p-diaminobenzene secondary donor (DAB) attached to either one or both imide nitrogen atoms of a perylene-3,4:9,10-bis(dicarboximide) (PDI) electron acceptor were prepared to give DAB-APy-PDI and DAB-APy-PDI-APy-DAB. In toluene, both triads are monomeric, but in methylcyclohexane, they self-assemble into ordered helical heptamers and hexamers, respectively, in which the PDI molecules are pi-stacked in a columnar fashion, as evidenced by small- and wide-angle X-ray scattering. Photoexcitation of these supramolecular assemblies results in rapid formation of DAB(+*)-PDI(-*) spin-polarized radical ion pairs having spin-spin dipolar interactions, which show that the average distance between the two radical ions is much larger in the assemblies (31 A) than it is in their monomeric building blocks (23 A). This work demonstrates that electron hopping through the pi-stacked PDI molecules is fast enough to compete effectively with charge recombination (40 ns) in these systems, making these materials of interest as photoactive assemblies for artificial photosynthesis and organic photovoltaics. PMID- 19645492 TI - A catalytic, Bronsted base strategy for intermolecular allylic C-H amination. AB - A Bronsted base activation mode for oxidative, Pd(II)/sulfoxide-catalyzed, intermolecular C-H allylic amination is reported. N,N-diisopropylethylamine was found to promote amination of unactivated terminal olefins, forming the corresponding linear allylic amine products with high levels of stereo-, regio-, and chemoselectivity. The predictable and high selectivity of this C-H oxidation method enables late-stage incorporation of nitrogen into advanced synthetic intermediates and natural products. PMID- 19645495 TI - Alkylsubstituted thienothiophene semiconducting materials: structure-property relationships. AB - A family of conjugated polymers with fused structures consisting of three to five thiophene rings and with the same alkyl side chains has been synthesized as a means to understand structure-property relationships. All three polymers showed well-extended conjugation through the polymer backbone. Ionization potentials (IP) ranged from 5.15 to 5.21 eV; these large values are indicative of their excellent oxidative stability. X-ray diffraction and AFM studies suggest that the polymer with the even number of fused thiophene rings forms a tight crystalline structure due to its tilted side chain arrangement. On the other hand, the polymers with the odd number of fused thiophene rings packed more loosely. Characterization in a field-effect transistor configuration showed that the mobility of the polymer with the even number of rings is 1 order of magnitude higher than its odd-numbered counterparts. Through this structure-property study, we demonstrate that proper design of the molecules and properly arranged side chain positions on the polymer backbone can greatly enhance polymer electronic properties. PMID- 19645496 TI - Solution structures of the actuator domain of ATP7A and ATP7B, the Menkes and Wilson disease proteins. AB - ATP7A and ATP7B are two human P(1B)-type ATPases that have a crucial role in maintaining copper(I) homeostasis. Among the various domains of these enzymes, one, called the Actuator or A-domain, has a regulatory function and is required for the phosphatase step of the catalytic cycle (dephosphorylation of the intermediate formed during ATP hydrolysis). Here we report the solution structures of the A-domain of both proteins, solved by heteronuclear NMR spectroscopy and a characterization of the dynamics of the A-domain of ATP7A. We observed that the catalytically important TGE loop protrudes from the structure ready for interaction with the phosphorylated site in the ATP-binding domain. The loop is rigid, suggesting that the catalytic step does not require substantial structural flexibility or rearrangements. The present structures were useful to rationalize the molecular effects of disease-causing mutations. In particular, it can be concluded that mutations occurring in the A-domain either destabilize the fold of the domain (such as Gly860Val in ATP7A) or affect the network of communication within the domain (such as Leu873Arg in ATP7A) or with the other domains of the enzyme (such as Gly853Arg in ATP7A). PMID- 19645498 TI - Synthesis, electronic and crystal structures, and physical studies of the superconductor Cs(~1)Mo12S14, final step of the condensation of the Mo6L8(i)L6(a) unit. AB - The ternary reduced molybdenum sulphide Cs(~1)Mo12S14 has been synthesized by solid-state reaction at 1400 degrees C for 96 h in sealed molybdenum crucibles. The compound crystallizes in the trigonal space group P31c with the following lattice parameters: a = 9.9793 (2) A, c = 6.3730 (2) A, Z = 1. Its crystal structure was determined from single crystal X-ray diffraction data and consists of interconnected Mo6S8(i)S6(a) units forming an original three-dimensional framework in which large tunnels are occupied randomly by the Cs+ ions. 133Cs static NMR studies are in favor of a static cesium disorder. Unlike Ba4Mo12S18 where some Mo6S8(i)S6(a) units are also connected through S(i-i) ligands, this connection mode does not lead to significant interactions in the title compound. Single-crystal resistivity measurements show that Cs(~1)Mo12S14 presents a metallic behavior with a superconducting transition at 7.7 K as confirmed by magnetic measurements. PMID- 19645499 TI - Direct palladium-catalyzed arylations of aryl bromides with 2/9-substituted pyrimido[5,4-b]indolizines. AB - C-5 arylated 2/9-substituted pyrimido[5,4-b]indolizines were synthesized via palladium-catalyzed direct arylation. A variety of substituents on both pyrimido[5,4-b]indolizines and aryl/heteroaryl bromides are tolerated, providing rapid access to substituted pyrimido[5,4-b]indolizines in good to excellent yields. PMID- 19645500 TI - Supported lipid bilayer templated J-aggregate growth: role of stabilizing cation pi interactions and headgroup packing. AB - Controlling the self-assembly of molecules into specific structural motifs has important implications for the design of materials with specific optical properties. We report here the results of a correlated confocal fluorescence atomic force microscopy (AFM) study of pseudoisocyanine iodide (PIC) self assembly on supported lipid bilayers. Through judicious selection of bilayer headgroup packing and chemistry, two types of PIC J-aggregates, distinguishable by their absorbance spectra, and both exhibiting strong resonant fluorescence and bathochromic shifts in absorbance relative to the monomer, were isolated. Remarkably, selective templating can be achieved using different zwitterionic headgroups, producing J-aggregates that display a larger bathochromic shift than their solution counterparts. Our correlated confocal-AFM studies coupled with FT IR spectroscopy suggested that zwitterionic phospholipids mediate J-aggregate formation through specific cation-pi interactions between PIC and the lipid headgroups with the PIC molecules oriented largely perpendicular to the bilayer normal. The existence of the two isoforms further suggests that bilayer headgroup packing plays a key role in controlling interchromophore organization and subsequent aggregate nucleation and growth. PMID- 19645501 TI - Phosphines bearing alkyne substituents: synthesis and hydrophosphination polymerization. AB - A synthetic route is described for a series of phosphines bearing pendant alkyne substituents, from the conversion of BrC(6)H(2)R(2)C[triple bond]CR' (R = Me, i Pr; R' = Ph, SiMe(3)) to [(mu-Br)Cu(Et(2)N)(2)PC(6)H(2)R(2)C[triple bond]CR'](2) and subsequently to Cl(2)PC(6)H(2)R(2)C[triple bond]CR' and H(2)PC(6)H(2)R(2)C[triple bond]CR'. Lithiation and subsequent alkylation yield the secondary phosphines R(H)PC(6)H(2)(i-Pr)(2)C[triple bond]CPh (R = CH(2)i-Pr, CH(2)Ph). Intermolecular hydrophosphination-polymerization is used to prepare the polymeric species [RPC(6)H(2)(i-Pr)(2)CH=CPh](n), which can then be sulfurized to give [RP(S)C(6)H(2)(i-Pr)(2)CH=CPh](n). The polymeric products were characterized by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and gel permeation chromatography. These data indicate a degree of polymerization (DP(n)) of up to 60. Discussion of the mechanism is augmented with gas-phase density functional theory calculations. PMID- 19645497 TI - Macrophages and inflammatory mediators in chemical toxicity: a battle of forces. AB - Macrophages function as control switches of the immune system, providing a balance between pro- and anti-inflammatory responses. To accomplish this, they develop into different subsets: classically (M1) or alternatively (M2) activated macrophages. Whereas M1 macrophages display a cytotoxic, proinflammatory phenotype, much like the soldiers of The Dark Side of The Force in the Star Wars movies, M2 macrophages, like Jedi fighters, suppress immune and inflammatory responses and participate in wound repair and angiogenesis. Critical to the actions of these divergent or polarized macrophage subpopulations is the regulated release of inflammatory mediators. When properly controlled, M1 macrophages effectively destroy invading pathogens, tumor cells, and foreign materials. However, when M1 activation becomes excessive or uncontrolled, these cells can succumb to The Dark Side, releasing copious amounts of cytotoxic mediators that contribute to disease pathogenesis. The activity of M1 macrophages is countered by The Force of alternatively activated M2 macrophages, which release anti-inflammatory cytokines, growth factors, and mediators involved in extracellular matrix turnover and tissue repair. It is the balance in the production of mediators by these two macrophage subpopulations that ultimately determines the outcome of the tissue response to chemical toxicants. PMID- 19645502 TI - Quantitative structure-activity relationship of botanical sesquiterpenes: spatial and contact repellency to the yellow fever mosquito, Aedes aegypti. AB - The plant terpenoids encompass a diversity of structures and have many functional roles in nature, including protection against pest arthropods. Previous studies in this laboratory have identified naturally occurring sesquiterpenes contained in essential oils from two plants, amyris (Amyris balsamifera) and Siam-wood (Fokienia hodginsii), that are significantly repellent to a spectrum of arthropod pests. In efforts to further examine the biological activity of this class of compounds 12 of these plant-derived sesquiterpenes have been isolated, purified, and assayed for spatial and contact repellency against the yellow fever mosquito, Aedes aegypti . These data were used to develop quantitative structure-activity relationships that identified key properties of the sesquiterpene molecule, including electronic and structural parameters that were used to predict optimal repellent activity. There were notable similarities in the models developed for spatial repellency over five time points and for contact repellency. Vapor pressure was an important component of all repellency models. Initial levels of spatial repellency were also related to polarizability of the molecule and lowest unoccupied molecular orbital (LUMO) energy, whereas the equation for late spatial repellency was dependent on other electronic features, including Mulliken population and electrotopological state descriptors. The model identified for contact repellency was the best fit and most significant model in this analysis and showed a relationship with vapor pressure, Mulliken population, and total energy. PMID- 19645503 TI - Characterization of the exogenous insert and development of event-specific PCR detection methods for genetically modified Huanong No. 1 papaya. AB - Genetically modified (GM) papaya (Carica papaya L.), Huanong No. 1, was approved for commercialization in Guangdong province, China in 2006, and the development of the Huanong No. 1 papaya detection method is necessary for implementing genetically modified organism (GMO) labeling regulations. In this study, we reported the characterization of the exogenous integration of GM Huanong No. 1 papaya by means of conventional polymerase chain reaction (PCR) and thermal asymmetric interlaced (TAIL)-PCR strategies. The results suggested that one intact copy of the initial construction was integrated in the papaya genome and which probably resulted in one deletion (38 bp in size) of the host genomic DNA. Also, one unintended insertion of a 92 bp truncated NptII fragment was observed at the 5' end of the exogenous insert. Furthermore, we revealed its 5' and 3' flanking sequences between the insert DNA and the papaya genomic DNA, and developed the event-specific qualitative and quantitative PCR assays for GM Huanong No. 1 papaya based on the 5' integration flanking sequence. The relative limit of detection (LOD) of the qualitative PCR assay was about 0.01% in 100 ng of total papaya genomic DNA, corresponding to about 25 copies of papaya haploid genome. In the quantitative PCR, the limits of detection and quantification (LOD and LOQ) were as low as 12.5 and 25 copies of papaya haploid genome, respectively. In practical sample quantification, the quantified biases between the test and true values of three samples ranged from 0.44% to 4.41%. Collectively, we proposed that all of these results are useful for the identification and quantification of Huanong No. 1 papaya and its derivates. PMID- 19645504 TI - Formation of hydroxymethylfurfural in domestic high-fructose corn syrup and its toxicity to the honey bee (Apis mellifera). AB - In the United States, high-fructose corn syrup (HFCS) has become a sucrose replacement for honey bees and has widespread use as a sweetener in many processed foods and beverages for human consumption. It is utilized by commercial beekeepers as a food for honey bees for several reasons: to promote brood production, after bees have been moved for commercial pollination, and when field gathered nectar sources are scarce. Hydroxymethylfurfural (HMF) is a heat-formed contaminant and is the most noted toxin to honey bees. Currently, there are no rapid field tests that would alert beekeepers of dangerous levels of HMF in HFCS or honey. In this study, the initial levels and the rates of formation of HMF at four temperatures were evaluated in U.S.-available HFCS samples. Different HFCS brands were analyzed and compared for acidity and metal ions by inductively coupled plasma mass spectroscopy. Levels of HMF in eight HFCS products were evaluated over 35 days, and the data were fit to polynomial and exponential equations, with excellent correlations. The data can be used by beekeepers to predict HMF formation on storage. Caged bee studies were conducted to evaluate the HMF dose-response effect on bee mortality. Finally, commercial bases such as lime, potash, and caustic soda were added to neutralize hydronium ion in HMF samples, and the rates of HMF formation were compared at 45 degrees C. PMID- 19645505 TI - Fatty acid selectivity of lipases during acidolysis reaction between triolein and saturated fatty acids varying from caproic to behenic acids. AB - The chain length selectivity of three immobilized lipases, namely, Lipozyme TL IM from Thermomyces lanoginosus, Lipozyme RM IM from Rhizomucor miehei, and Novozym 435 from Candida antarctica, was determined in acidolysis performed in hexane using the homologous series of even carbon number, saturated fatty acids (SFAs) of 6-22 carbons. Triolein with individual SFAs or a mixture of equimolar quantities of SFAs was used as the substrate. The effects of operating variables including the mole ratio of fatty acid to triolein, temperature, enzyme dosage, and time on incorporation were also investigated. Incorporation abilities of the enzymes tested were found to be significantly different for most of FAs at the experimental conditions evaluated. Lipases acted weakly on SFAs of which the carbon chain length was shorter than eight carbon atoms and higher than 18 carbon atoms. Lipases showed a bell-shaped distribution in incorporation vs chain length plot with a maximum around C12-C16. Among the experimental parameters tested, the effect of the substrate mole ratio was greater than those of the others, and the highest incorporation was observed for C12 (36.98%), C14 (37.63%), and C16 (38.66%) at a 4:1 substrate mole ratio with Lipozyme TL IM. Lipases caused significantly different levels of acyl migration from sn-1,3 to sn-2 positions. PMID- 19645506 TI - Magnolol inhibits human glioblastoma cell proliferation through upregulation of p21/Cip1. AB - Previously, we demonstrated that magnolol isolated from the bark of Magnolia officinalis has anticancer activity in colon, hepatoma, and leukemia cell lines. In this study, we show that magnolol concentration dependently (0-40 microM) decreased the cell number in a cultured human glioblastoma cancer cell line (U373) and arrested the cells at the G0/G1 phase of the cell cycle. Magnolol treatment decreased the protein levels of cyclins A and D1 and increased p21/Cip1, but not cyclins B and D3, cyclin-dependent kinase (CDK)2, CDK4, CDC25C, Weel, p27/Kip1, and p53. The CDK2-p21/Cip1 complex was increased, and the CDK2 kinase activity was decreased in the magnolol-treated U373. Pretreatment of U373 with p21/Cip1 specific antisense oligodeoxynucleotide prevented the magnolol induced increase of p21/Cip1 protein levels and the decrease of DNA synthesis. Magnolol at a concentration of 100 microM induced DNA fragmentation in U373. Our findings suggest the potential applications of magnolol in the treatment of human brain cancers. PMID- 19645507 TI - On the mechanism of nonspecific inhibitors of protein aggregation: dissecting the interactions of alpha-synuclein with Congo red and lacmoid. AB - Increasing evidence links the misfolding and aberrant self-assembly of proteins with the molecular events that underlie a range of neurodegenerative diseases, yet the mechanistical details of these processes are still poorly understood. The fact that many of these proteins are intrinsically unstructured makes it particularly challenging to develop strategies for discovering small molecule inhibitors of their aggregation. We present here a broad biophysical approach that enables us to characterize the mechanisms of interaction between alpha synuclein, a protein whose aggregation is closely connected with Parkinson's disease, and two small molecules, Congo red and Lacmoid, which inhibit its fibrillization. Both compounds are found to interact with the N-terminal and central regions of the monomeric protein although with different binding mechanisms and affinities. The differences can be attributed to the chemical nature of the compounds as well as their abilities to self-associate. We further show that alpha-synuclein binding and aggregation inhibition are mediated by small oligomeric species of the compounds that interact with distinct regions of the monomeric protein. These findings provide potential explanations of the nonspecific antiamyloid effect observed for these compounds as well as important mechanistical information for future drug discovery efforts targeting the misfolding and aggregation of intrinsically unstructured proteins. PMID- 19645508 TI - Stored human urine supplemented with wood ash as fertilizer in tomato (Solanum lycopersicum) cultivation and its impacts on fruit yield and quality. AB - This study evaluates the use of human urine and wood ash as fertilizers for tomato cultivation in a greenhouse. Tomatoes were cultivated in pots and treated with 135 kg of N/ha applied as mineral fertilizer, urine + ash, urine only, and control (no fertilization). The urine fertilized plants produced equal amounts of tomato fruits as mineral fertilized plants and 4.2 times more fruits than nonfertilized plants. The levels of lycopene were similar in tomato fruits from all fertilization treatments, but the amount of soluble sugars was lower and Cl( ) was higher in urine + ash fertilized tomato fruits. The beta-carotene content was greater and the NO(3)(-) content was lower in urine fertilized tomato fruits. No enteric indicator microorganisms were detected in any tomato fruits. The results suggest that urine with/without wood ash can be used as a substitute for mineral fertilizer to increase the yields of tomato without posing any microbial or chemical risks. PMID- 19645510 TI - Composition of aldrin, dieldrin, and photodieldrin enantiomers in technical and environmental samples. AB - Aldrin and dieldrin belong to the group of polycyclic chlorinated insecticides that are banned under the Stockholm Convention (POP Convention). Despite the fact that the use of these compounds ceased many years ago, aldrin and, in particular, dieldrin are still present in the environment from former applications, leading occasionally to contamination of agricultural produce and food, particularly Cucurbitaceae. These prochiral compounds have a complex stereochemistry. In the environment, aldrin is rapidly converted to its epoxide, dieldrin. Photolysis is one of the environmental transformation processes reported to be important for the compounds, leading to photoproducts such as photoaldrin and photodieldrin. In contrast to the parent compounds, photoaldrin and photodieldrin are chiral and exist as pairs of enantiomers. Although dieldrin and its metabolites have been extensively reviewed, the chirality of many of its metabolites has so far not been considered. In this study, the composition of technical aldrin and dieldrin from the 1950s and their photoproducts was investigated using both non enantioselective and enantioselective gas chromatography with detection by several mass spectrometric techniques. Full enantiomer resolution of photodieldrin was achieved using a column with a silylated gamma-cyclodextrin as chiral selector. Photoaldrin, however, showed peak broadening, indicating some marginal resolution of the enantiomers. Whereas photodieldrin was formed as a racemate from both aldrin and dieldrin by natural sunlight, the analysis of environmental and biological samples (soil, biota) indicated its presence mostly with enantiomer compositions clearly differing from 1:1. The presence of photodieldrin in soil, treated more than 40 years ago with aldrin or dieldrin, documents that the photoreaction of dieldrin plays some role in the transformation of the compounds in the environment and that enantioselective biological processes are involved in its further transformation. The preliminary data also indicate that photodieldrin probably is not bioaccumulated more than dieldrin. PMID- 19645509 TI - Mining the thiol proteome for sulfenic acid modifications reveals new targets for oxidation in cells. AB - Oxidation of cysteine to sulfenic acid has emerged as a biologically relevant post-translational modification with particular importance in redox-mediated signal transduction; however, the identity of modified proteins remains largely unknown. We recently reported DAz-1, a cell-permeable chemical probe capable of detecting sulfenic acid modified proteins directly in living cells. Here we describe DAz-2, an analogue of DAz-1 that exhibits significantly improved potency in vitro and in cells. Application of this new probe for global analysis of the sulfenome in a tumor cell line identifies most known sulfenic acid modified proteins: 14 in total, plus more than 175 new candidates, with further testing confirming oxidation in several candidates. The newly identified proteins have roles in signal transduction, DNA repair, metabolism, protein synthesis, redox homeostasis, nuclear transport, vesicle trafficking, and ER quality control. Cross-comparison of these results with those from disulfide, S-glutathionylation, and S-nitrosylation proteomes reveals moderate overlap, suggesting fundamental differences in the chemical and biological basis for target specificity. The combination of selective chemical enrichment and live-cell compatibility makes DAz-2 a powerful new tool with the potential to reveal new regulatory mechanisms in signaling pathways and identify new therapeutic targets. PMID- 19645511 TI - Residue depletion of gentamicin in swine tissues after intramuscular administration. AB - A sensitive and robust high-performance liquid chromatographic method with fluorescence detection (HPLC-FLD) was developed for the determination of gentamicin (GEN) residues in swine tissues. The limit of quantification (LOQ) of the method was 50 ng/g for muscle and 100 ng/g for liver and kidney. Mean recoveries at all fortification levels ranged from 82.34 to 93.20% with coefficient of variation (CV) below 5.39%. Residue depletion study of GEN in swine was performed after intramuscular injections twice daily at a dose of 4 mg/kg of bw with 12 h intervals for 5 consecutive days. The concentrations of GEN were determined in injection site, muscle, liver, and kidney by the HPLC-FLD method. The highest GEN concentration was measured in kidney, indicating that kidney was the primary target tissue for GEN residue. GEN concentrations in all examined tissues were below the maximum residue limit (MRL) recommended by the European Union (EU) at 50 days post-treatment. PMID- 19645512 TI - Ca(2+) cross-linked alginic acid nanoparticles for solubilization of lipophilic natural colorants. AB - The increased tendency toward healthy lifestyles has promoted natural food ingredients to the detriment of synthetic components of food products. The trend followed into the colorant arena, with consumers worried about potential health problems associated with synthetic colorants and demanding food products that use natural pigments. The goal of this study was to entrap a lipophilic natural pigment (beta-carotene) in a water-soluble matrix made of Ca(2+) cross-linked alginic acid, to allow its use as a colorant in water-based foods. The effects of different synthesis parameters such as type of solvent, alginic acid concentration, and calcium chloride concentration on nanoparticle characteristics (i.e., size, zeta potential, and morphology) were evaluated. The particle stability was assessed by measuring aggregation against pH, oxidation, and particle precipitation as a function of time. The particle synthesized measured 120-180 nm when formed with chloroform and 500-950 nm when synthesized with ethyl acetate. The particles were negatively charged (-70 to -80 mV zeta potential) and were stable at pH values ranging from 3 to 7. The presence of calcium was prevalent on the particles, indicating that the divalent ions were responsible for cross-linking lecithin with alginic acid and forming the matrix around the beta-carotene pockets. The addition of calcium increased nanoparticle density and improved beta-carotene protection against oxidation. It is concluded that the method proposed herein was capable of forming water-soluble nanoparticles with entrapped beta-carotene of controlled functionality, as a result of the type of solvent and the amounts of alginate and Ca(2+) used. PMID- 19645513 TI - DNA damage by low-energy electron impact: dependence on guanine content. AB - Single-stranded DNA oligonucleotides (33-mers) containing different numbers of guanines (n=1-4) were tethered to a gold surface and exposed to 1 eV electrons. The electrons induced DNA damage, which was analyzed with fluorescence and infrared spectroscopy methods. The damage was identified as strand breaks and found to correlate linearly with the number of guanines in the sequence. This sequence dependence indicates that the electron capture by the DNA bases plays an important role in the damage reaction mechanism. PMID- 19645514 TI - In situ crystallized zirconium phenylphosphonate films with crystals vertically to the substrate and their hydrophobic, dielectric, and anticorrosion properties. AB - The in situ crystallization technique has been utilized to fabricate zirconium phenylphosphonate (ZrPP) films with their hexagonal crystallite perpendicular to the copper substrate. The micro/nano roughness surface structure, as well as the intrinsic hydrophobic characteristic of the surface functional groups, affords ZrPP films excellent hydrophobicity with water contact angle (CA) ranging from 134 degrees to 151 degrees , without any low-surface-energy modification. Particularly, in the corrosive solutions such as acidic or basic solutions over a wide pH from 2 to 12, no obvious fluctuation in CA was observed for all the ZrPP film. The k values of the hydrophobic ZrPP films are in the low-k range (k < 3.0), meeting the development of ultra-large-scale integration (ULSI) circuits. The hydrophobicity feature is proposed to bear ZrPP film a more stable low-k value in an ambient atmosphere. Besides, the polarization current of ZrPP films is reduced by 2 orders of magnitude, compared to that of the untreated copper substrate. Even deposited in a vacuum oven for 30 days at room temperature, ZrPP films also show excellent corrosion resistance, indicating a stable anticorrosion property. PMID- 19645515 TI - Photodriven spin change of Fe(II) benzimidazole compounds anchored to nanocrystalline TiO(2) thin films. AB - Ferrous tris-chelate compounds based on 2-(2'-pyridyl)benzimidazole (pybzim) have been prepared and characterized for studies of spin equilibria in fluid solution and when anchored to the surface of mesoporous nanocrystalline (anatase) TiO(2) and colloidal ZrO(2) thin films. The solid state structure of Fe(pybzim)(3)(ClO(4))(2).CH(3)CN.H(2)O was determined by single-crystal X-ray diffraction at 110 K to be triclinic, P-1, a = 11.6873(18), b = 12.2318(12), c = 14.723(4) A, alpha = 89.864(13) degrees , beta = 71.430(17) degrees , gamma = 73.788(11) degrees , V = 1907.1(6) A(3), Z = 2, and R = 0.0491. The iron compound has a meridional FeN(6) distorted octahedral geometry with bond lengths expected for a low-spin iron center at 110 K. The visible absorption spectra of Fe(pybzim)(3)(2+) and Fe(pymbA)(3)(2+), where pymbA is 4-(2-pyridin-2-yl benzimidazol-1-ylmethyl)-benzoic acid, in methanol solution were dominated by metal-to-ligand charge-transfer (MLCT) bands. Variable-temperature UV-visible absorption spectroscopy revealed dramatic changes in the extinction coefficient consistent with a high-spin ((1)A) left harpoon over right harpoon low-spin ((5)T) equilibrium. Thermodynamic parameters for the temperature-dependent spin equilibrium of Fe(pymbA)(3)(2+) in methanol were determined to be DeltaH(HL) = 3270 +/- 210 cm(-1) and DeltaS(HL) = 13.3 +/- 0.8 cm(-1) K(-1). The corresponding values for Fe(pybzimEE)(3)(2+), where pybzimEE is (2-pyridin-2-yl-benzimidazol-1 yl)-acetic acid ethyl ester, in acetonitrile solution were determined to be 3072 +/- 34 cm(-1)and 10.5 +/- 0.1 cm(-1) K(-1). The temperature-dependent effective magnetic moments of Fe(pybzimEE)(3)(2+) in acetonitrile solution were also quantified by the Evans method. Pulsed 532 nm light excitation of Fe(pybzim)(3)(2+) or Fe(pymbA)(3)(2+) in solution resulted in an immediate bleach of the MLCT absorption bands. Relaxation back to the equilibrium state followed a first-order reaction mechanism. Arrhenius analysis of the (5)T --> (1)A rate constant yielded an activation energy, E(a), of 1090 +/- 20 cm(-1) and 710 +/- 10 cm(-1) for Fe(pybzim)(3)(2+) and Fe(pymbA)(3)(2+) in methanol, respectively. The compound Fe(pymbA)(3)(2+) was found to bind to colloidal TiO(2) and ZrO(2) thin films. The absorption spectra of the surface-attached compounds were quantified from 295 to 193 K. Pulsed light excitation of Fe(pymbA)(3)/TiO(2) and Fe(pymbA)(3)/ZrO(2) resulted in the immediate bleach of the MLCT absorption bands. Relaxation was nonexponential but was well described by kinetic models based on a Gaussian distribution of activation energies or a Levy distribution of lifetimes. An Arrhenius analysis of the Gaussian data yielded average activation energies of 660 +/- 80 cm(-1) and 730 +/- 40 cm(-1) for Fe(pymbA)(3)(ClO(4))(2) on TiO(2) and ZrO(2) surfaces, respectively. The Levy distribution analysis did not adequately fit the Arrhenius model. PMID- 19645516 TI - Probing the relative stability of thiolate- and dithiolate-protected Au monolayer protected clusters. AB - Dithiolate ligands based on (+/-)-alpha-lipoic acid derivatives have been investigated as ligands for both Au monolayer-protected clusters (MPCs) and mixed alkanethiol/dithiolate Au MPCs. The oxidative and thermal stability of the MPCs were investigated by a combination of UV-vis spectroscopy, TEM, and (1)H NMR experiments. Results show that the dithiolate-protected MPCs are much more prone to oxidation by oxygen under ambient conditions than their alkanethiolate protected MPC analogues; in addition, the Au core of the dithiolate-protected Au MPCs could be etched by KCN at much faster rates than both alkanethiolate protected and mixed monolayer MPCs. These results suggest that strategies to increase ligand-metal interactions by incorporating more thiolate linkers into the ligand must also take into account the packing efficiency and/or stability of such ligands on the metal surface, which can make them much more prone to oxidation under ambient conditions. PMID- 19645517 TI - PET lesion segmentation using automated iso-intensity contouring in head and neck cancer. AB - To improve the objectivity of the integration of positron emission tomography (PET), we used the conformality index (CI) to measure the goodness of fit of a given PET iso-SUV (standardized uptake value) level with the GTV defined on PET (GTV(PET)) and CT (GTV(CT)). Twenty-two datasets involving 20 head and neck cancer patients were identified. GTV(PET) and GTV(CT) were delineated manually.An iso-intensity method was developed to automatically segment GTV(PET-ISO) using (a) SUV and (b) maximum intensity thresholding (% Max), over a range of intensities. For each intensity, GTV(PET-ISO) was compared to GTV(PET) using the conformality index CI(PET) (and, similarly, to GTV(CT) using CICT). Comparing GTV(PET) to GTV(PET-ISO) vs comparing GTV(CT) to GTV(PET-ISO), the average peak CI was 0.68 +/- 0.09 vs 0.49 +/- 0.12 (p < 0.001), the optimum iso-SUV was 2.7 +/ 0.7 vs 2.9 +/- 1.0 (p=0. 253), and the % Max SUV was 21.8% +/- 7.6% vs 23.8% +/- 8.6% (p=0. 310), respectively. The radiation oncologist's volumes corresponded to a lower iso-SUV (3.02 +/- 0.58 vs 4.36 +/- 0.77, p< 0.001) and lower % Max SUV (24.1 +/- 9.1% vs 34.3 +/- 11.2%, p<0.001) than those drawn by the nuclear medicine physician. Though manual editing may still be necessary, PET iso contouring is one method to improve the objectivity of GTV definition in head and neck cancer patients. Iso-SUV's can also be used to study the differences between PET's role as a nuclear medicine diagnostic test versus a radiation oncology treatment planning tool. PMID- 19645518 TI - A comparison of treatment plans using linac-based intensity-modulated radiation therapy and helical tomotherapy for maxillary sinus carcinoma. AB - This study evaluated whether helical tomotherapy (TOMO) planning could achieve better isodose distribution for the maxillary sinus while concomitantly sparing the adjacent _critical normal organs than linac-based step-and-shoot IMRT (s IMRT) planning. TOMO and s-IMRT were established for 10 patients with maxillary sinus cancer. The prescription (66 Gy, 30 fractions) was used to cover the planning target volume (PTV) with a 95% isodose line. Each plan was independently optimized using the CORVUS planning system and Tomotherapy Hi-Art system. The treatment plans were compared using dose volume histogram (DVH), a dose homogeneity index (DHI) of the PTV, and equivalent uniform dose (EUD) and DVH of organs at risk (OARs). The TOMO plans demonstrated better dose homogeneity compared to the s-IMRT plans. The average V95% of the TOMO plans was similar to that of the s-IMRT (92.92% vs. 95.07%, respectively), but the average V107% was 0% for TOMO compared with 18.74% for s-IMRT. The average maximum dose reduction was 7 Gy, and DHI increased by 8% for PTV1 in TOMO compared with s-IMRT (79 Gy vs. 71 Gy and, 89% vs. 97%, respectively). The average EUD reduction for the optic nerve was 17%. In summary, planning with TOMO was superior to s-IMRT planning with respect to dose homogeneity within the PTV and sparing of the optic nerve. PMID- 19645519 TI - Simulated gamma knife head frame placement for radiosurgical pre-planning. AB - The Leksell Gamma Knife (GK) is capable of targeting intracranial lesions with a high degree of accuracy. A headframe is rigidly attached to the patient's skull to establish a stereotactic coordinate system and provide a means for precisely positioning the patient in stereotactic space. After stereotactic target localization and radiosurgical treatment planning the skull and headframe are then moved with sub-millimeter precision to bring a target volume to the radiological focus of the GK unit. However, for GK models 4C and earlier, the treatable intracranial volume may be limited by collisions between the skull/headframe and the GK collimator helmet, or by mechanical travel limits of the skull/headframe within the collimator helmet. Both of these treatment limiting conditions can be found only after the headframe has been placed on the patient. If the volume of interest cannot be treated with the initial headframe placement, additional headframe placements or a different course of treatment are needed. We have developed a software package that allows for simulated headframe placement and collision checks using pre-treatment day image sets, in order to minimize the need for multiple headframe placements. We performed a small validation experiment with an anthropomorphic head phantom to evaluate the software's capabilities for predicting a clinically useable headframe position. We also used the software in an IRB-approved retrospective review for twenty-five GK image sets for a group of patients that could not be treated with the initial headframe placement, to determine if the software tool could locate an optimized headframe position to enable GK radiosurgery of all identified targets with a single headframe placement. We found that four of the cases could have been completed with a single optimized headframe placement and twenty-four of the cases could not be treated with any single headframe placement. PMID- 19645520 TI - Advances in technology for intracranial stereotactic radiosurgery. AB - Stereotactic radiosurgery (SRS) refers to a single radiation treatment delivering a high dose to an intra-cranial target localized in three-dimensions by CT and/or MRI imaging. Traditionally, immobilization of the patient's head has been achieved using a rigid stereotactic head frame as the key step in allowing for accurate dose delivery. SRS has been delivered by both Cobalt-60 (Gamma Knife) and linear accelerator (linac) technologies for many decades. The focus of this review is to highlight recent advances and major innovations in SRS technologies relevant to clinical practice and developments allowing for non-invasive frame SRS. PMID- 19645521 TI - Sequential treatment of superior vena cava syndrome caused by of non-small cell carcinoma lung cancer (NSCLC) with vascular stenting and iodine-125 implantation. AB - Feasibility and efficacy of sequentially performed endovascular stenting and Iodine-125 brachytherapy for malignant superior vena cava syndrome (SVCS) were evaluated. Thirty-four patients with malignant SVCS caused by NSCLC underwent sequential treatment of endovascular stenting and Iodine-125 brachytherapy. SVCS was diagnosed in all patients by CT images or vena-cavography. Pathology diagnosis was acquired by image guided biopsy. Endovascular stent placement was performed as first-line treatment for symptom relief. CT-guided Iodine-125 seed implantation performed 24hr after stenting. Clinical end points were resolution of symptoms and local efficacy of primary malignancy regression. Symptom relief rate was >90% after 24hr and 97% after 3 months. No migration of seeds or restenosis occurred in any patient. The local efficacy (defined as either partial or complete response) was 53%, 79%, 88% and 74% after 1, 3, 6 and 12 months, respectively. Mean SVCS-free survival time was 305 days (range 120-960 days). Two patients were still alive at the time of this writing, Thirty-one died from progression and one died from acute heart disease. Sequentially performed endovascular stenting and Iodine-125 brachytherapy provides a safe and effective alternative for malignant SVCS caused by NSCLC. PMID- 19645522 TI - Towards solid tumor treatment by nanosecond pulsed electric fields. AB - Local and drug-free solid tumor ablation by large nanosecond pulsed electric fields leads to supra-electroporation of all cellular membranes and has been observed to trigger nonthermal cell death by apoptosis. To establish pore-based effects as the underlying mechanism to inducing _apoptosis, we use a multicellular system model (spatial scale 100 microm) that has irregularly shaped liver cells and a multiscale liver tissue model (spatial scale 200 mm). Pore histograms for the multicellular model demonstrate the presence of only nanometer sized pores due to nanosecond electric field pulses. The number of pores in the plasma membrane is such that the average tissue conductance during nanosecond electric field pulses is even higher than for longer irreversible electroporation pulses. It is shown, however, that these nanometer-sized pores, although numerous, only significantly change the permeability of the cellular membranes to small ions, but not to larger molecules. Tumor ablation by nanosecond pulsed electric fields causes small to moderate temperature increases. Thus, the underlying mechanism(s) that trigger cell death by apoptosis must be non-thermal electrical interactions, presumably leading to different ionic and molecular transport than for much longer irreversible electroporation pulses. PMID- 19645523 TI - Performance of a commercial Macro Monte Carlo dose calculation algorithm for determining output factors of clinical electron fields. AB - We compare measured output factors of clinical electron fields to those calculated by a commercial treatment planning system based on an electron Monte Carlo algorithm. The measured data is comprised of 195 fields with energies 6 to 18 MeV, applicator sizes 6 x 6 cm(2) to 25 x 25 cm(2), and source to surface distances (SSDs) of 97 to 107 cm. Due to a scarcity of clinical fields for the highest energies and the largest applicator sizes, additional measurements were made at arbitrarily chosen large field sizes at previously not used energies, for a total of 223 output factors. The difference between calculation and measurement ranged from -2.9% to 3.9%, with a mean difference of -0.2%. Half of the field shapes had a difference with magnitude less than 0.8%. Only 7 (3%) of the field shapes were outliers, having differences greater than 2%. All outliers had field widths at the normalization point < 3.5 cm, were applied at SSDs > 100 cm, were inserts for the 25 _ 25 cm(2) applicator, or had more than one of these characteristics. For narrow and elongated fields the TPS slightly overestimated output factors, whereas for field shapes with aspect ratio close to 1 the TPS slightly underestimated the output factors. No strong dependence of the difference on energy was observed. PMID- 19645524 TI - Exposure assessment of 17alpha-ethinylestradiol in surface waters of the United States and Europe. AB - An evaluation of measured and predicted concentrations of 17-ethinylestradiol in surface waters of the United States and Europe was conducted to develop expected long-term exposure concentrations for this compound. Measured environmental concentrations (MECs) in surface waters were identified from the literature. Predicted environmental concentrations (PECs) were generated for European and U.S. watersheds using the GREAT-ER and PhATE models, respectively. The majority of MECs are nondetect and generally consistent with model PECs and conservative mass balance calculations. However, the highest MECs are not consistent with concentrations derived from conservative (worst-case) mass balance estimates or model PECs. A review of analytical methods suggests that tandem or high resolution mass spectrometry methods with extract cleanup result in lower detection limits and lower reported concentrations consistent with model predictions and bounding estimates. Based on model results using PhATE and GREAT ER, the 90th-percentile low-flow PECs in surface water are approximately 0.2 and 0.3 ng/L for the United States and Europe, respectively. These levels represent conservative estimates of long-term exposure that can be used for risk assessment purposes. Our analysis also indicates that average concentrations are one to two orders of magnitude lower than these 90th-percentile estimates. Higher reported concentrations (e.g., greater than the 99th-percentile PEC of approximately 1 ng/L) could result from methodological problems or unusual environmental circumstances; however, such concentrations are not representative of levels generally found in the environment, warrant special scrutiny, and are not appropriate for use in risk assessments of long-term exposures. PMID- 19645525 TI - Life prevalence of upper respiratory tract diseases and asthma among children residing in rural area near a regional industrial park: cross-sectional study. AB - INTRODUCTION: The study described was initiated by the Israel Ministry of Health as an effort to respond to and deal with public concern about possible health disorders related to odorous emissions (composed of a great many of organic and inorganic chemicals) from the regional industrial park (IP) in the Negev, southern Israel. Previous ecological studies found that adverse health effects in the Negev Bedouin population were associated with residential proximity to the IP. The objective of the current study was to investigate a hypothesis concerning the link between the IP proximity and life prevalence (LP) of upper respiratory tract chronic diseases (URTCD) and asthma in children aged 0-14 years living in rural Negev, Israel, in small agricultural communities. METHODS: The cross sectional study was conducted in 7 localities simultaneously during 2002. The following indirect exposure indicators were used: (1) distance (less than 20 km/ more than 20 km) from the IP ('distance'); (2) presence (yes/no) of the dominant wind direction being from the IP toward a child's locality ('wind direction'); and (3) the child's mother having made odour complaints (yes/no) related to the IP ('odour complaints'). A 20 km cut-off point was used for 'distance' dichotomization as derived from the maximum range of 'odour complaints'. This gave 3 proximal and 4 distant localities, and division of these by the 'wind direction' gave one versus two localities. The study population consisted of 550 children born in the localities. Medical diagnoses were collected from local clinic records. The following were included in the interviewer-administered questionnaire for a child's parents: (1) demography (the child's birth date, gender, mother being married or not, parental origin and education, number of siblings); (2) the child's birth history (pregnancy and delivery) and breast feeding duration; (3) the child's parental respiratory health; and (4) environmental factors (parental smoking and occupational hazardous exposure, domestic use of pesticides, domestic animals, outdoor odour related to the IP emissions). For statistical analysis, Pearson's chi(2), t-tests and multivariate logistic regressions were used, as well as adjusted odds ratios (OR) within a 95% confidence interval. RESULTS: The multivariate analysis showed that increased LP of URTCD in children of proximal localities was statistically significant when associated with odour complaints (OR = 3.76 [1.16, 12.23]). In proximal localities, LP of URTCD was higher (at borderline level statistical insignificance p = 0.06) than in distant localities (OR = 2.31 [0.96, 5.55]). The following factors were found to be related to the excess of the LP of URTCD: (1) father's lower education (by distance: OR = 2.62 [1.23, 5.57]; by wind direction: OR = 4.07 [1.65, 10.03]); (2) in-vitro fertilization (by distance: OR = 3.03 [1.17, 7.87]; by wind direction: OR = 4.34 [1.48, 12.72]). In proximal localities, the increase in asthma LP was associated with: (1) wind direction (OR = 1.95 [1.01, 3.76]); (2) a child's male gender (OR = 2.95 [1.48, 5.87]); and (3) a child's mother's having had an acute infectious disease during pregnancy (OR = 4.84 [1.33, 17.63]). CONCLUSIONS: An increased LP of chronic respiratory morbidity among children living in small agricultural localities in the Negev was found to be associated with indirect measurements of exposure (distance, wind direction and odour complaints) to IP emissions. These results, in conjunction with previously reported findings in the Negev Bedouin population, indicate a need for environmental protection measures, and monitoring of air pollution and the health of the rural population. PMID- 19645527 TI - Clinical algorithm for improved prediction of ambulation and patient stratification after incomplete spinal cord injury. AB - The extent of ambulatory recovery after motor incomplete spinal cord injury (miSCI) differs considerably amongst affected persons. This makes individual outcome prediction difficult and leads to increased within-group variation in clinical trials. The aims of this study on subjects with miSCI were: (1) to rank the strongest single predictors and predictor combinations of later walking capacity; (2) to develop a reliable algorithm for clinical prediction; and (3) to identify subgroups with only limited recovery of walking function. Correlation and logistic regression analyses were performed on a dataset of 90 subjects with tetra- or paraparesis, recruited in a prospective European multicenter study. Eleven measures obtained in the subacute injury period, including clinical examination, tibial somatosensory evoked potentials (tSSEP), and demographic factors, were related to ambulatory outcome (WISCI II, 6minWT) 6 months after injury. The lower extremity motor score (LEMS) alone and in combination was identified as most predictive for later walking capacity in miSCI. Ambulatory outcome of subjects with tetraparesis was correctly predicted for 92% (WISCI II) or 100% (6minWT) of the cases when LEMS was combined with either tSSEP or the ASIA Impairment Scale, respectively. For individuals with paraparesis, prediction was less distinct, mainly due to low prediction rates for individuals with poor walking outcome. A clinical algorithm was generated that allowed for the identification of a subgroup composed of individuals with tetraparesis and poor ambulatory recovery. These data provide evidence that a combination of predictors enables a reliable prediction of walking function and early patient stratification for clinical trials in miSCI. PMID- 19645526 TI - Changes in calcium-binding protein expression in human cortical contusion tissue. AB - Traumatic brain injury (TBI) produces several cellular changes, such as gliosis, axonal and dendritic plasticity, and inhibition-excitation imbalance, as well as cell death, which can initiate epileptogenesis. It has been demonstrated that dysfunction of the inhibitory components of the cerebral cortex after injury may cause status epilepticus in experimental models; we proposed to analyze the response of cortical interneurons and astrocytes after TBI in humans. Twelve contusion samples were evaluated, identifying the expression of glial fibrillary acidic protein (GFAP) and calcium-binding proteins (CaBPs). The study was made in sectors with and without preserved cytoarchitecture evaluated with NeuN immunoreactivity (IR). In sectors with total loss of NeuN-IR the results showed a remarkable loss of CaBP-IR both in neuropil and somata. In sectors with conserved cytoarchitecture less drastic changes in CaBP-IR were detected. These changes include a decrease in the amount of parvalbumin (PV-IR) neurons in layer II, an increase of calbindin (CB-IR) neurons in layers III and V, and an increase in calretinin (CR-IR) neurons in layer II. We also observed glial fibrillary acidic protein immunoreactivity (GFAP-IR) in the white matter, in the gray-white matter transition, and around the sectors with NeuN-IR total loss. These findings may reflect dynamic activity as a consequence of the lesion that is associated with changes in the excitatory circuits of neighboring hyperactivated glutamatergic neurons, possibly due to the primary impact, or secondary events such as hypoxia ischemia. Temporal evolution of these changes may be the substrate linking severe cortical contusion and the resulting epileptogenic activity observed in some patients. PMID- 19645528 TI - Lack of axonal sprouting of spared propriospinal fibers caudal to spinal contusion injury is attributed to chronic axonopathy. AB - We have previously shown that a small percentage of long descending propriospinal tract (LDPT) axons are spared, whereas few short thoracic propriospinal (TPS) fibers survive 2 weeks following severe (50 mm weight drop) low thoracic spinal cord contusion injury (SCI). Here, we extended those findings to a moderate (25 mm weight drop) T9 SCI and assessed the effects of this lesion severity on propriospinal tract fibers at different time periods after injury. We anterogradely labeled fibers with fluororuby (FR) or WGA-HRP to determine their location and number 2, 4, 6, and 16 weeks post-SCI. Findings were compared with non-injured controls. At chronic time points, surviving FR-labeled LDPT fibers rostral to the injury remained as reactive endings or as putative regenerative sprouts. Caudal to the injury, spared LDPT fibers ran along a rim of lateral and ventral white matter, and ended as small abnormal-appearing putative terminal boutons or reactive endings within the intermediate gray matter of lumbosacral cord, with little axonal arborization and no evidence of injury-induced sprouting. One striking difference in the WGA-HRP experimental operates was the increased density of labeling of spared axons within the white matter caudal to the injury compared to controls. This labeling pattern was reminiscent of the labeling found after axotomy in studies by others, and raises a question as to contusion injury-induced impaired axonal transport. We hypothesize that axonal sprouting of axons after partial spinal cord injury seen in previous investigations was not found in the present investigation because of the additional pathological effects of contusion injury, similar to what is observed after traumatic brain injury. PMID- 19645531 TI - The retrospective application of a prediction model to patients who have had a decompressive craniectomy for trauma. AB - There is currently a resurgence of interest in the use of decompressive craniectomy. As the procedure is used more frequently, there may be an increasing number of patients surviving a severe traumatic brain injury with severe neurological impairment. The aim of this study was to determine if we could predict those cases that fall into this category. We used the web-based prediction model prepared by the CRASH collaborators and applied it to a cohort of patients who had a decompressive craniectomy in 2006 and 2007 at the two major trauma hospitals in Western Australia. All clinical and radiological data were reviewed and entered into the model, and predicted outcome and actual outcome were compared. Our analysis indicated that a significant cut-off point appeared at which the model predicted a 75% risk of an unfavorable outcome at 6 months; 19 of 27 patients with CRASH scores <75% returned to work, whereas none of the 14 patients with higher scores achieved this degree of rehabilitation at 18 months. Statistical analysis of the outcomes in our cohort confirmed that the CRASH model reliably predicted unfavorable outcome. This study demonstrated that our ability to predict poor outcome has improved. PMID- 19645529 TI - An in-vitro traumatic model to evaluate the response of myelinated cultures to sustained hydrostatic compression injury. AB - While a variety of in-vitro models have been employed to investigate the response of load-bearing tissues to hydrostatic pressure, long-term studies are limited by the need to provide for adequate gas exchange during pressurization. Applying compression in vitro may alter the equilibrium of the system and thereby disrupt the gas exchange kinetics. To address this, several sophisticated compression chamber designs have been developed. However, these systems are limited in the magnitude of pressure that can be applied and may require frequent media changes, thereby eliminating critical autocrine and paracrine signaling factors. To better isolate the cellular response to long-term compression, we created a model that features continuous gas flow through the chamber during pressurization, and a negative feedback control system to rigorously control dissolved oxygen levels. Monitoring dissolved oxygen continuously during pressurization, we find that the ensuing response exhibits characteristics of a second- or higher-order system which can be mathematically modeled using a second-order differential equation. Finally, we use the system to model chronic nerve compression injuries, such as carpal tunnel syndrome and spinal nerve root stenosis, with myelinated neuron Schwann cell co-cultures. Cell membrane integrity assay results show that co cultures respond differently to hydrostatic pressure, depending on the magnitude and duration of stimulation. In addition, we find that myelinated Schwann cells proliferate in response to applied hydrostatic compression. PMID- 19645530 TI - Bone marrow stromal cells elicit tissue sparing after acute but not delayed transplantation into the contused adult rat thoracic spinal cord. AB - Bone marrow stromal cells (BMSC) transplanted into the contused spinal cord may support repair by improving tissue sparing. We injected allogeneic BMSC into the moderately contused adult rat thoracic spinal cord at 15 min (acute) and at 3, 7, and 21 days (delayed) post-injury and quantified tissue sparing and BMSC survival up to 4 weeks post-transplantation. BMSC survival within the contusion at 7 days post-transplantation was significantly higher with an acute injection (32%) and 3 day delayed injection (52%) than with a 7- or 21-day delayed injection (9% both; p < 0.01). BMSC survival at 28 days post-transplantation was close to 0 in all paradigms, indicating rejection. In contused rats without a BMSC transplant (controls), the volume of spared tissue gradually decreased until 46% (p < 0.001) of the volume of a comparable uninjured spinal cord segment at 49 days post injury. In rats with BMSC, injected at 15 min, 3, or 7 days post-injury, spared tissue volume was significantly higher in grafted rats than in control rats at the respective endpoints (i.e., 28, 31, and 35 days post-injury). Acute and 3-day delayed but not 7- and 21-day delayed injection of BMSC significantly improved tissue sparing, which was strongly correlated (r = 0.79-1.0) to BMSC survival in the first week after injection into the contusion. Our data showed that neuroprotective effects of BMSC transplanted into a moderate rat spinal cord contusion depend strongly on their survival during the first week post-injection. Acutely injected BMSC elicit more tissue sparing than delayed injected BMSC. PMID- 19645532 TI - A bundle approach to reduce the incidence of external ventricular and lumbar drain-related infections. AB - OBJECT: An important complication of external CSF drainage is bacterial meningitis or ventriculitis, resulting in increased morbidity, mortality, and health care costs. In 2003, a high rate (37%) of probable drain-related infections was identified at the authors' hospital. A multidisciplinary working group was installed to reduce this incidence to < 10% within 1.5 years. METHODS: An intervention strategy based on 5 pillars (increased awareness, focused standard operating procedures, a diagnostic and therapeutic algorithm, timely administration of prophylaxis, and improvement of the drainage system) was designed and implemented from 2004 to 2006. During this period all patients with external CSF drainage were prospectively monitored. RESULTS: Between 2004 and 2006, there were 467 patients in whom 579 drains (external ventricular and external lumbar) had been placed. The overall incidence of drain-related infections was 16.2% in 2004, 8.9% in 2005, and 11.3% in 2006. For external lumbar drains the number of infections per 100 drain days was 2.4 in 2004, 0.6 in 2005, and 0.8 in 2006. For external ventricular drains these rates were 1.7, 1.0, and 1.2, respectively. Meanwhile, the causative noncutaneous microorganisms, indicative for systemic-contamination during manipulation, decreased. By retrospective analysis, the proportion of patients with a probable drain-related infection decreased from 37% in 2003 to 9% in 2005 and 2006. CONCLUSIONS: The authors' multidisciplinary approach in which different preventive measures were combined was associated with a significant reduction in the incidence of drain related secondary meningitis, and thus provides an important improvement of patient safety. PMID- 19645533 TI - Risk profile associated with convexity meningioma resection in the modern neurosurgical era. AB - OBJECT: Although meningiomas are commonly found along the supratentorial convexity, the risk profile associated with this subset of lesions in the modern neurosurgical era is unknown. METHODS: The authors retrospectively reviewed the clinical course of patients with supratentorial convexity meningiomas treated during the past 10 years. All patients had undergone MR imaging within 72 hours after surgery and at least 1 year of clinical follow-up. Patients with multiple meningiomas, hemangiopericytomas, malignant meningiomas, or tumor-prone syndromes were excluded from analysis. RESULTS: Between 1997 and 2007, 141 consecutive patients (median age 48 years, range 18-95 years) underwent resection of a supratentorial convexity meningioma. The most common signs or symptoms at presentation were headache (48%), seizures (34%), and weakness (21%). The mean tumor volume was 146.3 cm3 (range 1-512 cm3). There were no intraoperative complications or deaths. Medical or neurosurgical morbidity was noted in the postoperative course of 14 patients, equating to a 10% overall complication rate. Postoperative surgical complications included hematoma requiring evacuation, CSF leakage, and operative site infection. Medical complications included pulmonary embolus and deep vein thrombosis requiring treatment. A Simpson Grade 0 or 1 resection was achieved in 122 patients (87%). One hundred six tumors (75%) were WHO Grade I, whereas 35 (25%) were WHO Grade II. The median clinical follow-up was 2.9 years (range 1-10 years), and the median radiographic follow-up was 3.7 years (range 1-10 years). Six patients (4%) had radiographic evidence of tumor recurrence, with 3 (2%) undergoing repeat resection. CONCLUSIONS: With the conservative recommendations for surgery for asymptomatic meningiomas and the advent of radiosurgery during the past 10 years, microsurgically treated convexity meningiomas are now typically large in size. Nevertheless, the patient's clinical course following microsurgical removal of these lesions is expected to be uncomplicated. The authors' findings provide a defined risk profile associated with the resection of supratentorial convexity meningiomas in the modern neurosurgical era. PMID- 19645534 TI - Endovascular recanalization of the completely occluded internal carotid artery using a flow reversal system at the subacute to chronic stage. AB - OBJECT: The efficacy and pitfalls of endovascular recanalization were evaluated in cases of internal carotid artery (ICA) occlusion in the subacute to chronic stage. METHODS: Fourteen cases (15 lesions) of symptomatic ICA occlusion with hemodynamic compromise or recurrent symptoms were treated at the subacute to chronic stage using an endovascular technique. The Parodi embolic protection system was used during the recanalization procedure to prevent embolic stroke by reversing the flow from the distal ICA to the common carotid artery. RESULTS: Recanalization of the occluded ICA was possible in 14 of 15 lesions. The occlusion points were 10 cervical ICAs and 4 petrous/cavernous ICAs in successfully recanalized cases. Ischemic symptoms disappeared completely after the treatment, and new ischemic symptoms did not appear related to the treated lesion. Single photon emission computed tomography findings demonstrated the improvement of hemodynamic compromise in all cases. One case showed right middle cerebral artery branch occlusion during the procedure, but this patient's neurological symptoms were stable due to preexisting hemiparesis. Endovascular recanalization was possible and effective in improving hemodynamic compromise. However, there are still several problems with this technique, such as hyperperfusion syndrome after recanalization, cerebral embolism during treatment, durability after treatment, and identification of the occlusion point before treatment. CONCLUSIONS: Endovascular recanalization using an embolic protection device can be considered as an alternative treatment for symptomatic ICA occlusion with hemodynamic compromise or refractoriness to antiplatelet therapy, even in the subacute to chronic stage of the illness. PMID- 19645535 TI - Screening for blunt cerebrovascular injury: selection criteria for use of angiography. AB - OBJECT: Blunt cerebrovascular injury (BCI) to the carotid and vertebral arteries is being recognized with increasing frequency in trauma victims. Yet, only broadly defined criteria exist for the use of screening angiography. In this study, the authors systematically identified the associated injuries that predict BCI and provide guidelines for the types of injuries best evaluated by angiography. METHODS: Criteria for screening angiography were developed with intentionally broad inclusion to maximize sensitivity. Screening criteria for each patient and angiographic results (5-point scale of BCI) were recorded prospectively. Injuries most often associated with a positive angiogram were identified. Dissection grades of 0-1 were classified as minor. RESULTS: Of 365 patients evaluated for trauma by angiography between January 2000 and December 2005, 40 patients with penetrating trauma were excluded. Of the 325 patients included in the study, 100 (30.8%) had positive angiographic findings, including 79 (24.3%) with major injuries. Fractures of the cervical spine and midface (or mandibular ramus) were associated with major BCI (identified in 30.7% of patients with cervical fractures and 30.8% of patients with midface fractures). However, thoracic trauma and soft tissue injury of the neck were rarely associated with a significant BCI (0 and 3 cases, respectively). Horner syndrome and cervical bruit were associated with arterial dissection in 9 of 10 patients. Skull base fractures and unexplained neurological findings were associated with major BCI in 13 (18.3%) of 71 and 11 (16.9%) of 65 patients, respectively. CONCLUSIONS: Cervical and facial fractures resulting from blunt trauma were highly associated with BCI. After significant thoracic trauma or soft tissue injury to the neck, angiography should be reserved for patients with unexplained neurological findings or expanding hematomas of the neck. PMID- 19645536 TI - Decompressive craniectomy for the treatment of traumatic brain injury: does an age limit exist? AB - OBJECT: It is generally believed that the outcome of traumatic brain injury is not improved by decompressive craniectomy in patients older than 30-50 years. A literature search was performed to assess the level of evidence with respect to the effect of age on outcome in these cases. METHODS: References were identified by PubMed searches of journal articles published between 1995 and December 2008. The inclusion criteria were as follows: 1) clinical series including adults; and 2) focus on age as a prognostic factor. Technical notes and laboratory investigations were excluded. RESULTS: Fourteen English-language articles were finally selected. In 5 of the 14 studies, the authors performed no statistical analysis. In 6 studies they concluded that age was not significantly related to outcome (with 1 of these studies showing a correlation between age and outcome only after 65 years). Three studies showed a correlation between age and outcome. CONCLUSIONS: With respect to age and effectiveness of decompressive craniectomy, there are no robust data to establish any degree of core evidence and the referred age thresholds are arbitrary. PMID- 19645537 TI - Neurosurgical mortality rates: what variables affect mortality within a single institution and within a national database? AB - OBJECT: Mortality rate is a common outcome measure used by patients, families, physicians, insurers, and health care policy makers to evaluate and measure the quality of health care. The mortality index is a heavily used metric to measure survival, and is a key indicator in hospital report cards and national rankings. The significance of this metric is belied by the literature, which fails to accurately detail the overall mortality rate within the neurosurgical population. Given that there is no gold standard that can be used as a baseline, it is difficult to make durable interinstitutional comparisons concerning performance. In Part I of this paper, the authors examined an academic neurosurgical program's mortality rate and the effect of certain variables on this rate. In Part II, they assumed a broader perspective, examining a group of institutions, the University HealthSystem Consortium (UHC) Clinical Database/Resource Manager, and identifying factors that may be responsible for variability in the mortality index between hospitals. METHODS: Over a 36-month period, the authors' neurosurgical service performed 3650 procedures. Monthly "mortality and morbidity" conference logs were reviewed to collect information on the number of deaths. Deaths were classified according to elective or nonelective admission status. Additionally, the authors reviewed the UHC Clinical Database/Resource Manager for information regarding mortality rates in various other neurosurgical programs. These data reflected a 12-month period. Comparisons of hospital mortality indices were based on the percentage of transferred patients (both emergency department [ED] and inpatient), whether a hospital was a designated Level 1 trauma center, whether a hospital was designated a certified stroke center, and also based on the number of Medicaid patients treated. RESULTS: Sixty-two patients met the criteria to be considered neurosurgery-related deaths at the authors' institution (1.7% of all cases): 9 elective admissions (15%), 3 nonelective direct admissions (5%), 24 transfer patients (39%), and 26 ED admissions (42%). Causes of death included trauma (40%), stroke (33%), tumor (14%), spinal disease (8%), and infection (6%). Evaluation of the UHC data revealed that a mortality index of >or= 1.00 was seen in the following hospital types: trauma centers, hospitals with 11-20% Medicaid patients, and those with > 50,000 ED admissions. A nonstatistically significant trend toward increasing mortality rates was seen in hospitals with a lower percentage of elective neurosurgical cases, in Level 1 trauma centers, and in hospitals that were not certified stroke centers. Significance was seen in comparisons of hospitals with the highest and lowest mortality index quartiles in the following groups: trauma centers, hospitals with > 10% Medicaid patients, and hospitals with a high number of ED visits. CONCLUSIONS: Many variables appear to impact the mortality rate within the neurosurgical population. The authors' observations have illuminated some of the reasons why: the data are elusive, documentation is variable, and the modes of statistical analysis are questionable. The first step in addressing this issue is to identify that there is a problem. The authors believe that this study has done so. Presently there is no definitive or reliable source for rating the quality of overall neurosurgical care, nor is there a good and complete source for understanding the quality of neurosurgical care in the US. It is important to view these results as the initial steps to a better understanding of patient outcomes, their measures, and their impact on neurosurgical practice. PMID- 19645538 TI - The safety and effectiveness of a dural sealant system for use with nonautologous duraplasty materials. AB - OBJECT: The DuraSeal dural sealant system, a polyethylene glycol hydrogel, has been shown to be safe and effective when used with commercial and autologous duraplasty materials. The authors report on the safety and effectiveness of this sealant when used in conjunction with nonautologous duraplasty materials. METHODS: In this retrospective, nonrandomized, multicenter study, the safety and efficacy of a dural sealant system was assessed in conjunction with primarily collagen-based nonautologous duraplasty materials in a sample of 66 patients undergoing elective cranial procedures at 3 institutions. This cohort was compared with 50 well-matched patients from the DuraSeal Pivotal Trial who were treated with this sealant system and autologous duraplasty material. RESULTS: The key end points of the study were the incidences of CSF leaks, surgical site infections, and meningitis 90 days after surgery. The incidence of postoperative CSF leakage was 7.6% in the study group (retrospective population) and 6.0% in the Pivotal Trial population. The incidence of meningitis was 0% and 4.0% in the retrospective and Pivotal Trial groups, respectively. There were no serious device-related adverse events or unanticipated adverse device effects noted for either population. CONCLUSIONS: This study demonstrates that the DuraSeal sealant system is safe and effective when used for watertight dural closure in conjunction with nonautologous duraplasty materials. PMID- 19645539 TI - Neurosurgical management of intracranial epidermoid tumors in children. Clinical article. AB - OBJECT: Epidermoid tumors are benign lesions representing 1% of all intracranial tumors. There have been few pediatric series of intracranial epidermoid tumors reported previously. The authors present their experience in the management of these lesions. METHODS: The neurosurgical database at the Hospital for Sick Children was searched for children with surgically managed intracranial epidermoid tumors. The patients' charts were reviewed for demographic data, details of clinical presentation, surgical therapy, and follow-up. Ethics board approval was obtained for this study. RESULTS: Seven children, all girls, were identified who met the inclusion criteria between 1980 and 2007. The average age at surgery was 11.2 years (range 8-15 years), and the mean maximal tumor diameter was 2.1 cm. Headache was the most common presenting symptom, and 1 tumor was found incidentally. Most patients had normal neurological examinations, but meningism was found in 2 cases. There were 3 cerebellopontine angle lesions, 1 pontomedullary lesion, and 3 supratentorial tumors. Hydrocephalus developed in 1 patient after aseptic meningitis, and she underwent shunt placement. There were no operative deaths. Complete resection could be performed in 2 patients. One patient experienced a small recurrence that did not require a repeated operation, while 1 subtotally resected lesion recurred and the patient underwent a second operation. CONCLUSIONS: Intracranial epidermoid tumors are rare in the pediatric population. Total resection is desirable to minimize the risk of postoperative aseptic meningitis, hydrocephalus, and tumor recurrence. Aggressive neurosurgical resection may be associated with cranial nerve or ischemic deficits, however. In these cases, neurosurgical judgment at the time of surgery is warranted to ensure maximum resection while minimizing postoperative neurological deficits. PMID- 19645540 TI - Role of Rac1-regulated signaling in medulloblastoma invasion. Laboratory investigation. AB - OBJECT: Medulloblastomas are the most common malignant brain tumors in children. These tumors are highly invasive, and patients harboring these lesions are frequently diagnosed with distant spread. In this study, the authors investigated the role of Rac1, a member of the Rho family of small guanosine triphosphatases, in medulloblastoma invasion. METHODS: Three established medulloblastoma cell lines were used: DAOY, UW-228, and ONS-76. Specific depletion of Rac1 protein was accomplished by transient transfection of small interfering RNA. Cell invasion through extracellular matrix (Matrigel) was quantified using a transwell migration assay. Mitogen activated protein kinase activation was determined using phospho-MAP kinase-specific antibodies, and inhibition of MAP kinase pathways was achieved by specific small molecule inhibitors. Localization of Rac1 and its expression levels were determined by immunohistochemical analysis using a Rac1 specific antibody, and Rac1 activation was qualitatively assessed by Rac1 plasma membrane association. RESULTS: Small interfering RNA-mediated depletion of Rac1 strongly inhibited medulloblastoma cell invasion. Although depletion of Rac1 inhibited the proliferation of UW-228 cells, and of ONS-76 cells to a lesser extent, it stimulated the proliferation of DAOY cells. Depletion of Rac1 also inhibited the activation of the ERK and JNK MAP kinase pathways, and inhibition of either pathway diminished invasion and proliferation. Immunohistochemical analysis demonstrated that the Rac1 protein was overexpressed in all medulloblastoma tumors examined, and indicated that Rac1 was hyperactive in 6 of 25 tumors. CONCLUSIONS: The authors' data show that Rac1 is necessary for the invasive behavior of medulloblastoma cells in vitro, and plays a variable role in medulloblastoma cell proliferation. In addition, these results indicate that Rac1 stimulates medulloblastoma invasion by activating the ERK and JNK pathways. The authors suggest that Rac1 and signaling elements controlled by this guanosine triphosphatase may serve as novel targets for therapeutic intervention in malignant medulloblastomas. PMID- 19645541 TI - Surgical treatment of ectopic recurrence of craniopharyngioma. Report of 4 cases. AB - Local recurrence following radical resection is one of the most common complications of pediatric craniopharyngioma. Only 28 cases of ectopic recurrence of craniopharyngioma have been reported in the literature, and only 13 cases occurred in patients originally treated as children. In this consecutive series of 86 children who underwent radical resection of primary and recurrent craniopharyngiomas, 4 patients (4.7%) experienced ectopic tumor recurrence, accounting for 27% of all recurrences after gross-total resection. The authors report on the successful surgical treatment of these 4 patients and the impact of ectopic craniopharyngioma recurrence on survival. PMID- 19645542 TI - Surgical treatment of juvenile nasopharyngeal angiofibroma with intracranial extension. Clinical article. AB - OBJECT: The purpose of this study was to describe the surgical treatment and outcomes of patients with intracranial extension of juvenile nasopharyngeal angiofibroma (JNA). METHODS: Twenty-one patients who underwent operations for JNAs between 1994 and 2008 were enrolled in the study. Seven patients (33%) had intracranial tumor extension. The middle cranial fossa and cavernous sinus were involved in 4 patients who underwent operations via the combined infratemporal fossa-midfacial degloving approach. The anterior skull base was involved in 3 patients who underwent the subcranialmidfacial degloving approach. RESULTS: Complete tumor removal was achieved in all patients. Postoperative complications included 1 case of soft-tissue infection. None of the patients had tumor recurrence after a mean follow-up of 42 months (range 29-85 months). No adjuvant therapy was required in any patient. CONCLUSIONS: Combined approaches can be used effectively for treatment of JNAs with intracranial extension without the need for adjuvant therapy. PMID- 19645543 TI - Isolated cerebellar Rosai-Dorfman granuloma mimicking Lhermitte-Duclos disease. Case report. AB - Rosai-Dorfman disease (RDD) is an idiopathic histioproliferative disorder that rarely involves the CNS. Rosai-Dorfman disease is exceedingly rare in the pediatric population and has never been observed in the cerebellum of a child. The authors present the case of a 14-year-old male with a cerebellar lesion having radiographic characteristics of Lhermitte-Duclos disease. After a period of observation with a presumptive diagnosis of Lhermitte-Duclos disease, the child underwent suboccipital craniotomy and resection of the lesion due to continuous suboccipital headaches. Histological examination of the tissue demonstrated RDD. The published literature on RDD is reviewed with an emphasis on differential diagnosis. PMID- 19645544 TI - Recovery of sensorineural hearing loss following operative management of a posterior fossa arachnoid cyst. Case report. AB - Arachnoid cysts are benign, intraarachnoid cysts filled with cerebrospinal fluid that are usually encountered in the middle cranial fossa. If present in the posterior fossa, they usually produce nonspecific signs and symptoms such as headaches, dizziness and vertigo. We report the rare presentation of a young girl with right-sided sensorineural hearing loss and tinnitus secondary to a right cerebellopontomedullary arachnoid cyst. The patient underwent a suboccipital retrosigmoid (retromastoid) craniectomy with fenestration of the arachnoid cyst. Subsequently, the patient experienced improvement in hearing with near-complete resolution of sensorineural hearing loss. To the authors' knowledge, postoperative near-complete resolution of hearing loss secondary to posterior fossa arachnoid cysts in a pediatric patient has not been previously reported. The authors also review the literature with respect to posterior fossa arachnoid cysts and discuss their clinical features, diagnosis, and management. PMID- 19645545 TI - Sporadic unilateral vestibular schwannoma in the pediatric population. Clinical article. AB - OBJECT: Vestibular schwannomas (VSs) are rare in the pediatric population. Most often, these lesions manifest as a bilateral disease process in the setting of neurofibromatosis Type 2. Even in the absence of additional clinical diagnostic criteria, the presentation of a unilateral VS in a young patient may be a harbinger of future penetrance for this hereditary tumor syndrome. METHODS: The authors retrospectively reviewed the charts of a cohort of 7 patients who presented with apparently sporadic, unilateral VSs. These patients had previously undergone surgery via translabyrinthine, retrosigmoid, or combined approaches. Clinical outcomes were reviewed with emphasis on facial nerve function and follow up for signs and symptoms of a heritable disorder. RESULTS: All patients underwent microsurgical resection in a multidisciplinary effort by the senior authors. The average tumor size was 4.57 cm, with an average duration of symptoms prior to definitive diagnosis of 31.2 months. The tumor size at the time of presentation followed a trend different from reports in adults, while the duration of symptoms did not. At a follow-up average of 6.3 years (range 1-12 years), 100% of patients demonstrated good facial function (House-Brackmann Grade I or II). No patient in this cohort demonstrated symptoms, objective signs, or genetic analysis indicating the presence of neurofibromatosis Type 2. CONCLUSIONS: Diagnosis and management of sporadic, unilateral VSs in children is complicated by clinical presentations and surgical challenges unique from their adult counterparts. Careful consideration should be given to a heritable genetic basis for sporadic unilateral VS in the pediatric population. Results of genetic testing do not preclude the necessity for long-term follow-up and systemic investigation. In patients who present with large tumors, preliminary experience leads the authors to suggest that a combined retrosigmoid-translabyrinthine approach offers the greatest opportunity for preservation of facial nerve function. PMID- 19645546 TI - Symptomatic intracystic hemorrhage in pineal cysts. Report of 3 cases. AB - Pineal cysts are benign and often asymptomatic intracranial entities. Occasionally they can lead to neurological symptoms through growth or due to intracystic hemorrhage. The purpose of the current report is to describe their clinical characteristics and treatment options. In the current study, the authors illustrate the course of disease in 3 patients who developed neurological symptoms due to hemorrhage into a pineal cyst. Two of their patients had additional cerebral disease, and regular MR imaging examinations were conducted. This circumstance allowed documentation of growth and intracystic hemorrhage. After the occurrence of new neurological symptoms with severe headache, MR images showed a fluid-fluid interface due to intracystic hemorrhage. The third patient presented with acute triventricular hydrocephalus and papilledema due to aqueductal stenosis caused by intracystic hemorrhage. In all 3 cases, excision of the pineal cysts via an infratentorial/supracerebellar approach was performed. Histological examination revealed the characteristic structure of pineal cyst in all cases, with hemorrhagic residues in the form of hemosiderin deposits. All patients recovered fully after surgical removal of the cysts. Furthermore, resolution of occlusive hydrocephalus could be demonstrated in those cases with ventricular enlargement. Pineal cysts without neurological symptoms are often discovered as incidental findings on cranial MR images. In contrast, neurological symptoms such as severe headache, diplopia, or Parinaud syndrome, may occur as a result of pineal apoplexy due to intracystic hemorrhage. The authors' cases confirm that MR imaging can identify intracystic hemorrhage by a characteristic fluid-fluid interface. Their experience suggests that microsurgical resection of cysts may be an effective and curative treatment option. PMID- 19645548 TI - Hemiparkinsonism due to a pontomesencephalic cavernoma: improvement after resection. Case report. AB - Cavernous angiomas of the upper brainstem causing hemiparkinsonism are very rare. Due to their difficult-to-reach localization, brainstem cavernomas, in particular those in anterior locations, continue to present a therapeutic challenge. The authors report on a 16-year-old boy with a pontomesencephalic cavernoma who developed hemiparkinsonism and hemiparesis after hemorrhage. After complete surgical removal of the pontomesencephalic cavernoma via a pterional transsylvian approach, his symptoms resolved. Although pontomesencephalic cavernomas occupying the ventral portion of the brainstem are regarded as problematic for resection, the pterional transsylvian approach provides an excellent route for removal of cavernomas that are in contact with the ventral surface of the midbrain in the interpeduncular cistern. Surgical removal of this type of lesion is recommended because resolution of clinical symptoms, including hemiparkinsonism, can be achieved. PMID- 19645547 TI - Mixed germ cell tumor of the midbrain. Case Report. AB - This 14-year-old boy presented with left hemiparesis, gait disturbance, and multiple cranial nerve palsies. Magnetic resonance imaging revealed a multicystic mass with hemorrhagic fluid-fluid levels in the right midbrain, suggesting the presence of a cavernous malformation. Diffusion tensor imaging showed the mass to be close to the right corticospinal tract and ipsilateral medial lemniscus. Subtotal removal of the mass was performed via a right subtemporal approach. The histopathological diagnosis was of a mixed germ cell tumor (GCT) comprising mature teratoma and germinoma cells with syncytiotrophoblastic giant cells. The patient underwent postoperative chemotherapy and radiotherapy, and no tumor progression was found during 1 year of follow-up. Intracranial GCTs arise mainly in the pineal and the suprasellar area. Germ cell tumors in the brainstem are rare, with only 12 reported cases. Among these, 4 were in the midbrain and histologically were pure germinomas. To the authors' knowledge, this is the first reported case of a mixed GCT in the midbrain combining mature teratoma and germinoma cells. PMID- 19645549 TI - Hypothalamic lipoma associated with severe obesity. Report of 2 cases. AB - The association between hypothalamic dysfunction and obesity is well documented in both clinical and experimental models. The authors describe 2 children who developed obesity that could not be explained by endocrinological, genetic, or eating disorders. In both cases, cranial MR imaging revealed the typical appearance of a lipoma in the paramedian hypothalamus. In the absence of other etiologies, the authors hypothesized that in these 2 children obesity was caused by their hypothalamic lipomas. To the authors' knowledge, these are the first cases of hypothalamic lipomas likely to be causing obesity that have been described in children. These cases highlight the importance of performing cranial MR imaging in children with otherwise unexplained obesity. PMID- 19645550 TI - Endoscopic disconnection of hypothalamic astrocytoma causing gelastic epilepsy. Case report. AB - The authors report on a case of juvenile pilocytic astrocytoma (JPA) and concomitant hypothalamic hamartoma (HH) with gelastic epilepsy that was successfully treated with endoscopic disconnection. This 6-year-old girl presented with prolonged, medically intractable gelastic seizures that were often followed by generalized tonic seizures. An enhancing, low-grade hypothalamic tumor was identified on MR images obtained when she was 11 months old, but no surgical intervention was attempted at that time apart from bur hole drainage of a chronic subdural hemorrhage. In the first surgery, performed when she was 6 years of age, the authors attempted disconnection and tumor sampling; the lesion was revealed to be a JPA. A second endoscopic disconnection was performed 1 year later to improve seizure control and obtain a pathological specimen from the nonenhancing contralateral side. The pathological results after the second surgery revealed that the enhancing mass was a spontaneously regressing JPA and the contralateral nonenhancing mass was an HH. The HH was found as latent tumor and the JPA was the mass causing gelastic epilepsy. To the authors' knowledge, this is the first report of a patient with a spontaneously regressing JPA and concomitant HH, both of which were treated by endoscopic disconnection. PMID- 19645552 TI - Postoperative cerebrospinal fluid wound leakage as a predictor of shunt infection: a prospective analysis of 205 cases. Clinical article. AB - OBJECT: The purpose of this study was to audit some of the risk factors for CSF shunt infections within the authors' practice and analyze the statistical significance of these factors. METHODS: The authors used their own contemporaneously collected shunt database in this study. All shunt procedures performed over a 2-year period between March 2000 and February 2002 at Great Ormond Street Hospital, London, were analyzed. For the purposes of this study, positive CSF cultures were a prerequisite for a data set to qualify as a shunt infection. The authors studied the effects of patient age, the etiology of hydrocephalus, whether the surgery was primary shunt placement versus a revision, the surgeon's level of experience, whether the surgery was performed on an elective or emergency basis, and the presence or absence of a perioperative CSF leak. Statistical analyses were performed. RESULTS: Two hundred and five patients with a mean (+/- SD) age at surgery of 27.9 +/- 43.0 months were included in this study. Shunt infections developed in 17 patients (8.3%) at a median of 42 days postoperatively (range 14-224 days). The presence of a perioperative CSF leak was the only variable that showed a statistically significant association with the occurrence of a shunt infection, with an infection rate of 57.1% compared to 4.7% in cases with no leak (OR 27.0 [95% CI 7.7-94.3]). The cause of hydrocephalus, elective versus emergency surgery, level of surgeon experience, a primary versus a revision procedure, and patient age did not have a bearing on the infection risk. CONCLUSIONS: The presence of a perioperative CSF leak puts pediatric patients at a very high risk of shunt infection. Aside from prevention, the optimal management of such CSF leaks require further investigation. PMID- 19645553 TI - Shunt malfunction causing acute neurological deterioration in 2 patients with previously asymptomatic Chiari malformation Type I. Report of two cases. AB - Patients with symptomatic Chiari malformation Type I (CM-I) typically exhibit a chronic, slowly progressive disease course with evolution of symptoms. However, some authors have reported acute neurological deterioration in the setting of CM I and acquired Chiari malformations. Although brainstem dysfunction has been documented in patients with CM-II and hydrocephalus or shunt malfunction, to the authors' knowledge only 1 report describing ventriculoperitoneal (VP) shunt malfunction causing neurological deterioration in a patient with CM-I exists. The authors report on their experience with the treatment of previously asymptomatic CM-I in 2 children who experienced quite different manifestations of acute neurological deterioration secondary to VP shunt malfunction. Presumably, VP shunt malfunction created a positive rostral pressure gradient across a stenotic foramen magnum, resulting in tetraparesis from foramen magnum syndrome in 1 patient and acute ataxia and cranial nerve deficits from syringobulbia in the other. Although urgent shunt revisions yielded partial recovery of neurological function in both patients, marked improvement occurred only after posterior fossa decompression. PMID- 19645551 TI - Infection rates following initial cerebrospinal fluid shunt placement across pediatric hospitals in the United States. Clinical article. AB - OBJECT: Reported rates of CSF shunt infection vary widely across studies. The study objective was to determine the CSF shunt infection rates after initial shunt placement at multiple US pediatric hospitals. The authors hypothesized that infection rates between hospitals would vary widely even after adjustment for patient, hospital, and surgeon factors. METHODS: This retrospective cohort study included children 0-18 years of age with uncomplicated initial CSF shunt placement performed between January 1, 2001, and December 31, 2005, and recorded in the Pediatric Health Information System (PHIS) longitudinal administrative database from 41 children's hospitals. For each child with 24 months of follow up, subsequent CSF shunt infections and procedures were determined. RESULTS: The PHIS database included 7071 children with uncomplicated initial CSF shunt placement during this time period. During the 24 months of follow-up, these patients had a total of 825 shunt infections and 4434 subsequent shunt procedures. Overall unadjusted 24-month CSF shunt infection rates were 11.7% per patient and 7.2% per procedure. Unadjusted 24-month cumulative incidence rates for each hospital ranged from 4.1 to 20.5% per patient and 2.5-12.3% per procedure. Factors significantly associated with infection (p < 0.05) included young age, female sex, African-American race, public insurance, etiology of intraventricular hemorrhage, respiratory complex chronic condition, subsequent revision procedures, hospital volume, and surgeon case volume. Malignant lesions and trauma as etiologies were protective. Infection rates for each hospital adjusted for these factors decreased to 8.8-12.8% per patient and 1.4-5.3% per procedure. CONCLUSIONS: Infections developed in > 11% of children who underwent uncomplicated initial CSF shunt placements within 24 months. Patient, hospital, and surgeon factors contributed somewhat to the wide variation in CSF shunt infection rates across hospitals. Additional factors may contribute to variation in CSF shunt infection rates between centers, but further study is needed. Benchmarking and future prospective multicenter studies of CSF shunt infection will need to incorporate these and other patient, hospital, and surgeon factors. PMID- 19645555 TI - How long should cerebrospinal fluid cultures be held to detect shunt infections? Clinical article. AB - OBJECT: Infections of CSF hardware may be indolent, and some patients have received antibiotic treatment for various reasons before CSF is obtained to check for a shunt infection. At present, there are few data in the literature to guide the decision as to how long to hold CSF specimens when attempting to diagnose hardware infections, and institutions vary in the duration at which cultures are considered "final." METHODS: The authors reviewed the microbiology data from CSF specimens obtained from shunts, ventriculostomies, reservoirs, and lumbar drains at their institution over a 36-month period to discover how long after collection cultures became positive. The authors also sought to discover whether this time was affected by prior treatment with antibiotics. RESULTS: Of 158 positive CSF specimens obtained from hardware, the time to recovery ranged between 1-10 days, with a mean of 3.02 days (SD 2.37 days, 95% CI 2.66-3.38 days). One hundred and twenty-seven positive specimens were associated with clinical infections, and approximately 25% of these grew organisms after > 3 days, with some as long as 10 days after specimens were obtained. The most common organisms grown from individual patients were coagulase-negative Staphylococcus spp (34 cultures), Propionibacterium spp (21), Bacillus spp (6), Pseudomonas aeruginosa (4), and Staphylococcus aureus (4 cultures). Mean and maximum days to recovery were different across species, with S. aureus showing the shortest and Propionibacterium spp showing the longest incubation times. There appeared to be no significant difference in the time to recovery between specimens obtained in patients who had received prior antibiotic treatment versus those who had not. CONCLUSIONS: A substantial number of positive CSF specimens obtained in patients with clinical infections grew bacteria after > 3 days, with some requiring as long as 10 days. Thus, a routine 10-day observation period for CSF specimens can be justified. PMID- 19645554 TI - Outcome of ventriculoperitoneal shunt placement in Grade IV tubercular meningitis with hydrocephalus: a retrospective analysis in 95 patients. Clinical article. AB - OBJECT: Hydrocephalus is the most common complication of tubercular meningitis (TBM). Relieving hydrocephalus by ventriculoperitoneal (VP) shunt placement has been considered beneficial in patients in Palur Grade II or III. The role of VP shunt placement in those of Grade IV is controversial and the general tendency is to avoid its use. Some authors have suggested that patients in Grade IV should receive a shunt only if their condition improves with a trial placement of an external ventricular drain (EVD). In the present study, the authors assessed the outcome of VP shunt placement in patients in Grade IV TBM with hydrocephalus to examine the factors predicting outcome and to determine whether a trial with an EVD is absolutely necessary prior to shunt placement. METHODS: Ninety-five consecutive cases of TBM with hydrocephalus in which the patients underwent VP shunt placement were retrospectively analyzed, and direct VP shunts were placed whenever possible. An EVD was placed first only in the presence of deranged blood parameters. Outcomes were assessed both in the short and long term. RESULTS: The mean patient age was 17.5 years (range 1-55 years). Fifty-two patients underwent direct VP shunt placement, and the remaining 43 received EVDs first. Overall, 33 and 45% of patients had favorable short- and long-term outcomes, respectively. Age older than 3 years and duration of altered sensorium < or = 3 days were predictive of a favorable short-term outcome. Glasgow Coma Scale score at presentation was predictive of long-term outcome. Of the patients who did not improve with placement of an EVD prior to VP shunt insertion, 24 and 18% had favorable short- and long-term outcomes, respectively; this was not significantly different from the outcome in the patients who underwent direct VP shunt placement. CONCLUSIONS: Direct VP shunt placement is an effective option in patients with Grade IV TBM with hydrocephalus. Age and duration of altered sensorium are predictive of short-term outcome, while Glasgow Coma Scale score at presentation predicts long-term outcome. Ventriculoperitoneal shunts should be considered even in patients who do not improve with an EVD. PMID- 19645556 TI - Endoscopic third ventriculostomy. PMID- 19645557 TI - Introduction: surgery of limbic and paralimbic gliomas. PMID- 19645558 TI - Embryological development of the human insula and its implications for the spread and resection of insular gliomas. AB - The human insular cortex, or the lobus insularis, is considered the developmentally most primitive lobe of the telencephalon. Covered by an overlying cortical lid, the insula has functions that are distinct from yet related to those of the adjacent temporal lobe and deep limbic structures. In the first part of this paper the authors outline the development of the human insula, including the cellular heterogeneity comprising the various parts of the insular lobe. Using the understanding gained from the development of the insula they then address implications of insular development for cortical development and connection as well as for tumorigenesis and tumor spread from the insula to other cortical structures, most notably the temporal lobe. An understanding of cortico insular development and interconnection allows for both a better understanding of insular pathology and also facilitates planning of resection of cortico-insular gliomas to avoid damage to eloquent structures. PMID- 19645559 TI - Surgical anatomy and functional connectivity of the limbic system. AB - OBJECT: The goal in this study was to highlight the potential of currently available imaging techniques for surgical planning of procedures in and around the limbic system. METHODS: The authors review traditional and newer imaging techniques as applied to neurosurgical planning. Today MR imaging techniques play a preponderant role. The various applications of functional techniques such as diffusion weighted, diffusion tensor, perfusion, and functional MR imaging methods are discussed. RESULTS: In addition to the high-resolution studies of anatomy that can be acquired, especially at higher field strengths (>or= 3 T), MR imaging now also offers the possibility of acquiring functional, metabolic, hemodynamic, and molecular information on normal and pathological brain processes. CONCLUSIONS: The knowledge obtained using the various imaging techniques contributes substantially to understanding the disease processes in a way that drastically improves surgical planning. PMID- 19645560 TI - Tumor-associated epilepsy. AB - Tumor-associated epilepsy is an important contributor to morbidity in patients with brain tumors. Proposed pathophysiological mechanisms to explain these effects range from neuronal and glial dysfunction to deranged vascular homeostasis, to ionic and pH changes. Perilesional tissue alterations play a vital role in the generation of tumor-associated seizures. Clinical studies have determined that tumor-associated seizures are usually focal with secondary generalization and often resistant to antiepileptic drugs. Tumor histopathological characteristics and location are independent factors that impact seizure burden. Further understanding of the mechanisms of tumor associated epilepsy may lead to new types of treatments targeted at perilesional tissue alterations. PMID- 19645561 TI - Brain tumors in the mesial temporal lobe: long-term oncological outcome. AB - OBJECT: Surgical treatment of brain tumors in the mesial temporal lobe (MTL) is a highly demanding procedure. Only a few studies describing the surgery of MTL tumors have been reported, and they have been focused on the operative techniques and immediate results of the surgery. The authors have analyzed the long-term oncological outcome in patients with MTL tumors. METHODS: Thirty-six patients with an MTL tumor were studied. The mean patient age at surgery was 32 years (range 13-62 years). The tumors were confined to the MTL (Schramm Type A) in 25 patients (69%). Extension of the tumor into the fusiform gyrus (Schramm Type C) and temporal stem (Schramm Type D) was observed in 4 and 7 patients (11 and 19%), respectively. There was a significant difference in the tumor size according to Schramm types (p = 0.001). Complete tumor resection was achieved in 26 patients (72%). All tumors were low-grade lesions except for 1 anaplastic astrocytoma. RESULTS: After a median follow-up period of 50.5 months, 7 patients showed progression of the disease. The actuarial progression-free survival rates were 97% in the 1st year, 84% in the 2nd year, and 80% in the 5th year. The degree of tumor resection was significantly related to the tumor control failure (p < 0.001) and malignant transformation of a low-grade tumor (p < 0.001). Univariate analyses using a Cox proportional hazards model showed that the following factors were significantly associated with a failure to control the tumor: 1) extent of the tumor (Schramm Type D; p = 0.003, relative risk [RR] 12.04); 2) size of the tumor (p = 0.033, RR 1.052/mm); 3) patient age at surgery >or= 50 years (p = 0.007, RR 8.312); and 4) short duration of epilepsy (< 6 months; p = 0.001, RR 21.54). CONCLUSIONS: Surgery is the principal treatment for MTL tumors, despite its technical difficulty. Complete tumor resection is strongly recommended for long-term tumor control. The MTL tumors are heterogeneous in their prognosis. Older age, short duration of epilepsy, and tumor size are all associated with poor outcome. Patients with these characteristics may have a more aggressive form of the disease than those with MTL tumors associated with chronic epilepsy. PMID- 19645562 TI - Chronic epilepsy associated with temporal tumors: long-term surgical outcome. AB - OBJECT: The authors undertook a study to review the clinical features and outcome in patients who underwent surgery for intractable chronic epilepsy caused by temporal lobe tumors. METHODS: The Rush Surgical Epilepsy Database was queried to identify patients with chronic intractable epilepsy who underwent resection of temporal lobe tumors between 1981 and 2005 at Rush University Medical Center. Medical records were reviewed for age of the patient at seizure onset, delay to referral for surgery, seizure frequency and characteristics, preoperative MR imaging results, extent of resection, pathological diagnosis, complications, duration of follow-up period, and seizure improvement. RESULTS: Thirty-eight patients were identified, all with low-grade tumors. Gangliogliomas were the most common (36.8%), followed in descending order by dysembryoplastic neuroepithelial tumors (26.3%) and low-grade diffuse astrocytoma (10.5%). The mean duration between seizure onset and surgery was 15.4 years. Complex partial seizures were the most common presenting symptom. Detailed operative data were available for 28 patients; of these, 89.3% underwent complete resection of the amygdala, and 82.1% underwent partial or complete resection of hippocampus, in addition to lesionectomy. The mean follow-up duration was 7.7 years (range 1.0-23.1 years), with 78.9% of patients having seizure status that improved to Engel Class I, 15.8% to Engel Class II, and 5.3% to Engel Class III. Permanent complications were noted in 2.6% of patients. CONCLUSIONS: The authors' examination of the long term follow-up data in patients with temporal lobe tumors causing chronic intractable epilepsy demonstrated excellent results in seizure improvement after surgery. PMID- 19645563 TI - Functional outcome after language mapping for insular World Health Organization Grade II gliomas in the dominant hemisphere: experience with 24 patients. AB - OBJECT: Despite the report of recent experiences of insular surgery in the past decade, there has been no series specifically dedicated to studying functional outcome following resection of insular WHO Grade II gliomas involving the dominant hemisphere, in patients with no or only mild preoperative language deficit. In this article, the authors analyze the contribution of awake mapping for preservation of brain function, especially language, in a homogeneous series of 24 patients who underwent surgery for insular Grade II gliomas within the dominant insular lobe. METHODS: Twenty-four patients underwent surgery for an insular Grade II glioma involving the dominant hemisphere (22 left, 2 right), revealed by seizures in all but 1 case. The preoperative neurological examination result was normal in 17 patients (71%), whereas 7 patients presented with language disorders detected using an accurate language assessment performed by a speech therapist. All surgeries were performed on awake patients utilizing intra operative language mapping involving cortical and subcortical stimulation. RESULTS: There were no intrasurgical complications or postsurgical sensorimotor deficits. Despite an immediate postoperative language worsening in 12 cases (50%), all patients recovered to a normal status within 3 months, and 6 cases even improved in comparison with their preoperative examination results. The 24 patients returned to normal social and professional lives. Moreover, the surgery had a favorable impact on epilepsy in all but 4 cases (83%). On control MR imaging, 62.5% of resections were total or subtotal. Three patients underwent a second or third awake surgery, with no additional deficit. All but 2 patients (92%) are alive after a mean follow-up of 3 years (range 3-133 months). CONCLUSIONS: Although insular surgery was long believed to be too risky, the present results show that the rate of permanent deficit, especially dysphasia, following resection of Grade II gliomas involving the dominant insula has been dramatically reduced (none in this patient series), thanks to the systematic use of intraoperative awake mapping, even in cases of repeated operations. Furthermore, patient quality of life may be improved due to a decrease of epilepsy after surgery. Thus, the authors suggest systematically considering resection when an insular Grade II glioma is diagnosed after seizures in a patient with no or mild deficit, even a glioma invading the dominant hemisphere. PMID- 19645564 TI - Gliomas of the cingulate gyrus: surgical management and functional outcome. AB - OBJECT: In this paper, the authors' goal was to summarize their experience with the surgical treatment of gliomas arising from the cingulate gyrus. METHODS: The authors analyzed preoperative data, surgical strategies, complications, and functional outcome in a series of 34 patients (mean age 42 years, range 12-69 years; 14 females) who underwent 38 operations between May 2001 and November 2008. RESULTS: In 7 cases (18%) the tumor was located in the posterior (parietal) part of the cingulate gyrus, and in 31 (82%) the tumor was in the anterior (frontal) part. In 10 cases (26%) the glioma was solely located in the cingulate gyrus, and in 28 cases (74%) the tumor extended to the supracingular frontal/parietal cortex. Most cases (23 [61%]) had seizures as the presenting symptom, 8 patients (24%) suffered from a hemiparesis/hemihypesthesia, and 4 patients (12%) had aphasic symptoms. The authors chose an interhemispheric approach for tumor resection in 11 (29%) and a transcortical approach in 27 (71%) cases; intraoperative electrophysiological monitoring was applied in 23 (61%) and neuronavigation in 15 (39%) cases. A > 90% resection was achieved in 32 (84%) and > 70% in another 5 (13%) cases. Tumors were classified as low-grade gliomas in 11 cases (29%). A glioblastoma multiforme (WHO Grade IV, 10 cases [26%]) and oligoastrocytoma (WHO Grade III, 9 cases [24%]) were the most frequent histopathological results. Postoperatively, patients in 13 cases suffered from a transient supplementary motor area syndrome (34%), all of whom had tumors in the anterior cingulate gyrus. In the early postoperative period (30 days) a new deficit occurred in 5 cases (13%, mild motor deficits or aphasic symptoms). One patient had a major bleeding episode 2 days after surgery and was in a persistent vegetative state. CONCLUSIONS: Gliomas arising from the cingulate gyrus are rare. A gross-total resection is often possible and acceptably safe; intraoperative monitoring and neuronavigation are helpful adjuncts. In case of resection of gliomas arising from the anterior cingulate gyrus a supplementary motor area syndrome has to be considered, particularly when the tumor extends to the supracingular cortex. PMID- 19645565 TI - Endoscopic third ventriculostomy. PMID- 19645566 TI - Crossover trials. PMID- 19645567 TI - Coil over clip. PMID- 19645569 TI - Forsterite exposure causes less oxidative DNA damage and lung injury than chrysotile exposure in rats. AB - Chrysotile (CH) is a pathogenic waste building material that can potentially be rendered innocuous via conversion to forsterite (FO) by heating at high temperatures. We compared the ability of FO and CH to cause oxidative DNA damage and lung injury. A single 1-mg intratracheal dose of CH or FO was administered to rats. Significant changes were observed 3 to 7 days after CH injection in alveolar macrophages, neutrophils, eosinophils, lymphocytes, total protein, and lactate dehydrogenase. High concentrations of 8-hydroxy-29-deoxyguanosine (8 OHdG) were also observed in the macrophages, other infiltrating inflammatory cells, granulomas, and in bronchiolar and alveolar epithelial cells. The overexpression of 8-OHdG was limited to airway epithelial and inflammatory cells surrounding the fibrotic foci 540 days after injection, indicating that the inflammatory effects of CH were persistent yet decreased with time. Compared to the CH group, acute lung inflammation observed in the FO group was less apparent and exhibited no progressive fibrosing lesions. The expression of 8-OHdG was transient and weak in the bronchiolar epithelial cells as well as in the inflammatory cells, consistent with low concentrations of 8-OHdG observed in the lungs. These findings confirm that FO causes significantly less inflammation and oxidative DNA damage in the lungs than CH. PMID- 19645570 TI - Suppression of Th1- and Th2-type immune responses in infant mouse spleen after prenatal and postnatal exposure to low-level toluene and peptidoglycan. AB - The aim of the present study was to investigate the effect of low-level concentrations, under the occupational acceptable limits, of toluene exposure and peptidoglycan (PGN) stimulation on Th1/Th2 immunity in infant mice. Pregnant BALB/c mice and their offspring were exposed to low-level toluene inhalation (0, 5, and 50 ppm) for 4 wk (from the late prenatal stage to early postnatal stage) in a whole-body exposure chamber. Some of the pregnant mice and their offspring were stimulated with PGN during toluene exposure. We measured total immunoglobulins of different subclasses in plasma, and production and expression level of cytokines in the lung and spleen, and transcription factors related to Th1/Th2 immunity in the spleen of infant (3 wk old) mice. Exposure of mice to 5 or 50 ppm toluene resulted in increased immunoglobulin (Ig) G1 and decreased IgG2a and IgE antibodies in the plasma; significantly decreased T-bet, GATA-3, and Foxp3 mRNA in the spleen; and a tendency toward decreased interferon (IFN) gamma mRNA in spleen. Exposure of mice to low-level toluene together with PGN stimulation resulted in decreased IgG1 as well as IgG2a antibodies in the plasma and Foxp3 mRNA in spleen as compared with control or PGN-treated mice. These findings suggest that low-level toluene exposure and PGN stimulation from the late prenatal to early postnatal stage suppressed the splenic parameter related to Th1/Th2 immunity in infant mice. PMID- 19645571 TI - Positional specification in a neural stem cell line involves modulation of Musashi1 expression. AB - In this study, we have used an in vitro co-culture system to investigate the competency of a conditionally immortalized multipotential neural progenitor cell line (MHP36) to adopt "dorsal" or "striatal" telencephalic fates. We report that MHP36 cells, unlike primary fetal neural progenitors cells, do not express either dorsal or ventral telencephalic positional specification genes; at both the mRNA and protein levels, but that they quickly turn on expression of the appropriate set of proteins when cultured in either a dorsal (cortical) or a ventral (striatal) environment. This control has 2 components: transcriptional activation of positional specification genes, and translational control whereby only the appropriate set of mRNAs appears as immunoreactive protein. We show furthermore that this positional specification gene expression is modulated by the RNA binding protein Musashi1. We postulate that it is the ability of MHP36 cells to adopt either cortical or striatal positional specification that is key to their functional efficacy in a number of models of neurological disease. PMID- 19645572 TI - Antenatal steroids and antioxidant enzyme activity in preterm infants: influence of gender and timing. AB - Antenatal steroids have improved the survival of preterm infants; however, the mechanism of action is not fully understood. We aimed to establish an association between antenatal steroids and antioxidant activity and postnatal oxidative stress. In a prospective cohort study, extremely preterm neonates receiving antenatal steroids (CORT) or not (NOCORT) were enrolled. An association between antenatal steroids and activities of antioxidant enzymes and glutathione cycle enzymes in cord blood was found. In addition, reduced oxidative stress (GSH/GSSG ratio, CORT vs. NOCORT, 35.68 + or - 12.20 vs. 28.38 + or - 9.92; p < 0.01) and, decreased oxidation of proteins (ortho-tyrosine/phenylalanine ratio, CORT vs. NOCORT, 8.66 + or - 2.45 vs. 12.55 + or - 4.41; p < 0.01) and DNA (8oxodG/2dG ratio, CORT vs. NOCORT, 6.73 + or - 2.18 vs. 9.53 + or - 3.83; p < 0.01) also was found. Antenatal steroids were associated with reduced oxygen supplementation, mechanical ventilation, and conditions such as bronchopulmonary dysplasia, intra periventricular hemorrhage, or retinopathy of prematurity. The maximal effectiveness was when steroids were administered 2-4 days before delivery. Female preterm infants had less oxidative stress and increased antioxidant activity and better clinical outcomes than did male infants, independent of receiving or not antenatal steroids. Antenatal steroids are accompanied by a reduction in postnatal oxidative-stress-derived conditions and increased antioxidant enzyme activity. Both these effects seem to be influenced by specific timing and female gender. PMID- 19645575 TI - Evaluation of an osmotic pump for fentanyl administration in cats as a model for nondomestic felids. AB - OBJECTIVE: To evaluate the reliability of an SC implanted osmotic pump (OP) for fentanyl administration in cats and to compare serum concentrations of fentanyl delivered via an OP and a transdermal patch (TP). Animals-8 spayed female cats. PROCEDURES: In a crossover design, cats received fentanyl at 25 microg/h via a TP or an OP. All cats were anesthetized for the pump or patch placement (0 hours) and again when it was removed (96 hours). Venous blood samples were collected for measurement of serum fentanyl concentrations at 0, 6, 12, 24, 36, 48, 72, and 96 hours and at 24 and 48 hours after device removal. After a 3-week washout period, the experiment was repeated with each cat receiving the other treatment. RESULTS: Mean serum fentanyl concentrations at 24, 36, 72, and 96 hours were greater when the OP was used than when the TP was used. Mean residence time and half-life were greater when the TP was used. Fentanyl concentration changed significantly faster in initial and elimination phases when the OP was used. Marked interindividual variation in serum fentanyl concentrations was evident with both administration methods. No adverse effects were evident with either method. CONCLUSIONS AND CLINICAL RELEVANCE: Use of the OP to administer fentanyl to cats resulted in a shorter initial lag phase to a therapeutic serum concentration, higher bioavailability, and faster elimination after removal, compared with use of a TP. These advantages, in addition to the inability of cats to remove the OP, may make OPs useful for fentanyl administration in nondomestic felids. PMID- 19645574 TI - Effect of intravenous administration of tramadol hydrochloride on the minimum alveolar concentration of isoflurane in rabbits. AB - OBJECTIVE: To evaluate the effect of IV administration of tramadol hydrochloride on the minimum alveolar concentration of isoflurane (ISOMAC) that prevented purposeful movement of rabbits in response to a noxious stimulus. ANIMALS: Six 6- to 12-month-old female New Zealand White rabbits. PROCEDURES: Anesthesia was induced and maintained with isoflurane in oxygen. A baseline ISOMAC was determined by clamping a pedal digit with sponge forceps until gross purposeful movement was detected or a period of 60 seconds elapsed. Subsequently, tramadol (4.4 mg/kg) was administered IV and the posttreatment ISOMAC (ISOMAC(T)) was measured. RESULTS: Mean +/- SD ISOMAC and ISOMAC(T) values were 2.33 +/- 0.13% and 2.12 +/- 0.17%, respectively. The ISOMAC value decreased by 9 +/- 4% after tramadol was administered. Plasma tramadol and its major metabolite (M1) concentrations at the time of ISOMAC(T) determination varied widely (ranges, 181 to 636 ng/mL and 32 to 61 ng/mL, respectively). Intervals to determination of ISOMAC(T) and plasma tramadol and M1 concentrations were not correlated with percentage change in the ISOMAC. Heart rate decreased significantly immediately after tramadol administration but by 10 minutes afterward was not different from the pretreatment value. Systolic arterial blood pressure decreased to approximately 60 mm Hg for approximately 5 minutes in 3 rabbits after tramadol administration. No adverse effects were detected. CONCLUSIONS AND CLINICAL RELEVANCE: As administered, tramadol had a significant but clinically unimportant effect on the ISOMAC in rabbits. Higher doses of tramadol may provide clinically important reductions but may result in a greater degree of cardiovascular depression. PMID- 19645576 TI - Effect of administration of propofol and xylazine hydrochloride on recovery of horses after four hours of anesthesia with desflurane. AB - OBJECTIVE: To compare characteristics of horses recovering from 4 hours of desflurane anesthesia with and without immediate postanesthetic IV administration of propofol and xylazine. Animals-8 healthy horses (mean +/- SEM age, 6.6 +/- 1.0 years; mean body weight, 551 +/- 50 kg). PROCEDURES: Horses were anesthetized twice. Both times, anesthesia was induced with a combination of xylazine hydrochloride, diazepam, and ketamine hydrochloride and then maintained for 4 hours with desflurane in oxygen. Choice of postanesthetic treatment was randomly assigned via a crossover design such that each horse received an IV injection of propofol and xylazine or saline (0.9% NaCl) solution after the anesthetic episode. Recovery events were quantitatively and qualitatively assessed. Venous blood samples were obtained before and after anesthesia for determination of serum creatine kinase activity and plasma propofol concentration. RESULTS: Anesthetic induction and maintenance were unremarkable in all horses. Compared with administration of saline solution, postanesthetic administration of propofol and xylazine resulted in an increased interval to emergence from anesthesia but improved quality of recovery-related transition to standing. Compared with administration of saline solution, administration of propofol also delayed the rate of decrease of end-tidal concentrations of desflurane and carbon dioxide and added to conditions promoting hypoxemia and hypoventilation. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol and xylazine administered IV to horses after 4 hours of desflurane anesthesia improved the quality of transition from lateral recumbency to standing but added potential for harmful respiratory depression during the postanesthetic period. PMID- 19645578 TI - Hematologic and serum biochemical reference intervals for free-ranging common bottlenose dolphins (Tursiops truncatus) and variation in the distributions of clinicopathologic values related to geographic sampling site. AB - OBJECTIVE: To develop robust reference intervals for hematologic and serum biochemical variables by use of data derived from free-ranging bottlenose dolphins (Tursiops truncatus) and examine potential variation in distributions of clinicopathologic values related to sampling sites' geographic locations. ANIMALS: 255 free-ranging bottlenose dolphins. PROCEDURES: Data from samples collected during multiple bottlenose dolphin capture-release projects conducted at 4 southeastern US coastal locations in 2000 through 2006 were combined to determine reference intervals for 52 clinicopathologic variables. A nonparametric bootstrap approach was applied to estimate 95th percentiles and associated 90% confidence intervals; the need for partitioning by length and sex classes was determined by testing for differences in estimated thresholds with a bootstrap method. When appropriate, quantile regression was used to determine continuous functions for 95th percentiles dependent on length. The proportion of out-of range samples for all clinicopathologic measurements was examined for each geographic site, and multivariate ANOVA was applied to further explore variation in leukocyte subgroups. RESULTS: A need for partitioning by length and sex classes was indicated for many clinicopathologic variables. For each geographic site, few significant deviations from expected number of out-of-range samples were detected. Although mean leukocyte counts did not vary among sites, differences in the mean counts for leukocyte subgroups were identified. CONCLUSIONS AND CLINICAL RELEVANCE: Although differences in the centrality of distributions for some variables were detected, the 95th percentiles estimated from the pooled data were robust and applicable across geographic sites. The derived reference intervals provide critical information for conducting bottlenose dolphin population health studies. PMID- 19645577 TI - Influence of bone cements on bone-screw interfaces in the third metacarpal and third metatarsal bones of horses. AB - OBJECTIVE: To compare biomechanical strength, interface quality, and effects of bone healing in bone-implant interfaces that were untreated or treated with calcium phosphate cement (Ca-cement), magnesium phosphate cement (Mg-cement), or polymethylmethacrylate (PMMA) in horses. ANIMALS: 6 adult horses. PROCEDURES: 4 screw holes were created (day 0) in each third metacarpal and third metatarsal bone of 6 horses. In each bone, a unicortical screw was placed in each hole following application of Ca-cement, Mg-cement, PMMA, or no treatment (24 screw holes/treatment). Screws were inserted to 2.82 N m torque. Horses were euthanized and bones were harvested at day 5 (16 screw holes/treatment) or day 182 (8 screw holes/treatment). Radiography, biomechanical testing, histomorphometry, and micro computed tomography were performed to characterize the bone-implant interfaces. RESULTS: Use of Mg-cement increased the peak torque to failure at bone-implant interfaces, compared with the effects of no treatment and Ca-cement, and increased interface toughness, compared with the effects of no treatment, Ca cement, and PMMA. Histologically, there was 44% less Ca-cement and 69% less Mg cement at the interfaces at day 182, compared with amounts present at day 5. Within screw threads, Ca-cement increased mineral density, compared with PMMA or no treatment. In the bone adjacent to the screw, Mg-cement increased mineral density, compared with PMMA or no treatment. One untreated and 1 Ca-cement treated screw backed out after day 5. CONCLUSIONS AND CLINICAL RELEVANCE: In horses, Mg-cement promoted bone-implant bonding and adjacent bone osteogenesis, which may reduce the risk of screw loosening. PMID- 19645579 TI - Changes in tracheal dimensions during inspiration and expiration in healthy dogs as detected via computed tomography. AB - OBJECTIVE: To determine the degree of fluctuation in tracheal dimensions between forced inspiration and passive expiration in healthy dogs of various sizes. ANIMALS: 10 client-owned dogs with no evidence of respiratory disease or tracheal collapse. PROCEDURES: Anesthetized dogs underwent a computed tomographic examination during forced inspiration and induced but passive expiration to assess tracheal dimensions. Tracheal height, width, and cross-sectional area were measured at inspiration and expiration, and percentage change in dimension was calculated for each variable. RESULTS: Measurements were acquired in 10 dogs that ranged in body weight from 3.5 to 47.8 kg. Tracheal cross-sectional area at inspiration and expiration was associated with body weight at all 3 tracheal regions. The percentage change in tracheal height and cross-sectional area was associated with body weight in the cervical but not the thoracic-inlet or thoracic regions. The tracheal cross-sectional area changed by as much as 24.2% (mean, 5.5%), 20.0% (mean, 6.0%), and 18.6% (mean, 6.0%) in the cervical, thoracic-inlet, and thoracic regions, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: The change in tracheal cross-sectional area from inspiration to expiration was as great as 24% in healthy dogs, and the area was associated with body weight. Respiratory fluctuations appeared to result in changes in tracheal dimension during respiration similar to those reported for humans. PMID- 19645580 TI - Effect of firocoxib or flunixin meglumine on recovery of ischemic-injured equine jejunum. AB - OBJECTIVE: To determine whether treatment of horses with firocoxib affects recovery of ischemic-injured jejunum, while providing effective analgesia. ANIMALS: 18 horses. PROCEDURES: Horses (n = 6 horses/group) received saline (0.9% NaCl) solution (1 mL/50 kg, IV), flunixin meglumine (1.1 mg/kg, IV, q 12 h), or firocoxib (0.09 mg/kg, IV, q 24 h) before 2 hours of jejunal ischemia. Horses were monitored via pain scores and received butorphanol for analgesia. After 18 hours, ischemic-injured and control mucosa were placed in Ussing chambers for measurement of transepithelial resistance and permeability to lipopolysaccharide. Histomorphometry was used to determine denuded villus surface area. Western blots for cyclooxygenase (COX)-1 and COX-2 were performed. Plasma thromboxane B(2) and prostaglandin E(2) metabolite (PGEM) concentrations were determined. RESULTS: Pain scores did not significantly increase after surgery in horses receiving flunixin meglumine or firocoxib. Transepithelial resistance of ischemic-injured jejunum from horses treated with flunixin meglumine was significantly lower than in saline- or firocoxib-treated horses. Lipopolysaccharide permeability across ischemic-injured mucosa was significantly increased in horses treated with flunixin meglumine. Treatment did not affect epithelial restitution. Cyclooxygenase-1 was constitutively expressed and COX-2 was upregulated after 2 hours of ischemia. Thromboxane B(2) concentration decreased with flunixin meglumine treatment but increased with firocoxib or saline treatment. Flunixin meglumine and firocoxib prevented an increase in PGEM concentration after surgery. CONCLUSIONS AND CLINICAL RELEVANCE: Flunixin meglumine retarded mucosal recovery in ischemic-injured jejunum, whereas firocoxib did not. Flunixin meglumine and firocoxib were effective visceral analgesics. Firocoxib may be advantageous in horses recovering from ischemic intestinal injury. PMID- 19645581 TI - Stability of canine pancreatic lipase immunoreactivity concentration in serum samples and effects of long-term administration of prednisone to dogs on serum canine pancreatic lipase immunoreactivity concentrations. AB - OBJECTIVE: To evaluate stability of canine pancreatic lipase immunoreactivity (cPLI) in serum samples and to determine the effect of long-term administration of prednisone on serum cPLI concentrations. SAMPLE POPULATION: 8 canine serum samples for the stability evaluation and serum samples obtained from 6 healthy young adult heterozygous (carrier) dogs with X-linked hereditary nephritis for determining the effect of prednisone administration. PROCEDURES: To evaluate stability of serum cPLI concentration, an aliquot of each serum sample was stored at each of 4 temperatures between -80 degrees and 24 degrees C; samples were analyzed on days 0, 3, 7, 14, and 21. To determine the effect of long-term prednisone administration, pretreatment serum samples were obtained (days 0 and 14) and prednisone was administered (2.2 mg/kg, q 24 h, PO) on days 15 through 42, with serum samples obtained on days 28 and 42. Additional serum samples were obtained on days 56 and 70. RESULTS: Mean serum cPLI concentrations did not change significantly from day 0 to day 21 regardless of storage temperature. Serum cPLI concentrations in dogs after prednisone administration were within the reference range for all dogs at all time points, and results of repeated-measures ANOVA revealed that serum cPLI concentrations did not change significantly over time. CONCLUSIONS AND CLINICAL RELEVANCE: Serum cPLI concentrations measured in canine serum samples stored at room temperature, in a refrigerator, or in a freezer at -20 degrees or -80 degrees C were stable for at least 21 days. Also, long-term prednisone administration to dogs did not significantly affect serum cPLI concentrations. PMID- 19645582 TI - Association of HOXA10, ZFPM2, and MMP2 genes with scrotal hernias evaluated via biological candidate gene analyses in pigs. AB - OBJECTIVE: To evaluate the associations between 14 biological candidate genes and scrotal hernias in pigs. ANIMALS: 1,534 Pietrain-based pigs, including 692 individuals from 298 pig families and 842 male pigs without family information. PROCEDURES: Pigs were classified as affected or unaffected for scrotal hernias. Single nucleotide polymorphisms of candidate genes were analyzed via PCR assays and genotyped. Statistical analyses were performed on the family-trio and the case-control data. RESULTS: 2 genes involved in collagen metabolism (homeobox A10 [HOXA10] and matrix metalloproteinases 2 [MMP2]) and 1 gene encoding zinc finger protein multitype 2 (ZFPM2, important in the development of diaphragmatic hernia) were significantly associated with hernias. Pigs with these genotypes had high odds of developing scrotal hernias in the case and control groups (2 ZFPM2 variants: odds ratio, 4.3 [95% confidence interval, 2.78 to 6.64] and 4.45[95%confidenceinterval,2.88to6.88]). Anothergene, collagentypeII A 1(COL2A1),was potentially involved in hernia development. CONCLUSIONS AND CLINICAL RELEVANCE: HOXA10, ZFPM2, MMP2, and COL2A1 could have important roles in pig hernia development and potentially be useful for marker-assisted selection in the pig industry. IMPACT FOR HUMAN MEDICINE: Pigs are used for the study of many human diseases because of their physiologic similarities. Genes associated with scrotal hernias in this study may be directly used in understanding the molecular mechanisms underlying this defect in humans. PMID- 19645583 TI - Identification of chromosomal regions associated with cranial cruciate ligament rupture in a population of Newfoundlands. AB - OBJECTIVE: To identify chromosomal regions associated with cranial cruciate ligament rupture (CCLR) in a population of Newfoundlands. ANIMALS: 90 client owned Newfoundlands. PROCEDURES: A pedigree was constructed for dogs that did or did not have CCLR (determined on the basis of physical examination and radiographic findings). From this pedigree, affected and unaffected dogs were selected for genotyping on the basis of their predicted statistical likelihood of being homozygous CCLR-unaffected (n = 53) or homozygous CCLR-affected (37) dogs. Genotyping was performed for 532 microsatellite markers (MSATs). Comparisons of genotypes and allele frequencies were made between CCLR-affected and CCLR unaffected dogs. RESULTS: In the selected population, 495 MSATs were informative with a mean interval between markers of 5.5 centimorgans. Eighty-six MSATs were significantly associated with the CCLR trait, whereas 4 markers (located on 4 chromosomes) were significantly associated with the trait when false discovery rate (q value) was controlled at the 0.05 level. Subsequent initial validation confirmed significant trait association for 3 of the 4 MSATs. CONCLUSIONS AND CLINICAL RELEVANCE: In the population of Newfoundlands, 4 MSATs that were located on 4 chromosomes were significantly associated with the CCLR trait. Three of those markers were validated in part via genotyping additional closely located markers. The MSATs that were associated with the CCLR trait were identified in all regions (except for those on chromosome 24). Newfoundlands with CCLR could be used to study the disease process associated with anterior cruciate ligament injuries that occur in young female human athletes. PMID- 19645584 TI - Use of interfering RNAs targeted against feline herpesvirus 1 glycoprotein D for inhibition of feline herpesvirus 1 infection of feline kidney cells. AB - OBJECTIVE: To evaluate the use of RNA interference targeted against feline herpesvirus 1 (FHV-1) glycoprotein D for inhibition of FHV-1 infection of feline kidney cells. SAMPLE POPULATION: Crandell-Rees feline kidney cells. PROCEDURES: Crandell-Rees feline kidney cells were transfected with small interfering RNAs (siRNAs) that were designed to inhibit expression of FHV-1 glycoprotein D. The effectiveness of the treatment was determined via measurement of amounts of glycoprotein D mRNA, intracellular glycoprotein D, and glycoprotein D expressed on the surface of infected cells and comparison with appropriate control sample data. RESULTS: 2 of 6 siRNAs tested were highly effective in reducing expression (ie, knockdown) of glycoprotein D mRNA; there were 77% and 85% reductions in mRNA in treated samples, compared with findings in the control samples. The knockdown of glycoprotein D mRNA resulted in reduced glycoprotein D protein production, as evidenced by 27% and 43% decreases in expression of glycoprotein D on the surface of siRNA-treated, FHV-1-infected cells and decreased expression of the protein within infected cells, compared with control samples. Treatment with these siRNAs also resulted in inhibition of FHV-1 replication, with reductions of 84% and 77% in amounts of virus released into cell culture supernatant, compared with findings in control samples. CONCLUSIONS AND CLINICAL RELEVANCE: 2 chemically produced siRNAs that targeted the glycoprotein D gene significantly reduced FHV-1 titers in treated cells, suggesting that glycoprotein D is necessary for production of infective virions. This gene is a potential target for RNA interference as a means of inhibition of FHV-1 infection of feline cells. PMID- 19645585 TI - Determination of mechanical properties of canine carpal ligaments. AB - OBJECTIVE: To evaluate the mechanical properties of canine carpal ligaments for use in a finite element model of the canine antebrachium. SAMPLE POPULATION: 26 forelimbs obtained from cadavers of 13 dogs euthanized for reasons unrelated to this study. PROCEDURES: 6 ligaments (medial collateral, lateral collateral, palmar ulnocarpal, palmar radiocarpal, accessorometacarpal-V, and accessorometacarpal-IV) were evaluated. Quasistatic tensile tests were performed on all specimens (n = 8 specimens/ligament) by use of a servohydraulic materials testing system in conjunction with a 6-df load cell. Each specimen was preconditioned for 10 cycles by applying 2% strain by use of a Haversine waveform. Tension was subsequently applied to each specimen at a strain rate of 0.5%/s until ligament failure. RESULTS: Significant differences in modulus of elasticity were detected among the ligaments. Elastic modulus did not differ significantly between the 2 accessorometacapal ligaments, between the 2 collateral ligaments, or between the 2 palmar carpal ligaments. Ligaments were classified into 3 groups (accessorometacarpal ligaments, intra-articular ligaments, and palmar carpal ligaments), and significant differences were detected among the 3 ligament groups. The accessorometacarpal ligaments had a relatively high elastic modulus, compared with results for the other ligaments. The medial and lateral collateral ligaments had the lowest elastic modulus of any of the ligaments tested. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicated a strong function-elastic modulus relationship for the 6 ligaments tested. The mechanical properties described here will be of use in creating a finite element model of the canine antebrachium. PMID- 19645586 TI - Effects of intravenous administration of pirfenidone on horses with experimentally induced endotoxemia. AB - OBJECTIVE: To characterize effects of IV administration of pirfenidone on clinical, biochemical, and hematologic variables and circulating tumor necrosis factor (TNF)-alpha concentrations in horses after infusion of a low dose of endotoxin. ANIMALS: 18 healthy adult horses. PROCEDURES: Horses were randomly assigned to 3 groups (n = 6 horses/group) and administered an IV infusion of 30 ng of endotoxin/kg or saline (0.9% NaCl) solution during a 30-minute period. Lipopolysaccharide-pirfenidone horses received endotoxin followed by pirfenidone (loading dose of 11.6 mg/kg and then constant rate infusion [CRI] at 9.9 mg/kg/h for 3 hours). Lipopolysaccharide-saline horses received endotoxin followed by infusion (loading dose and CRI for 3 hours) of saline solution. Saline pirfenidone horses received saline solution followed by pirfenidone (loading dose and then CRI for 3 hours). Physical examination variables were recorded and blood samples collected at predetermined intervals throughout the 24-hour study period. Blood samples were used for CBCs, biochemical analyses, and determinations of TNF alpha concentrations. RESULTS: IV infusion of pirfenidone after administration of a low dose of endotoxin failed to attenuate the clinical, clinicopathologic, or cytokine alterations that developed secondary to endotoxin exposure. Intravenous infusion of pirfenidone after administration of saline solution induced mild transient clinical signs, but associated clinicopathologic changes were not detected. CONCLUSIONS AND CLINICAL RELEVANCE: IV administration of pirfenidone was tolerated with only mild transient clinical adverse effects during infusion. However, administration of pirfenidone did not protect horses from the systemic effects of experimentally induced endotoxemia. Further studies of related, but more potent, drugs may be warranted. PMID- 19645587 TI - Effect of triheptanoin on muscle metabolism during submaximal exercise in horses. AB - OBJECTIVE: To compare effects of corn oil or a 7-carbon fat (triheptanoin) on acylcarnitine, lipid, and carbohydrate metabolism in plasma or muscle of exercising horses. ANIMALS: 8 Thoroughbred geldings. PROCEDURES: Horses received isocaloric diets containing 650 mL of oil (triheptanoin or corn oil)/d for 18 or 25 days in a crossover design with a 26-day washout period. On day 17 or 24 of each feeding period, the respective oil (217 mL) was nasogastrically administered; 120 minutes later, horses performed a 90-minute submaximal exercise test (SET). Blood and muscle samples were obtained before oil administration and immediately before (blood only), during (blood only), immediately after, and 24 hours after SETs. RESULTS: Compared with values before oil administration, triheptanoin administration increased plasma insulin and C7:0-, C5:0- and C3:0 acylcarnitine concentrations, whereas corn oil administration increased plasma NEFA concentrations. During SETs, plasma C7:0-, C5:0-, and C3:0-acylcarnitine concentrations were higher when triheptanoin, rather than corn oil, was administered to horses. Plasma glucose, NEFA, and C2:0-, C18:1-, and C18:2 acylcarnitine concentrations increased during SETs similarly for both oils. Respiratory quotient and muscle lactate, citrate, malate, glycogen, and ATP concentrations changed similarly from before to after SETs for both oils. Compared with muscle concentrations immediately after SETs, those for glucose-6 phosphate and citrate 24 hours after SETs were lower and for glycogen were similar to values before SETs. CONCLUSIONS AND CLINICAL RELEVANCE: Fatigue was not associated with depletion of citric acid cycle intermediates for either oil. Triheptanoin induced a significantly higher insulin secretion and did not appear to enhance muscle glycogen repletion. PMID- 19645588 TI - New insights into the structural characteristics and functional relevance of the human cytochrome P450 2D6 enzyme. AB - To date, the crystal structures of at least 12 human CYPs (1A2, 2A6, 2A13, 2C8, 2C9, 2D6, 2E1, 2R1, 3A4, 7A1, 8A1, and 46A1) have been determined. CYP2D6 accounts for only a small percentage of all hepatic CYPs (< 2%), but it metabolizes approximately 25% of clinically used drugs with significant polymorphisms. CYP2D6 also metabolizes procarcinogens and neurotoxins, such as 1 methyl-4-phenyl-1,2,3,6-tetrahydropyridine, 1,2,3,4-tetrahydroquinoline, and indolealkylamines. Moreover, the enzyme utilizes hydroxytryptamines and neurosteroids as endogenous substrates. Typical CYP2D6 substrates are usually lipophilic bases with an aromatic ring and a nitrogen atom, which can be protonated at physiological pH. Substrate binding is generally followed by oxidation (5-7 A) from the proposed nitrogen-Asp301 interaction. A number of homology models have been constructed to explore the structural features of CYP2D6, while antibody studies also provide useful structural information. Site directed mutagenesis studies have demonstrated that Glu216, Asp301, Phe120, Phe481, and Phe483 play important roles in determining the binding of ligands to CYP2D6. The structure of human CYP2D6 has been recently determined and shows the characteristic CYP fold observed for other members of the CYP superfamily. The lengths and orientations of the individual secondary structural elements in the CYP2D6 structure are similar to those seen in other human CYP2 members, such as CYP2C9 and 2C8. The 2D6 structure has a well-defined active-site cavity located above the heme group with a volume of approximately 540 A(3), which is larger than equivalent cavities in CYP2A6 (260 A(3)), 1A2 (375 A(3)), and 2E1 (190 A(3)), but smaller than those in CYP3A4 (1385 A(3)) and 2C8 (1438 A(3)). Further studies are required to delineate the molecular mechanisms involved in CYP2D6 ligand interactions and their implications for drug development and clinical practice. PMID- 19645589 TI - Sodium-nitroprusside-induced cyanide toxicity in pediatric patients. AB - BACKGROUND: Sodium nitroprusside (SNP) is often used as a continuous infusion intravenous vasodilator in pediatric patients. However, cyanide toxicity can occur with SNP therapy. Scant literature is available determining the safety of SNP therapy, the incidence of cyanide toxicity or the risk factors for cyanide toxicity in pediatric patients. OBJECTIVE: To review the literature concerning the safety of intravenous SNP with regard to cyanide toxicity in the pediatric patient population. METHODS: A MedLine search was used to identify articles pertaining to SNP therapy and cyanide toxicity in pediatric patients. CONCLUSIONS: Sodium nitroprusside seems to be safe when used in critically ill pediatric patients. Cyanide toxicity may occur in patients with specific risk factors. Routine monitoring of cyanide levels may not be warranted. PMID- 19645590 TI - MetaPocket: a meta approach to improve protein ligand binding site prediction. AB - The identification of ligand-binding sites is often the starting point for protein function annotation and structure-based drug design. Many computational methods for the prediction of ligand-binding sites have been developed in recent decades. Here we present a consensus method metaPocket, in which the predicted sites from four methods: LIGSITE(cs), PASS, Q-SiteFinder, and SURFNET are combined together to improve the prediction success rate. All these methods are evaluated on two datasets of 48 unbound/bound structures and 210 bound structures. The comparison results show that metaPocket improves the success rate from approximately 70 to 75% at the top 1 prediction. MetaPocket is available at http://metapocket.eml.org . PMID- 19645591 TI - RUNX3 gene methylation in epithelial ovarian cancer tissues and ovarian cancer cell lines. AB - Methylation plays an important role in the regulation of gene expression in many cancer tissues. RUNX3 is an important tumor suppressor gene located on human chromosome 1p36.1, and many tumors do not express it due to methylation of the promoter region of the CpG island. The molecular mechanisms involved in RUNX3 gene expression and epithelial ovarian cancer are not fully understood. This study investigates the relationship between RUNX3 methylation and expression in ovarian cancer. The methylation of the RUNX3 gene promoter region was measured in 32 primary epithelial ovarian cancer samples and corresponding nonmalignant ovarian tissues, 36 benign epithelial ovarian tumor tissues, and 10 normal ovarian tissues by methylation-specific PCR (MSP) and RT-PCR. The relationships between RUNX3 methylation status, expression, and clinicopathologic characteristics were analyzed. RUNX3 methylation was further assessed by MSP and RT-PCR before and after 5-aza-2'-deoxycytidine (5-aza-dc) treatment in normal and cancer cell lines. We detected RUNX3 methylation in 53.1% of primary ovarian cancer tumors, 16.7% of benign ovarian tumors, and 28% of nonmalignant tissues surrounding ovarian cancers. No methylation was detected in normal ovarian tissues. No significant correlation between RUNX3 methylation and clinicopathological characteristics was observed. The RT-PCR results found RUNX3 expression in all normal ovarian tissues (10/10) and in most of the unmethylated ovarian cancer tissues (12/15); in contrast, it was not detected in most of the RUNX3-methylated ovarian cancer tissues (16/17). Our data suggest that methylation plays a critical role in the regulation of RUNX3 repression, and that it is significantly correlated with RUNX3 mRNA expression in ovarian cancer tissues (p = 0.006). PMID- 19645592 TI - A network biology study on circadian rhythm by integrating various omics data. AB - Circadian rhythm is fundamentally important in physiological processes of mammals. To reveal its underlying mechanism, we probed functional interactions among genes, motivated by the basic molecular observation on gene expression data in circadian rhythm that a large number of genes oscillate in a coordinated manner. In this study, a reverse-engineering strategy was applied to infer and analyze the structure and function of a circadian rhythm-related gene regulatory network. Specifically, our method integrated four phase-shift time-course gene expression datasets in rat suprachiasmatic nucleus, protein-protein interactions, phosphorylations of a set of key circadian genes, and prior information of cis regulatory elements, to construct the gene regulatory network related to circadian rhythm of the rat. By follow-up analysis, we identified four new regulatory hubs that may play crucial roles in the regulation of circadian rhythm. Furthermore, we found that feedback loop motifs were significantly enriched in the predicted network, which may contribute to the genome-wide oscillations of the circadian clock. Compared to the small-scale gene regulatory network conducted by experimental method, our study provides a system-wide overview on the gene regulations, which not only reveals the global network structure but also gives valuable insights into the essential mechanism of circadian rhythm. PMID- 19645593 TI - A bayesian approach to protein inference problem in shotgun proteomics. AB - The protein inference problem represents a major challenge in shotgun proteomics. In this article, we describe a novel Bayesian approach to address this challenge by incorporating the predicted peptide detectabilities as the prior probabilities of peptide identification. We propose a rigorious probabilistic model for protein inference and provide practical algoritmic solutions to this problem. We used a complex synthetic protein mixture to test our method and obtained promising results. PMID- 19645594 TI - Spectrum fusion: using multiple mass spectra for de novo Peptide sequencing. AB - We report on a new algorithm for combining the information from several mass spectra of the same peptide. The algorithm automatically learns peptide fragmentation patterns, so that it can handle spectra from any instrument and fragmentation technique. We demonstrate the utility of the algorithm, and the power of multiple spectra, by showing that combining pairs of spectra (one CID and one ETD) greatly improves de novo sequencing success rates. PMID- 19645595 TI - Inferring ancestries efficiently in admixed populations with linkage disequilibrium. AB - Much effort has recently been invested in developing methods for determining the ancestral origin of chromosomal segments in admixed individuals. Motivations for this task are the study of population history such as bottleneck effects and migration, the assessment of population stratification for adequate adjustment of association studies, and the enhancement of mapping by admixture linkage disequilibrium (MALD). In this article, we present a novel framework for the inference of ancestry at each chromosomal location. The uniqueness of our method stems from the ability to incorporate complex probability models that account for linkage-disequilibrium in the ancestral populations. We provide an inference algorithm that is polynomial in the number of markers even though the underlying problem seems to be inherently exponential in nature. We demonstrate the validity of our model and conclude that, with sufficient ancestral haplotypes, this framework can provide higher accuracy in inferring ancestral origin. PMID- 19645596 TI - Maximum likelihood genome assembly. AB - Whole genome shotgun assembly is the process of taking many short sequenced segments (reads) and reconstructing the genome from which they originated. We demonstrate how the technique of bidirected network flow can be used to explicitly model the double-stranded nature of DNA for genome assembly. By combining an algorithm for the Chinese Postman Problem on bidirected graphs with the construction of a bidirected de Bruijn graph, we are able to find the shortest double-stranded DNA sequence that contains a given set of k-long DNA molecules. This is the first exact polynomial time algorithm for the assembly of a double-stranded genome. Furthermore, we propose a maximum likelihood framework for assembling the genome that is the most likely source of the reads, in lieu of the standard maximum parsimony approach (which finds the shortest genome subject to some constraints). In this setting, we give a bidirected network flow-based algorithm that, by taking advantage of high coverage, accurately estimates the copy counts of repeats in a genome. Our second algorithm combines these predicted copy counts with matepair data in order to assemble the reads into contigs. We run our algorithms on simulated read data from Escherichia coli and predict copy counts with extremely high accuracy, while assembling long contigs. PMID- 19645597 TI - Algorithms for joint optimization of stability and diversity in planning combinatorial libraries of chimeric proteins. AB - In engineering protein variants by constructing and screening combinatorial libraries of chimeric proteins, two complementary and competing goals are desired: the new proteins must be similar enough to the evolutionarily-selected wild-type proteins to be stably folded, and they must be different enough to display functional variation. We present here the first method, Staversity, to simultaneously optimize stability and diversity in selecting sets of breakpoint locations for site-directed recombination. Our goal is to uncover all "undominated" breakpoint sets, for which no other breakpoint set is better in both factors. Our first algorithm finds the undominated sets serving as the vertices of the lower envelope of the two-dimensional (stability and diversity) convex hull containing all possible breakpoint sets. Our second algorithm identifies additional breakpoint sets in the concavities that are either undominated or dominated only by undiscovered breakpoint sets within a distance bound computed by the algorithm. Both algorithms are efficient, requiring only time polynomial in the numbers of residues and breakpoints, while characterizing a space defined by an exponential number of possible breakpoint sets. We applied Staversity to identify 2-10 breakpoint plans for different sets of parent proteins taken from the purE family, as well as for parent proteins TEM-1 and PSE 4 from the beta-lactamase family. The average normalized distance between our plans and the lower bound for optimal plans is around 2%. Our plans dominate most (60-90% on average for each parent set) of the plans found by other possible approaches, random sampling or explicit optimization for stability with implicit optimization for diversity. The identified breakpoint sets provide a compact representation of good plans, enabling a protein engineer to understand and account for the trade-offs between two key considerations in combinatorial chimeragenesis. PMID- 19645599 TI - Automatic parameter learning for multiple local network alignment. AB - We developed Graemlin 2.0, a new multiple network aligner with (1) a new multi stage approach to local network alignment; (2) a novel scoring function that can use arbitrary features of a multiple network alignment, such as protein deletions, protein duplications, protein mutations, and interaction losses; (3) a parameter learning algorithm that uses a training set of known network alignments to learn parameters for our scoring function and thereby adapt it to any set of networks; and (4) an algorithm that uses our scoring function to find approximate multiple network alignments in linear time. We tested Graemlin 2.0's accuracy on protein interaction networks from IntAct, DIP, and the Stanford Network Database. We show that, on each of these datasets, Graemlin 2.0 has higher sensitivity and specificity than existing network aligners. Graemlin 2.0 is available under the GNU public license at http://graemlin.stanford.edu . PMID- 19645600 TI - Laparoscopic management of complex ureteropelvic junction obstruction. AB - BACKGROUND: Ureteropelvic junction (UPJ) obstruction is associated with complex anatomic problems, such as pelvic kidneys, giant hydronephrosis, crossed fused ectopia with L-shaped kidneys, and poses a real challenge in management. In this paper, we describe simple laparoscopic techniques for the management of these cases of atypical and complex UPJ obstruction. MATERIALS AND METHODS: From 2004 to 2008, 9 cases of UPJ obstruction with atypical anatomic problems were operated on laparoscopically at PGIMER (Chandigarh, India). The different surgical procedures performed lap-aroscopically were pyelovesicostomy (5 cases), ureterocalicostomy (1 case), calicovesicostomy (1 case), heminephrectomy (1 case), and ureteropyelostomy (1 case) as per the merits of each case. The four port technique was followed for pyelovesicostomy, calicovesicostomy, and ureterocalicostomy (two 10-mm ports, one each at the umbilicus and lateral border of the ipsilateral rectus, and two 5-mm ports, one each at the lateral border of the contralateral rectus and midway between the umbilicus and symphysis pubis). Pyelovesicostomy and calicovesicostomy were stented with a suprapubically placed Foley catheter. Mean operating time was 140 minutes, with an average intraoperative blood loss of 50 mL. RESULTS: There were no intraoperative complications. The patients recovered well from the surgery. Postoperative nephrostograms confirmed anastomotic patency and good drainage. On follow-up, patients are asymptomatic with normal renal functions. Patients with calicovesicostomy and pyelovesicostomy were advised double voiding, and they need to be on long-term, perhaps lifelong, follow-up. CONCLUSIONS: In pelvic kidneys with UPJ obstruction and in select cases of giant hydronephrotic kidneys, anastomosis of the bladder with the most dependent part of the pelvicalyceal system ensures adequate drainage. Ureterocalicostomy is the choice of treatment in cases of UPJ obstruction with an intrarenal pelvis where calicovesicostomy is not feasible. Laparoscopic performance of these procedures is feasible and simple. PMID- 19645598 TI - Evolutionary history reconstruction for Mammalian complex gene clusters. AB - Clusters of genes that evolved from single progenitors via repeated segmental duplications present significant challenges to the generation of a truly complete human genome sequence. Such clusters can confound both accurate sequence assembly and downstream computational analysis, yet they represent a hotbed of functional innovation, making them of extreme interest. We have developed an algorithm for reconstructing the evolutionary history of gene clusters using only human genomic sequence data, which allows the tempo of large-scale evolutionary events in human gene clusters to be estimated. We further propose an extension of the method to simultaneously reconstructing the evolutionary histories of orthologous gene clusters in multiple primates, which will facilitate primate comparative sequencing studies that aim to reconstruct their evolutionary history more fully. PMID- 19645601 TI - The endoscopic perineal approach to the presacral space: an excision biopsy. AB - Presacral tumors in adulthood are rare. Several surgical difficulties exist, because of limited access of the presacral area. The patient in this report was a 72-year-old man without comorbidities referred by the urologist because of a presacral mass. Standard diagnostic evaluation disclosed no conclusive diagnosis. The perineal endoscopic approach was used to reach the presacral space. An excision biopsy, using this new technique, was performed to obtain a conclusive diagnosis. This perineal endoscopic excision biopsy was performed without complications. Postoperative pathology showed a lipoma. The patient was discharged in good health 2 days after the procedure. We concluded that this new perineal endoscopic technique is a safe, feasible approach for reaching the presacral space to resect a tumor, acquire a histologic diagnosis of an unknown tumor, or both. PMID- 19645602 TI - Laparoscopic lumbar hernia repair in a child with lumbocostovertebral syndrome. AB - Lumbocostovertebral syndrome is the association of a congenital lumbar hernia with rib and vertebral anomalies. We report the first case of a laparoscopic repair of a lumbar hernia in a child with lumbocostovertebral syndrome. Laparoscopic lumbar hernia repair appears to be safe and feasible in children. PMID- 19645603 TI - Laparoscopic decortication of large renal cysts: a comparison between the transperitoneal and retroperitoneal approaches. AB - BACKGROUND: We compared the operative outcomes and follow-up results of laparoscopic decortication of large, simple renal cysts, performed by the transperitoneal (TP) and retroperitoneal (RP) approaches, and identified selection criteria for each approach. MATERIALS AND METHODS: Between 2000 and 2007, 53 patients with renal cysts underwent laparoscopic decortication via the TP (n = 25) and RP approaches (n = 28), according to the location of the cysts. Operative and follow-up data were collected retrospectively, and the approaches were compared with regard to intra- and postoperative parameters, complications, and success rate. RESULTS: Among the 53 patients, 48 (90.5%) had their cysts completely removed, and in 5 (9.5%), the cyst size was reduced to less than one half of the initial cyst volume. Thirty-three patients (84.6%) had their symptoms completely relieved within 3 months, while 6 patients (15.3%) had continued mild pain. There were no significant differences in the symptomatic response and radiologic findings between the two approaches. The RP approach had the advantages of reduced operation time, time to oral intake and ambulation, as well as analgesic use. One patient in the RP group required laparoscopy to control postoperative bleeding. CONCLUSIONS: Based on the cyst location, as the major selection criteria, both approaches were comparable with regard to symptomatic improvement and radiologic findings. The retroperitoneal approach had the advantages of reduced operation time, time to oral intake and ambulation, as well as analgesic use. Therefore, we prefer to perform laparoscopic decortication by the retroperitoneal approach without mobilization of the bowel. PMID- 19645604 TI - Totally laparoscopic central bisectionectomy for hepatocellular carcinoma. AB - A central bisectionectomy of the liver removes segments 4, 5, and 8, and this is a technically demanding operation because it requires two transection planes. Until now, the laparoscopic approach for this operative procedure has been rarely attempted. We report in this article on a totally laparoscopic central bisectionectomy that was performed in a 49-year-old male who had centrally located hepatocellular carcinoma (HCC), and this tumor was in contact with the middle hepatic vein. The operative procedure was performed by using five trocars with the patient placed in the lithotomy position. The operative time was 430 minutes, the estimated blood loss was about 800 mL, and no perioperative transfusion was needed. The postoperative pathology confirmed a HCC with a 1-cm free resection margin. The patient was discharged on postoperative day 13 without any significant complications. This case shows the feasibility and safety of performing the totally laparoscopic central bisectionectomy for resecting HCC. PMID- 19645606 TI - The safety of laparoscopy in pediatric patients with ventriculoperitoneal shunts. AB - INTRODUCTION: In pediatric patients requiring abdominal operations, ventriculoperitoneal (VP) shunts for hydrocephalus are a frequently encountered comorbidity. Laparoscopy has not been extensively evaluated in this population, and there are concerns about the safety of insufflation under pressure with the shunt in place. There are a paucity of data in the literature to address this issue. Further, there is a relative lack of long-term follow-up in the literature to document shunt function over time after abdominal procedures. Therefore, we reviewed our experience in patients with VP shunts who underwent either open or laparoscopic abdominal procedures to determine the safety of laparoscopy in these patients. METHODS: We conducted a retrospective review of all pediatric patients with VP shunts who underwent laparoscopic and/or open abdominal operations at a single institution from 1998 to 2008. Complications were defined as a shunt- or surgery-related event (including any shunt revisions) within 6 months of abdominal surgery. Continuous variables were compared by using an independent sampled, two-tailed Student's t-test. Discrete variables were analyzed with Fisher's exact test with Yates correction, where appropriate. Significance was defined as P < or = 0.05. RESULTS: A total of 99 intra-abdominal operations were performed on patients with VP shunts: 51 were laparoscopic and 48 were open. Mean age was 3.17 versus 2.93 years, respectively (P = 0.77). The most common procedure performed in both groups was fundoplication with gastrostomy. There were no episodes of air embolism into the shunt. There was 1 shunt infection in the laparoscopic group and 3 in the open group (P = 0.56). CONCLUSIONS: Our data suggest that laparoscopy is safe in patients with ventriculoperitoneal shunts. PMID- 19645605 TI - Combined endolaparoscopic intragastric excision for gastric neoplasms. AB - BACKGROUND: The aim of this study was to describe our technique of combined endolaparoscopic approach to the management of intraluminal gastric neoplasms and to review the clinical outcome. METHODS: Between February 2006 and January 2008, a total of 12 patients with gastric neoplasm < or =4 cm with a mainly intraluminal component received the combined endolaparoscopic intragastric excision and were prospectively analyzed. All lesions were localized endoscopically and then treated by using a combined endoscopic submucosal dissection and laparoscopic intragastric technique. RESULTS: Eight of 12 lesions were gastrointestinal stromal tumours. The remaining lesions were adenomatous polyp with focal intramucosal adenocarcinoma, leiomyoma, and pancreatic heterotopia. All except 1 case was successfully treated with this technique (91.6%). There were no mortalities, and there was only 1 case of reactionary hemorrhage from the port site requiring a reoperation. The median operating time was 120 minutes, with a median blood loss of 35 mL. Length of hospital stay ranged from 3 to 12 days. There were no recurrences during the follow-up period. CONCLUSIONS: This combined endolaparoscopic intragastric excision technique is a truly minimally invasive alternative for selected gastric neoplasm. It is safe and feasible with a satisfactory short-term outcome. PMID- 19645607 TI - Acetylcholine-esterase inhibitor pyridostigmine decreases T cell overactivation in patients infected by HIV. AB - HIV infection is characterized by persistent immune activation, increased production of proinflammatory cytokines, and rapid T cell turnover. The autonomic nervous system exerts a regulatory effect on the inflammatory response mediated by acetylcholine. We investigated whether an acetylcholine esterase inhibitor would diminish the T cell overactive phenotype characteristic of chronically infected HIV patients. We carried out a proof-of-concept, placebo-controlled study involving 19 subjects chronically infected with HIV-1. Nine patient received pyridostigmine and 10 took a placebo. T cell activation measured by expression of CD69 (p = 0.025) diminished in those taking pyridostigmine. The drug also diminished in vitro T cell proliferation induced by PMA and ionomycin (p = 0.026). IFN-gamma release was diminished in the pyridostigmine group (p = 0.016) and expression of IL-4 (p = 0.010) and IL-10 (p = 0.015) increased. Here we showed that pyridostigmine is able to modify T cell overactivation and proliferation in patients chronically infected with HIV. Pyridostigmine led to an increase in the antiinflammatory cytokine IL-10 and a decrease in T cell proliferation and production of the proinflammatory cytokine IFN-gamma. PMID- 19645612 TI - Genetic-targeted therapy of thyroid cancer: a real promise. PMID- 19645613 TI - The case for obtaining a diagnostic whole-body scan prior to iodine 131 treatment of differentiated thyroid cancer. PMID- 19645614 TI - The low utility of pretherapy scans in thyroid cancer patients. PMID- 19645615 TI - Role of transforming growth factor beta in the regulation of thyroid function and growth. AB - Transforming growth factor beta (TGF-beta) exists in nature as three isoforms. They exert their effects by binding to a type II receptor located at the cell membrane. The TGF-beta-type II receptor complex then recruits type I receptor, and this new complex stimulates the phosphorylation of Smads 2 and 3, which are subsequently transferred to the nucleus, where they regulate gene transcription. The thyroid gland expresses the TGF-beta1 gene mRNA and synthesizes the protein, which under physiologic conditions regulates thyroid growth and function. Different studies have demonstrated that TGF-beta1 inhibits cell proliferation and a number of functional parameters. These include cyclic adenosine monophosphate (AMP) formation, iodine uptake and organification, hormone secretion, and the expression of thyroglobulin, thyroid peroxidase, and Na(+)/I( ) symporter. The expression of the TGF-beta1 gene and protein may be stimulated by iodine under normal conditions. Since TGF-beta1 mimics some of the inhibitory actions of iodine, its participation in thyroid autoregulation has been proposed; however, this concept is still debated. In thyroid tumors, the inhibitory action of TGF-beta1 on cell proliferation is progressively lost as the tumor becomes more undifferentiated. The alterations in the signaling pathway of TGF-beta1 are not the same in tumors from different species. Even within the same species, such as the pig thyroid, the results may be different depending on whether monolayers or follicular suspensions are employed. The data suggest that it is not entirely possible to apply the results obtained in animal studies to normal or pathological human thyroid tissue. More studies are required to provide the information needed to develop treatments, based on targeting the signaling pathway of TGF-beta1, for undifferentiated thyroid cancer and other thyroid diseases. PMID- 19645616 TI - Retinoic Acid receptor-related orphan receptor alpha-enhanced thyroid hormone receptor-mediated transcription requires its ligand binding domain which is not, by itself, sufficient: possible direct interaction of two receptors. AB - BACKGROUND: Natural mutant staggerer (sg) mice harbor a mutated retinoic acid receptor-related orphan receptor alpha (RORalpha). A genetic deletion corresponding to the ligand-binding domain (LBD) of RORalpha results in aberrant cerebellar development in the sg mice. These mice show similar neurotrophin expression to that seen in perinatal hypothyroid animals. RORalpha augments thyroid hormone receptor (TR)-mediated transcription, which may be partly responsible for the similar cerebellar abnormalities between sg and hypothyroid animals. The objective of this study is to examine further the mechanisms of augmentation of TR action by RORalpha. We examined whether TR directly binds to ROR and which regions of TR or ROR are required for the TR-ROR interaction. METHODS: A transient transfection-based reporter gene assay was performed to measure the activity of TR-mediated transcription in CV-1 cells. To examine TR RORalpha binding mammalian two-hybrid and glutathione-S-transferase (GST) pull down assays were carried out. RESULTS: Although full-length RORalpha augmented TRalpha1- or beta1-mediated transcription, such augmentation was not observed with sg-type mutant RORalpha (RORsg) that contained the RORalpha N-terminal and DNA-binding domain (DBD) and a part of the LBD. On the other hand, the transcription of Gal4-DBD-fused TRbeta1-LBD was suppressed by RORalpha, indicating that RORalpha does not interact with TR-LBD. Full-length TRbeta1 bound to RORalpha or RORsg in GST pull-down assays; however, RORalpha-LBD did not bind to TRalpha1 or beta1. CONCLUSION: The full-length forms of both RORalpha and TR are essential for the augmentation of TR-mediated transcription by RORalpha. PMID- 19645618 TI - Risky sexual behaviors and sexually transmitted diseases: a comparison study of cocaine-dependent individuals in treatment versus a community-matched sample. AB - Cocaine users routinely engage in high-risk sexual behaviors that place them at an elevated risk of contracting HIV and other blood-borne infections. The purpose of the present study was to compare trading sex for drugs and/or money, having 10 or more sexual partners in 1 year, and sexually transmitted diseases (STDs) of cocaine-dependent individuals in treatment for their dependence across race and gender and against participants who live in their community. Cocaine-dependent individuals (n = 459) were identified through nine publicly and privately funded inpatient and outpatient chemical dependency treatment centers in the St. Louis area during 2001-2006. Community-based participants (n = 459) were matched to cocaine-dependent participants on age, ethnicity, gender, and zip code of residence. Mean age of the sample was 36 years old, 50% were Caucasians, 50% were African American, and 47% were male. Nearly half of cocaine-dependent participants in treatment had traded sex for drugs and/or money and over one third had more than 10 sexual partners in 1 year with a risk concentrated among African Americans even after controlling for income and educational attainment. Participants recruited from the community with some exposure to cocaine reported similar rates of high risk sexual behaviors as the cocaine dependent subjects from treatment settings. It is important for clinicians to recognize that once released from treatment, cocaine-dependent individuals may be returning to high risk environments where sexual risk behaviors are occurring in the context of cocaine use. PMID- 19645620 TI - Health-related beliefs and decisions about accessing HIV medical care among HIV infected persons who are not receiving care. AB - In the United States, the publically supported national HIV medical care system is designed to provide HIV medical care to those who would otherwise not receive such care. Nevertheless, many HIV-infected persons are not receiving medical care. Limited information is available from HIV-infected persons not currently in care about the reasons they are not receiving care. From November 2006 to February 2007, we conducted five focus groups at community-based organizations and health departments in five U.S. cities to elicit qualitative information about barriers to entering HIV care. The 37 participants were mostly male (n = 29), over the age of 30 (n = 34), and all but one had not received HIV medical care in the previous 6 months. The focus group discussions revealed health belief related barriers that have often been overlooked by studies of access to care. Three key themes emerged: avoidance and disbelief of HIV serostatus, conceptions of illness and appropriate health care, and negative experiences with, and distrust of, health care. Our findings point to the potentially important influence of these health-related beliefs on individual decisions about whether to access HIV medical care. We also discuss the implications of these beliefs for provider-patient communication, and suggest that providers frame their communications with patients such that they are attentive to the issues identified by our respondents, to better engage patients as partners in the treatment process. PMID- 19645619 TI - Demographic, psychological, and behavioral modifiers of the Antiretroviral Treatment Access Study (ARTAS) intervention. AB - The present study sought to identify demographic, structural, behavioral, and psychological subgroups for which the Antiretroviral Treatment Access Study (ARTAS) intervention had stronger or weaker effects in linking recently diagnosed HIV-positive persons to medical care. The study, carried out from 2001 to 2003, randomized 316 participants to receive either passive referral or a strengths based linkage intervention to facilitate entry into HIV primary care. The outcome was attending at least one HIV primary care visit in each of two consecutive 6 month periods. Participants (71% male; 29% Hispanic; 57% black non-Hispanic), were recruited from sexually transmitted disease clinics, hospitals and community based organizations in four U.S. cities. Thirteen effect modifier variables measured at baseline were examined. Subgroup differences were formally tested with interaction terms in unadjusted and adjusted log-linear regression models. Eighty-six percent (273/316) of participants had complete 12-month follow-up data. The intervention significantly improved linkage to care in 12 of 26 subgroups. In multivariate analysis of effect modification, the intervention was significantly (p < 0.05) stronger among Hispanics than other racial/ethnic groups combined, stronger among those with unstable than stable housing, and stronger among those who were not experiencing depressive symptoms compared to those who were. The ARTAS linkage intervention was successful in many but not all subgroups of persons recently diagnosed with HIV infection. For three variables, the intervention effect was significantly stronger in one subgroup compared to the counterpart subgroup. To increase its scope, the intervention may need to be tailored to the specific needs of groups that did not respond well to the intervention. PMID- 19645621 TI - Adherence to antiretroviral therapy in conflict areas: a study among patients receiving treatment from Lacor Hospital, Uganda. AB - The interaction between limited resources, living in conflict areas, and complexity of HIV treatment may impact negatively on adherence to antiretroviral therapy (ART). Nonadherence may lead to development of resistant strains that may further increase the costs of management. The aim of this study was to compare the level of adherence to ART among internally displaced persons (IDPs) and non IDPs and determine the factors associated with nonadherence. A cross-sectional study was conducted from January to February 2008 among adults receiving ART from Lacor Hospital. Systematic sampling was used to select 200 participants. Adherence was assessed through patients' self-reports over a 4-day period. Data were collected using an interviewer-administered questionnaire and analyzed in SPSS version 12 (SPSS Inc, Chicago, IL). Patients were considered to be adherent if they took 95% or more of their medicines. Adherence rates among IDP and non IDP patients were compared using Mann-Whitney U test. Factors associated with nonadherence were determined using logistic regression. The overall mean 4-day adherence was 99.5%. There was no significant difference in adherence between IDPs and non-IDPs (99.6% and 99.5%, respectively). Being on first-line regimen of ART (odds ratio [OR] = 22.22, 95% confidence interval [CI] = 1.48-333.33) and feeling that staff at the health centre were condemning (OR = 22.22, 1.53-333.33) were independently associated with nonadherence. Our study was limited in using only self-reports to assess adherence. In conclusion, patients in conflict areas can achieve high levels of adherence. Interventions to reduce nonadherence should address health provider-patient interaction and patients on first-line regimens. PMID- 19645622 TI - Effects of severity of traumatic brain injury and brain reserve on cognitive control related brain activation. AB - Functional magnetic resonance imaging (fMRI) has revealed more extensive cognitive-control related brain activation following traumatic brain injury (TBI), but little is known about how activation varies with TBI severity. Thirty patients with moderate to severe TBI and 10 with orthopedic injury (OI) underwent fMRI at 3 months post-injury using a stimulus response compatibility task. Regression analyses indicated that lower total Glasgow Coma Scale (GCS) and GCS verbal component scores were associated with higher levels of brain activation. Brain-injured patients were also divided into three groups based upon their total GCS score (3-4, 5-8, or 9-15), and patients with a total GCS score of 8 or less produced increased, diffuse activation that included structures thought to mediate visual attention and cognitive control. The cingulate gyrus and thalamus were among the areas showing greatest increases, and this is consistent with vulnerability of these midline structures in severe, diffuse TBI. Better task performance was associated with higher activation, and there were differences in the over-activation pattern that varied with TBI severity, including greater reliance upon left-lateralized brain structures in patients with the most severe injuries. These findings suggest that over-activation is at least partially effective for improving performance and may be compensatory. PMID- 19645624 TI - Evaluating the psychological effects of genetic testing in symptomatic patients: a systematic review. AB - Most research on the effects of genetic testing is performed in individuals at increased risk for a specific disease (presymptomatic subjects) but not in patients already affected by disease. If results of these studies in presymptomatic subjects can be applied to patients is unclear. We performed a systematic review to evaluate the effects of genetic testing in patients and describe the methodological instruments used. About 2611 articles were retrieved and 16 studies included. Studies reported great variety in designs, methods, and patient outcomes. In total, 2868 participants enrolled of which 62% were patients. Patients appeared to have a lower perceived general health and higher levels of anxiety and depression than presymptomatic subjects before genetic testing. In the long term no psychological impairment was shown. We conclude that patients differ from presymptomatic subjects and may be more vulnerable to negative effects of genetic testing. Conclusions from earlier research on presymptomatic genetic testing cannot be generalized to patients, and more standardized research is needed. PMID- 19645623 TI - Apolipoprotein E4 as a predictor of outcomes in pediatric mild traumatic brain injury. AB - The epsilon4 allele of the apolipoprotein E (APOE) gene has been linked to negative outcomes among adults with traumatic brain injury (TBI) across the spectrum of severity, with preliminary evidence suggesting a similar pattern among children. This study investigated the relationship of the APOE epsilon4 allele to outcomes in children with mild TBI. Participants in this prospective, longitudinal study included 99 children with mild TBI between the ages of 8 and 15 recruited from consecutive admissions to Emergency Departments at two large children's hospitals. Outcomes were assessed acutely in the Emergency Department and at follow-ups at 2 weeks, 3 months, and 12 months post-injury. Among the 99 participants, 28 had at least one epsilon4 allele. Children with and without an epsilon4 allele did not differ demographically. Children with an epsilon4 allele were significantly more likely than those without an epsilon4 allele to have a Glasgow Coma Scale score of less than 15, but the groups did not differ on any other measures of injury severity. Those with an epsilon4 allele exhibited better performance than children without an epsilon4 allele on a test of constructional skill, but the groups did not differ on any other neuropsychological tests. Children with and without an epsilon4 allele also did not differ on measures of post-concussive symptoms. Overall, the findings suggest that the APOE epsilon4 allele is not consistently related to the outcomes of mild TBI in children. PMID- 19645625 TI - A substitution involving the NLGN4 gene associated with autistic behavior in the Greek population. AB - Autism is a neurodevelopmental disorder characterized by clinical, etiologic, and genetic heterogeneity. During the last decade, predisposing genes and genetic loci were under investigation. Recently, mutations in two X-linked neuroligin genes, neuroligin 3 (NLGN3) and neuroligin 4 (NLGN4), have been implicated in the pathogenesis of autism. In our ongoing survey, we screened 169 patients with autism for mutations linked with autism. In the preliminary study of specific exons of NLGN3 and NLGN4 genes, we identified the p.K378R substitution (c.1597 A > G) in exon 5 of the NLGN4 gene in a patient who was found to have mild autism and normal IQ at 3 years of age. The same mutation has previously been found in a patient with autism. It is important that, for the first time, a specific mutation in neuroligins is confirmed in a molecular screen in another homogeneous ethnic population. This finding further contributes to consideration of neuroligins as probable candidate genes for future molecular genetic studies, suggesting that a defect of synaptogenesis may predispose to autism. PMID- 19645626 TI - Mutations in MYH9 exons 1, 16, 26, and 30 are infrequently found in Japanese patients with nonsyndromic deafness. AB - Mutations in MYH9 result in the autosomal dominant giant platelet disorders with leukocyte inclusion bodies with varying degrees of Alport manifestations, including nephritis, deafness, and cataracts. A specific MYH9 mutation in exon 16, R705H, causes nonsyndromic deafness DFNA17. We searched for mutations in MYH9 exons 1, 16, 26, and 30 in a total of 157 Japanese patients with nonsyndromic deafness without known cause of hearing loss, but no mutations were found. We conclude that mutations in MYH9 are infrequently found in patients with nonsyndromic deafness and suggest that MYH9 mutations infrequently cause isolated sensorineural hearing loss. Thus, MYH9 may not currently be a good candidate gene for efficient screening of genetic causes in nonsyndromic deafness. PMID- 19645627 TI - Low prevalence and variable clinical presentation of troponin I and troponin T gene mutations in hypertrophic cardiomyopathy. AB - Hypertrophic cardiomyopathy (HCM) is an autosomal dominant disorder caused by mutations in cardiac sarcomeric proteins. Troponin I (TNNI3) and troponin T (TNNT2) are important parts of the sarcomere in heart muscle, and mutations in their genes are responsible for development of HCM. The prevalence of mutations in these two genes is low; hence, the data on clinical outcome are scarce. Yet, some of these mutations were shown to be malignant with a high incidence of sudden death. Here, we describe the disease course in three families affected with TNNI3 and one family with TNNT2 gene mutations. In TNNI3-HCM, the phenotypic manifestation ranged from clinically silent to sudden cardiac death with the worst prognosis observed in carriers of Ala157Val mutation in exon 7. In contrast, TNNT2-HCM was associated with favorable prognosis. Thus, the findings of the present study add evidence on the phenotypic presentation of this genetic disease. PMID- 19645629 TI - LMNA, ZMPSTE24, and LBR are not mutated in scleroderma. AB - Scleroderma is a rare multisystemic disease of unknown etiology presumed to develop in genetically predisposed patients. Since patients affected with scleroderma develop clinical features similar to those observed in some laminopathies, we decided to screen at the genomic level a cohort of 27 patients affected with either localized or systemic scleroderma for mutations in three lamin-related genes: LMNA, encoding A-type lamins; ZMPSTE24, encoding a protease involved in lamin A processing; and LBR, encoding the lamin B receptor. No mutation was retrieved, whereas 25 polymorphic sequence variations were identified, 7 of which were unreported. Functional analyses performed for three of these allowed exclusion of an impact on splicing. Multiplex ligation-dependent probe amplification analysis showed no LMNA deletion or duplication. Altogether our results suggest that LMNA, ZMPSTE24, and LBR sequence variations are not major genetic determinants involved in scleroderma pathogenesis. PMID- 19645628 TI - Efficient molecular genetic diagnosis of enlarged vestibular aqueducts in East Asians. AB - CONTEXT: Enlargement of the vestibular aqueduct (EVA) is a commonly detected inner ear anomaly related to hearing loss and often associated with mutations of SLC26A4 encoding pendrin, a transmembrane exchanger of Cl(-), I(-), and HCO(3)( ). Here we describe the phenotypes of 27 Korean EVA subjects and their SLC26A4 genotypes determined by bidirectional nucleotide sequencing. RESULTS: The detected variants include two novel missense substitutions (p.V138L and p.P542R). We characterized the ability of p.V138L and p.P542R pendrin products to traffic to the plasma membrane in COS-7 cells and to transport Cl(-), I(-), and HCO(3)(-) in Xenopus oocytes. The results indicate that p.P542R is a benign polymorphic variant, whereas p.V138L is a pathogenic mutation. Since this and other studies of East Asian EVA cohorts show that the majority of SLC26A4 mutations affect either or both of two amplicons (exons 7-8 and 19), we developed a hierarchical protocol that integrates direct sequencing with denaturing high-performance liquid chromatography analyses for detection of SLC26A4 mutations in these populations. We validated the cost efficiency of the integrated protocol by a simulated screen of published East Asian EVA cohorts with known SLC26A4 genotypes. CONCLUSIONS: Our study further defines the spectrum of SLC26A4 mutations among East Asians and demonstrates a rapid and efficient protocol for their detection. PMID- 19645630 TI - Engineered adenovirus serotypes for overcoming anti-vector immunity. AB - Adenovirus (Ad)-based gene transfer has been successfully utilised in gene therapy and vaccine applications. To date, an increasing number of human clinical trials utilise recombinant Ad-based vectors as a gene transfer platform. In particular, progress has been made recently in utilising Ad-based vectors as a vaccine platform in HIV, cancer immunotherapy approaches and in vaccination for other infections. Despite these successes, the scientific and bio-industrial communities have recently recognised that innate and pre-existing immunity against Ad vectors can constitute a serious obstacle to the development and application of this technology. It is essential to overcome vector-mediated immune responses, such as production of inflammatory cytokines and pre-existing immunity to Ad, because the induction of these responses not only shortens the period of gene expression but also leads to serious side effects. This review focuses on the biology of Ad infection and the approaches that are being adopted to overcome immunity against the Ad-based vectors. PMID- 19645631 TI - Immunotherapy for HIV-associated non-Hodgkin's lymphoma. AB - The onset of the AIDS epidemic in 1981 was followed by descriptions of many opportunistic infections as well as several unusual cancers. Non-Hodgkin's lymphoma (NHL) was classified as an AIDS-defining illness within 4 years, and is up to 200 times more common in HIV-positive patients. Immunotherapy for cancer has a surprisingly long heritage, but it is only recently that this approach has become established in oncology practice. Here, against a background of the history of immunotherapy, we review clinicopathological features of HIV associated NHL and discuss current cancer immunotherapeutic treatments including immune reconstitution using highly active antiretroviral therapy (HAART), anti CD20 monoclonal antibodies, radioimmunotherapy, stem cell transplantation, cytokine therapy and vaccination. As the prognosis for HIV-associated NHL nears that of the general population, these approaches are of increasing importance and value. PMID- 19645632 TI - Fibrinogen concentrate--a potential universal hemostatic agent. AB - BACKGROUND: Human fibrinogen concentrates have been commercially available for decades for substitution therapy in hypofibrinogenemia, dysfibrinogenemia and afibrinogenemia. Accumulating new data suggest that fibrinogen plays a critical role in achieving and maintaining hemostasis, particularly in patients suffering from acquired fibrinogen deficiency during massive bleeding, where benefit from early intervention with fibrinogen concentrate appears to be important. OBJECTIVE/METHODS: This work focuses on pasteurized fibrinogen concentrate, with special emphases on product characteristics, pharmacodynamics, pharmacokinetics, laboratory monitoring, dosing, clinical efficacy, safety and tolerability. Future clinical and laboratory perspectives on fibrinogen are discussed and outlined. RESULTS/CONCLUSION: Pasteurized fibrinogen concentrate is derived from human plasma. Its half life is 2.7 days in patients with congenital fibrinogen deficiency. For congenital and acquired deficiency in vivo recovery rates vary from 60% to 109%. Reportedly, administration of pasteurized fibrinogen in patients with congenital deficiency is efficacious. Acquired deficiency of fibrinogen appears to be an early event in seriously bleeding patients, preceding critical levels of platelets or other coagulation factors. Experimental animal studies, as well as clinical observations suggest a beneficial role of early substitution with fibrinogen in management of critical traumatic and surgical bleeds. Pasteurized fibrinogen concentrate is well tolerated and associated with a low incidence of adverse thrombo-embolic events. PMID- 19645633 TI - Biodegradable amphiphilic polymer-drug conjugate micelles. AB - The coupling of drugs to macromolecular carriers received an important impetus from Ringsdorf's notion of polymer-drug conjugates. Several water-soluble polymers, poly(ethylene glycol), poly[N-(2-hydroxypropyl) methacrylamide], poly(l glutamic acid) and dextran, are studied intensively and have been utilized successfully in clinical research. The promising results arising from clinical trials with polymer-drug conjugates (e.g., paclitaxel, doxorubicin, camptothecins) have provided a firm foundation for other synthetic polymers, especially biodegradable polymers, used as drug delivery vehicles. This review discusses biodegradable polymeric micelles as an alternative drug-conjugate system. Particular focus is on A-B or B-A-B type biodegradable amphiphilic block copolymer such as polylactide, morpholine-2,5-dione derivatives and cyclic carbonates, which can form a core-shell micellar structure, with the hydrophobic drug-binding segment forming the hydrophobic core and the hydrophilic segment as a hydrated outer shell. Polymeric micelles can be designed to avoid uptake by cells of reticuloendothelial system and thus enhance their blood lifetime via the enhanced permeability and retention effect. Active tumor-targeting may be achieved by modifying the micelle surface with specific ligands. The potential application areas are discussed and future challenges are highlighted. PMID- 19645634 TI - The potential adverse effects of aromatase inhibitors on wound healing: in vitro and in vivo evidence. AB - BACKGROUND: Estrogens and several other endogenous substances are recognised as being important in the process of wound healing. However, the effect of aromatase and aromatase inhibition in the wound healing process has yet to be fully defined. OBJECTIVE: A review of the in vitro and in vivo evidence on the effect of aromatase inhibition on wound healing. METHODS: The primary medical search engines used for the study were Ovid MEDLINE (1950 - March 2009) and EMBASE (1980 - March 2009) databases. RESULTS/CONCLUSION: The delayed healing of cutaneous wounds in aged individuals may in part reflect the decline in circulating levels of dehydroepiandrosterone (DHEA) and estrogens. The beneficial response on wound healing that DHEA and estrogen exert may be blocked by aromatase inhibition. Based on animal models, aromatase inhibitors may adversely affect cutaneous wound healing in the acute setting. So far, there have been no clinical trials investigating the adverse affect of aromatase inhibitors on the process of cutaneous wound healing in humans. Postmenopausal patients who take aromatase inhibitors as an adjunct to breast cancer therapy may, therefore, be at increased risk of delayed wound healing. Further studies are necessary to assess the extent of the effects on the wound healing process. PMID- 19645635 TI - Pancreatic islet inflammation in type 2 diabetes: from alpha and beta cell compensation to dysfunction. AB - Evidence in support of the concept of local pancreatic islet inflammation as a mechanism of beta cell failure in type 2 diabetes is accumulating. Observations in human islets from type 2 diabetic patients and rodent models of the disease indicate the increased presence of IL-1 driven cytokines and chemokines in pancreatic islets, concomitant with immune cell infiltration. Inflammation is the body's protective response to harmful stimuli and tissue damage. However, under chronic stress (e.g. metabolic stress in obesity and type 2 diabetes) the body's own defensive response may become deleterious to tissue function. Here, we summarize the current evidence that islet inflammation is a feature of type 2 diabetes, and discuss its role with respect to alpha and beta cell compensation and eventual beta cell failure. PMID- 19645636 TI - Rapid impact of rotavirus vaccination in the United States: implications for Australia. AB - Australia is in a unique position to assess the impact of two different rotavirus vaccines. PMID- 19645637 TI - The new age of pharmacovigilance. AB - The Therapeutic Goods Administration is strengthening pharmacovigilance, but strategies to encourage the conduct of pharmacoepidemiological research in Australia are needed. PMID- 19645638 TI - Testosterone for low libido in postmenopausal women not using systemic oestrogen therapy. AB - Results are promising but long-term safety remains uncertain. PMID- 19645639 TI - Understanding Australia's influenza pandemic policy on the strategic use of the antiviral drug stockpile. AB - Targeted post-exposure prophylaxis represents a more efficient use of the stockpile than treatment alone. PMID- 19645640 TI - Swine flu update: bringing home the bacon. AB - In 6 weeks, swine influenza A(H1N1) virus has spread from 10 to 74 countries. Australia has the fifth highest number of cases and the third highest rate of infection among the top five affected nations. People who are hospitalised with or die from this novel virus are more likely to have predisposing risk factors. There is a predilection for younger age groups and sparing of older age groups. This may be a property of influenza A viruses in general rather than being specific to swine influenza A. If unchecked, the sheer number of cases may lead to much higher numbers of deaths and hospitalised patients than would normally be attributed to a standard influenza season. Paradoxically, the low case-fatality rate of the virus raises the question of how best to approach management of this outbreak. It is uncertain how an expected vaccine against the novel virus will be used. PMID- 19645641 TI - Summary of the Australasian Society for Infectious Diseases and the Thoracic Society of Australia and New Zealand guidelines: treatment and prevention of H1N1 influenza 09 (human swine influenza) with antiviral agents. PMID- 19645642 TI - Epidemiological characteristics of pandemic influenza H1N1 2009 and seasonal influenza infection. AB - The median age of patients with pandemic influenza H1N1 2009 infection was reported as 20-25 years in initial case series from Europe and the United States. This has been lowered to 13 years in the US after testing of more patients, but this may reflect differential increased testing of school-aged children as part of the pandemic response. The median age of patients with seasonal influenza A(H1N1) infection identified through sentinel surveillance in Western Australia and Victoria in 2007-2008 was 18 and 22 years, respectively. For pandemic influenza H1N1 2009 infection, the median age of the first 244 patients identified in WA was 22 years, and median age of the first 135 patients identified through sentinel surveillance in Victoria was 21 years. Other comparisons of the epidemiological features of pandemic and seasonal influenza are difficult because much less laboratory testing is done for seasonal than for pandemic influenza. While early surveillance data indicated co-circulation of both pandemic and seasonal strains in WA and Victoria, more recent data from both states indicate an increasing predominance of pandemic influenza. If the evolving pandemic allows, we should take advantage of the increased testing being conducted for pandemic influenza to learn more about the real impact of laboratory-confirmed seasonal influenza. PMID- 19645643 TI - Australia's influenza containment plan and the swine flu epidemic in Victoria. AB - What lessons can be learnt from Australia's initial response to the outbreak? PMID- 19645644 TI - The general practice experience of the swine flu epidemic in Victoria--lessons from the front line. AB - The swine influenza (H1N1 09) outbreak in Victoria has provided an excellent opportunity to review the Australian Health Management Plan for Pandemic Influenza (AHMPPI) and to assess its performance in practice. General practitioners play a major role in seasonal flu management, and it was expected that the AHMPPI would enable GPs on the front line to maintain this central role during the swine flu pandemic. The role of front-line GPs has been made extremely difficult by deficiencies in implementation of the AHMPPI, including resource supply failures, time-consuming administrative burdens, delays in receiving laboratory test results and approval for provision of oseltamivir to patients, and a lack of clear communication about policy changes as the situation progressed. We must use this experience to ensure timely and appropriate review of the AHMPPI and the way it is implemented. Better consultation with front-line clinicians, particularly GPs, is crucial and must occur as a matter of urgent priority. PMID- 19645645 TI - Life-threatening respiratory failure from H1N1 influenza 09 (human swine influenza). AB - We present the first six cases of H1N1 influenza 09 (confirmed by a polymerase chain reaction test from nasopharyngeal swabs) in patients requiring admission to intensive care in Australia (in three hospitals in the north-western suburbs of Melbourne). These cases highlight the small but significant risk of life threatening respiratory failure associated with H1N1 influenza 09 infection. PMID- 19645646 TI - Early evidence for direct and indirect effects of the infant rotavirus vaccine program in Queensland. AB - OBJECTIVE: To assess the impact of introducing a publicly funded infant rotavirus vaccination program on disease notifications and on laboratory testing and results. DESIGN AND SETTING: Retrospective analysis of routinely collected data (rotavirus notifications [2006-2008] and laboratory rotavirus testing data from Queensland Health laboratories [2000-2008]) to monitor rotavirus trends before and after the introduction of a publicly funded infant rotavirus vaccination program in Queensland in July 2007. MAIN OUTCOME MEASURES: Age group-specific rotavirus notification trends; number of rotavirus tests performed and the proportion positive. RESULTS: In the less than 2 years age group, rotavirus notifications declined by 53% (2007) and 65% (2008); the number of laboratory tests performed declined by 3% (2007) and 15% (2008); and the proportion of tests positive declined by 45% (2007) and 43% (2008) compared with data collected before introduction of the vaccination program. An indirect effect of infant vaccination was seen: notifications and the proportion of tests positive for rotavirus declined in older age groups as well. CONCLUSIONS: The publicly funded rotavirus vaccination program in Queensland is having an early impact, direct and indirect, on rotavirus disease as assessed using routinely collected data. Further observational studies are required to assess vaccine effectiveness. Parents and immunisation providers should ensure that all Australian children receive the recommended rotavirus vaccine doses in the required timeframe. PMID- 19645647 TI - Injection of medications used in opioid substitution treatment in Australia after the introduction of a mixed partial agonist-antagonist formulation. AB - OBJECTIVES: To examine the levels and predictors of injection of buprenorphine naloxone (BNX)--a combination of a partial opioid agonist and an opioid antagonist for treating opioid dependence--which was specifically developed to limit injecting. Comparison was made with injecting of two other opioid substitution treatment medications, methadone and buprenorphine (BPN); severe harms have been documented after injection of the latter. DESIGN AND PARTICIPANTS: Injecting was studied in regular injecting drug users ("IDUs") and current opioid substitution treatment clients ("clients"). Regular IDUs are interviewed annually in each Australian capital city (about 900 per year) and data for 2003-2007 were used; 399 clients were interviewed in 2007. Data on injection of opioid substitution treatment medications between 2003 and 2007 were adjusted for availability of medications (from national sales data for methadone, BPN and BNX). Predictors of injecting were analysed by multiple regression analyses. SETTING: Capital cities of all Australian states and territories. MAIN OUTCOME MEASURE: Injection of opioid substitution treatment medications among individuals both in and out of treatment. RESULTS: In the year after its introduction in Australia, BNX was injected less frequently and by fewer regular IDUs and clients compared with BPN, particularly when differences in the availability of medications were taken into account. Some individuals did nonetheless regularly inject BNX. Injection of methadone, BPN and BNX was more likely to occur among those injecting other pharmaceutical opioids. CONCLUSIONS: A partial opioid agonist-antagonist combination appears to be less commonly and less frequently injected by clients in treatment and IDUs who are not. Further studies are needed to evaluate longer-term trends in use and harms. PMID- 19645648 TI - Smoking questions on the Australian death notification form: adopting international best practice? AB - Australia's achievement in tobacco control has been remarkable, but relies on indirect estimates of tobacco-attributed mortality, and on using relative risks from Western countries to calculate tobacco's impact. To accelerate the decline in smoking, more precise measures of tobacco's relative importance among different population subgroups are required. We propose that more direct and accurate measures of tobacco-attributed mortality are needed, which could be achieved by adding a small set of voluntary questions about the smoking status of the deceased to a revised death notification form. Ideally, this form should also record the smoking status of the next-of-kin or family informant, as this would help establish a living control group. Such information will provide data on tobacco-attributed deaths with incomparable precision, allowing accurate monitoring of the current state of the smoking epidemic, and its evolution over time. This is particularly pertinent for sections of the population in which tobacco control measures have been less successful. A number of practical concerns have been raised, but we do not believe these are insurmountable. PMID- 19645649 TI - The widening gap between clinical, teaching and research work. AB - Demand for medical education is increasing, and clinicians are struggling to maintain involvement in teaching and research activities. The settings of clinical training are changing and diversifying. The traditional model of medical education and the sustainability of academic medicine are under strain. Better support is required to ensure continued integration of research and education with clinical activities. Better coordination is required to overcome fragmentation within the medical education system, to ensure appropriate recognition for teaching and research across all clinical settings. PMID- 19645650 TI - Two cases of anticholinergic syndrome associated with consumption of bitter lupin flour. PMID- 19645651 TI - Starting at strengths . . .an Indigenous early years intervention. PMID- 19645652 TI - Extracorporeal membrane oxygenation. AB - Extracorporeal membrane oxygenation (ECMO) is a technique that involves oxygenation of blood outside the body, and provides support to selected patients with severe respiratory or cardiac failure. The two major ECMO modalities are venoarterial and venovenous. Data from several randomised trials support the use of ECMO in neonatal respiratory failure, and a recent randomised controlled trial of ECMO in adults has produced encouraging results. The evidence base for ECMO use in cardiac disease is developing, but progress has been slowed by considerations of clinical equipoise and evolving indications for ECMO. Advancing ECMO technology and increasing experience with ECMO techniques have improved patient outcomes, reduced complications and expanded the potential applications of ECMO. Awareness of the indications and implications of ECMO among doctors managing patients with severe but potentially reversible respiratory or cardiac failure may help facilitate better communication between health care teams and improve patient recovery. PMID- 19645653 TI - Envenoming by the rough-scaled snake (Tropidechis carinatus): a series of confirmed cases. AB - OBJECTIVE: To describe demographic, geographical and clinical features of envenoming by the rough-scaled snake (RSS) (Tropidechis carinatus). DESIGN, SETTING AND PARTICIPANTS: Prospective cohort study of RSS snakebite victims, recruited between January 2004 and December 2008, as part of the Australian Snakebite Project. RSS envenoming cases were confirmed by snake identification and/or venom-specific enzyme immunoassay. MAIN OUTCOME MEASURES: Clinical and laboratory features of envenoming. RESULTS: There were 24 confirmed cases of RSS envenoming, nearly all occurring in coastal areas between northern New South Wales and south-eastern Queensland. Twenty-three patients had local bite-site effects and 17 had at least three non-specific systemic effects (eg, nausea, headache). All 24 had venom-induced consumption coagulopathy (VICC), and 19 had an international normalised ratio>3.0. Six had bleeding from the bite site or intravenous cannula site, 10 had blood detected on urinalysis, and one had a major intra-abdominal haemorrhage. Mild neurotoxicity developed in two patients, and one patient developed myotoxicity with generalised myalgia, myoglobinuria and a peak creatine kinase level of 59 700 IU/L. Twenty-three patients were treated with antivenom (21 with tiger snake antivenom, two with polyvalent antivenom). Free venom was undetectable in 19 of 20 blood samples taken after antivenom administration. CONCLUSION: RSS envenoming occurs predominantly in coastal areas of northern NSW and southern Queensland, and within this range, most envenoming is due to the RSS rather than tiger snakes. Clinically it is characterised by VICC, with mild neurotoxicity and myotoxicity in some cases. Tiger snake antivenom appears to be effective against RSS envenoming. PMID- 19645654 TI - Reasons for termination of pregnancy in women aged 35 and over. PMID- 19645655 TI - Estimating coverage of the National HPV Vaccination Program: where are we at? PMID- 19645656 TI - Doctors and the pharmaceutical industry: time for a national policy? PMID- 19645657 TI - The quality of medication information in Australia: the need for more clinical expertise and accountability. PMID- 19645658 TI - The Australian Medical Council draft code of professional conduct: good practice or creeping authoritarianism? PMID- 19645659 TI - What changes are needed to the current direction and interpretation of clinical cancer research to meet the needs of the 21st century? PMID- 19645660 TI - Australian doctors need to catch up with population policy. PMID- 19645661 TI - Evolution of a house: Darwin's link to Pambula. PMID- 19645662 TI - Molecular mechanisms of homocysteine toxicity. AB - Hyperhomocysteinemia is a risk factor for a number of cardiovascular and neurodegenerative processes as well as a complicating factor in normal pregnancy. Toxic effects of homocysteine and the product of its spontaneous oxidation, homocysteic acid, are based on their ability to activate NMDA receptors, increasing intracellular levels of ionized calcium and reactive oxygen species. Even a short-term exposure of cells to homocysteic acid at concentrations characteristic of hyperhomocysteinemia induces their apoptotic transformation. The discovery of NMDA receptors both in neuronal tissue and in several other tissues and organs (including immunocompetent cells) makes them a target for toxic action of homocysteine. The neuropeptide carnosine was found to protect the organism from homocysteine toxicity. Treatment of pregnant rats with carnosine under conditions of alimentary hyperhomocysteinemia increases viability and functional activity of their progeny. PMID- 19645663 TI - Aggregation of frog rhodopsin to oligomers and their dissociation to monomer: application of BN- and SDS-PAGE. AB - After solubilization of frog rod outer segments (ROS) with mild detergents (digitonin, n-dodecyl-beta-D-maltoside, Chaps, Triton X-100) and subsequent one dimensional blue native polyacrylamide gel electrophoresis (1D BN-PAGE), the position of rhodopsin (Rh) on the gradient gel does not match the monomer with molecular weight of 40 kDa but appears self-associated into aggregate of Rh (RhA) with molecular mass varying in different detergents from 85 to 125 kDa. Short term treatment (~2 h) of the excised BN-PAGE strip containing RhA by denaturing detergent mixture (10% SDS + 1 mM dithiothreitol (DTT)) followed by 2D SDS-PAGE revealed dissociation of the RhA into opsin monomer and unidentified proteins. Long-term treatment (approximately 2 days) of RhA that included extraction, denaturation, concentration, and electrophoresis induced, along with dissociation of RhA into opsin monomer + unidentified proteins, also formation of opsin dimers, trimers, and higher oligomers owing to a secondary aggregation of opsin. Direct solubilization of the ROS by harsh SDS + DTT detergent mixture followed by 1D SDS-PAGE revealed only opsin monomer that upon heating disappeared, transforming into higher oligomers owing to secondary aggregation. The data show that degree of Rh oligomerization depends on specific conditions in which it stays. In the native state in the photoreceptor membrane as well as in mild detergents frog Rh exists mainly as dimers or higher oligomers. After solubilization with denaturing detergents, RhA can dissociate into monomers that then spontaneously self-associate into higher oligomers under the influence of various factors (for example, heating). PMID- 19645664 TI - Activation and damage of endothelial cells upon hypoxia/reoxygenation. Effect of extracellular pH. AB - Disturbances of blood flow upon vascular occlusions and spasms result in hypoxia and acidosis, while its subsequent restoration leads to reoxygenation and pH normalization (re-alkalization) in ischemic sites of the vascular bed. The effect of hypoxia/reoxygenation on activation and stimulation of apoptosis in cultured human endothelial cells was studied. The cells were subjected to hypoxia (2% O2, 5% CO2, 93% N(2)) for 24 h followed by reoxygenation (21% O2, 5% CO2, 74% N(2)) for 5 h. Reoxygenation was carried out at different pH-6.4 (preservation of acidosis after hypoxia), 7.0, and 7.4 (partial and complete re-alkalization, respectively). Hypoxia only slightly (by approximately 30%) increased the cell adhesion molecule ICAM-1 content on the cell surface, whereas reoxygenation more than doubled its expression. The reoxygenation effect depended on the medium acidity, and ICAM-1 increase was more pronounced at pH 7.0 compared to that at pH 6.4 and 7.4. Neither hypoxia nor reoxygenation induced expression of two other cell adhesion molecules, VCAM and E-selectin. Incubation of cells under hypoxic conditions but not reoxygenation stimulated secretion of von Willebrand factor and increased its concentration in the culture medium by more than 4 times. The percentage of cells containing apoptosis marker, activated caspase-3, was increased by approximately 1.5 times upon hypoxia as well as hypoxia/reoxygenation. Maximal values were achieved when reoxygenation was performed at pH 7.0. These data show that hypoxia/reoxygenation stimulate pro inflammatory activation (ICAM-1 expression) and apoptosis (caspase-3 activation) of endothelial cells, and the extracellular pH influences both processes. PMID- 19645665 TI - Epigenetic DNA-(cytosine-5-carbon) modifications: 5-aza-2'-deoxycytidine and DNA demethylation. AB - DNA (cytosine-5-carbon) methylation is one of the hallmarks of mammalian chromatin modifications. Distinct methylation pattern can generate synergistic or antagonistic interaction affinities for CpG-islands associated with methylated or unmethylated cytosine binding proteins, which also may dictate histone modifications and dynamic transition between transcriptionally silent or transcriptionally active chromatin states. The enzymes and cofactors associated with DNA-methylation reactions are convincing in terms of chemistry and chemical thermodynamics. The mechanism of demethylation, the candidate enzyme(s) exhibiting direct demethylase activity, and associated cofactors are not firmly established. Use of azanucleosides, such as 5-azacytidine and 5-aza-2' deoxycytidine (AzadC), in cell culture produces re-expression of certain genes, which otherwise were repressed in association with hypermethylated CpG-rich promoters. Hence the notion developed that AzadC is a demethylating agent. Here we discuss the broad global pictures with the following points: first, chemical definition and recent advances regarding the mechanism of DNA (cytosine-5-carbon) methylation ((Me)CpG-DNA or (Me)CpNpG-DNA formation) and (Me)CpG/(Me)CpNpG-DNA demethylation, and then with the mechanistic basis of inactivation of DNA methyltransferase 1 by AzadC. This will clarify that: (i) AzadC has nothing to do with DNA-demethylation; (ii) it cannot prevent even de novo methylation in non replicating cells; (iii) it can only prevent replication coupled maintenance as well as de novo methylations. Finally, we would like to suggest that terming/designating AzadC as DNA-demethylating agent is a serious misuse of chemistry and chemical terminology. PMID- 19645666 TI - High salt stress in coupled and uncoupled thylakoid membranes: a comparative study. AB - The effect of high salt concentration on photosystem II (PS II) electron transport rates and chlorophyll a fluorescence induction kinetics was investigated in coupled and uncoupled spinach thylakoid membranes. With increase in salt concentration, the rates of electron transport mediated by PS II and the F(v)/F(m) ratio were affected more in uncoupled thylakoids as compared to coupled thylakoid membranes. The uncoupled thylakoid membranes seemed to behave like coupled thylakoid membranes at high NaCl concentration (approximately 1 M). On increasing the salt concentration, the uncoupler was found to be less effective and Na+ probably worked as a coupling enhancer or uncoupling suppressor. We suggest that positive charge of Na+ mimics the function of positive charge of H+ in the thylakoid lumen in causing coupled state. The function of NaCl (monovalent cation) could be carried out by even lower concentration of Ca2+ (divalent cation) or Al3+ (trivalent cation). We conclude that this function of NaCl as coupling enhancer is not specific, and in general a positive charge is required for causing coupling in uncoupled thylakoid membranes. PMID- 19645667 TI - Site-directed mutagenesis of cytochrome c: reactions with respiratory chain components and superoxide radical. AB - Three forms of horse heart cytochrome c with specific substitutions of heme cleft surface located amino acid residues involved in specific interactions with ubiquinol:cytochrome c reductase (complex III) and cytochrome c oxidase (complex IV) were constructed, and their reactions with superoxide radical produced by NADH:ubiquinone reductase (complex I) were studied. The proteins with six (K27E/E69K/K72E/K86E/K87E/E90K and K8E/E62K/E69K/K72E/K86E/K87E) and eight (K8E/K27E/E62K/E69K/K72E/K86E/K87E/E90K) substitutions were inactive in the cytochrome c oxidase reaction, and their reduction rates by complex III were significantly lower than that seen with acetylated cytochrome c. The reduction of these modified cytochromes c under conditions where complex I generates superoxide was almost completely (about 90%) inhibited by superoxide dismutase. The genetically modified cytochromes c are useful analytical reagents for studies on superoxide generation by the mitochondrial respiratory chain. Quantitative comparison of superoxide-mediated cytochrome c reduction with hydrogen peroxide mediated Amplex Red oxidation suggests that complex I within its native environment (submitochondrial particles) produces both superoxide (~50%) and hydrogen peroxide (~50%). PMID- 19645668 TI - Resistance of alpha-crystallin quaternary structure to UV irradiation. AB - The damaging effect of UV radiation (lambda > 260 nm) on bovine alpha-crystallin in solution was studied by small-angle X-ray scattering, gel permeation chromatography, electrophoresis, absorption and fluorescence spectroscopy, and differential scanning calorimetry. The results obtained show that damage to even a large number of subunits within an alpha-crystallin oligomer does not cause significant rearrangement of its quaternary structure, aggregation of oligomers, or the loss of their solubility. Due to the high resistance of its quaternary structure, alpha-crystallin is able to prevent aggregation of destabilized proteins (especially of gamma- and beta-crystallins) and so to maintain lens transparency throughout the life of an animal (the chaperone-like function of alpha-crystallin). PMID- 19645669 TI - Synergism of ammonium and palmitic acid in uncoupling of electron transfer and ATP synthesis in chloroplasts. AB - Uncoupling by ammonium of electron transfer and ATP synthesis during linear transfer of electrons from water to photosystem 1 acceptors was studied in pea chloroplasts. It was shown that 40 microM palmitic acid decreased several-fold the ammonium concentrations necessary for 50% inhibition of ATP synthesis. The protonophore carbonyl cyanide m-chlorophenylhydrazone has no such property. The enhancement by palmitate of ammonium-induced uncoupling is accompanied by acceleration of basal electron transfer and decrease in the photoinduced uptake of hydrogen ions (H+). In the absence of ammonium, palmitate has no effect on basal transport and stimulates uptake of hydrogen ions. This means that in the case of combined action of palmitate and ammonium an additional leakage of H+ takes place, resulting in dissipation of the pH gradient. Synergic action of two metabolites, free fatty acid and ammonium, is supposed to provide for functioning of a system of mild regulation of energy coupling processes in native plant cell chloroplasts. Possible mechanisms of synergism are discussed. PMID- 19645670 TI - Probing for actinase activity of protealysin. AB - The ability of protealysin, a thermolysin-like metallopeptidase from Serratia proteamaculans 94, to cleave actin and matrix metalloprotease MMP2 is reported. In globular actin, protealysin and S. proteamaculans 94 cell extracts are shown to hydrolyze the Gly42-Val43 peptide bond within the DNase-binding loop and the Gly63-Ile64 and Thr66-Ile67 peptide bonds within the nucleotide cleft of the molecule. At enzyme/substrate mass ratio of 1 : 50 and below, a 36 kDa-fragment produced by the cleavage between Gly42 and Val43 was virtually resistant to further breakdown. Judging from the results of zymography, protealysin transforms proMMP2 into a 66 kDa polypeptide characteristic of mature MMP2, indicating that protealysin can activate MMP2. Upon incubation of S. proteamaculans 94 with human larynx carcinoma Hep-2 cells intracellular bacteria were detected in about 10% of Hep-2 cells, this being the first evidence for invasion of eukaryotic cells with bacteria of this species. Thus, S. proteamaculans 94 turned out to be one more bacterial strain in which synthesis of actin-specific metalloprotease is coupled with bacterial invasion. These results are consistent with the idea of the actinase activity of bacterial metalloproteases being a factor that may promote bacterial invasion of eukaryotic cells. PMID- 19645672 TI - Safranine O as a fluorescent probe for mitochondrial membrane potential studied on the single particle level and in suspension. AB - The permeant cationic dye safranine O is often used to measure mitochondrial membrane potential due to the dependence of both its absorption and fluorescence on mitochondrial energization, which causes its oligomerization inside mitochondria. In the present study we have used fluorescent correlation spectroscopy (FCS) to record the fluorescence changes on a micro level, i.e. under conditions permitting resolution of contributions from single particles (molecules of the dye and stained mitochondria). We have shown that the decrease in fluorescence signal from a suspension of energized mitochondria stained with a high safranine concentration (10 microM) is explained by the decrease in dye concentration in the medium in parallel with the accumulation of the dye inside the mitochondria, which results in fluorescence quenching. With 1 microM safranine O, the fluorescence rise after energization is caused by the accumulation of the dye up to a level not sufficient for full fluorescence quenching and also by the higher intensity of mitochondrial fluorescence on immersion of the dye in the hydrophobic milieu. Besides the estimation of the inner mitochondrial membrane potential, this approach also assesses the concentration of fluorescent particles. The non-monotonic dependence of the FCS parameter 1/G(tau-->0) on the concentration of mitochondrial protein suggests heterogeneity of the system with respect to fluorescence of particles. An important advantage of the described method is its high sensitivity, which allows measurements with low concentrations and quantities of mitochondrial protein in samples (less than 10 microg). PMID- 19645671 TI - Enzymological properties of endo-(1-4)-beta-glucanase Eg12p of Penicillium canescens and characteristics of structural gene egl2. AB - Gene egl2 of secreted endo-(1-4)-beta-glucanase of glycosyl hydrolase family 5 of the mycelial fungus Penicillium canescens was cloned. The gene was expressed in P. canescens under control of a strong promoter of the bgaS gene encoding beta galactosidase of P. canescens, and endoglucanase producing strains were obtained. Chromatographically purified recombinant 48 kDa protein had pH and temperature optima 3.4 and 60 degrees C, respectively, exhibited specific activity of 33 IU, and had K(m) and V(max) in CM-cellulose hydrolysis of 10.28 g/liter and 0.26 micromol/sec per mg, respectively. PMID- 19645673 TI - Fusion of barnase to antiferritin antibody F11 VH domain results in a partially folded functionally active protein. AB - A chimeric protein, VH-barnase, was obtained by fusing the VH domain of anti human ferritin monoclonal antibody F11 to barnase, a bacterial RNase from Bacillus amyloliquefaciens. After refolding from inclusion bodies, the fusion protein formed insoluble aggregates. Off-pathway aggregation was significantly reduced by adding either purified GroEL/GroES chaperones or arginine, with 10-12 fold increase in the yield of the soluble protein. The final protein conformation was identical by calorimetric criteria and CD and fluorescence spectroscopy to that obtained without additives, thus suggesting that VH-barnase structure does not depend on folding conditions. Folding of VH-barnase resulted in a single calorimetrically revealed folding unit, the so-called "calorimetric domain", with conformation consistent with a molten globule that possessed well-defined secondary structure and compact tertiary conformation with partial exposure of hydrophobic patches and low thermodynamic stability. The unique feature of VH barnase is that, despite the partially unfolded conformation and coupling into a single "calorimetric domain", this immunofusion retained both the antigen-binding and RNase activities that belong to the two heterologous domains. PMID- 19645674 TI - Sulfation of N-acyl dopamines in rat tissues. AB - Sulfation of N-acyl dopamines has been shown for the first time in cytosolic fractions of rat liver and nervous system. Sulfation of dopamine amides of docosahexaenoic and oleic acids occurred in all tissues studied, N-arachidonoyl dopamine was sulfated in the liver and spinal cord, and N-stearoyl dopamine was sulfated only in the liver. Depending on the substrate and tissue, the sulfation activity varied from 0.5 to 3.5 nmol/min per mg total protein. Kinetic parameters of N-docosahexaenoyl dopamine sulfation in the brain were determined. The findings characterize the sulfation system as the most productive metabolic pathway of N-acyl dopamines, but the role of this system in the body is unclear because of high K(m) value. PMID- 19645675 TI - Comparison of redox state of cells of tatar buckwheat morphogenic calluses and non-morphogenic calluses obtained from them. AB - Intracellular content of hydrogen peroxide and of the product of lipid peroxidation malonic dialdehyde as well as activity of antioxidant enzymes catalase, ascorbate peroxidase, and superoxide dismutase were studied in cells of morphogenic and derived from them non-morphogenic calluses of tatar buckwheat Fagopyrum tataricum L. Non-morphogenic calluses were characterized by significantly higher content of hydrogen peroxide and malonic dialdehyde, low catalase activity, and high activity of superoxide dismutase compared to morphogenic cultures. The results may indicate that cells of non-morphogenic calluses are in the state of continuous oxidative stress. Nevertheless, proliferative activity of non-morphogenic cultures and the biomass increase significantly exceeded these parameters in morphogenic calluses. An analogy is drawn between animal cancer cells and non-morphogenic plant calluses. PMID- 19645676 TI - Comparative study of immobilized and soluble NADH:FMN-oxidoreductase-luciferase coupled enzyme system. AB - The properties of a coupled enzyme system (NAD(P)H:FMN-oxidoreductase and luciferase) from luminous bacteria were studied. The enzymes and their substrates were immobilized in polymer gels of different types: starch (polysaccharide) and gelatin (polypeptide). Maximum activity yield (100%) was achieved with the enzymes immobilized in starch gel. An increase in K(m) (app) was observed in both immobilized systems as compared with the soluble coupled enzyme system. Immobilization in starch and gelatin gels increased the resistance of the NAD(P)H:FMN-oxidoreductase and luciferase coupled enzyme system to the effects of external physical and chemical factors. The optimum pH range expanded both to the acidic and alkaline regions. The resistance to concentrated salt solutions and high temperature also increased. The coupled enzyme system immobilized in starch gel (with activation energy 30 kJ/mol) was characterized by the best thermostability. The immobilized coupled enzyme system can be used to produce a stable and highly active reagent for bioluminescent analysis. PMID- 19645677 TI - Insights into the physics and the solutions of fractional-order differential equations. Preface. PMID- 19645678 TI - Insights into the fractional order initial value problem via semi-infinite systems. AB - This paper considers various aspects of the initial value problem for fractional order differential equations. The main contribution of this paper is to use the solutions to known spatially distributed systems to demonstrate that fractional differintegral operators require an initial condition term that is time-varying due to past distributed storage of information. PMID- 19645679 TI - A solution to the fundamental linear fractional order differential equation. AB - This paper provides a solution to the fundamental linear fractional order differential equation, namely, cdtqx(t) + ax(t) = bu(t). The impulse response solution is shown to be a series, named the F-function, which generalizes the normal exponential function. The F-function provides the basis for a qth order "fractional pole". Complex plane behavior is elucidated and a simple example, the inductor terminated semi-infinite lossy line, is used to demonstrate the theory. PMID- 19645680 TI - Generalized functions for the fractional calculus. PMID- 19645681 TI - R-function relationships for application in the fractional calculus. AB - The F-function, and its generalization the R-function, are of fundamental importance in the fractional calculus. It has been shown that the solution of the fundamental linear fractional differential equation may be expressed in terms of these functions. These functions serve as generalizations of the exponential function in the solution of fractional differential equations. Because of this central role in the fractional calculus, this paper explores various intrarelationships of the R-function, which will be useful in further analysis. Relationships of the R-function to the common exponential function, et, and its fractional derivatives are shown. From the relationships developed, some important approximations are observed. Further, the inverse relationships of the exponential function, et, in terms of the R-function are developed. Also, some approximations for the R-function are developed. PMID- 19645683 TI - The contribution of DNA base damage to human cancer is modulated by the base excision repair interaction network. AB - Base excision repair (BER) is a major mode of repair of DNA base damage. BER is required for maintenance of genetic stability, which is important in the prevention of cancer. However, direct genetic associations between BER deficiency and human cancer have been difficult to firmly establish, and the first generation mouse models deficient in individual DNA-glycosylases, which are the enzymes that give lesion specificity to the BER pathway, generally do not develop spontaneous tumors. This review summarizes our current understanding of the contribution of DNA base damage to human cancer, with a particular focus on DNA glycosylases and two of the main enzymes that prevent misincorporation of damaged deoxynucleotide triphosphates into DNA: the dUTPase and MTH1. The available evidence suggests that the most important factors determining individual susceptibility to cancer are not mutations in individual DNA repair enzymes but rather the regulation of expression and modulation of function by protein modification and interaction partners. With this in mind, we present a comprehensive list of protein-protein interactions involving DNA-glycosylases or either of the two enzymes that limit incorporation of damaged nucleotides into DNA. Interacting partners with a known role in human cancer are specifically highlighted. PMID- 19645682 TI - Proteomics: the tool to bridge the gap between the facts and fables of telomerase. AB - Genomic analysis has provided a huge cohort of data that has shed light on the regulation and structure of telomerase and will continue to influence its study profoundly. However, genomic and proteomic data need to be collated in order to bridge the gap between telomerase regulation and its crucial role in carcinogenesis. This review highlights significant advances in understanding the regulation of telomerase activity in the realm of genomics and proteomics focusing on the importance of telomerase as a future prognostic and diagnostic marker. PMID- 19645687 TI - Predicting enzyme subclasses by using support vector machine with composite vectors. AB - Based on enzyme sequence, using composite vectors with amino acid composition, low-frequency power spectral density, increment of diversity by combining a different form of pseudo amino acid composition to express the information of sequence, a support vector machine (SVM) for predicting enzyme subclasses is proposed. By the jackknife test, success rates of our algorithm are higher than other methods. PMID- 19645688 TI - Ribosome display and selection of human anti-placental growth factor scFv derived from ovarian cancer patients. AB - Ribosome display is a powerful cell-free technology to select a desired antibody together with its encoding mRNA. In this study, a human single-chain variable fragment (scFv) library was generated from the peripheral blood lymphocyte RNA of 10 ovarian cancer patients and then panned against bead-conjugated human PlGF, a protein that may contribute to the growth and metastasis of ovarian cancer. A selected scFv antibody was evaluated by Western blot and its affinity constant was determined by noncompetitive enzyme immunoassay. This study highlights the ribosomal display technology for the selection of human antibody from patient derived gene pools. PMID- 19645689 TI - Rotation testing in gene set enrichment analysis for small direct comparison experiments. AB - Gene Set Enrichment Analysis (GSEA) is a method for analysing gene expression data with a focus on a priori defined gene sets. The permutation test generally used in GSEA for testing the significance of gene set enrichment involves permutation of a phenotype vector and is developed for data from an indirect comparison design, i.e. unpaired data. In some studies the samples representing two phenotypes are paired, e.g. samples taken from a patient before and after treatment, or if samples representing two phenotypes are hybridised to the same two-channel array (direct comparison design). In this paper we will focus on data from direct comparison experiments, but the methods can be applied to paired data in general. For these types of data, a standard permutation test for paired data that randomly re-signs samples can be used. However, if the sample size is very small, which is often the case for a direct comparison design, a permutation test will give very imprecise estimates of the p-values. Here we propose using a rotation test rather than a permutation test for estimation of significance in GSEA of direct comparison data with a limited number of samples. Our proposed rotation test makes GSEA applicable to direct comparison data with few samples, by depending on rotations of the data instead of permutations. The rotation test is a generalisation of the permutation test, and can in addition be used on indirect comparison data and for testing significance of other types of test statistics outside the GSEA framework. PMID- 19645690 TI - Relevant nursing leadership: an evidence-based programmatic response. AB - Community and student demand for relevant nursing leadership graduate programs provided the impetus for this study. The aims were to identify components of highly competent nursing leadership, and strategies to integrate those components into education and practice. Nursing leaders gathered in five focus groups. A semi-structured interview guide was used to elicit narratives about nursing leadership. Interpretive analysis proceeded from identification of themes to uncovering of paradigm cases. Essential nursing leadership competencies comprised communication skills such as listening, conflict resolution, the ability to communicate a vision, motivate, and inspire. Additionally, leaders needed technological adroitness, fiscal dexterity, and the courage to be proactive during rapid change. Implications included a revision in the leadership focus of the nursing masters program, and the necessity that nurse retention should be enhanced by better educated nurse leaders who are grounded in practice and ready to provide a vision for the future. PMID- 19645691 TI - Using popular films to enhance classroom learning: the good, the bad, and the interesting. AB - Popular history films sometimes contain major historical inaccuracies. Two experiments investigated how watching such films influences people's ability to remember associated texts. Subjects watched film clips and studied texts about various historical topics. Whereas the texts contained only correct information, the film clips contained both correct information (consistent with the text) and misinformation (contradicted by the text). Before watching each clip, subjects received a specific warning, a general warning, or no warning about the misinformation. One week later, they returned for a cued-recall test about the texts. Watching a film clip increased correct recall of consistent information relative to recall of the same information when subjects did not see the clip. However, when the information in the film contradicted the text, subjects often (falsely) recalled misinformation from the film. The specific warning substantially reduced this misinformation effect. Teachers should use popular history films with caution and should warn students about major inaccuracies in the films. PMID- 19645692 TI - Evidence of differential meta-accuracy: people understand the different impressions they make. AB - This article reexamines the prevailing conclusion that people are unaware of the different impressions they make, or that their differential meta-accuracy is poor. This conclusion emerged from research employing contextually undifferentiated designs that may have constrained differences in actual impressions, thereby limiting participants' ability to demonstrate differential meta-accuracy. We argue that an alternative, contextually differentiated approach may reveal evidence for differential meta-accuracy because (a) people tend to behave differently in different social contexts, (b) interaction partners from different social contexts witness differing behaviors and form differing impressions of a target person, and (c) contextual information used to infer the impression one makes on others is relatively differentiated across contexts, resulting in differentiated metaperceptions. We assessed differential meta accuracy across social contexts (i.e., parents, hometown friends, and college friends) and found that, in contrast to researchers' prevailing conclusion, people can indeed detect the relative impressions they make on others. PMID- 19645694 TI - Preserved implicit knowledge of a forgotten childhood language. AB - Previous research suggests that a language learned during early childhood is completely forgotten when contact to that language is severed. In contrast with these findings, we report leftover traces of early language exposure in individuals in their adult years, despite a complete absence of explicit memory for the language. Specifically, native English individuals under age 40 selectively relearned subtle Hindi or Zulu sound contrasts that they once knew. However, individuals over 40 failed to show any relearning, and young control participants with no previous exposure to Hindi or Zulu showed no learning. This research highlights the lasting impact of early language experience in shaping speech perception, and the value of exposing children to foreign languages even if such exposure does not continue into adulthood. PMID- 19645693 TI - Color-binding errors during rivalrous suppression of form. AB - How does a physical stimulus determine a conscious percept? Binocular rivalry provides useful insights into this question because constant physical stimulation during rivalry causes different visual experiences. For example, presentation of vertical stripes to one eye and horizontal stripes to the other eye results in a percept that alternates between horizontal and vertical stripes. Presentation of a different color to each eye (color rivalry) produces alternating percepts of the two colors or, in some cases, a color mixture. The experiments reported here reveal a novel and instructive resolution of rivalry for stimuli that differ in both form and color: perceptual alternation between the rivalrous forms (e.g., horizontal or vertical stripes), with both eyes' colors seen simultaneously in separate parts of the currently perceived form. Thus, the colors presented to the two eyes (a) maintain their distinct neural representations despite resolution of form rivalry and (b) can bind separately to distinct parts of the perceived form. PMID- 19645695 TI - Gut reactions: moral conviction, religiosity, and trust in authority. AB - Theory and research point to different ways moral conviction and religiosity connect to trust in political authorities to decide controversial issues of the day. Specifically, we predicted that stronger moral convictions would be associated with greater distrust in authorities such as the U.S. Supreme Court making the "right" decisions regarding controversial issues. Conversely, we predicted that stronger religiosity would be associated with greater trust in authorities. We tested these hypotheses using a survey of a nationally representative sample of Americans (N = 727) that assessed the degree to which people trusted the U.S. Supreme Court to rule on the legal status of physician assisted suicide. Results indicated that greater religiosity was associated with greater trust in the U.S. Supreme Court to decide this issue, and that stronger moral convictions about physician-assisted suicide were associated with greater distrust in the U.S. Supreme Court to decide this issue. Also, the processes underlying religious trust and distrust based on moral convictions were more quick and visceral than slow and carefully considered. PMID- 19645696 TI - Regression analysis with a misclassified covariate from a current status observation scheme. AB - Naive use of misclassified covariates leads to inconsistent estimators of covariate effects in regression models. A variety of methods have been proposed to address this problem including likelihood, pseudo-likelihood, estimating equation methods, and Bayesian methods, with all of these methods typically requiring either internal or external validation samples or replication studies. We consider a problem arising from a series of orthopedic studies in which interest lies in examining the effect of a short-term serological response and other covariates on the risk of developing a longer term thrombotic condition called deep vein thrombosis. The serological response is an indicator of whether the patient developed antibodies following exposure to an antithrombotic drug, but the seroconversion status of patients is only available at the time of a blood sample taken upon the discharge from hospital. The seroconversion time is therefore subject to a current status observation scheme, or Case I interval censoring, and subjects tested before seroconversion are misclassified as nonseroconverters. We develop a likelihood-based approach for fitting regression models that accounts for misclassification of the seroconversion status due to early testing using parametric and nonparametric estimates of the seroconversion time distribution. The method is shown to reduce the bias resulting from naive analyses in simulation studies and an application to the data from the orthopedic studies provides further illustration. PMID- 19645697 TI - Statistical metrics for quality assessment of high-density tiling array data. AB - High-density tiling arrays are designed to blanket an entire genomic region of interest using tiled oligonucleotides at very high resolution and are widely used in various biological applications. Experiments are usually conducted in multiple stages, in which unwanted technical variations may be introduced. As tiling arrays become more popular and are adopted by many research labs, it is pressing to develop quality control tools as was done for expression microarrays. We propose a set of statistical quality metrics analogous to those in expression microarrays with application to tiling array data. We also develop a method to estimate the significance level of an observed quality measurement using randomization tests. These methods have been applied to multiple real data sets, including three independent ChIP-chip experiments and one transcriptom mapping study, and they have successfully identified good quality chips as well as outliers in each study. PMID- 19645698 TI - Risk-group-specific dose finding based on an average toxicity score. AB - We propose a Bayesian dose-finding design that accounts for two important factors, the severity of toxicity and heterogeneity in patients' susceptibility to toxicity. We consider toxicity outcomes with various levels of severity and define appropriate scores for these severity levels. We then use a multinomial likelihood function and a Dirichlet prior to model the probabilities of these toxicity scores at each dose, and characterize the overall toxicity using an average toxicity score (ATS) parameter. To address the issue of heterogeneity in patients' susceptibility to toxicity, we categorize patients into different risk groups based on their susceptibility. A Bayesian isotonic transformation is applied to induce an order-restricted posterior inference on the ATS. We demonstrate the performance of the proposed dose-finding design using simulations based on a clinical trial in multiple myeloma. PMID- 19645699 TI - Incorporating predictor network in penalized regression with application to microarray data. AB - We consider penalized linear regression, especially for "large p, small n" problems, for which the relationships among predictors are described a priori by a network. A class of motivating examples includes modeling a phenotype through gene expression profiles while accounting for coordinated functioning of genes in the form of biological pathways or networks. To incorporate the prior knowledge of the similar effect sizes of neighboring predictors in a network, we propose a grouped penalty based on the L(gamma)-norm that smoothes the regression coefficients of the predictors over the network. The main feature of the proposed method is its ability to automatically realize grouped variable selection and exploit grouping effects. We also discuss effects of the choices of the gamma and some weights inside the L(gamma)-norm. Simulation studies demonstrate the superior finite-sample performance of the proposed method as compared to Lasso, elastic net, and a recently proposed network-based method. The new method performs best in variable selection across all simulation set-ups considered. For illustration, the method is applied to a microarray dataset to predict survival times for some glioblastoma patients using a gene expression dataset and a gene network compiled from some Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. PMID- 19645700 TI - Regression calibration in semiparametric accelerated failure time models. AB - In large cohort studies, it often happens that some covariates are expensive to measure and hence only measured on a validation set. On the other hand, relatively cheap but error-prone measurements of the covariates are available for all subjects. Regression calibration (RC) estimation method (Prentice, 1982, Biometrika 69, 331-342) is a popular method for analyzing such data and has been applied to the Cox model by Wang et al. (1997, Biometrics 53, 131-145) under normal measurement error and rare disease assumptions. In this article, we consider the RC estimation method for the semiparametric accelerated failure time model with covariates subject to measurement error. Asymptotic properties of the proposed method are investigated under a two-phase sampling scheme for validation data that are selected via stratified random sampling, resulting in neither independent nor identically distributed observations. We show that the estimates converge to some well-defined parameters. In particular, unbiased estimation is feasible under additive normal measurement error models for normal covariates and under Berkson error models. The proposed method performs well in finite-sample simulation studies. We also apply the proposed method to a depression mortality study. PMID- 19645701 TI - A Bayesian chi-squared goodness-of-fit test for censored data models. AB - We propose a Bayesian chi-squared model diagnostic for analysis of data subject to censoring. The test statistic has the form of Pearson's chi-squared test statistic and is easy to calculate from standard output of Markov chain Monte Carlo algorithms. The key innovation of this diagnostic is that it is based only on observed failure times. Because it does not rely on the imputation of failure times for observations that have been censored, we show that under heavy censoring it can have higher power for detecting model departures than a comparable test based on the complete data. In a simulation study, we show that tests based on this diagnostic exhibit comparable power and better nominal Type I error rates than a commonly used alternative test proposed by Akritas (1988, Journal of the American Statistical Association 83, 222-230). An important advantage of the proposed diagnostic is that it can be applied to a broad class of censored data models, including generalized linear models and other models with nonidentically distributed and nonadditive error structures. We illustrate the proposed model diagnostic for testing the adequacy of two parametric survival models for Space Shuttle main engine failures. PMID- 19645702 TI - Forecasting pollen concentration by a two-step functional model. AB - A functional regression model to forecast the cypress pollen concentration during a given time interval, considering the air temperature in a previous interval as the input, is derived by means of a two-step procedure. This estimation is carried out by functional principal component (FPC) analysis and the residual noise is also modeled by FPC regression, taking as the explicative process the pollen concentration during the earlier interval. The prediction performance is then tested on pollen data series recorded in Granada (Spain) over a period of 10 years. PMID- 19645703 TI - Controlling false discoveries in multidimensional directional decisions, with applications to gene expression data on ordered categories. AB - Microarray gene expression studies over ordered categories are routinely conducted to gain insights into biological functions of genes and the underlying biological processes. Some common experiments are time-course/dose-response experiments where a tissue or cell line is exposed to different doses and/or durations of time to a chemical. A goal of such studies is to identify gene expression patterns/profiles over the ordered categories. This problem can be formulated as a multiple testing problem where for each gene the null hypothesis of no difference between the successive mean gene expressions is tested and further directional decisions are made if it is rejected. Much of the existing multiple testing procedures are devised for controlling the usual false discovery rate (FDR) rather than the mixed directional FDR (mdFDR), the expected proportion of Type I and directional errors among all rejections. Benjamini and Yekutieli (2005, Journal of the American Statistical Association 100, 71-93) proved that an augmentation of the usual Benjamini-Hochberg (BH) procedure can control the mdFDR while testing simple null hypotheses against two-sided alternatives in terms of one-dimensional parameters. In this article, we consider the problem of controlling the mdFDR involving multidimensional parameters. To deal with this problem, we develop a procedure extending that of Benjamini and Yekutieli based on the Bonferroni test for each gene. A proof is given for its mdFDR control when the underlying test statistics are independent across the genes. The results of a simulation study evaluating its performance under independence as well as under dependence of the underlying test statistics across the genes relative to other relevant procedures are reported. Finally, the proposed methodology is applied to a time-course microarray data obtained by Lobenhofer et al. (2002, Molecular Endocrinology 16, 1215-1229). We identified several important cell-cycle genes, such as DNA replication/repair gene MCM4 and replication factor subunit C2, which were not identified by the previous analyses of the same data by Lobenhofer et al. (2002) and Peddada et al. (2003, Bioinformatics 19, 834-841). Although some of our findings overlap with previous findings, we identify several other genes that complement the results of Lobenhofer et al. (2002). PMID- 19645704 TI - Hierarchical and joint site-edge methods for medicare hospice service region boundary analysis. AB - Hospice service offers a convenient and ethically preferable health-care option for terminally ill patients. However, this option is unavailable to patients in remote areas not served by any hospice system. In this article, we seek to determine the service areas of two particular cancer hospice systems in northeastern Minnesota based only on death counts abstracted from Medicare billing records. The problem is one of spatial boundary analysis, a field that appears statistically underdeveloped for irregular areal (lattice) data, even though most publicly available human health data are of this type. In this article, we suggest a variety of hierarchical models for areal boundary analysis that hierarchically or jointly parameterize both the areas and the edge segments. This leads to conceptually appealing solutions for our data that remain computationally feasible. While our approaches parallel similar developments in statistical image restoration using Markov random fields, important differences arise due to the irregular nature of our lattices, the sparseness and high variability of our data, the existence of important covariate information, and most importantly, our desire for full posterior inference on the boundary. Our results successfully delineate service areas for our two Minnesota hospice systems that sometimes conflict with the hospices' self-reported service areas. We also obtain boundaries for the spatial residuals from our fits, separating regions that differ for reasons yet unaccounted for by our model. PMID- 19645705 TI - A global sensitivity test for evaluating statistical hypotheses with nonidentifiable models. AB - We consider the problem of evaluating a statistical hypothesis when some model characteristics are nonidentifiable from observed data. Such a scenario is common in meta-analysis for assessing publication bias and in longitudinal studies for evaluating a covariate effect when dropouts are likely to be nonignorable. One possible approach to this problem is to fix a minimal set of sensitivity parameters conditional upon which hypothesized parameters are identifiable. Here, we extend this idea and show how to evaluate the hypothesis of interest using an infimum statistic over the whole support of the sensitivity parameter. We characterize the limiting distribution of the statistic as a process in the sensitivity parameter, which involves a careful theoretical analysis of its behavior under model misspecification. In practice, we suggest a nonparametric bootstrap procedure to implement this infimum test as well as to construct confidence bands for simultaneous pointwise tests across all values of the sensitivity parameter, adjusting for multiple testing. The methodology's practical utility is illustrated in an analysis of a longitudinal psychiatric study. PMID- 19645706 TI - Sociodemographic differences in early access to liver transplantation services. AB - The question of whether health care inequities occur before patients with end stage liver disease (ESLD) are waitlisted for transplantation has not previously been assessed. To determine the impact of gender, race and insurance on access to transplantation, we linked Pennsylvania sources of data regarding adult patients discharged from nongovernmental hospitals from 1994 to 2001. We followed the patients through 2003 and linked information to records from five centers responsible for 95% of liver transplants in Pennsylvania during this period. Using multinomial logistic regressions, we estimated probabilities that patients would undergo transplant evaluation, transplant waitlisting and transplantation itself. Of the 144,507 patients in the study, 4361 (3.0%) underwent transplant evaluation. Of those evaluated, 3071 (70.4%) were waitlisted. Of those waitlisted, 1537 (50.0%) received a transplant. Overall, 57,020 (39.5%) died during the study period. Patients were less likely to undergo evaluation, waitlisting and transplantation if they were women, black and lacked commercial insurance (p < 0.001 each). Differences were more pronounced for early stages (evaluation and listing) than for the transplantation stage (in which national oversight and review occur). For early management and treatment decisions of patients with ESLD to be better understood, more comprehensive data concerning referral and listing practices are needed. PMID- 19645707 TI - Combining cariporide with glyceryl trinitrate optimizes cardiac preservation during porcine heart transplantation. AB - Sodium-hydrogen exchange inhibitors, such as cariporide, are potent cardioprotective agents, however, safety concerns have been raised about intravenously (i.v.) administered cariporide in humans. The aim of this study was to develop a preservation strategy that maintained cariporide's cardioprotective efficacy during heart transplantation while minimizing recipient exposure. We utilized a porcine model of orthotopic heart transplantation that incorporated donor brain death and 14 h static heart storage. Five groups were studied: control (CON), hearts stored in Celsior; CAR1, hearts stored in Celsior with donors and recipients receiving cariporide (2 mg/kg i.v.) prior to explantation and reperfusion, respectively; CAR2, hearts stored in Celsior supplemented with cariporide (10 mumol/L); GTN, hearts stored in Celsior supplemented with glyceryl trinitrate (GTN) (100 mg/L); and COMB, hearts stored in Celsior supplemented with cariporide (10 mumol/L) plus GTN (100 mg/L). A total of 5/5 CAR1 and 5/6 COMB recipients were weaned from cardiopulmonary bypass compared with 1/5 CON, 1/5 CAR2 and 0/5 GTN animals (p = 0.001). Hearts from the CAR1 and COMB groups demonstrated similar cardiac function and troponin release after transplantation. Supplementation of Celsior with cariporide plus GTN provided superior donor heart preservation to supplementation with either agent alone and equivalent preservation to that observed with systemic administration of cariporide to the donor and recipient. PMID- 19645709 TI - Antifungal prophylaxis with voriconazole or itraconazole in lung transplant recipients: hepatotoxicity and effectiveness. AB - Invasive fungal infections (IFI) are common after lung transplantation and there are limited data for the use of antifungal prophylaxis in these patients. Our aim was to compare the safety and describe the effectiveness of universal prophylaxis with two azole regimens in lung transplant recipients. This is a retrospective study in lung transplant recipients from July 2003 to July 2006 who received antifungal prophylaxis with itraconazole or voriconazole plus inhaled amphotericin B to compare the incidence of hepatotoxicity. Secondary outcomes include describing the incidence of IFI, clinical outcomes after IFI and mortality. Sixty-seven consecutive lung transplants received antifungal prophylaxis, 32 itraconazole and 35 voriconazole and inhaled amphotericin B. There were no significant differences between groups in the acute physiology and chronic health evaluation (APACHE) score at the time of transplantation, demographic characteristics, comorbidities and concomitant use of hepatotoxic medications. Hepatotoxicity occurred in 12 patients receiving voriconazole and inhaled amphotericin B and in no patients receiving itraconazole (p < 0.001). There was no significant difference between groups with regard to the percentage of transplants with IFI, but one case of zygomycosis occurred in a transplant treated with voriconazole. Voriconazole prophylaxis after lung transplantation was associated with a higher incidence of hepatotoxicity and similar clinical effectiveness when compared to itraconazole. PMID- 19645708 TI - An anti-CD103 immunotoxin promotes long-term survival of pancreatic islet allografts. AB - Previous studies using knockout mice document a key role for the integrin CD103 in promoting organ allograft rejection and graft-versus-host disease. However, a determination of whether blockade of the CD103 pathway represents a viable therapeutic strategy for intervention in these processes has proven problematic due to the lack of reagents that efficiently deplete CD103+ cells from wild type hosts. To circumvent this problem, we conjugated the nondepleting anti-CD103 monoclonal antibody, M290, to the toxin, saporin, to produce an immunotoxin (M290 SAP) that efficiently depletes CD103+ cells in vivo. Herein, we show that M290 SAP dramatically reduces the frequency and absolute numbers of CD103-expressing leukocytes in the blood, spleen, mesenteric lymph nodes and intestinal epithelium of treated mice. We further demonstrate that M290-SAP promotes indefinite islet allograft survival in a fully MHC mismatched mouse model. The prolonged islet allograft survival resulting from M290-SAP treatment was associated with multiple effects in the host immune system including not only depletion of CD103 expressing leukocytes, but also an increase in CD4+CD25+FoxP3+ T regulatory cells and a predominance of effector-memory CD8 T cells. Regardless of the underlying mechanisms, these data document that depletion of CD103-expressing cells represents a viable strategy for therapeutic intervention in allograft rejection. PMID- 19645710 TI - Characteristic changes in coronary artery at the early hyperglycaemic stage in a rat type 2 diabetes model and the effects of pravastatin. AB - BACKGROUND AND PURPOSE: Diabetes is a risk factor for the development of coronary artery disease but it is not known whether the functions of endothelium-derived nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in coronary arteries are altered in the early stage of diabetes. Such alterations and the effects of pravastatin were examined in left anterior descending coronary arteries (LAD) from Otsuka Long-Evans Tokushima Fatty (OLETF) rats (type 2 diabetes model) at the early hyperglycaemic stage [vs. non-diabetic Long-Evans Tokushima Otsuka (LETO) rats]. EXPERIMENTAL APPROACH: Isometric tension, membrane potential and superoxide production were measured, as were protein expression of NAD(P)H oxidase components and endothelial NO synthase (eNOS). KEY RESULTS: Superoxide production and the protein expressions of both the nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] oxidase components and eNOS were increased in OLETF rats. These changes were normalized by pravastatin administration. Not only acetylcholine (ACh)-induced endothelial NO production but also functions of endothelium-derived NO [from (i) the absolute tension induced by epithio-thromboxane A(2) (STA(2)) or high K(+); (ii) enhancement of the STA(2)-contraction by a nitric oxide synthase (NOS) inhibitor; and (iii) the ACh-induced endothelium-dependent relaxation of high K(+)-induced contraction] or EDHF [from (iv) ACh-induced endothelium-dependent smooth muscle cell hyperpolarization and relaxation in the presence of a NOS inhibitor] were similar between LETO and OLETF rats [whether or not the latter were pravastatin-treated or -untreated]. CONCLUSIONS AND IMPLICATIONS: Under conditions of increased vascular superoxide production, endothelial function is retained in LAD in OLETF rats at the early hyperglycaemic stage, partly due to enhanced endothelial NOS protein expression. Inhibition of superoxide production may contribute to the beneficial vascular effects of pravastatin. PMID- 19645711 TI - Antinociceptive effects of NCX-701 (nitro-paracetamol) in neuropathic rats: enhancement of antinociception by co-administration with gabapentin. AB - BACKGROUND AND PURPOSE: Neuropathic pain is characterized by a poor response to classic analgesics. In the present study, we have assessed the antinociceptive activity of NCX-701 (nitro-paracetamol) in neuropathic rats, after systemic and intrathecal (i.t.) administration. In addition, we analysed the possible benefit of the combination of NCX-701 and gabapentin, a well-known potent analgesic, in the treatment of neuropathic pain. EXPERIMENTAL APPROACH: The antinociceptive effects of i.v. and i.t. NCX-701 and paracetamol were studied in spinal cord neuronal responses from neuropathic adult male Wistar rats, using the recording of single motor units technique. The effect of i.v. and i.t. NCX-701 in combination with i.v. gabapentin was studied by isobolographic analysis. KEY RESULTS: The experiments showed that NCX-701, but not paracetamol, dose dependently reduced the nociceptive responses evoked by noxious mechanical and electrical stimulation, after i.v. (ID(50) 542 +/- 5 micromol kg(-1) for noxious mechanical stimulation) or i.t. (ID(50) 932 +/- 16 nmol kg(-1)) administration. The combined administration of i.v. or i.t. NCX-701 and i.v. gabapentin induced a more intense antinociceptive effect than any of the two drugs given alone. The isobolographic analysis showed a synergistic effect. CONCLUSIONS AND IMPLICATIONS: NCX-701 is an effective antinociceptive compound in situations of neuropathy-induced sensitization, with an action mainly located in the spinal cord. The combination of NCX-701 and gabapentin induces a synergistic enhancement of the depression of nociceptive responses evoked by natural noxious stimulation. The use of NCX-701 alone or in combination with gabapentin might open up new and promising perspectives in the treatment of neuropathic pain. PMID- 19645712 TI - Chronic treatment with pravastatin prevents early cardiovascular changes in spontaneously hypertensive rats. AB - BACKGROUND AND PURPOSE: This study investigates the effect of pravastatin on blood pressure, cardiovascular remodelling and impaired endothelial function induced as early signs of cardiovascular disease in young spontaneously hypertensive rats (SHR). EXPERIMENTAL APPROACH: Eight-week-old SHR were treated for 4 weeks with pravastatin (20 mg kg(-1) day(-1)). Systolic blood pressure was measured periodically during the study using the tail-cuff method. At the end of the study, the left ventricular weight /body weight ratio was used as an index of left ventricular hypertrophy (LVH). Vascular function, superoxide (O(2)(-*)) production and structure were studied in aortic rings. Lipid peroxidation was measured in plasma (thiobarbituric acid reactive substances assay). KEY RESULTS: Systolic blood pressure was lower in treated SHR than in control SHR, at the end of the study (171 +/- 1 vs. 159 +/- 2 mmHg, P < 0.05), and LVH was significantly reduced by pravastatin (2.7 +/- 0.02 vs. 2.5 +/- 0.01 mg g(-1), P < 0.05). Vascular responses to sodium nitroprusside and phenylephrine were similar in both groups; nevertheless, the relaxation response to acetylcholine was higher in the treated rats (45.6 +/- 2.6 vs. 58.1 +/- 3.2 %, P < 0.05). Vascular O(2)(-*) and plasma thiobarbituric acid reactive substances were reduced by pravastatin treatment, and urinary nitrites was elevated. Finally aortic wall became thinner after pravastatin treatment. CONCLUSIONS AND IMPLICATIONS: Chronic treatment with pravastatin attenuated the increase of systolic blood pressure in SHR, prevented early LVH and improved vascular structure and function. These effects were accompanied by decreased measures of oxidative stress and improvements in NO production. PMID- 19645713 TI - Inhibition of vascular calcium-gated chloride currents by blockers of KCa1.1, but not by modulators of KCa2.1 or KCa2.3 channels. AB - BACKGROUND AND PURPOSE: Recent pharmacological studies have proposed there is a high degree of similarity between calcium-activated Cl(-) channels (CaCCs) and large conductance, calcium-gated K(+) channels (K(Ca)1.1). The goal of the present study was to ascertain whether blockers of K(Ca)1.1 inhibited calcium activated Cl(-) currents (I(ClCa)) and if the pharmacological overlap between K(Ca)1.1 and CaCCs extends to intermediate and small conductance, calcium activated K(+) channels. EXPERIMENTAL APPROACHES: Whole-cell Cl(-) and K(+) currents were recorded from murine portal vein myocytes using the whole-cell variant of the patch clamp technique. CaCC currents were evoked by pipette solutions containing 500 nM free [Ca(2+)]. KEY RESULTS: The selective K(Ca)1.1 blocker paxilline (1 microM) inhibited I(ClCa) by approximately 90%, whereas penitrem A (1 microM) and iberiotoxin (100 and 300 nM) reduced the amplitude of I(ClCa) by approximately 20%, as well as slowing channel deactivation. Paxilline also abolished the stimulatory effect of niflumic acid on the CaCC. In contrast, an antibody against the Ca(2+)-binding domain of murine K(Ca)1.1 had no effect on I(ClCa) while inhibiting spontaneous K(Ca)1.1 currents. Structurally different modulators of small and intermediate conductance calcium-activated K(+) channels (K(Ca)2.1 and K(Ca)2.3), namely 1-EBIO, (100 microM); NS309, (1 microM); TRAM-34, (10 microM); UCL 1684, (1 microM) had no effect on I(ClCa). CONCLUSIONS AND IMPLICATIONS: These data show that the selective K(Ca)1.1 blockers also reduce I(ClCa) considerably. However, the pharmacological overlap that exists between CaCCs and K(Ca)1.1 does not extend to the calcium-binding domain or to other calcium-gated K(+) channels. PMID- 19645714 TI - Highly frequent anti-idiotype antibody in cynomolgus monkeys developed against mouse-derived regions of anti-Fas antibody humanized by complementarity determining region grafting. AB - BACKGROUND AND PURPOSE: We investigated the immunogenicity of a humanized anti human Fas monoclonal antibody, R-125224, in cynomolgus monkeys to estimate its efficacy, as well as its toxicity in clinical situations. EXPERIMENTAL APPROACH: R-125224 was intravenously administered to cynomolgus monkeys at single doses of 0.4, 1.2, 6 and 30 mg kg(-1), and the plasma concentrations of R-125224 and anti R-125224 antibody (ARA) were measured. We conducted a competitive enzyme-linked immunosorbent assay to determine which part of R-125224 was recognized by ARA. We also examined the retention of radioactivity in mononuclear cells and granulocytes after the injection of [(125)I]-R-125224 to a collagen-induced arthritis monkey model. KEY RESULTS: After i.v. administration of R-125224, the elimination of the plasma R-125224 concentrations was accelerated at around 10 days post-dose, and 10 of 12 monkeys were ARA positive. From an epitope analysis of ARA, the ARA produced in monkeys recognized the mouse-derived regions located in complementarity determining regions, but could not recognize the human IgG. After the injection of [(125)I]-R-125224 to a collagen-induced arthritis monkey model, a significantly longer retention of the radioactivity in mononuclear cells compared to granulocytes was observed. CONCLUSIONS AND IMPLICATIONS: In monkeys, the development of antibodies against R-125224 is rapid and highly frequent. Our hypothesis is that this highly frequent development of ARA might be due to the binding of R-125224 to immune cells, and its circulation in monkey blood might contribute to an increase in its chances of being recognized as an immunogen. PMID- 19645716 TI - Rationing the access to high cost medicines in developing countries. PMID- 19645715 TI - Fructose-1,6-bisphosphate reduces inflammatory pain-like behaviour in mice: role of adenosine acting on A1 receptors. AB - BACKGROUND AND PURPOSE: D-Fructose-1,6-bisphosphate (FBP) is an intermediate in the glycolytic pathway, exerting pharmacological actions on inflammation by inhibiting cytokine production or interfering with adenosine production. Here, the possible antinociceptive effect of FBP and its mechanism of action in the carrageenin paw inflammation model in mice were addressed, focusing on the two mechanisms described above. EXPERIMENTAL APPROACH: Mechanical hyperalgesia (decrease in the nociceptive threshold) was evaluated by the electronic pressure metre test; cytokine levels were measured by elisa and adenosine was determined by high performance liquid chromatography. KEY RESULTS: Pretreatment of mice with FBP reduced hyperalgesia induced by intraplantar injection of carrageenin (up to 54%), tumour necrosis factor alpha (40%), interleukin-1 beta (46%), CXCL1 (33%), prostaglandin E(2) (41%) or dopamine (55%). However, FBP treatment did not alter carrageenin-induced cytokine (tumour necrosis factor alpha and interleukin-1 beta) or chemokine (CXCL1) production. On the other hand, the antinociceptive effect of FBP was prevented by systemic and intraplantar treatment with an adenosine A(1) receptor antagonist (8-cyclopentyl-1,3-dipropylxanthine), suggesting that the FBP effect is mediated by peripheral adenosine acting on A(1) receptors. Giving FBP to mice increased adenosine levels in plasma, and adenosine treatment of paw inflammation presented a similar antinociceptive mechanism to that of FBP. CONCLUSIONS AND IMPLICATIONS: In addition to anti-inflammatory action, FBP also presents an antinociceptive effect upon inflammatory hyperalgesia. Its mechanism of action seems dependent on adenosine production but not on modulation of hyperalgesic cytokine/chemokine production. In turn, adenosine acts peripherally on its A(1) receptor inhibiting hyperalgesia. FBP may have possible therapeutic applications in reducing inflammatory pain. PMID- 19645717 TI - Clinical research law in Jordan. PMID- 19645718 TI - Functional analysis of pyrimidine biosynthesis enzymes using the anticancer drug 5-fluorouracil in Caenorhabditis elegans. AB - Pyrimidine biosynthesis enzymes function in many cellular processes and are closely associated with pyrimidine antagonists used in cancer chemotherapy. These enzymes are well characterized from bacteria to mammals, but not in a simple metazoan. To study the pyrimidine biosynthesis pathway in Caenorhabditis elegans, we screened for mutants exhibiting resistance to the anticancer drug 5 fluorouracil (5-FU). In several strains, mutations were identified in ZK783.2, the worm homolog of human uridine phosphorylase (UP). UP is a member of the pyrimidine biosynthesis family of enzymes and is a key regulator of uridine homeostasis. C. elegans UP homologous protein (UPP-1) exhibited both uridine and thymidine phosphorylase activity in vitro. Knockdown of other pyrimidine biosynthesis enzyme homologs, such as uridine monophosphate kinase and uridine monophosphate synthetase, also resulted in 5-FU resistance. Uridine monophosphate kinase and uridine monophosphate synthetase proteins are redundant, and show different, tissue-specific expression patterns in C. elegans. Whereas pyrimidine biosynthesis pathways are highly conserved between worms and humans, no human thymidine phosphorylase homolog has been identified in C. elegans. UPP-1 functions as a key regulator of the pyrimidine salvage pathway in C. elegans, as mutation of upp-1 results in strong 5-FU resistance. PMID- 19645719 TI - RasGEF1A and RasGEF1B are guanine nucleotide exchange factors that discriminate between Rap GTP-binding proteins and mediate Rap2-specific nucleotide exchange. AB - The highly conserved RasGEF1 family of proteins contain a C-terminal CDC25-Ras exchange motif domain and an N-terminal RasGEF-N domain, and are of unknown function and specificity. Using purified RasGEF1A and RasGEF1B proteins, as well as Ras family proteins, we established that RasGEF1A and RasGEF1B function as very specific exchange factors for Rap2, a member of the Rap subfamily of Ras like G-proteins. They do not act on Rap1 or other members of the Ras subfamily. Although Rap2 was implicated in the regulation of cell adhesion, the establishment of cell morphology, and the modulation of synapses in neurons, no specific guanine nucleotide exchange factor for Rap2 was previously identified. Using reciprocal site-directed mutagenesis, we analyzed residues that allow RasGEF1 proteins to discriminate between Rap1 and Rap2, and we were able to identify Phe39 in the switch I region of Rap2 as a specificity residue. Mutation of the corresponding Ser39 in Rap1 changed the specificity and allowed the nucleotide exchange of Rap1(S39F) to be stimulated by RasGEF1B. PMID- 19645720 TI - Advanced glycation end products and lipopolysaccharide synergistically stimulate proinflammatory cytokine/chemokine production in endothelial cells via activation of both mitogen-activated protein kinases and nuclear factor-kappaB. AB - It has been well documented that both endogenous inflammatory mediator advanced glycation end products (AGEs) and exogenous inflammatory inducer lipopolysaccharide play key roles in the initiation and development of inflammatory diseases. However, the combined inflammation-stimulatory effect of AGEs and lipopolysaccharide on endothelial cells, and, furthermore, the underlying signal transduction pathways involved, have not been fully elucidated. We found that in vitro co-stimulation with AGE-human serum albumin (HSA) and lipopolysaccharide exhibits a synergistic effect on proinflammatory cytokine/chemokine interleukin-6, interleukin-8 and monochemoattractant protein-1 production in human umbilical vein endothelial cells. Similar to lipopolysaccharide, AGE-HSA stimulation induced mitogen-activated protein kinase phosphorylation and nuclear factor-kappaB nuclear translocation in human umbilical vein endothelial cells, which was further enhanced by a combination of the two stimulants. Pharmacological inhibitions of each individual signaling pathway, including p38, extracellular signal-regulated kinase 1/2, Jun N-terminal kinase and nuclear factor-kappaB, revealed that activation of all of these four pathways is necessary for the effective induction of interleukin-6, interleukin-8 and monochemoattractant protein-1 by both AGE-HSA and lipopolysaccharide. These results suggest that AGEs and lipopolysaccharide cooperatively induce proinflammatory cytokine/chemokine production by activating mitogen-activated protein kinases and nuclear factor-kappaB in endothelial cells, thus amplifying the inflammatory response and resulting in tissue damage. PMID- 19645721 TI - Deviation of the neurosporaxanthin pathway towards beta-carotene biosynthesis in Fusarium fujikuroi by a point mutation in the phytoene desaturase gene. AB - Carotenoids are widespread terpenoid pigments with applications in the food and feed industries. Upon illumination, the gibberellin-producing fungus Fusarium fujikuroi (Gibberella fujikuroi mating population C) develops an orange pigmentation caused by an accumulation of the carboxylic apocarotenoid neurosporaxanthin. The synthesis of this xanthophyll includes five desaturation steps presumed to be catalysed by the carB-encoded phytoene desaturase. In this study, we identified a yellow mutant (SF21) by mutagenesis of a carotenoid overproducing strain. HPLC analyses indicated a specific impairment in the ability of SF21-CarB to perform the fifth desaturation, as implied by the accumulation of gamma-carotene and beta-carotene, which arise through four-step desaturation. Sequencing of the SF21 carB allele revealed a single mutation resulting in an exchange of a residue conserved in other five-step desaturases. Targeted carB allele replacement proved that this single mutation is the cause of the SF21 carotenoid pattern. In support, expression of SF21 CarB in engineered carotene-producing Escherichia coli strains demonstrated its reduced ability to catalyse the fifth desaturation step on both monocyclic and acyclic substrates. Further mutagenesis of SF21 led to the isolation of two mutants, SF73 and SF98, showing low desaturase activities, which mediated only two desaturation steps, resulting in accumulation of the intermediate zeta-carotene at low levels. Both strains contained an additional mutation affecting a CarB domain tentatively associated with carotenoid binding. SF21 exhibited higher carotenoid amounts than its precursor strain or the SF73 and SF98 mutants, although carotenogenic mRNA levels were similar in the four strains. PMID- 19645722 TI - Mutagenic probes of the role of Ser209 on the cavity shaping loop of human monoamine oxidase A. AB - The available literature implicating human monoamine oxidase A (MAO A) in apoptotic processes reports levels of MAO A protein that do not correlate with activity, suggesting that unknown mechanisms may be involved in the regulation of catalytic function. Bioinformatic analysis suggests Ser209 as a possible phosphorylation site that may be relevant to catalytic function because it is adjacent to a six-residue loop termed the 'cavity shaping loop' from structural data. To probe the functional role of this site, MAO A Ser209Ala and Ser209Glu mutants were created and investigated. In its membrane-bound form, the MAO A Ser209Glu phosphorylation mimic exhibits catalytic and inhibitor binding properties similar to those of wild-type MAO A. Solubilization in detergent solution and purification of the Ser209Glu mutant results in considerable decreases in these functional parameters. By contrast, the MAO A Ser209Ala mutant exhibits similar catalytic properties to those of wild-type enzyme when purified. Compared to purified wild-type and Ser209Ala MAO A proteins, the Ser209Glu MAO A mutant shows significant differences in covalent flavin fluorescence yield, CD spectra and thermal stability. These structural differences in the purified MAO A Ser209Glu mutant are not exhibited in quantitative structure-activity relationship patterns using a series of para-substituted benzylamine analogs similar to the wild-type enzyme. These data suggest that Ser209 in MAO A does not appear to be the putative phosphorylation site for regulation of MAO A activity and demonstrate that the membrane environment plays a significant role in stabilizing the structure of MAO A and its mutant forms. PMID- 19645723 TI - Pfkfb3 is transcriptionally upregulated in diabetic mouse liver through proliferative signals. AB - The ubiquitous isoform of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (uPFK-2), a product of the Pfkfb3 gene, plays a crucial role in the control of glycolytic flux. In this study, we demonstrate that Pfkfb3 gene expression is increased in streptozotocin-induced diabetic mouse liver. The Pfkfb3/-3566 promoter construct linked to the luciferase reporter gene was delivered to the liver via hydrodynamic gene transfer. This promoter was upregulated in streptozotocin-induced diabetic mouse liver compared with transfected healthy cohorts. In addition, increases were observed in Pfkfb3 mRNA and uPFK-2 protein levels, and intrahepatic fructose-2,6-bisphosphate concentration. During streptozotocin-induced diabetes, phosphorylation of both p38 mitogen-activated protein kinase and Akt was detected, together with the overexpression of the proliferative markers cyclin D and E2F. These findings indicate that uPFK-2 induction is coupled to enhanced hepatocyte proliferation in streptozotocin induced diabetic mouse liver. Expression decreased when hepatocytes were treated with either rapamycin or LY 294002. This shows that uPFK-2 regulation is phosphoinositide 3-kinase-Akt-mammalian target of rapamycin dependent. These results indicate that fructose-2,6-bisphosphate is essential to the maintenance of the glycolytic flux necessary for providing energy and biosynthetic precursors to dividing cells. PMID- 19645724 TI - Biochemical and molecular characterization of purified chicken pancreatic phospholipase A2. AB - Chicken pancreatic phospholipase A(2) (ChPLA(2)) was purified from delipidated pancreases using ammonium sulfate and ethanol precipitation, followed by sequential column chromatography steps on MonoQ Sepharose and size exclusion HPLC columns. ChPLA(2) was found to be a nonglycosylated monomeric protein with a molecular mass of 14 kDa and a specific activity of 400 U x mg(-1) in the presence of 1 mM sodium taurodeoxycholate and 4 mM CaCl(2) with phosphatidylcholine as substrate. The N-terminal sequence of the first 15 amino acids of ChPLA(2) was determined, and showed a high degree of homology with known mammal pancreatic phospholipases A(2). The gene encoding the mature ChPLA(2) was cloned and sequenced. The deduced amino acid sequence of the mature ChPLA(2) confirmed the high level of identity with mammal pancreatic PLA(2). To investigate the structure-activity relationships, a 3D model of group IB ChPLA(2) was built using the porcine pancreatic phospholipase A(2) structure as template. PMID- 19645726 TI - High-level production and characterization of a G-protein coupled receptor signaling complex. AB - Elucidation of the molecular details of signal transduction through G-protein coupled receptors (GPCRs) awaits the solution of high-resolution structures of the receptor species involved in passing the extracellular information across the plasma membrane. The critical challenge in this effort is the production of sufficient quantities of active and homogeneous receptor species amenable to crystallization screening. We describe here the high-level expression in mammalian cells and characterization of a fusion complex between the kappa opioid receptor and its cognate G-protein alpha subunit, G alpha(i1). Optimization of growth conditions resulted in the highest level of active binding sites reported to date for either opioid receptors or GPCR-G alpha fusions. In cells, the kappa opioid receptor was stabilized against proteolysis in the context of the fusion protein and was competent to bind both agonists and antagonists. Coupling of the kappa opioid receptor with the G alpha subunit was demonstrated by changes in agonist affinity in the presence of guanine nucleotides and by agonist-induced increases in the rate of guanine nucleotide hydrolysis. In addition to representing a physiologically relevant signaling complex, the additional hydrophilic surface area provided by the G-protein may enhance the chances of producing well-diffracting crystals from the purified complex. PMID- 19645725 TI - The interaction of the Escherichia coli protein SlyD with nickel ions illuminates the mechanism of regulation of its peptidyl-prolyl isomerase activity. AB - The sensitive to lysis D (SlyD) protein from Escherichia coli is related to the FK506-binding protein family, and it harbours both peptidyl-prolyl cis-trans isomerase (PPIase) and chaperone-like activity, preventing aggregation and promoting the correct folding of other proteins. Whereas a functional role of SlyD as a protein-folding catalyst in vivo remains unclear, SlyD has been shown to be an essential component for [Ni-Fe]-hydrogenase metallocentre assembly in bacteria. Interestingly, the isomerase activity of SlyD is uniquely modulated by nickel ions, which possibly regulate its functions in response to external stimuli. In this work, we investigated the solution structure of SlyD and its interaction with nickel ions, enabling us to gain insights into the molecular mechanism of this regulation. We have revealed that the PPIase module of SlyD contains an additional C-terminal alpha-helix packed against the catalytic site of the domain; unexpectedly, our results show that the interaction of SlyD with nickel ions entails participation of the novel structural features of the PPIase domain, eliciting structural alterations of the catalytic pocket. We suggest that such conformational rearrangements upon metal binding underlie the ability of nickel ions to regulate the isomerase activity of SlyD. PMID- 19645727 TI - Unprecedented pathogen-inducible complex oxylipins from flax--linolipins A and B. AB - Oxylipins constitute a large family of bioregulators, biosynthesized via unsaturated fatty acid oxidation. This study reports the detection of an unprecedented family of complex oxylipins from flax leaves. Two major members of this family, compounds 1 and 2, were isolated and purified. Their structures were evaluated using NMR and MS analyses. Both compounds were identified as monogalactosyldiacylglycerol species. Compound 1 contains one alpha-linolenoyl residue and one residue of (9Z,11E,1'Z,3'Z)-12-(1',3'-hexadienyloxy)-9,11 dodecadienoic, (omega5Z)-etherolenic acid at positions sn-1 and sn-2, respectively. Compound 2 possesses (omega5Z)-etherolenic acid residues at both position sn-1 and position sn-2. We suggest the trivial names linolipin A and linolipin B for compounds 1 and 2, respectively, and the collective name linolipins for this new family of complex oxylipins. The linolipin content of flax leaves increased significantly in response to pathogenesis. Thus, accumulation of esterified antimicrobial divinyl ethers may be of relevance to plant defense. PMID- 19645728 TI - Intestinal dysbiosis: a possible mechanism of alcohol-induced endotoxemia and alcoholic steatohepatitis in rats. AB - BACKGROUND: Clinical and animal data indicate that gut-derived endotoxin and other luminal bacterial products are necessary cofactors for development of alcoholic liver disease (ALD). Although gut leakiness is clearly an important cause of endotoxemia in ALD, it cannot fully explain endotoxemia in all ALD subjects and thus other factors may be involved. One possible factor is a change in gut microbiota composition (dysbiosis). Thus, the aim of our study was to interrogate the gut bacterial microbiota in alcohol-fed rats to see if chronic alcohol consumption affects gut bacteria composition. METHOD: Male Sprague-Dawley rats were given either alcohol or dextrose intragastrically by gavage twice daily for up to 10 weeks. A subgroup of rats was also given either a probiotic (lactobacillus GG) or a prebiotic (oats) by gavage. Ileal and colonic mucosal attached microbiota composition were interrogated by Length Heterogeneity PCR (LH PCR) fingerprinting. RESULTS: Bacterial microbiota composition in alcohol-fed rats is not different from dextrose-fed rats at weeks 4 and 6. Mucosa-associated microbiota composition in the colon is altered at 10 weeks of daily alcohol gavage. Both LGG and oats prevented alcohol-induced dysbiosis up to 10 weeks of alcohol treatment. CONCLUSION: Daily alcohol consumption for 10 weeks alters colonic mucosa-associated bacterial microbiota composition in rats. Our data showed, for the first time, that daily alcohol consumption can affect colonic microbiome composition and suggest that dysbiosis may be an important mechanism of alcohol-induced endotoxemia. Further studies are needed to determine how dysbiotic microbiota contributes to development of ALD and whether therapeutic interventions targeted towards dysbiotic microbiota can prevent complications of alcoholism like ALD. PMID- 19645730 TI - Parietal gray matter volume loss is related to spatial processing deficits in long-term abstinent alcoholic men. AB - BACKGROUND: We previously demonstrated relatively intact cognitive function (with the exception of suggestive evidence for persistent deficits in spatial information processing) in middle-aged long-term abstinent alcoholics (LTAA, abstinent for 6 months or more) compared to age and gender comparable nonalcoholic controls (NAC) (Fein et al., 2006). METHODS: In the current study, we examine cortical gray matter volumes in the same samples to determine whether gray matter volumes in LTAA are consistent with the cognitive results--i.e., exhibiting gray matter volumes comparable to NAC in most brain regions, except for possible indications of persistent shrinkage in the parietal lobe subserving spatial information processing. RESULTS: We found gray matter shrinkage in LTAA in the parietal lobe consistent with the spatial processing deficits in this same sample. More compelling, in LTAA, the magnitude of parietal gray matter shrinkage was negatively associated with spatial processing domain performance and positively associated with alcohol dose. Gray matter volume deficits were present in the occipital and other cortical tissue, but poorer visuospatial test performance correlated significantly with smaller volumes in the parietal cortex only. CONCLUSIONS: Taken together, the cognitive and structural imaging data provide compelling evidence that chronic alcohol abuse results in shrinkage of the parietal cortex with associated deficits in spatial information processing. PMID- 19645729 TI - Microstructural corpus callosum anomalies in children with prenatal alcohol exposure: an extension of previous diffusion tensor imaging findings. AB - BACKGROUND: Several studies have now shown corpus callosum abnormalities using diffusion tensor imaging (DTI) in children with fetal alcohol spectrum disorders (FASD) in comparison with nonexposed controls. The data suggest that posterior regions of the callosum may be disproportionately affected. The current study builds on previous efforts, including our own work, and moves beyond midline corpus callosum to probe major inter-hemispheric white matter pathways with an improved DTI tractographic method. This study also expands on our prior work by evaluating a larger sample and by incorporating children with a broader range of clinical effects including full-criteria fetal alcohol syndrome (FAS). METHODS: Participants included 33 children with FASD (8 FAS, 23 partial FAS, 2 static encephalopathy) and 19 nonexposed controls between the ages of 10 and 17 years. Participants underwent DTI scans and intelligence testing. Groups (FASD vs. controls) were compared on fractional anisotropy (FA) and mean diffusivity (MD) in 6 white matter tracts projected through the corpus callosum. Exploratory analyses were also conducted examining the relationships between DTI measures in the corpus callosum and measures of intellectual functioning and facial dysmorphology. RESULTS: In comparison with the control group, the FASD group had significantly lower FA in 3 posterior tracts of the corpus callosum: the posterior mid-body, the isthmus, and the splenium. A trend-level finding also suggested lower FA in the genu. Measures of white matter integrity and cognition were correlated and suggest some regional specificity, in that only posterior regions of the corpus callosum were associated with visual-perceptual skills. Correlations between measures of facial dysmorphology and posterior regions of the corpus callosum were nonsignificant. CONCLUSIONS: Consistent with previous DTI studies, these results suggest that microstructural posterior corpus callosum abnormalities are present in children with prenatal alcohol exposure and cognitive impairment. These abnormalities are clinically relevant because they are associated with cognitive deficits and appear to provide evidence of abnormalities associated with prenatal alcohol exposure independent of dysmorphic features. As such, they may yield important diagnostic and prognostic information not provided by the traditional facial characteristics. PMID- 19645731 TI - An assay for evoked locomotor behavior in Drosophila reveals a role for integrins in ethanol sensitivity and rapid ethanol tolerance. AB - BACKGROUND: Ethanol induces similar behavioral responses in mammals and the fruit fly, Drosophila melanogaster. By coupling assays for ethanol-related behavior to the genetic tools available in flies, a number of genes have been identified that influence physiological responses to ethanol. To enhance the utility of the Drosophila model for investigating genes involved in ethanol-related behavior, we explored the value of an assay that measures the sedative effects of ethanol on negative geotaxis, an evoked locomotor response. METHODS: We established eRING (ethanol Rapid Iterative Negative Geotaxis) as an assay for quantitating the sedative effects of ethanol on negative geotaxis (i.e., startle-induced climbing). We validated the assay by assessing acute sensitivity to ethanol and rapid ethanol tolerance in several different control strains and in flies with mutations known to disrupt these behaviors. We also used eRING in a candidate screen to identify mutants with altered ethanol-related behaviors. RESULTS: Negative geotaxis measured in eRING assays was dose-dependently impaired by ethanol exposure. Flies developed tolerance to the intoxicating effects of ethanol when tested during a second exposure. Ethanol sensitivity and rapid ethanol tolerance varied across 4 control strains, but internal ethanol concentrations were indistinguishable in the 4 strains during a first and second challenge with ethanol. Ethanol sensitivity and rapid ethanol tolerance, respectively, were altered in flies with mutations in amnesiac and hangover, genes known to influence these traits. Additionally, mutations in the beta integrin gene myospheroid and the alpha integrin gene scab increased the initial sensitivity to ethanol and enhanced the development of rapid ethanol tolerance without altering internal ethanol concentrations. CONCLUSIONS: The eRING assay is suitable for investigating genetic mechanisms that influence ethanol sensitivity and rapid ethanol tolerance. Ethanol sensitivity and rapid ethanol tolerance depend on the function of alpha and beta integrins in flies. PMID- 19645732 TI - Impaired terminal differentiation of pulmonary macrophages in a Guinea pig model of chronic ethanol ingestion. AB - BACKGROUND: Alcoholic patients have an increased risk of respiratory infections, which is partially due to an impaired immune response of alveolar macrophages. The mechanisms by which alcohol impairs alveolar macrophage function are poorly understood. In this study, we demonstrated in a guinea pig model that chronic ethanol ingestion significantly impaired alveolar macrophage differentiation and function. METHODS: Isolated alveolar macrophages were separated into 4 different subpopulations with varying densities and levels of maturation. RESULTS: Compared to control values, chronic ethanol ingestion decreased the percentage of alveolar macrophages in the mature fractions by approximately 60%. Alveolar macrophage function in each subpopulation was determined by measuring phagocytosis of fluorescein isothiocyanate-labeled Staphylococcus aureus. Alveolar macrophages from ethanol-fed animals had approximately 80% decrease in the phagocytic index. Western blot and immunohistochemical analysis of the differential markers granulocyte/macrophage colony-stimulating factor (GM-CSF) receptor alpha (GM-CSFR alpha), PU.1, CD11c, and CD11b verified that alcoholic macrophages displayed impaired terminal differentiation. While oral supplementation with the glutathione precursor S-adenosyl-methionine (SAM) did not alter the maturational status of control animals, SAM supplementation shifted the distribution of macrophages to more mature fractions, normalized the phagocytic index; as well as normalized expression of CD11c, CD11b, PU.1, and GM-CSFR-alpha. Chronic ethanol ingestion also impaired the differentiation status of interstitial macrophages which was normalized by SAM supplementation. CONCLUSION: This improvement in the maturational status suggested that ethanol-induced oxidant stress is a central feature in impaired terminal differentiation of macrophages in the interstitial and alveolar space. Therefore, strategies targeting pulmonary oxidant stress may restore macrophage differentiation and function even after chronic ethanol ingestion. PMID- 19645733 TI - Alcohol biomarkers in patients admitted for trauma. AB - BACKGROUND: To assess the value of blood alcohol levels (BAL) and carbohydrate deficient transferrin (CDT) in trauma patients. METHODS: A prospective study was conducted among 213 patients admitted to a university hospital after trauma. Outcomes of interest included the development of alcohol withdrawal, infections, respiratory problems, cardiac events, thromboembolism, and length of stay. RESULTS: The majority (78%) of the trauma patients in the study was males over the age of 18. Seventy-five percent were reported drinking an alcohol-containing beverage in the previous 30 days, 34% had > or =5 heavy drinking days, and 18.7% met current DSM-IV criteria for alcohol abuse and 13.1% current criteria for dependence. Twenty-two percent (n = 48) had a positive BAL and 14% (n = 30) a CDT level >2.5%. Twelve percent (n = 27) of the sample developed alcohol withdrawal and 55% (n = 113) had one or more adverse health events during their hospitalization. The development of alcohol withdrawal was associated with an admission CDT >2.5% (chi(2): 4.77, p < 0.029) and/or a positive BAL (chi(2): 54.01, p < 0.001). The alcohol biomarkers identified 13 male and 3 female high risk patients (7.4% of the total sample) who denied excessive alcohol use, and who would have been missed if these markers were not used. A composite morbidity trauma score composed of 25 adverse health events was associated with a positive BAL (p < 0.022). CONCLUSION: The study provides additional empirical evidence that supports the use of BAL in all patients admitted for trauma. The usefulness of CDT in trauma patients remains unclear and will require larger samples in more critically ill patients. PMID- 19645734 TI - Current experimental perspectives on the clinical progression of alcoholic liver disease. AB - Chronic alcohol abuse is an important cause of morbidity and mortality throughout the world. Liver damage due to chronic alcohol intoxication initially leads to accumulation of lipids within the liver and with ongoing exposure this condition of steatosis may first progress to an inflammatory stage which leads the way for fibrogenesis and finally cirrhosis of the liver. While the earlier stages of the disease are considered reversible, cirrhotic destruction of the liver architecture beyond certain limits causes irreversible damage of the organ and often represents the basis for cancer development. This review will summarize current knowledge about the molecular mechanisms underlying the different stages of alcoholic liver disease (ALD). Recent observations have led to the identification of new molecular mechanisms and mediators of ALD. For example, plasminogen activator inhibitor 1 was shown to play a central role for steatosis, the anti-inflammatory adipokine, adiponectin profoundly regulates liver macrophage function and excessive hepatic deposition of iron is caused by chronic ethanol intoxication and increases the risk of hepatocellular carcinoma development. PMID- 19645735 TI - Wheat blast: histopathology and transcriptome reprogramming in response to adapted and nonadapted Magnaporthe isolates. AB - * Blast disease (causal agent Magnaporthe oryzae) has presented as a new and serious field disease of wheat in South America. Here, we investigated the responses of wheat to both adapted and nonadapted isolates of the blast fungus Magnaporthe, examining cellular defence and transcriptional changes. * Resistance towards the nonadapted isolate was associated with the formation of appositions, here termed halos, beneath attempted Magnaporthe grisea penetration sites that wheat-adapted, M. oryzae isolates were able to breach. * Transcriptome analysis indicated extensive transcriptional reprogramming following inoculation with both wheat-adapted and nonadapted isolates of Magnaporthe. Functional annotation of many of the differentially expressed transcripts classified into the categories: cell rescue and defence, plant metabolism, cellular transport and regulation of transcription (although a significant number of transcripts remain unclassified). * Defence-related transcripts induced in common by adapted and nonadapted isolates were differentially regulated in response to M. oryzae and M. grisea isolates over time. Differential expression of genes involved in cellular transport indicated the importance of this process in plant defence. Functional characterisation of these transcripts and their role in defence may eventually lead to the identification of broad-spectrum resistance mechanisms in wheat towards Magnaporthe. PMID- 19645736 TI - NbHB1, Nicotiana benthamiana homeobox 1, is a jasmonic acid-dependent positive regulator of pathogen-induced plant cell death. AB - Induction of cell death is an important component of plant defense against pathogens. There have been many reports on the role of phytohormones in pathogen induced cell death, but jasmonic acid (JA) has not been implicated as a regulator of the response. Here, we report the function of NbHB1, Nicotiana benthamiana homeobox1, in pathogen-induced cell death in connection with JA signaling. Involvement of NbHB1 in cell death was analysed by gain- and loss-of-function studies using Agrobacterium-mediated transient overexpression and virus-induced gene silencing, respectively. Expression of NbHB1 following pathogen inoculations and various treatments was monitored by reverse transcription polymerase chain reaction. Transcript levels of NbHB1 were upregulated by infection with virulent and avirulent bacterial pathogens. Ectopic expression of NbHB1 accelerated cell death following treatment with darkness, methyl jasmonate, or pathogen inoculation. Conversely, when NbHB1 was silenced, pathogen-induced cell death was delayed. NbHB1-induced cell death was also delayed by silencing of NbCOI1, indicating a requirement for JA-mediated signaling. Overexpression of the domain deleted proteins of NbHB1 revealed that the homeodomain, leucine zipper, and part of the variable N-terminal region were necessary for NbHB1 functionality. These results strongly suggest the role of NbHB1 in pathogen-induced plant cell death via the JA-mediated signaling pathway. PMID- 19645737 TI - Fire feedbacks facilitate invasion of pine savannas by Brazilian pepper (Schinus terebinthifolius). AB - * Fire disturbance can mediate the invasion of ecological communities by nonnative species. Nonnative plants that modify existing fire regimes may initiate a positive feedback that can facilitate their continued invasion. Fire sensitive plants may successfully invade pyrogenic landscapes if they can inhibit fire in the landscape. * Here, we investigated whether the invasive shrub Brazilian pepper (Schinus terebinthifolius) can initiate a fire-suppression feedback in a fire-dependent pine savanna ecosystem in the southeastern USA. * We found that prescribed burns caused significant (30-45%) mortality of Brazilian pepper at low densities and that savannas with more frequent fires contained less Brazilian pepper. However, high densities of Brazilian pepper reduced fire temperature by up to 200 degrees C, and experienced as much as 80% lower mortality. * A cellular automaton model was used to demonstrate that frequent fire may control low-density populations, but that Brazilian pepper may reach a sufficient density during fire-free periods to initiate a positive feedback that reduces the frequency of fire and converts the savanna to an invasive-dominated forest. PMID- 19645738 TI - The thanatos mutation in Arabidopsis thaliana cellulose synthase 3 (AtCesA3) has a dominant-negative effect on cellulose synthesis and plant growth. AB - Genetic functional analyses of mutants in plant genes encoding cellulose synthases (CesAs) have suggested that cellulose deposition requires the activity of multiple CesA proteins. Here, a genetic screen has led to the identification of thanatos (than), a semi-dominant mutant of Arabidopsis thaliana with impaired growth of seedlings. Homozygous seedlings of than germinate and grow but do not survive. In contrast to other CesA mutants, heterozygous plants are dwarfed and display a radially swollen root phenotype. Cellulose content is reduced by approximately one-fifth in heterozygous and by two-fifths in homozygous plants, showing gene-dosage dependence. Map-based cloning revealed an amino acid substitution (P578S) in the catalytic domain of the AtCesA3 gene, indicating a critical role for this residue in the structure and function of the cellulose synthase complex. Ab initio analysis of the AtCesA3 subdomain flanking the conserved proline residue predicted that the amino acid substitution to serine alters protein secondary structure in the catalytic domain. Gene dosage-dependent expression of the AtCesA3 mutant gene in wild-type A. thaliana plants resulted in a than dominant-negative phenotype. We propose that the incorporation of a mis folded CesA3 subunit into the cellulose synthase complex may stall or prevent the formation of functional rosette complexes. PMID- 19645739 TI - Unusual transfer of CutA into the secretory pathway, evidenced by fusion proteins with acetylcholinesterase. AB - The mouse CutA protein exists as long and short components of 20 and 15 kDa, produced by the use of different in-frame ATGs initiation codons, and by proteolytic cleavage. We recently showed that, surprisingly, the longer, uncleaved component resides mostly in the secretory pathway and is secreted, whereas the shorter component resides mostly in the cytoplasm. To confirm these subcellular localizations, we constructed fusion proteins in which the catalytic domain of rat acetylcholinesterase was placed downstream of the CutA variants. The acquisition of an active conformation and N-glycosylation of the fusion proteins proved their transfer into the secretory pathway. We show that the CutA AChE fusion proteins produced and secreted active, N-glycosylated molecules, while an AChE mutant lacking its secretory signal peptide did not produce any significant activity. Thus, an N-terminal CutA domain actually drives AChE into the endoplasmic reticulum and allows its secretion. This was observed with full length CutA, starting at Met1, and at a much lower level with the shorter mutants starting at Met24 and Met44, although the latter is not predicted to possess any signal peptide. These experiments illustrate the value of using AChE as a reporter and reveals an unusual protein trafficking and secretory process. PMID- 19645740 TI - PPARgamma2 protects against obesity by means of a mechanism that mediates insulin resistance. AB - BACKGROUND: Many studies have focused on the physiological parameters and genetic predisposition of subjects presenting both obesity and insulin resistance (IR) and it has been suggested that the peroxisome proliferator-activated receptor gamma 2 (PPARgamma2) Pro12Ala variant may contribute to the observed variability in insulin sensitivity. We investigated whether the PPARgamma2 mRNA expression levels are associated with IR in morbid obesity in adipose and muscle tissues. MATERIALS AND METHODS: In this study, tissue biopsies were obtained from 26 morbidly obese (MO) patients and eight controls. The MO patients were divided into two groups: those with a low homeostasis model assessment of IR (HOMA-IR < 5) (MO-nonIR) and those with a high HOMA-IR (HOMA-IR > or = 8) (MO-IR). PPARgamma1, PPARgamma2 and aP2 mRNA expression levels were measured using quantitative RT-PCR. RESULTS: The study found that PPARgamma2 mRNA expression in visceral adipose tissue (VAT) was significantly lower in the MO patients (P = 0.002) than the controls. Moreover, the PPARgamma2 mRNA expression was lower in VAT (P < 0.05) and muscle tissue (P < 0.01), and higher in subcutaneous adipose tissue (SAT) (P < 0.01) in the MO-IR than the MO-nonIR group. By contrast, PPARgamma1 mRNA expression levels were not dependent on IR. Finally, the MO patients showed a significant negative correlation between PPARgamma2 mRNA expression and IR (r = -0.396, P = 0.020) in VAT and a positive correlation in SAT (r = 0.826, P < 0.001). The variable that best explained the IR was PPARgamma2 mRNA expression in SAT (P = 0.002). CONCLUSIONS: These data show that PPARgamma2 mRNA is expressed differently in the two types of MO patients and is associated with IR. PMID- 19645741 TI - Sex differences in the association between albumin and all-cause and vascular mortality. AB - BACKGROUND: Low serum albumin levels are associated with cardiovascular disease and mortality risk. This study evaluated the predictive value of low serum albumin for all-cause-mortality in a large Viennese patient cohort and investigated sex differences in the association between serum albumin and mortality. MATERIALS AND METHODS: Serum albumin concentrations of 285 930 patients, who attended the General Hospital Vienna between 1992 and 2002, were evaluated and linked with the Austrian Death Registry. The median observation period was 7.4 +/- 4.0 years and the death rate was 16.8%. For Cox regression analysis, albumin levels were divided into deciles, the highest category served as reference value. To analyse associations between albumin and mortality independent of liver function, results were adjusted for cholinesterase, which indicates protein synthesis capacity of the liver. RESULTS: Hazard ratios for all cause-mortality increased linearly with decreasing albumin levels from 1.05 in the 9th to 2.98 in the 1st decile. Adjusted for cholinesterase, the relative risk for mortality was still 1.91 in the lowest category. Compared with women, men had an average 50% increased risk of death in almost every decile, adjusting for cholinesterase reduced the sex difference to a 10-20% higher mortality risk for men. In critically ill patients, hazard ratios for all-cause-mortality ranged from 4.5 in the 9th decile to 9.5 in the lowest albumin category. CONCLUSION: This study demonstrates a strong inverse association between serum albumin and mortality in a large patient cohort. The predictive value of low albumin was remarkably higher in men than in women. PMID- 19645742 TI - Cytologic, histologic, and immunohistochemical features of maxillofacial alveolar rhabdomyosarcoma in a juvenile dog. AB - A 15-month-old castrated male dog with a history of intermittent epistaxis and sneezing was admitted for the examination of a maxillofacial mass. An impression smear of a biopsy sample from the cauliflower-shaped gingival mass contained numerous round cells, 5-25 microm in diameter, which contained a moderate amount of clear to pale blue cytoplasm and resembled lymphoid cells. Mitotic figures were frequently observed. The mass was diagnosed as malignant round cell neoplasia. On histologic examination the tumor was composed of diffusely arranged, small, atypical round cells with a small amount of fibrovascular stroma. Immunohistochemically, the cells were negative for CD3, CD18, CD20, CD79alpha, cytokeratin, melan-A, chromogranin A, alpha-smooth muscle actin, and myoglobin but positive for vimentin and desmin. The cells also had strong positive nuclear staining for myogenin and MyoD1. A diagnosis of solid-pattern alveolar rhabdomyosarcoma was made on the basis of morphologic and immunohistochemical results. Alveolar rhabdomyosarcoma should be considered in the differential diagnosis of tumors in juvenile dogs, especially when cytologic findings reveal round, undifferentiated cells. PMID- 19645743 TI - Comparative morphometric analysis of recurrent and nonrecurrent canine basal cell carcinomas: a preliminary report. AB - BACKGROUND: Most reports of canine basal cell carcinomas (BCCs) focus on morphologic appearance rather than biologic behavior. Rare recurrences and no metastases have been reported in dogs. Quantitative nuclear morphometry may be useful in predicting tumor recurrence. OBJECTIVE: The aim of the present study was to compare quantitative nuclear parameters of canine BCCs that did not recur within 60 weeks of excision with those that recurred. METHODS: Cytologic specimens obtained from spontaneous BCCs from 11 dogs were analyzed by computerized nuclear morphometry. The dogs were monitored by their owners over a period of 60 weeks to detect local recurrence of the tumor; recurrent tumors were confirmed histologically. For each initial tumor specimen, nuclei of at least 100 neoplastic cells were measured by 2 independent observers, and mean nuclear area (MNA), mean nuclear perimeter (MNP), and mean nuclear diameter (MND) were calculated. RESULTS: Six nonrecurrent and 5 recurrent tumors were analyzed. Neoplastic cells from BCCs that subsequently recurred had higher MNA (102.41 +/- 4.57 microm(2)), MNP (36.27 +/- 0.61 microm), and MND (11.21 +/- 0.27 microm) than cells from nonrecurrent BCCs (MNA 87.66 +/- 4.79 microm(2), MNP 33.51 +/- 0.78 microm, MND 10.36 +/- 0.29 microm) (P<.001; Mann-Whitney U-test). CONCLUSION: Based on these preliminary results, nuclear morphometry may be a useful tool to predict local recurrence of BCCs in dogs. PMID- 19645745 TI - Cystic fibrosis: defining a disease under-diagnosed in Pakistan. AB - OBJECTIVE: Cystic fibrosis is frequently missed in the Pakistani population due to lack of appropriate diagnostic tools. Thus our aim was to define unknown disease-causing mutations to help create suitable diagnostic tests and improve understanding of what appears to be an aggressive and under-diagnosed disease in this population. METHODS: Patients with elevated sweat chloride values and clinically suspected CF were recruited from Aga Khan University, Pakistan. Mutations DF508, S549R, S549N, Y569D, 296 + 12(T>C), G553X, G551D and G551X were screened for by allele specific polymerase chain reactions. CFTR exons 10, 11 and 12 were sequenced by direct DNA sequencing. RESULTS: Of 150 patients tested by PCR, 26 (17.3%) were positive for DeltaF508. One patient was a F508/S549N compound heterozygote. Eighty-three of 87 patients sequenced for mutations in exon 10 were normal; 42/43 for exon 11 and 29 for exon 12 were normal. CONCLUSION: This first step in defining mutations involved in Pakistani CF suggests that DeltaF508 is uncommon and S549 was the only additional mutation identified in CFTR exons 10, 11 and 12. Identification of the remaining mutations and their frequency is required to design appropriate tests and improve understanding and management of the disease. PMID- 19645746 TI - PolyADP-ribosylation is required for long-term memory formation in mammals. AB - PolyADP-ribosylation is a post-translational modification of nuclear proteins, catalyzed by polyADP-ribose polymerases (PARPs). In the nucleus, polyADP ribosylation catalyzed by PARP-1 alters protein-protein and protein-DNA interactions, and is implicated in chromatin remodeling, DNA transcription, and repair. Previous results linked the activation of PARP-1 with long-term memory formation during learning in the marine mollusk Aplysia ( Science 2004, 304:1820 1822). Furthermore, PARP-1 was highly activated in mammalian cerebral neurons treated with neurotrophins and neurotrophic peptides promoting neurite outgrowth and synaptic plasticity. Here, we examine the possibility that PARP-1 activation is required for memory formation during learning in mammals. Mice were tested in two learning paradigms, object recognition and fear conditioning. PolyADP ribosylation of PARP-1 and histone H1 were detected in their cerebral cortex and hippocampus immediately after their training session. Moreover, in both behavioral paradigms, suppression of PARP activity in the CNS during learning impaired their long-term memory formation, without damaging their short-term memory. These findings implicate PARP-1 activation in molecular processes underlying long-term memory formation during learning. PMID- 19645747 TI - Identification and characterization of a novel amphioxus dopamine D-like receptor. AB - Dopamine receptors function to control many aspects of motor control and other forms of behaviour in both vertebrates and invertebrates. They can be divided into two main groups (D(1) and D(2)) based on sequence similarity, ligand affinity and effector coupling. However, little is known about the pharmacology and functionality of dopamine receptors in the deuterostomian invertebrates, such as the cephalochordate amphioxus (Branchiostoma floridae) which has recently been placed as the most basal of all the chordates. A bioinformatic study shows that amphioxus has at least three dopamine D(1)-like receptor sequences. One of these receptors, AmphiD(1)/beta, was found to have high levels of sequence similarity to both vertebrate D(1) receptors and to beta-adrenergic receptors. Here, we report on the cloning of AmphiD(1)/beta from an adult amphioxus cDNA library, and its pharmacological characterization subsequent to its expression in both mammalian cell lines and Xenopus oocytes. It was found that AmphiD(1)/beta has a similar pharmacology to vertebrate D(1) receptors, including responding to benzodiazepine ligands. The pharmacology of the receptor exhibits 'agonist specific coupling' depending upon the second messenger pathway to which it is linked. Moreover, no pharmacological characteristics were observed to suggest that AmphiD(1)/beta may be an amphioxus orthologue of vertebrate beta-adrenergic receptors. PMID- 19645749 TI - The ubiquitin ligase E6-AP promotes degradation of alpha-synuclein. AB - Parkinson's disease (PD) is a common neurodegenerative disorder caused mainly because of the loss of dopaminergic neurons in the substantia nigra. Protein inclusions called Lewy bodies are the most common pathological hallmark of PD and other synucleinopathies. Because the main component of these inclusions is alpha synuclein, aggregation of this protein is thought to be a key pathogenic event in this disease. In the present investigation we report that E6 associated protein (E6-AP), a HECT (homologous to E6-AP C-terminus) domain ubiquitin ligase is a component of Lewy bodies in post-mortem PD brain. In the cell culture model, we demonstrate that endogenous E6-AP colocalizes with alpha-synuclein in juxtanuclear aggregates. E6-AP is also recruited to the centrosome upon inhibition of the proteasome function suggesting its involvement in the degradation of misfolded proteins. Over-expression of E6-AP enhances the degradation of wild type as well as the mutant forms of alpha-synuclein in a proteasome-dependent manner. E6-AP also promotes the degradation of the more toxic oligomeric forms of alpha-synuclein. Our data suggests that E6-AP is involved in the clearance of alpha-synuclein. PMID- 19645748 TI - Increased lipid peroxidation in Down's syndrome mouse models. AB - Elevated oxidative stress has been suggested to be associated with the features of Down's syndrome (DS). We previously reported increased oxidative stress in cultured cells from the embryonic brain of Ts1Cje, a mouse genetic DS model. However, since in vivo evidence for increased oxidative stress is lacking, we here examined lipid peroxidation, a typical marker of oxidative stress, in the brains of Ts1Cje and another DS mouse model Ts2Cje with an overlapping but larger trisomic segment. Accumulations of proteins modified with the lipid peroxidation derived products, 13-hydroperoxy-9Z,11E-octadecadienoic acid and 4-hydroxy-2 nonenal were markedly increased in Ts1Cje and Ts2Cje brains. Analysis with oxidation-sensitive fluorescent probe also showed that reactive oxygen species themselves were increased in Ts1Cje brain. However, electron spin resonance analysis of microdialysate from the hippocampus of Ts1Cje showed that antioxidant activity remained unaffected, suggesting that the reactive oxygen species production was accelerated in Ts1Cje. Proteomics approaches with mass spectrometry identified the proteins modified with 13-hydroperoxy-9Z,11E octadecadienoic acid and/or 4-hydroxy-2-nonenal to be involved in either ATP generation, the neuronal cytoskeleton or antioxidant activity. Structural or functional impairments of these proteins by such modifications may contribute to the DS features such as cognitive impairment that are present in the Ts1Cje mouse. PMID- 19645750 TI - Reactive oxygen species in rostral ventrolateral medulla modulate cardiac sympathetic afferent reflex in rats. AB - AIM: The aim of the present study was to investigate whether reactive oxygen species (ROS) in rostral ventrolateral medulla (RVLM) modulate cardiac sympathetic afferent reflex (CSAR) and the enhanced CSAR response caused by microinjection of angiotensin II (Ang II) into the paraventricular nucleus (PVN). METHODS: Under urethane and alpha-chloralose anaesthesia, renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) were recorded in sinoaortic denervated and cervical-vagotomized rats. The CSAR was evaluated by the RSNA response to epicardial application of capsaicin (1.0 nmol). RESULTS: Bilateral RVLM microinjection of tempol (a superoxide anion scavenger) or polyethylene glycol-superoxide dismutase (PEG-SOD, an analogue of endogenous superoxide dismutase) attenuated the CSAR, but did not cause significant change in baseline RSNA and MAP. NAD(P)H oxidase inhibitors apocynin or phenylarsine oxide (PAO) also showed similar effects, but SOD inhibitor diethyldithio-carbamic acid (DETC) enhanced the CSAR and baseline RSNA, and increased the baseline MAP. Bilateral PVN microinjection of Ang II (0.3 nmol) enhanced the CSAR and increased RSNA and MAP, which was inhibited by the pre-treatment with RVLM administration of tempol, PEG-SOD, apocynin or PAO. The pre-treatment with DETC in the RVLM only showed a tendency in potentiating the CSAR response of Ang II in the PVN, but significantly potentiated the RSNA and MAP responses of Ang II. CONCLUSION: These results suggest that the NAD(P)H oxidase-derived ROS in the RVLM modulate the CSAR. The ROS in the RVLM is necessary for the enhanced CSAR response caused by Ang II in the PVN. PMID- 19645751 TI - Lowered albumin extravasation rate in heart but not in other organs in beta3 integrin-deficient mice. AB - AIM: The vascular protein permeability is dependent on the integrity of the vascular wall. The heart capillaries in male mice lacking beta3 integrins have an immature phenotype. Previously, we have demonstrated a role for alphavbeta3 integrins in control of interstitial fluid pressure (Pif) and thereby in the fluid flux during inflammation. We wanted to explore a possible role for alphavbeta3 integrins in controlling capillary protein permeability during control situation and inflammation. METHODS: We performed double-tracer and microdialysis experiments on beta3-integrin-deficient mice and wild type control mice. We also measured blood pressure and heart rate in the two mice strains. RESULTS: We found reduced albumin extravasation (during 25 min) in the heart capillaries (0.053 +/- 0.003 vs. 0.087 +/- 0.009 mL g(-1) dw, P < 0.05), and an increased cardiac mass/body weight (5.3 x 10(-3) +/- 0.3 x 10(-3) vs. 3.8 x 10( 3) +/- 0.1 x 10(-3), P < 0.01) in the beta3-integrin-deficient mice (n = 6) compared with the controls (n = 6). Heart rate and blood pressure were the same in mice with and without beta3-integrins. No difference in permeability was found in other tissues studied, or under local inflammation. CONCLUSION: These results show a function for the alphavbeta3 integrin in the regulation of protein permeability, selective for the heart capillaries. PMID- 19645752 TI - Impaired contractile function and mitochondrial respiratory capacity in response to oxygen deprivation in a rat model of pre-diabetes. AB - AIM: Obesity is a major contributor to the global burden of disease and is closely associated with the development of type 2 diabetes and cardiovascular diseases. This study tested the hypothesis that mitochondrial respiratory capacity of the pre-diabetic heart is decreased leading to impaired contractile function and tolerance to ischaemia/reperfusion. METHODS: Eight-week-old male Wistar rats were fed a high caloric diet for 16 weeks after which anthropometric, metabolic, cardiac and mitochondrial parameters were evaluated vs. age-matched lean controls. Cardiac function (working heart perfusions) and mitochondrial respiratory capacity were assessed at baseline and in response to acute oxygen deprivation. RESULTS: Rats fed the high caloric diet exhibited increased body weight and visceral fat vs. the control group. Heart weights of obese rats were also increased. Triglyceride, fasting plasma insulin and free fatty acid levels were elevated, while high-density lipoprotein cholesterol levels were reduced in the obese group. Contractile function was attenuated at baseline and further decreased after subjecting hearts to ischaemia-reperfusion. Myocardial infarct sizes were increased while ADP phosphorylation rates were diminished in obese rats. However, no differences were found for mtDNA levels and the degree of oxidative stress-induced damage. CONCLUSIONS: These data show that decreased mitochondrial bioenergetic capacity in pre-diabetic rat hearts may impair respiratory capacity and reduce basal contractile function and tolerance to acute oxygen deprivation. PMID- 19645753 TI - Risk ranking for foodborne microbial hazards in New Zealand: burden of disease estimates. AB - Priority setting for food safety management at a national level requires risks to be ranked according to defined criteria. In this study, two approaches (disability-adjusted life years (DALYs) and cost of illness (COI)) were used to generate estimates of the burden of disease for certain potentially foodborne diseases (campylobacteriosis, salmonellosis, listeriosis (invasive, perinatal, and nonperinatal), infection with Shiga toxin-producing Escherichia coli (STEC), yersiniosis, and norovirus infection) and their sequelae in New Zealand. A modified Delphi approach was used to estimate the food-attributable proportion for these diseases. The two approaches gave a similar ranking for the selected diseases, with campylobacteriosis and its sequelae accounting for the greatest proportion of the overall burden of disease by far. PMID- 19645754 TI - An exposure assessment of methyl mercury via fish consumption for the Japanese population. AB - The objective of this article was to propose an exposure assessment model to describe the relationship between fish consumption and body methyl mercury (MeHg) levels in the Japanese population. Individual MeHg intake was estimated by the summation of species-specific fish consumption multiplied by species-specific fish MeHg levels. The distribution of fish consumed by individuals and the MeHg level in each fish species were assigned based on published data from Japanese government institutions. The probability of MeHg intake for a population was accomplished through a Monte Carlo simulation by the random sampling of fish consumption and species-specific MeHg levels. Internal body MeHg levels in blood and hair were estimated using a one-compartment model. Overall, the mean value of MeHg intake for the Japanese population was estimated to be 6.76 microg/day or 0.14 microg/kg body weight per day (bw/day), while the mean value for the hair mercury level was 2.02 microg/g. Compared with the survey data that tabulated hair mercury levels in a cross-section of the Japanese population, the simulation results matched the hair mercury survey data very well for women, but somewhat underestimated for men and all of the population. This exposure assessment model is a useful attempt at further risk assessment with respect to a risk-benefit analysis. PMID- 19645755 TI - Abandoned metal mine stability risk evaluation. AB - The abandoned mine legacy is critical in many countries around the world, where mine cave-ins and surface subsidence disruptions are perpetual risks that can affect the population, infrastructure, historical legacies, land use, and the environment. This article establishes abandoned metal mine failure risk evaluation approaches and quantification techniques based on the Canadian mining experience. These utilize clear geomechanics considerations such as failure mechanisms, which are dependent on well-defined rock mass parameters. Quantified risk is computed using probability of failure (probabilistics using limit equilibrium factors of safety or applicable numerical modeling factor of safety quantifications) times a consequence impact value. Semi-quantified risk can be based on failure-case-study-based empirical data used in calculating probability of failure, and personal experience can provide qualified hazard and impact consequence assessments. The article provides outlines for land use and selection of remediation measures based on risk. PMID- 19645756 TI - Accidents and unpleasant incidents: worry in transport and prediction of travel behavior. AB - Worry on nine different means of transport was measured in a Norwegian sample of 853 respondents. The main aim of the study was to investigate differences in worry about accidents and worry about unpleasant incidents, and how these two sorts of worry relate to various means of transport as well as transport behavior. Factor analyses of worry about accidents suggested a division between rail transport, road transport, and nonmotorized transport, whereas analyses of worry about unpleasant incidents suggested a division between transport modes where you interact with other people and "private" transport modes. Moreover, mean ratings of worry showed that respondents worried more about accidents than unpleasant incidents on private transport modes, and more about unpleasant incidents than accidents on public transport modes. Support for the distinction between worry about accidents and unpleasant incidents was also found when investigating relationships between both types of worry and behavioral adaptations: worry about accidents was more important than worry about unpleasant incidents in relation to behavioral adaptations on private means of transport, whereas the opposite was true for public means of transport. Finally, predictors of worry were investigated. The models of worry about accidents and worry about unpleasant incidents differed as to what predictors turned out significant. Knowledge about peoples' worries on different means of transport is important with regard to understanding and influencing transport and travel behavior, as well as attending to commuters' welfare. PMID- 19645757 TI - Bayesian modeling of measurement errors and pesticide concentration in dietary risk assessments. AB - We propose new models for dealing with various sources of variability and uncertainty that influence risk assessments for dietary exposure. The uncertain or random variables involved can interact in complex ways, and the focus is on methodology for integrating their effects and on assessing the relative importance of including different uncertainty model components in the calculation of dietary exposures to contaminants, such as pesticide residues. The combined effect is reflected in the final inferences about the population of residues and subsequent exposure assessments. In particular, we show how measurement uncertainty can have a significant impact on results and discuss novel statistical options for modeling this uncertainty. The effect of measurement error is often ignored, perhaps due to the laboratory process conforming to the relevant international standards, for example, or is treated in an ad hoc way. These issues are common to many dietary risk analysis problems, and the methods could be applied to any food and chemical of interest. An example is presented using data on carbendazim in apples and consumption surveys of toddlers. PMID- 19645759 TI - Modelling the impact of an influenza A/H1N1 pandemic on critical care demand from early pathogenicity data: the case for sentinel reporting. AB - Projected critical care demand for pandemic influenza H1N1 in England was estimated in this study. The effect of varying hospital admission rates under statistical uncertainty was examined. Early in a pandemic, uncertainty in epidemiological parameters leads to a wide range of credible scenarios, with projected demand ranging from insignificant to overwhelming. However, even small changes to input assumptions make the major incident scenario increasingly likely. Before any cases are admitted to hospital, 95% confidence limit on admission rates led to a range in predicted peak critical care bed occupancy of between 0% and 37% of total critical care bed capacity, half of these cases requiring ventilatory support. For hospital admission rates above 0.25%, critical care bed availability would be exceeded. Further, only 10% of critical care beds in England are in specialist paediatric units, but best estimates suggest that 30% of patients requiring critical care will be children. Paediatric intensive care facilities are likely to be quickly exhausted and suggest that older children should be managed in adult critical care units to allow resource optimisation. Crucially this study highlights the need for sentinel reporting and real-time modelling to guide rational decision making. PMID- 19645760 TI - Critical care bed capacity during the flu pandemic: implications for anaesthetic and critical care departments. PMID- 19645762 TI - Compost facilities as a reservoir of Legionella pneumophila and other Legionella species. AB - Data on the presence of Legionellae outside the aquatic environment are scarce. Alternative ecosystems that could act as a reservoir for Legionella spp. have been investigated to identify unconventional contaminated substrates that are able to produce bioaerosols. We considered eight green waste collection sites including three composting facilities. Legionella pneumophila sg 1-15, Legionella bozemanii, Legionella cincinnatiensis, Legionella jamestowniensis, Legionella micdadei and L. oakridgensis were isolated from samples taken at six of the eight sites. The degree of contamination ranged from 10(3) to 10(8) CFU/g. Compost facilities appear to comprise an important reservoir for Legionellae. PMID- 19645763 TI - Antifungal compounds redirect metabolic pathways in yeasts: metabolites as indicators of modes of action. AB - AIMS: Metabolic pathways, e.g. biosynthesis of ergosterol or carbohydrate metabolism including respiration, are well-known targets of several fungicides. With our study we wanted to prove that metabolite profiles can be used to classify fungicides according to their mode of action and that concentrations of key metabolites are changed even without detectable reduced growth rates. METHODS AND RESULTS: We exposed the yeasts Candida albicans and Saccharomyces cerevisiae to inhibitors of the electron transport chain and to compounds known to interact with osmotic stress defence pathways. Glycerol and ethanol were chosen as key metabolites of branches of glucose catabolism. Increased glycerol concentrations were observed not only when the osmotic stress response was activated, but also as response to the inhibition of the electron transfer chain, whereas elevated ethanol levels were observed only when the respiratory pathways were blocked. CONCLUSIONS: The treatment of the yeasts Candida albicans and Saccharomyces cerevisiae with antimycotic compounds led to a redirection of metabolic pathways, which could be followed by the quantification of both the metabolites ethanol and glycerol. Only the combination of both concentration profiles allowed the clear distinction between inhibitors of the respiratory chain and effects on the osmotic stress response pathway. IMPACT OF STUDY: The extension of the number of metabolites to a comprehensive quantitative metabolic profile of compound-treated test organisms can be an additional tool in fungicide research allowing the detection of compounds which act on fungi and, moreover, the elucidation of modes of action. PMID- 19645764 TI - qPCR quantification and genetic characterization of Clostridium perfringens populations in biosolids composted for 2 years. AB - AIM: The ability of Clostridium perfringens to survive for a long time in the environment makes it a suitable indicator of faecal pollution, but its use as a routine indicator organism in biosolids and composted biosolids has not yet been adopted. This study was performed to improve our understanding of C. perfringens persistence in composted biosolids by monitoring its presence and studying its genetic diversity. METHODS AND RESULTS: A culture-independent TaqMan qPCR assay targeting the cpn60 gene was adapted to enumerate C. perfringens in composted biosolid samples varying in age from 1 to 24 months. The pathogen was detected in all compost samples under study, but no correlation between composting time and number of cpn60 copies was observed. Rep-PCR detected 14 different C. perfringens genotypes, all belonging to toxinotype A, which is the most common biotype found in human and animal gastrointestinal tracts. CONCLUSIONS: Composting did not significantly decrease the number of C. perfringens cells. High genetic diversity of C. perfringens isolates present in composted biosolids is reported for the first time. SIGNIFICANCE AND IMPACT OF STUDY: This study evaluated tools for surveillance of composting processes, source tracking and risk assessment of composted biosolids. PMID- 19645765 TI - Survey of bacterial populations present in US-produced linerboard with high recycle content. AB - AIMS: To survey paperboard products from 17 US mills for bacterial populations and for bacteria potentially harmful to human health. METHODS AND RESULTS: Culturable aerobic bacteria were isolated from paperboard products using selective and nonselective medium. Resulting colonies from samples from three regions of the United States were identified using fatty acid methyl ester analysis. Percentages of bacteria species found were Bacillus megaterium (47), Bacillus licheniformis (15), Bacillus pumilus (12), Paenibacillus macerans (5), Paenibacillus pabuli (3), Bacillus subtilis (2), Bacillus cereus (2), Bacillus coagulans (1), Bacillus circulans (1), Bacillus brevis (1), Bacillus thuringiensis (1), Paenibacillus polymyxa (1), Cellulomonas turbata (1), Cellulomonas flavigena (1), unidentified Bacillus sp. (3) and unidentified bacteria (1). CONCLUSIONS: Recycled paperboard contained high populations of bacteria, and a positive correlation was found between recycle content and bacterial populations. Escherichia coli, Salmonella, Shigella or confirmed coliform bacteria were not found in any product. SIGNIFICANCE AND IMPACT OF THE STUDY: Populations of bacteria did not differ significantly from original counts over a 4-month period of dry storage, indicating that bacteria persist in paperboard over long periods and may re-enter the recycling process. The predominance of heat-tolerant endospore-forming bacteria explains the high bacteria counts found in paperboard made from recycled materials. PMID- 19645766 TI - Untreated and enzyme-modified bovine whey products reduce association of Salmonella Typhimurium, Escherichia coli O157:H7 and Cronobacter malonaticus (formerly Enterobacter sakazakii) to CaCo-2 cells. AB - AIMS: Adhesion of a micro-organism to a cell surface is often considered to be the first step in pathogenesis. Inhibiting this process may have therapeutic effects in vivo. This study investigates the inhibitory effects of various bovine whey products on the association of Salm. Typhimurium, E. coli O157:H7 and C. malonaticus (formerly Enterobacter sakazakii) to the human CaCo-2 cell line. Invasion of CaCo-2 cells by Salm. Typhimurium and C. malonaticus was also examined. METHODS AND RESULTS: Infection assays were performed by incubating pathogenic acteria with CaCo-2 cells in the presence of untreated (UT) or enzyme modified (EM) whey products. Associated micro-organisms were directly quantified by plate counts. Invasion of CaCo-2 cells by Salm. Typhimurium and C. malonaticus in the presence/absence of test materials was also quantified using gentamicin protection assays. At a concentration of 40 mg ml(-1), some UT whey products reduced association and invasion, but this effect was enhanced following hydrolysis with porcine pancreatic lipase. CONCLUSIONS: Both UT and EM sweet whey protein concentrates (WPCs) were found to be particularly effective inhibitors of association and invasion. All EM whey products significantly (P < 0.05) inhibited invasion of C. malonaticus into epithelial cells, causing a 2-log reduction in the quantity of these micro-organisms internalized. SIGNIFICANCE AND IMPACT OF THE STUDY: The present study suggests that whey products can inhibit association to and invasion of CaCo-2 cells by selected micro-organisms and may be useful in the treatment and/or prevention of foodborne infections. PMID- 19645767 TI - Material-dependent growth of human skin bacteria on textiles investigated using challenge tests and DNA genotyping. AB - AIMS: To investigate the influence of different fibre materials on the colonization of textiles by skin bacteria present in human sweat. METHODS AND RESULTS: The total bacterial content of axillary sweat samples was determined using DNA quantification, and the diversity of bacteria present was investigated. Fabrics made of different fibres were then challenged with these sweat samples; the bacterial DNA was quantified, and the bacterial taxa present were determined. We found differences in the overall colonization, with polyester and polyamide showing the highest bacterial mass. Also, significant differences in the various taxa of bacteria present on the different materials were found. In general, synthetic materials showed a selective growth of bacterial taxa underrepresented in sweat. In contrast, a cellulose-based material showed only very few taxa, identically with those predominant in sweat. CONCLUSIONS: Our investigations demonstrated that besides the bacterial content of sweat itself, the type of material has a strong impact on the bacterial colonization of textiles. SIGNIFICANCE AND IMPACT OF THE STUDY: Odour generation is one of several effects resulting from an interaction of skin bacteria with textiles, and it is a common experience that there are differences in odour generation by different materials. Our investigations suggest that a selective growth of potentially odour-producing bacteria may account for this. PMID- 19645768 TI - Growth and reducing capacity of Listeria monocytogenes under different initial redox potential. AB - AIMS: To determine the reducing capacity of Listeria monocytogenes and to highlight the effect of redox potential on its growth parameters. METHODS AND RESULTS: The reducing capacity of L. monocytogenes was monitored in Brain Heart Infusion Broth media at different initial redox potential (Eh) and pH at 37 degrees C. The effect of Eh obtained by gas flushing (air, N(2) and N(2)-H(2)) or by adding potassium ferricyanide and dithiotreitol in concentration from 1 to 10 mmol l(-1)on L. monocytogenes growth parameters at pH 6.0, 7.0 and 8.0 was investigated. A total change of 539 mV (+ or - 44 mV) from an initial redox value of +330 + or - 8 mV to a more negative potential in redox curves was observed resulting from L. monocytogenes growth at pH 7.0 at 37 degrees C. A significant influence of pH and redox potential on L. monocytogenes lag phase of growth was shown (P < 0.05). CONCLUSIONS: Listeria monocytogenes exhibited longer lag phase in reducing conditions and at pH 6.0. The method used to modify the redox potential was shown to have no effect on growth parameters at pH 7.0. SIGNIFICANCE AND IMPACT OF THE STUDY: The provided information on the extending lag time and the possible delayed growth of this major pathogen in reducing conditions might be useful for its control in foods. PMID- 19645769 TI - In vitro evaluation of the activity of microencapsulated carvacrol against Escherichia coli with K88 pili. AB - AIMS: The aim of the current study is to develop encapsulation of essential oils for oral delivery to the small intestine of pigs in order to retain their antimicrobial activity. METHODS AND RESULTS: Carvacrol was used as a model essential oil and successfully encapsulated in microcapsules made from Ca alginate hydrogel using an emulsion-extrusion technology with high encapsulation efficiency. This encapsulation method did not compromise the antimicrobial activity when tested against Escherichia coli K88 in a culture medium, as well as in a simulated gastrointestinal model. In the simulated gastrointestinal model, <20% of encapsulated carvacrol was released in the simulated gastric fluid; the rest was nearly completely released in the intestinal fluid after 6 h of incubation. CONCLUSIONS: Encapsulation in Ca-alginate microcapsules could effectively reduce the early absorption of carvacrol in the upper gastrointestinal tract after oral administration, therefore, retains its potential antibacterial activity for the small intestine. SIGNIFICANCE AND IMPACT OF THE STUDY: The developed encapsulation method is expected to be suitable for encapsulation of other essential oils. The results from this study would increase the likelihood of success in the application of essential oils as antimicrobial agents for controlling enteric diseases in pigs. PMID- 19645770 TI - F-box proteins FBXO31 and FBX4 in regulation of cyclin D1 degradation upon DNA damage. PMID- 19645771 TI - Remaining complaints 1 year after treatment for acute Lyme neuroborreliosis; frequency, pattern and risk factors. AB - BACKGROUND AND PURPOSE: To chart remaining complaints 1 year after treatment for neuroborreliosis, and to identify risk factors for a non-favorable outcome. METHODS: We followed patients treated for neuroborreliosis prospectively, and assessed outcome by a composite clinical score. The impact on outcome of clinical, demographic and laboratory factors were analyzed by univariate analyses and logistic regression. RESULTS: Out of 85 patients 41 (48%) had remaining complaints; 14 had objective findings and 27 subjective symptoms. Remaining complaints were associated with pre-treatment symptom duration >or=6 weeks (OR = 4.062, P = 0.044), high pre-treatment cerebrospinal fluid (CSF) cell count (OR = 1.005, P = 0.001), and female gender (OR = 3.218, P = 0.025). Presence of CSF oligoclonal bands (OCBs) was not analyzed in the logistic regression model due to many missing observations, but was found to be more frequent both pre-treatment (P = 0.004) and after 12 months (P = 0.015) among patients with remaining complaints as compared to patients with complete recovery. Further evaluation showed that objective remaining findings, and not subjective symptoms, were associated with pre-treatment symptom duration >or=6 weeks. No difference in outcome was observed between patients treated with IV ceftriaxone and patients treated with oral doxycycline. CONCLUSION: Remaining complaints are common after neuroborreliosis. The majority of the complaints are subjective. Pre-treatment symptom duration >or=6 weeks, high pre-treatment CSF cell count, and female gender seem to be risk factors for remaining complaints. Presence of CSF OCBs may also predict a non-favorable outcome, but this should be further studied. Whether subjective and objective complaints are associated with different risk factors is also an issue for future studies. PMID- 19645772 TI - Penumbra and reperfusion in acute ischaemic stroke: what's in a name? PMID- 19645773 TI - Ogataea populialbae sp. nov., a yeast species from white poplar. AB - During a survey of methylotrophic yeasts in natural habitats in Hungary, the yeast community associated with the exudates of white poplar (Populus alba) was found to be unique among the tree exudates hitherto investigated. Nineteen methanol-assimilating yeast strains representing an undescribed ascomycetous species were isolated from tree exudates of P. alba collected at different locations in Hungary. Analysis of the D1/D2 large subunit rRNA gene sequences placed the strains in the Ogataea clade and the new species is described as Ogataea populialbae. The type culture is NCAIM Y.01853(T) (CBS 11363, NRRL Y 48632). PMID- 19645774 TI - "Early View": a new initiative of the Breast Journal. PMID- 19645775 TI - Curcumin suppresses the paclitaxel-induced nuclear factor-kappaB in breast cancer cells and potentiates the growth inhibitory effect of paclitaxel in a breast cancer nude mice model. AB - Most anticancer agents activate nuclear factor kappa B (NF-kappaB), which can mediate cell survival, proliferation, and metastasis. Curcumin has been shown to inhibit the growth of various cancer cells, without toxicity to normal cells. The antitumor effects of curcumin could be due in part to the inactivation of NF kappaB. We hypothesize that blocking NF-kappaB activity may augment paclitaxel cancer chemotherapy. In this study, we investigated whether the inactivation of NF-kappaB by curcumin would enhance the efficacy of paclitaxel for inhibiting breast cancer growth in vitro and in vivo. We confirmed that curcumin inhibited paclitaxel-induced activation of NF-kappaB and potentiated the growth inhibitory effect of paclitaxel in MDA-MB-231 breast cancer cells. The combination of curcumin with paclitaxel elicited significantly greater inhibition of cell growth and more apoptosis, compared with either agent alone. In an experimental breast cancer murine model using MDA-MB-231 cells, combination therapy with paclitaxel and curcumin significantly reduced tumor size and decreased tumor cell proliferation, increased apoptosis, and decreased the expression of matrix metalloprotease 9 compared with either agent alone. These results clearly suggest that a curcumin-paclitaxel combination could be a novel strategy for the treatment of breast cancer. PMID- 19645776 TI - Pathologic nipple discharge in patients with radiologically invisible mass: review of 28 consecutive sub-areolar explorations. AB - The carcinoma frequency of clinically and radiologically negative pathologic nipple discharges (PNDs) and the optimum management strategy of these cases are still unclear. In this study, the frequency of cancer and the situation of the classic surgical intervention in patients with PND and invisible mammographic and ultrasonographic results are reviewed. The data pertaining to the cases of sub areolar exploration and major duct excision in a surgery clinic of university hospital from December 2002 to June 2007 have been examined in detail. In 28 cases with PND, which did not have any findings during conventional radiologic examinations, 21% of cases had malignant, and 7% of cases had atypical ductal hyperplasia. The frequency of invasive or in situ carcinoma is not low in clinically and radiologically negative PNDs. Sub-areolar exploration and major duct excision seems to be an appropriate and definitive diagnostic and therapeutic option in this special patient group. PMID- 19645777 TI - Axillary recurrence after negative sentinel lymph node biopsy: frequency and factors influencing recurrence on the long term. AB - Sentinel lymph node (SLN) biopsy is a less invasive method for determining tumor stage. Purpose of this study was to determine the frequency of axillary recurrence after negative SLN biopsy for women with breast cancer. A total of 121 patients with a negative SLN biopsy, from January 1, 2000 to December 31, 2004, were identified from a maintained pathology database. Retrospective chart review and data analysis were performed until September 1, 2006, to determine frequency of axillary recurrence and identify variables predictive of recurrence. Two hundred and sixty eight patients had undergone SLN biopsy in the researched period, of which 121 were SLN negative and had no further axillary treatment. The median follow-up was 44 months (range, 15-76 months). Three patients (2.5%) developed isolated axillary recurrence. Five patients (4.1%) developed distant disease recurrence. Grade 3 tumor differentiation was significantly associated with tumor recurrence. Tumor size, hormone receptor state, and mitotic activity/2 mm(2) were not significantly associated with disease recurrence. Patients with a negative SLN biopsy with no further axillary treatment, show a low rate of axillary recurrence. SLN biopsy is a less invasive and accurate method for determining tumor stage and a negative SLN biopsy provides good regional control of the axilla on the long term. PMID- 19645778 TI - Prognostic implications of positive nonsentinel lymph nodes removed during selective sentinel lymphadenectomy for breast cancer. AB - Nonsentinel lymph nodes (SLNs) are commonly removed at the time of selective sentinel lymphadenectomy (SSL). Their predictive value for the rest of the nodal basin is unknown. A retrospective review of 436 breast cancer patients who underwent SSL between 12/97 and 04/03 at a single institution. One-hundred nineteen patients had non-SLNs removed at SSL; eight were positive (6.7%). Positive non-SLNs predicted that SLNs would also be positive (p = 0.008). There was no difference in rates of additional positive nodes found on completion axillary node dissection between the non-SLN and SLN positive patients (p = 0.62). After adjustment for covariates, the presence of positive non-SLNs was not associated with poorer disease free survival (p = 0.24), time to systemic recurrence (p = 0.57), or overall survival (p = 0.70). Positive non-SLNs removed during SSL are not a significant risk factor for additional positive nodes on completion axillary nodal dissection (CALND) or for worse survival than positive SLNs. PMID- 19645779 TI - Fulvestrant in advanced breast cancer following tamoxifen and aromatase inhibition: a single center experience. AB - Fulvestrant is a pure estrogen receptor (ER) antagonist with no agonist effects. We describe the experience of a single center involving 45 postmenopausal women with advanced breast cancer where fulvestrant was utilized following progression on tamoxifen and a third generation aromatase inhibitor. Patients received fulvestrant as first line one (2%), second line 18 (40%), third line 13 (29%), fourth line 10 (22%), and fifth line three (7%) treatment. Median duration of treatment with Fulvestrant was 4 months (range 1-20 months). One patient had a partial response, 14 other (31%) experienced clinical benefit (CB) (defined as response or stable disease for at least 6 months). The median time to progression (TTP) from initiation of fulvestrant was 4 months (range 1-20 months) and the median survival was 10 months (range 1-55 months). In those patients who experienced CB the median TTP was 10 months (range 6-20) and median survival was 21 months (range 7-55). Fulvestrant was well tolerated; two patients experienced side effects severe enough to stop therapy. Despite the fact that fulvestrant was used in the majority of cases, later in the treatment sequence CB was seen in a number of patients. This data suggest fulvestrant is well tolerated and is a useful treatment option in patients with advanced breast cancer who progress on prior endocrine treatment. PMID- 19645780 TI - Mammary ductoscopy and ductal washings for the evaluation of patients with pathologic nipple discharge. AB - The majority of breast diseases result from lesions of the ductal epithelium. Mammary ductoscopy allows for visualization of intraductal abnormalities, and ductoscopic lavage provides thousands of cells for analysis. We reviewed our experience of 89 cases of patients with pathologic nipple discharge (PND) undergoing ductoscopy-directed duct excision and collection of ductal washings. Patients undergoing ductoscopy-directed duct excision with ductal washings had an 88% abnormal pathology rate. Most abnormalities were benign (71% papillomas), but the atypia rate for this group was 62%. The combination of visualization and pathologic analysis of washings provided the highest predictive value for the diagnosis of papilloma. Cellular yields for this technique were excellent with most specimens yielding >5,000 epithelial cells per high powered field and with evaluable ductal cells in 82% of specimens. Mammary ductoscopy offers the advantage of a high lesion localization rates with intraoperative guidance. The most accurate tool was the combination of ductal washings and ductoscopic visualization, but preoperative use of these techniques is not helpful in most cases. Greater than 90% of patients with PND are found to have a lesion on pathologic examination when using this technique for directed duct excision. Of interest, ductal washings obtained from symptomatic patients with benign diseases are often atypical. PMID- 19645781 TI - Significance of periductal lymphatic and blood vascular densities in intraductal carcinoma of the breast. AB - We investigated the significance of periductal lymphatic and blood vascular densities in intraductal carcinomas (IDC) of the breast. Thirty five cases of pure IDC treated by partial or total mastectomy were reviewed. Seven cases with normal breast tissue and 48 cases of invasive breast carcinoma were included as controls. All cases were immunostained with D2-40 and CD31. Positively stained microvessels were counted in densely vascular/lymphatic foci (hot spots) at 400x (=0.17 mm(2)) in the periductal areas. IDC without comedonecrosis showed a mean periductal D2-40 lymphatic microvessel density (LMD) of 5.8 +/- 5 (range 0-18), and a CD31 microvessel density (MD) of 14 +/- 8.9 (range 1-40). IDC with comedonecrosis showed periductal D2-40 LMD of 8.4 +/- 3.8 (range 4-18), and a CD31 MD of 24.3 +/- 7.6 (range 14-40). There was a significant difference between periductal D2-40 LMD and CD31 MD counts in IDC with and without comedonecrosis. There was a positive correlation of periductal D2-40 LMD and CD31 MD counts with high nuclear grade (r = 0.39 and 0.56) of IDC as well as with the presence of comedonecrosis (r = 0.49 and 0.59). Both D2-40 LMD and CD31 MD did not correlate significantly with tumor size, estrogen status, or progesterone status. As IDC with comedonecrosis and/or high nuclear grade has a worse prognosis than IDC without comedonecrosis and/or with low nuclear grade, it appears that lymphatic and blood vascular density evaluated by D2-40 and CD31, respectively, are independent prognostic indicators for patients with IDC of the breast and may be an indicator of early or unrecognized invasion or "regression." PMID- 19645782 TI - Ipsilateral breast tumor recurrence: is there any evidence for benefit of further systemic therapy? AB - To date, there are no standard guidelines for treating patients with ipsilateral breast tumor recurrence (IBTR). Current practice is to resect the recurrence with a radical intent followed possibly by radiotherapy if the patient has not received this before, but the role of further adjuvant medical (hormone or chemotherapy) therapy remains undefined. Currently Phase III trials are underway to answer this question. In this review, we will focus on published data relating to IBTR and discuss recent trials. The results from the Phase III trials will not be available for sometime. At the time of IBTR, it is reasonable to change the endocrine therapy with indirect evidence from sequencing of impact on outcome. There is currently no conclusive evidence to suggest that further adjuvant chemotherapy post loco-regional recurrence impacts on survival, though the use of noncross-resistant chemotherapy drugs may make sense in those at highest risk. Biopsy at IBTR is helpful to distinguish whether it is a true recurrence or a new primary tumor and receptor phenotyping may be helpful for HER2. Future trials in IBTR need to address the following issues: to be able to distinguish between true recurrence and new primary (consensus required on definitions); pathologic processing relating to margins needs to be standardized (1 or 5 mm wide specimens); documentation of the pattern of IBTR in relation to each histopathologic subtype and methods used for pathologic examination by centers. Regional nodal recurrence including supraclavicular node recurrence is not dealt with in this review. PMID- 19645783 TI - Aesthetic correction of tuberous breast deformity: lessons learned with a single stage procedure. AB - Tuberous breast deformity is a pathologic condition of the breast affecting teenage women. The aberration of breast shape in tuberous breast deformity consisting of a constricting ring at the breast base, breast tissue deficiency, and herniation of breast tissue into the nipple-areola-complex with areola enlargement and additional asymmetry makes the surgical correction challenging. In the present study, 15 patients were operated using a surgical procedure, which addresses all aspects of the deformity at a one-stage operation. The described technique results in a periareolar scar only, and the use of tissue expanders or skin flaps is unnecessary. Minor periareolar scar revision surgery was necessary in eight of 15 patients (53%) because of hypertrophic or expanded scarring. In two patients, implant dislocation occurred and therefore surgical revision was necessary. In all cases, an excellent final aesthetic result with a high patient satisfaction was achieved. PMID- 19645785 TI - Rethinking TNM: a breast cancer classification to guide to treatment and facilitate research. AB - The TNM(UICC) classification of breast cancer categorizes tumor size, regional lymph node involvement, and distant metastases. Treatment is influenced by these characteristics, but requires knowledge of several other factors. In fact, effective treatment is dependent on disease extent, hormone receptor status, and other biologic characteristics of the cancer. We propose a new classification [tumor node metastasis (TNM)] that not only includes relevant biologic characteristics and can expand to include others as they are validated but also specifies tumor size exactly (T2.3 indicates a cancer of maximum diameter 2.3 cm), provides more information on regional lymph node involvement, and specifies the site(s) of distant metastases. We also propose abolishing the term "carcinoma" for non-invasive neoplastic conditions and the term "infiltrating" for carcinomas. The new classification is sufficiently similar to the TNM(UICC) classification to permit valid comparison of patients classified by both systems, but is more logical, provides information useful for guiding therapy, and is flexible enough to satisfy present and future clinical and research needs. PMID- 19645784 TI - Sexual Adjustment and Body Image Scale (SABIS): a new measure for breast cancer patients. AB - The purpose of this study was to develop and validate a self-report measure of body image and sexual adjustment in breast cancer patients: the Sexual Adjustment and Body Image Scale (SABIS). Three hundred and fifty three women diagnosed with primary breast cancer that had completed initial surgical treatment completed the SABIS and five measures of psychological, psychosocial, and sexual functioning. Psychometric properties of the SABIS were examined and it was found to be a reliable and valid means of assessing body image and sexuality in breast cancer patients following surgery. PMID- 19645786 TI - Long-term results of breast conservation in Chinese women with breast cancer. AB - Between July 1989 and December 2002, 172 women with Stage I/II breast cancer were treated by breast conservation therapy (BCT). All underwent quadrantectomy and axillary node clearance. Minimum follow-up was 5 years and 79 (52%) were followed for >10 years. At 5 years, local relapse-free and overall survival rates were 98.3% and 98.3%. The 10-year rates were 95% and 94%, respectively. The 10-year local recurrence rate was higher in patients with involved margins (33.3% versus 2.7%, p = 0.0272). Furthermore 10-year death rates in margin positive patients were higher (18.2% versus 2.5%, p = 0.0486). Excellent or good cosmetic results were achieved in 54%. BCT is a reasonable option for early stage breast cancer in Chinese women but margin status is the most important determinant of local recurrence. Negative margins are required for optimal local control and minimization of distant metastasis. PMID- 19645787 TI - Calcifying fibrous pseudotumor of the breast. AB - Calcifying fibrous pseudotumor (CFP) is classified as a benign fibrous lesion, and is a rare pathologic entity. Previous reports have described CFPs in the extremities, chest wall, pleura, scrotum, mediastinum, neck, and visceral peritoneum. We present the first reported case of a CFP in the breast. CFP should be considered in the differential diagnosis for patients presenting with coarse indeterminate calcifications of the breast. PMID- 19645788 TI - Signet ring cell histiocytosis in axillary lymph nodes: a sheep in wolves' clothing? A potentially under-recognized pitfall in the diagnosis of metastatic breast cancer. PMID- 19645789 TI - "Cholesteroloma": a rare cause of "indeterminate" microcalcifications on mammography. PMID- 19645790 TI - Barium sulphate particles in breast mimicking malignant type microcalcification. PMID- 19645791 TI - Unilateral calcifying lupus mastitis in a male breast. PMID- 19645792 TI - Spontaneous expulsion of benign phyllodes. PMID- 19645794 TI - Internal mammary chain sentinel biopsy in invasive breast cancer: an investigational procedure? PMID- 19645793 TI - Comparison of two score systems in Bcl-2 and Bax protein expression in invasive ductal carcinoma of breast and relation with oestrogen and progestrone receptors. PMID- 19645795 TI - Humeral metastasis in breast cancer patients: radiotherapeutic management of 21 cases. PMID- 19645796 TI - The impact of mammography in a public university affiliated hospital in an urban community. PMID- 19645797 TI - Shared management of a rare necrotizing soft tissue infection of the breast. PMID- 19645801 TI - Urinary incontinence in older adults receiving home care diagnosis and strategies. AB - INTRODUCTION: Urinary incontinence (UI) is a major health problem mostly affecting older people. With the shift toward healthcare delivery in the home setting, it is necessary for home healthcare workers to know how to manage UI in the elderly. Little is known about the care for patients receiving home care suffering from UI. The aim of this study was to assess the prevalence of UI in older adults receiving home care and to gain insight into caring for patients with UI. METHOD: A cross-sectional survey using data from the Dutch National Prevalence Measurement of Health Care Problems was conducted. RESULTS: Of the 2866 patients, 46% were suffering from UI. In 49% of these patients the type of UI was diagnosed. Patients with a diagnosis suffered more from their UI and were offered more strategies when compared with patients without a diagnosis. Most patients used pads. Relatively few patients were offered bladder training or pelvic floor muscle exercises (PFME). DISCUSSION: Urinary incontinence is a highly prevalent condition in older patients receiving home care. In half of the patients with UI no diagnosis regarding the type of incontinence was made. However, to treat or manage UI it is essential to assess the type of UI, as UI is treatable even in older people. As this study had a cross-sectional design, only strategies being offered at a fixed point in time are documented. CONCLUSION: Despite studies reporting the success of behavioural interventions for adults suffering from UI, most patients use pads. With the aging of the population and the increasing number of older adults suffering from UI, home care agencies need to acquire the knowledge and skills to address UI. PMID- 19645802 TI - Family decision-making in advanced dementia: narrative and ethics. AB - BACKGROUND: Traditionally, family members become decision-makers for ageing parents with cognitive impairment. Our understanding of how families negotiate the ethical issues in this decision-making is still developing. AIM: To describe and understand the ethical thinking used in end-of-life decision-making by family surrogates on behalf of their cognitively impaired elders. METHODS: Qualitative research with eight focus groups that included 39 family members of severely impaired nursing home residents in Minnesota. Transcripts were analysed using a thematic approach. FINDINGS: The family surrogates described their decision making as a process based in the families' stories and as extensions of the elders' identities. Four themes emerged from the analysis of the families' decision-making: (i) acquisition of decision-making authority, (ii) decision making for short-term or long-term time frames, (iii) justifying the decisions and (iv) advocacy for the elders. CONCLUSIONS: The families in these focus groups used the elders' life stories to frame their decisions for care. Providers working in primary care settings who work with families in making care decisions for cognitively impaired elderly patients may find narrative ethics more pertinent than principle-based ethics in understanding families' perspectives and priorities, while also recognizing their decision-making transition from using the principle of autonomy to that of beneficence. PMID- 19645803 TI - A difficult mission to work as a nurse in a residential care home--some registered nurses' experiences of their work situation. AB - The aim of the study was to describe Registered Nurses' (RNs) experiences of their work environment in residential care homes for older persons. Twelve RNs were interviewed and latent content analysis was used for analysing the data. The data were collected in the spring of 2006. The findings revealed that these RNs experienced a paradoxical work environment: feeling appreciated and valuable, whilst at the same time feeling underestimated and frustrated. They felt appreciated and valuable when they provided nursing care and trust and support to others. The RNs experienced a positive work environment when the border between social and nursing care were clear. They also felt frustrated when they were expected to 'be everywhere and to know everything', but at the same time they felt invisible and underestimated. They experienced themselves as 'lonely fixers', having the ability to solve practical problems when the older persons were discharged from hospital and expected to be able to provide specialist nursing care without having specialised competence and specialist staff team members. In conclusion, it is important that the RNs can identify the border for nursing care. When these are clear, the nursing care objectives are apparent and the RNs become more autonomous, visible and listened to. The manager should listen to and support the RNs, with continuous supervision and competence development being mandatory elements. It is a difficult task for RNs working in residential care homes to meet all of the expectations placed on them, resulting in a risk of moral distress, making mistakes and developing illnesses caused by stress. PMID- 19645804 TI - Nurses' experiences and perceptions of influencing barriers to postoperative pain management. AB - Despite decades of research and the availability of effective analgesic approaches, many patients continue to experience moderate to severe pain after surgery. Greater research efforts are needed to identify the factors that impede effective pain management. Despite the fact that a variety of research and clinical studies on all aspects of pain have been conducted in many countries, the factors affecting pain management have not been completely identified. AIM: To identify nurses' experiences and perceptions about the barriers to postoperative pain management. METHODS: A qualitative approach was adopted using content analysis of semi-structured interviews carried out with 26 Iranian registered nurses from three large educational hospitals in Tehran city. The data were analysed using constant comparative method. FINDINGS: Ninety-three primary codes were achieved. Four main themes emerged from the data. From the participants' points of view, 'lack of educational preparation', 'nurses' limited authority', 'limited nurse-patient relationship', and 'disturbances in pain management interventions' are considered barriers to pain management. CONCLUSION: The conclusion embraces implications for clinical practice to improve the knowledge of nurses and nursing manager and insight in postoperative pain management. Clearly, programmes for change must address not only knowledge improvement, but also the wider complex influences on barriers to pain management. PMID- 19645805 TI - Nursing students' attitudes towards HIV/AIDS patients in Finland, Estonia and Lithuania. AB - This paper presents baseline data on attitudes towards HIV/AIDS patients and homophobic levels among nursing students in three Baltic Sea countries: Finland, Estonia and Lithuania. The aim is to describe and compare nursing students' attitudes in these three countries and to explore how attitudes towards HIV/AIDS correlate with background variables. The total sample comprised 471 nursing students. The respondents demonstrated average attitude scores towards patients with HIV/AIDS and rather positive attitudes towards homosexually oriented patients. Significant country differences were found, with Finnish nursing students showing the most positive attitudes towards HIV/AIDS patients and homosexually oriented patients. Previous experience of HIV/AIDS patients was the single factor with the greatest positive impact on nursing students' attitudes. Nursing students' willingness to provide care for an HIV/AIDS patient was associated with a positive attitude towards these patients. Length of employment experience correlated negatively with general attitude, and older nursing students with more work experience showed a more negative attitude towards homosexual patients. Proper education to achieve a sound knowledge base and good nursing skills promotes a more positive attitude to HIV/AIDS. It is important that nursing students are sensitive and show respect for the patient's human dignity. There is need for greater harmonization of education in the three countries. PMID- 19645806 TI - Primacy of existential pain and suffering in residents in chronic pain in nursing homes: a phenomenological study. AB - The study's rationale: Chronic pain is a major health problem among the elderly, both in the community and within nursing homes. AIMS AND OBJECTIVES: The purpose of the study was to examine the essentials of the experience of residents in chronic pain in nursing homes. METHODOLOGICAL DESIGN AND METHODS: The research approach was interpretive phenomenology. Data were collected in 23 dialogues with 12 residents, ages 74-97. Mean age was 86 years. RESULTS: The main finding is the primacy of existential pain and suffering in residents in chronic pain in nursing homes. Indeed they recounted a culmination of existential pain and suffering, e.g. loss of loved ones, loss of former home, health and independence, as well as loss of connectedness. Many seemed to be in some kind of grief and their work towards reconciliation to their life and circumstances seemed an ongoing process with successful results while others seemed more haltering or even stuck. Living with chronic pain in a nursing home is indeed a challenge and many blocks to successful pain management were identified. The main sources of strength were loved ones who were seen as lifelines. Nurses seemed distant in their narratives of pain management. STUDY LIMITATIONS: Frailty of residents is a limitation as a few were starting to forget from one interview to the other and some were actually in pain at the time of our dialogue. CONCLUSIONS: It is important to support a healthy process of grieving and reconciliation in elderly people who live with chronic pain in nursing homes. Those who suffer in silence with their pain and discomforts and do not seek help should be identified and cared for. The residents' own sources of strength should be identified and supported. Multi professional collaboration with educational thrust is needed towards quality pain management of elderly people in nursing homes where existential pain and suffering is not excluded. PMID- 19645807 TI - Knowledge, attitudes and practice among nursing staff concerning pressure ulcer prevention and treatment--a survey in a Swedish healthcare setting. AB - The aim of this study was to investigate (i) attitudes among Registered Nurses (RNs) and Nursing Assistants (NAs) regarding pressure ulcer prevention, (ii) knowledge among RNs and NAs of pressure ulcer prevention and treatment, (iii) practice of risk assessment and documentation regarding pressure ulcers among RNs and NAs and (iv) to identify perceived possibilities and barriers in pressure ulcer prevention and treatment. In this cross-sectional study, a total of 230 questionnaires were distributed to an equal number of RNs and NAs in both municipality as well as hospital care settings. The response rate was 67% (n = 154). In general, all respondents displayed good knowledge on prevention and treatment of pressure ulcers and demonstrated a positive attitude towards this area of care. However, answers provided to some questions indicate that recent research findings and guidelines have not succeeded in reaching out to these occupational groups. Furthermore, only 37% (n = 55) of the participants said that they have an agreed strategy for the prevention of pressure ulcers in their unit. These shortcomings may affect the quality of care provided to the patient and lead to pressure ulcers developing as a consequence. Today, evidence-based methods for risk assessment are available but are not adopted and used in practice. The study highlights the need to further reduce the gap between research and practice. PMID- 19645808 TI - 'I lose all these hours...'--exploring gender and consequences of dilemmas experienced in everyday life with coeliac disease. AB - Few studies have focused on gendered consequences of coeliac disease (CD), despite the fact that women with coeliac disease report lower health-related quality of life than men do. The aim of this study was to explore consequences of dilemmas in everyday lives for women and men, as personally affected by CD or as close relatives to someone affected by the disease and to put these experiences into context regarding household activities. This QUAL-quan study included 28 men and 38 women. A mix method design was used. The critical incident technique that captures, in a structured way, the qualities of experiences was used in interviews to identify dilemmas and their consequences. To describe the social context of these dilemmas, a quantitative questionnaire was developed on food preparations and purchase, as well as on cooking and meal behaviours. The study was approved by the Research Ethics Committee of the Faculty of Health Sciences. The consequences were found in cognitive, social, emotional and physical aspects of human life. The overall pattern of these consequences was similar in women and men irrespective of being personally affected or a close relative. The main consequences identified were: daily concerns about gluten, constant preparation, being different, emotional pressure and body sensations because of CD. Descriptive data extracted from the questionnaire showed that women and men reported having a different social situation in relation to preparing food, making decisions about purchases, buying food products and preparing meals. The clinical implications of these findings are that healthcare professionals need to develop family-oriented information in relation to CD. It is necessary to inform the close relatives irrespective of sex of the possible consequences of the disease and to take in to account the different social context that women and men report in relation to food preparations. PMID- 19645809 TI - Elderly people's perceptions of how they want to be cared for: an interview study with healthy elderly couples in Northern Sweden. AB - Many countries encounter a demographic change where the number of elderly people will increase. As a result, the number of very old people needing care, services and medical assistance will increase. Care in the private home is often described as providing the best alternative for many elderly people. The aim of this study was to describe elderly people's perceptions of how they wanted to be cared for, from a perspective of becoming in need of assistance with personal care, in the future. Twelve couples of healthy elderly people living in a couple hood participated in an interview study. They were all 70 years and older and received no kind of professional care or social support. Open individual semi-structured interviews were conducted with the support of written vignettes. The vignettes were formed as scenarios that described three levels of caring needs where the elderly people would become ill. A qualitative content analysis was used to analyse the interviews. The findings were interpreted in one main theme: maintaining the self and being cared for with dignity to the end. The theme was built from three categories: at home as long as possible, professional care at nursing home when advanced care is needed and fear of being abandoned. The categories reflect the perception that when minimum help was needed, care and support by the partner and nursing staff were preferred. As the scenarios changed to being totally dependent on care, they preferred care in a nursing home. There was a pervading concern of the risk of not being seen as an individual person and becoming a nobody with no meaningful relations. Thus, there must be a singular goal to support old people, in all stages of their lives, through the recognition and affirmation of self, and providing care with dignity to the end. PMID- 19645810 TI - Sense of coherence and psychiatric morbidity in terms of anxiety and depression in patients with major depression before and after electric convulsive treatment. AB - The specific aim of this study was to explore if the Sense of Coherence (SOC) Scale reflects and overlaps with standardized psychiatric assessments of depression and anxiety leading to the main hypothesis that the degree of depression decreases while the SOC scores remain stable. Fifteen patients with a diagnosis of major depression according to Axis I in DSM-IV and planned electric convulsive treatment (ECT) participated in the study. The clinician-rated instruments, Montgomery Asberg Depression Rating Scale (MADRS) and Global Assessment of Function (GAF), and the self-assessment instruments such as SOC and the Comprehensive Psychopathological Rating Scale-Self Rating Scale for Affective Syndromes (CPRS-S-A) were used before and after the treatment. The patients showed statistically significant improvements in clinician-rated depression (p < 0.001) and functional status (p < 0.001), and in self-rated anxiety (p = 0.001) and depression (p = 0.003). There was no significant improvement in SOC (p = 0.213). No significant correlations were found between the SOC scores and any of the measures except for GAF after treatment (r = 0.57, p = 0.039); the lower the SOC scores the greater was the functional dysfunction. In conclusion, the SOC Scale seems not to be a measure of psychopathology in terms of depression or anxiety merely. PMID- 19645813 TI - Neuromedin U: physiology, pharmacology and therapeutic potential. AB - Neuromedin U (NmU), a multifunctional neuropeptide, belongs to a family of neuropeptides, the neuromedins. It is ubiquitously distributed with highest levels found in the gastrointestinal tract and pituitary. The conservation of structural elements of NmU across species, the widespread distribution of NmU and its receptors throughout the body point to a fundamental role in key physiological processes. Two G protein coupled receptors for NmU have been cloned NmU R1 and NmU R2. NmU R1 is expressed pre-dominantly in the periphery especially the gastrointestinal tract whereas NmU R2 is expressed pre-dominantly in the central nervous system. Current evidence suggests a role of NmU in pain, in regulation of feeding and energy homeostasis, stress, cancer, immune mediated inflammatory diseases like asthma, inflammatory diseases, maintaining the biological clock, in the regulation of smooth muscle contraction in the gastrointestinal and genitourinary tract, and in the control of blood flow and blood pressure. With the development of drugs selectively acting on receptors and knockout animal models, exact pathophysiological roles of NmU will become clearer. PMID- 19645814 TI - Evaluation of DNA damage and metabolic syndrome parameters in diabetic rabbits supplemented with antioxidants. AB - The aim of the present study is to evaluate the extent of DNA damage in diabetes and metabolic syndrome and to assess the variations after supplementation with antioxidants. We used comet assay to measure DNA damage in freshly isolated lymphocytes from a total of 12 rabbits, distributed into four experimental groups (n = 3 rabbits per group): non-diabetic (control, G1), diabetic (G2), diabetic supplemented with vitamin C (G3), and diabetic supplemented with vitamin E (G4). Also their serum was isolated for estimation of parameters that contribute to metabolic syndrome. Malondialdehyde (MDA), the marker of oxidative stress was also assessed. Mean values of DNA damage (tail length, expressed as mum), lipid peroxidation and concentration of blood glucose, MDA, C-reactive protein, and triglycerides were higher in G2; whereas the mean values of concentration of high density lipoprotein, serum paraoxonase-1 activity and small dense low-density lipoprotein oxidation time were reduced in G2 followed by G3, G4, and G1. A significant positive correlation was observed between the DNA damage and elevated parameters of metabolic syndrome (r = 0.66, 0.96, 0.89, 0.75, 0.88, 0.92, 0.99, P < 0.05) and a significant negative correlation (r = -0.91, -0.75, -0.98, P < 0.05) was found between the DNA damage and declined parameters of metabolic syndrome. These data indicate that the extent of DNA damage is more in diabetic rabbits as compared to the non-diabetic or antioxidant supplemented group. Abnormal metabolic parameters and their correlation with DNA damage, suggest the risk of development of metabolic syndrome in diabetic group but a possibility of repression by antioxidants because of their ability to counteract oxidative stress. PMID- 19645815 TI - Phenylacetic acids and the structurally related non-steroidal anti-inflammatory drug diclofenac bind to specific gamma-hydroxybutyric acid sites in rat brain. AB - Gamma-Hydroxybutyric acid (GHB) is a proposed neurotransmitter or neuromodulator with a yet unresolved mechanism of action. GHB binds to both specific high affinity GHB binding sites and to gamma-aminobutyric acid subtype B (GABA(B)) receptors in the brain. To separate specific GHB effects from GABA(B) receptor effects, it is imperative to develop GHB selective and potent compounds. We generated the compound, 4-(biphen-4-yl)-4-hydroxybutyric acid, which is the 4 hydroxyl analogue of the non-steroidal anti-inflammatory drug (NSAID) fenbufen (referred to as gamma-hydroxyfenbufen). When measured in a rat brain homogenate [(3)H]NCS-382 binding assay, gamma-hydroxyfenbufen inhibited [(3)H]NCS-382 binding with a 10-fold higher affinity than GHB (K(i) 0.44 microM), thus establishing it as a novel lead structure. The active metabolite of fenbufen, 4 biphenylacetic acid inhibited [(3)H]NCS-382 binding with a twofold higher affinity than GHB. Measuring the affinities of structurally related NSAIDs for the [(3)H]NCS-382 site identified diclofenac, a clinically relevant NSAID (Voltaren, Diclon) of the phenylacetic acid (PAA) type, as a GHB ligand (K(i) value of 5.1 microM). Other non-NSAID PAAs also exhibited affinities similar to GHB. Our data raise the interesting possibility that the widely used over-the counter drug compound, diclofenac, might affect GHB binding at relevant clinical dosages. Furthermore, the identification of PAAs as GHB ligands supplies new information about the structural preferences of the GHB ligand-binding site. PMID- 19645816 TI - Characterization and differential expression of a newly identified phosphorylated isoform of the human 20S proteasome beta7 subunit in tumor vs. normal cell lines. AB - The search of new pharmacological targets with original mechanism of action within the ubiquitin-proteasome pathway is still a goal to be reached in oncopharmacology. Modification by phosphorylation/dephosphorylation has been found to be involved in cancer and to regulate functional activity of proteasome. Until now, phosphorylated forms of alpha subunits of the 20S human proteasome have been mostly reported. Here, we have rationally designed a polyclonal antibody specifically directed against a phosphorylated peptide sequence bearing the beta7 subunit Ser249 residue of the human 20S proteasome. This anti-beta7 phosphoSer249 antibody appeared to be a probe of choice to detect the presence of a phosphorylated isoform of the beta7 subunit of the human 20S proteasome using mono or two-dimensional gel electrophoresis. PhosphoSer249 was sensitive to acid phosphatase treatment of native 20S proteasome. Dephosphorylation affected the peptidylglutamyl-peptide hydrolyzing activity whereas the chymotrypsin-like and trypsin-like activities remained unchanged. A comparative analysis between human normal and tumor cells showed a differential expression of the phosphoSer249 beta7 isoform with a significantly lower detection in the proteasome isolated from tumor cells, suggesting its possible use as a biomarker. PMID- 19645817 TI - Antioxidative and antiproliferative effects of astaxanthin during the initiation stages of 1,2-dimethyl hydrazine-induced experimental colon carcinogenesis. AB - Colon cancer is one of the major causes of cancer mortality worldwide. Several carotenoids with antioxidant properties are reported for their chemopreventive nature. In this study, we have evaluated the chemopreventive efficacy of astaxanthin on lipid peroxidation, antioxidant status, total number of aberrant crypt foci (ACF), and cell proliferation in 1,2 dimethylhydrazine (DMH)-induced colon carcinogenesis using a rat model. DMH was induced subcutaneously at a dosage of 40 mg/kg body weight, twice a week for 2 weeks. Astaxanthin was administered before and after the DMH induction, orally at a concentration of 15 mg/kg body weight throughout the experimental period. At the end of 16 weeks, pre treatment with astaxanthin markedly reduced the degree of histological lesions, ACF development and also lowered the number of argyrophilic nucleolar organizer regions. Our results also showed the decreased levels of colon enzymic and non enzymic antioxidants and increased levels of lipid peroxidation marker levels in DMH-induced rats, which were significantly reversed on astaxanthin administration. In conclusion, the results of this study suggest that astaxanthin has an affirmative and beneficial effect against chemically induced colonic pre neoplastic progression in rats induced by DMH. PMID- 19645818 TI - An animal model of testicular toxicity by cyclosporine: evaluation and protection. AB - CyclosporineA (CsA) improves the survival of patients who benefited from transplantation. However, its use is generally limited by its side effects. The aim of our study was to measure, in an experimental model, the changes of the testosterone plasma levels after 21 days of CsA treatment and to explain the mechanism of this modification. After treatment, the levels of CsA, testosterone, corticosterone, transaminases were measured. The cytotoxic effect of CsA was evaluated by microscopic observation. The experimental study showed that CsA had no effect on the plasmatic levels of hepatic enzymes - alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl-transferase - because their plasma concentrations in treated rats did not differ from those of the sham group. The plasma concentration of corticosterone was not modified, the plasma level of testosterone decreased when the dose of cyclosporine was increased to 4 mg/kg/day. The photonic microscope observation showed that the number of Leydig cells was increased and the electronic microscope observation showed mitochondria alteration. The treatment by CsA and trimetazidine did not correct the alteration caused by CsA. N-benzyl-N'-(2-hydrox-3, 4-dimethyloxybenzyl)-pipeazine did not protect the mitochondrial function but partially protected mitochondria structure from the deleterious effect induced by CsA. The decrease of the plasma level of testosterone induced by CsA was due to the inhibition of the mitochondrial 20-22 desmolase which blocked the formation of the testosterone precursor and the destruction of the mitochondria structure. PMID- 19645819 TI - Use of dextropropoxyphene + acetaminophen fixed-dose combination in psychiatric hospital in Bahrain: is there a cause for concern? AB - There are concerns about the safety of the dextropropoxyphene and acetaminophen fixed-dose combination, particularly in patients with psychiatric morbidity, which has led to a phased withdrawal of this fixed-dose combination in many countries. A retrospective prescription audit was conducted to evaluate the dextropropoxyphene + acetaminophen fixed-dose combination prescribing pattern in the major psychiatric hospital of Bahrain. The data analysis was performed using SPSS/PC+ version 14.0. Prescriptions with the dextropropoxyphene + acetaminophen fixed-dose combination comprised 11.8% of all dispensed prescriptions and in most instances for outpatients undergoing substance abuse rehabilitation. Nearly half of the patients received >or=20 tablets of this fixed-dose combination (mean +/- SD: 30.9 +/- 13.1; range 20-126) as multiple doses. The dextropropoxyphene + acetaminophen fixed-dose combination was often co-prescribed with psychotropics, such as benzodiazepines (BZDs) (25.4%), BZDs + antidepressants (62.9%), BZDs + antipsychotics (3.7%) and BZDs + anticonvulsants (1.9%). Approximately 40% of prescriptions with the dextropropoxyphene + acetaminophen fixed-dose combination were written 'as required' (prn), basis. Despite poor safety and efforts to restrict or withdraw worldwide, the dextropropoxyphene + acetaminophen fixed-dose combination continues to be irrationally prescribed to outpatients undergoing substance abuse rehabilitation in Bahrain. Health policy decision-makers should introduce a phased withdrawal of this drug from clinical use. In the meanwhile, it is important to create awareness among prescribers of the risks associated with over-dosage of the dextropropoxyphene + acetaminophen fixed-dose combination and its interaction with other psychotropic medications. PMID- 19645820 TI - Viability of Listeria monocytogenes in co-culture with Acanthamoeba spp. AB - Listeria monocytogenes is a human pathogen, ubiquitous in the environment, and can grow and survive under a wide range of environmental conditions. It contaminates foods via raw materials or food-processing environments. However, the current knowledge of its ecology and, in particular, the mode of environmental survival and transmission of this intracellular pathogen remains limited. Research has shown that several intracellular pathogens are able to survive or replicate within free-living amoebae. To examine the viability of L. monocytogenes in interaction with Acanthamoeba spp., bacteria were co-cultured with three freshly isolated amoebae, namely Acanthamoeba polyphaga, Acanthamoeba castellanii and Acanthamoeba lenticulata. The survival of bacteria and amoebae was determined using culture techniques and microscopy. Under the experimental conditions used, all amoebae were able to eliminate bacteria irrespective of the hly gene. Bacteria did not survive or replicate within amoeba cells. However, extra-amoebic bacteria grew saprophytically on materials released from amoebae, which may play an important role in the survival of bacteria under extreme environmental conditions. PMID- 19645821 TI - Biochemistry and molecular biology of lithotrophic sulfur oxidation by taxonomically and ecologically diverse bacteria and archaea. AB - Lithotrophic sulfur oxidation is an ancient metabolic process. Ecologically and taxonomically diverged prokaryotes have differential abilities to utilize different reduced sulfur compounds as lithotrophic substrates. Different phototrophic or chemotrophic species use different enzymes, pathways and mechanisms of electron transport and energy conservation for the oxidation of any given substrate. While the mechanisms of sulfur oxidation in obligately chemolithotrophic bacteria, predominantly belonging to Beta- (e.g. Thiobacillus) and Gammaproteobacteria (e.g. Thiomicrospira), are not well established, the Sox system is the central pathway in the facultative bacteria from Alphaproteobacteria (e.g. Paracoccus). Interestingly, photolithotrophs such as Rhodovulum belonging to Alphaproteobacteria also use the Sox system, whereas those from Chromatiaceae and Chlorobi use a truncated Sox complex alongside reverse-acting sulfate-reducing systems. Certain chemotrophic magnetotactic Alphaproteobacteria allegedly utilize such a combined mechanism. Sulfur chemolithotrophic metabolism in Archaea, largely restricted to Sulfolobales, is distinct from those in Bacteria. Phylogenetic and biomolecular fossil data suggest that the ubiquity of sox genes could be due to horizontal transfer, and coupled sulfate reduction/sulfide oxidation pathways, originating in planktonic ancestors of Chromatiaceae or Chlorobi, could be ancestral to all sulfur lithotrophic processes. However, the possibility that chemolithotrophy, originating in deep sea, is the actual ancestral form of sulfur oxidation cannot be ruled out. PMID- 19645822 TI - The role of rpoS gene and quorum-sensing system in ofloxacin tolerance in Pseudomonas aeruginosa. AB - The basis of the bactericidal action of antibiotics and the mechanisms of antibiotic tolerance are largely unknown. To elucidate one of the mechanisms of antibiotic tolerance, the present study investigated the role of Pseudomonas aeruginosa quorum sensing (QS) and the rpoS gene in antibiotic tolerance. The survival rates of the lasR and lasI mutants were observed to be lower than that of the parental strain in time-dependent killing studies with 8 microg mL(-1) ofloxacin, but the survival rates of the rhlR and rhlI mutants were not different from that of the parental strain. Moreover, a lasR-overexpressing strain was more tolerant to ofloxacin than the parental strain, but this was not the case for an rhlR-overexpressing strain. The mRNA expression levels of lasR, lasI, and rpoS in the wild-type strain in the presence of bactericidal concentration of ofloxacin were lower than that in the absence of ofloxacin. In addition, the significant loss of antibiotic tolerance in the lasR mutant was recovered by the overexpression of rpoS. These results suggest that the Las QS system in P. aeruginosa is involved in the development of ofloxacin tolerance, and the tolerance induced by the Las-system is regulated by rpoS gene. PMID- 19645824 TI - Extraction of high-quality epidermal RNA after ammonium thiocyanate-induced dermo epidermal separation of 4 mm human skin biopsies. AB - To obtain a separation of the epidermal and dermal compartments to examine compartment specific biological mechanisms in the skin, we incubated 4 mm human skin punch biopsies in ammonium thiocyanate. We wanted to test (i) the histological quality of the dermo-epidermal separation obtained by different incubation times; (ii) the amount and quality of extractable epidermal RNA and (iii) its impact on sample RNA expression profiles assessed by large-scale gene expression microarray analysis in both normal and inflamed skin. At 30-min incubation, the split between dermis and epidermis was not always histologically well-defined (i.e. occurred partly intra-epidermally), but also varied between subjects. Consequently, curettage along the dermal surface of the biopsy was added to the procedure. This modified method resulted in an almost perfect separation of the epidermal and dermal compartments, and satisfactory amounts of high-quality RNA were obtained. Hybridization to Affymetrix HG_U133A 2.0 GeneChips showed that ammonium thiocyanate incubation had a minute effect on gene expression resulting in only one significantly downregulated gene (cystatin E/M). We conclude that epidermis can be reproducibly and almost completely separated from the dermis of 4 mm skin biopsies by 30 min incubation in 3.8% ammonium thiocyanate combined with curettage of the dermal surface, producing high-quality RNA suitable for transcriptional analysis. Our refined method of dermo-epidermal separation will undoubtedly prove valuable in the many different settings, where the epidermal and dermal compartments need to be evaluated separately. PMID- 19645823 TI - Liver X receptor expression in human melanocytes, does it have a role in the pathogenesis of vitiligo? AB - Vitiligo is a common, non-contagious disorder. The basic pathogenesis of vitiligo generally, or for any of the putative subsets of vitiligo, remains unknown. The liver X receptors (LXRs), LXR-alpha and LXR-beta are members of the nuclear hormone receptor superfamily of ligand-activated transcription factors. Important genes involved in regulation of melanocytes are target genes of LXRs; it can be speculated that LXRs might be playing an important role in pathogenesis of pigmentary disorders. We have demonstrated in this study that there is expression of LXR-alpha/beta by human melanocytes at both transcriptional and translational levels. Our present data also revealed that the expression of LXR-alpha at both mRNA and protein level was significantly higher in perilesional skin as compared to the normal skin of vitiligo patient. PMID- 19645825 TI - Injury downregulates the expression of the human cathelicidin protein hCAP18/LL 37 in atopic dermatitis. AB - Reduced production of antimicrobial peptides was proposed to contribute to susceptibility for skin infections in atopic dermatitis (AD). Focusing on the human cathelicidin protein, hCAP18, the aim of the present study was to explore whether reduced hCAP18 expression is a constitutive trait in AD and if established inducers affect the expression of hCAP18 in the skin of AD. First, we compared levels of hCAP18 mRNA between lesional skin in AD and psoriasis and verified significantly lower expression of hCAP18 mRNA in AD. In non-lesional skin, however, there was no difference between AD, psoriasis and healthy, indicating that there is no constitutive defect in the production of hCAP18 in AD patients. In healthy skin, hCAP18 was reported to be rapidly induced following wounding and here we verified this pattern in healthy controls and in psoriasis. In AD lesions, however, the expression of hCAP18 mRNA was markedly suppressed following wounding. Obviously, the inflammation in AD lesions neutralizes the expected induction of hCAP18 and even induces suppression. Notably, the mechanism to upregulate hCAP18 following vitamin D treatment was functional in lesional as well as in non-lesional AD indicating that the CAMP gene is normally regulated in this respect. In addition, cultured primary keratinocytes from non-lesional skin of psoriasis, AD and healthy skin, upregulated hCAP18mRNA following treatment with vitamin D. Itching is a hallmark of AD and scratching inevitably injures the skin. Failure to upregulate hCAP18 in eczema following injury is likely to affect antimicrobial protection and tissue repair in AD. PMID- 19645826 TI - Parental consent for neuroimaging in paediatric research. AB - BACKGROUND: Functional magnetic resonance imaging (fMRI) is increasingly applied in paediatric research. Parents typically provide research consent for their children; yet, no study has examined the rates of consent, nor factors influencing parental decision making for consent. The present study aimed to determine the proportion of parents that would consent to their child undergoing an fMRI study, and to elicit the reasons, motivators and detractors affecting their decision. METHODS: Ninety parents of children aged 6 years were invited to participate in a postal survey study. RESULTS: Fifty-three parents (59%) responded and one-third (34%, 18/53) reported that they would consent. The main reason for consent was that participation could benefit children in the future (89%, 16/18). Common reasons for not consenting included that fMRI may be anxiety provoking (54%), or was an unnecessary medical procedure (23%). CONCLUSIONS: Our preliminary data suggest that researchers may have to approach three times the number of participants required in order to recruit a suitable number of healthy children to fMRI studies. Further research examining the influence of recruitment approaches (e.g. phone vs. postal) and the various factors influencing decision making regarding consent is required. For example, careful examination of the language used in describing the procedure could facilitate parental understanding about fMRI and alleviate anxiety associated with the procedure. This is an important consideration for recruitment to future fMRI studies given that anxiety was a key factor influencing parental non-consent. PMID- 19645827 TI - Social-behavioural functioning in paediatric chronic kidney disease. AB - Background The social-behavioural functioning of children and adolescents with chronic kidney disease (CKD) is not well studied and not fully understood, with available studies reflecting a mixed set of findings. The primary purpose of this paper is to compare the social-behavioural functioning of children with CKD with typical controls using multiple raters. A secondary analysis also examines the impact of disease severity on social-behavioural functioning. Methods Parental ratings and self-reports on the Behavior Assessment System for Children were obtained from a patient sample of 26 children and adolescents with CKD. This sample was comprised of those with end-stage renal disease (end-stage renal disease; n= 13) and those with chronic renal insufficiency (n= 13). For comparison, a typically developing control group (n= 33) also was ascertained. Results While behaviour ratings by parents and children fell within the average range, parent ratings showed an increased number of internalizing symptoms when compared with the CKD Group. Exploratory analyses revealed parental ratings showing more specific concerns on the Behavior Assessment System for Children individual clinical scales of Anxiety, Depression and Somatization. No differences were observed between the groups on the children's self-ratings, or in terms of numbers of children falling above the 90th percentile for both parent and child ratings. Secondary analyses did not produce any group differences between the chronic renal insufficiency and end-stage renal disease severity groupings. Conclusions These findings failed to show the presence of social behavioural difficulties in children with CKD, although there may be specific concerns for the presence of internalizing symptoms as per parent ratings. These findings suggest the need for follow-up of the subtle affective symptoms that might be present in children with CKD as recognizing these subthreshold social behavioural symptoms may be a critical part of their overall clinical care. PMID- 19645828 TI - Use of the Kidcope to identify socio-economically diverse Spanish school-age children's stressors and coping strategies. AB - BACKGROUND: The process by which children cope with stressful events is a very relevant topic. However, few systematic efforts have been made to design age specific measures. METHODS: This study examined problems commonly experienced by children, ages between 7 and 12 years, from two different sources: a primary school mainly enrolling families of medium socio-economic status, and an after school social care centre from a socially and economically deprived neighbourhood. Data were obtained using the younger version of the Kidcope. RESULTS: Almost 55% of the sample reported a problem related to others with no differences observed in age, gender or school group. The strategies that children considered the most effective were 'social support' (35%), 'emotional regulation' (33%) and 'wishful thinking' (32%). The children from disadvantaged backgrounds reported different problems mainly related with 'victimization and violence', 'moving house' and conflicts with 'norms and rules' and tended to use avoidant strategies to face them, which could be related to the perception of uncontrollability of these stressors. CONCLUSIONS: This study reported the first descriptive results in the type of problems and coping strategies of two different social groups of Spanish children using the Kidcope. The Kidcope can be useful to screen children for coping abilities at an early age living under stressful conditions in underprivileged sectors of society. PMID- 19645829 TI - Predictors of parenting self-efficacy in mothers and fathers of toddlers. AB - BACKGROUND: Researchers interested in child developmental outcomes have highlighted the role that parenting self-efficacy (PSE) plays in psychosocial child adjustment. PSE is a cognitive construct that can be broadly defined as an individual's appraisal of his or her competence in the parental role. PSE has emerged in the literature as an important variable when exploring variance in parenting skills. Despite this, much remains to be learned about PSE. Little is known about the predictors of PSE, with much of the existing research conducted in a piecemeal fashion that lacks a solid theoretical framework. In addition, PSE in fathers has been understudied and relatively little is known about PSE in families with toddler age children. Informed by Belsky's process model of parenting, this study explored similarities and differences in PSE and the predictors of PSE for mothers and fathers of toddlers. METHODS: A total of 62 cohabiting couples whose first-born child was 18-36 months old completed self report measures of PSE, general self-efficacy, depression, marital satisfaction, parenting stress, child difficultness and family functioning. RESULTS: For fathers, parenting stress and their relational functioning (i.e. marital satisfaction and family functioning) with their spouse predicted PSE scores. For mothers, general self-efficacy and relational functioning were predictive of PSE. CONCLUSIONS AND LIMITATIONS: The results of this study support the use of Belsky's process model of parenting to study the predictors of PSE. Important differences were found in the prediction models for mothers and fathers. Future studies need to clarify the nature of parental self-efficacy beliefs in fathers and continue to use comprehensive theoretical models to identify potentially relevant covariates of PSE. Limitations of the current investigation include reliance on self-report measures and the homogeneity of the sample. PMID- 19645830 TI - Effect of benazepril on survival and cardiac events in dogs with asymptomatic mitral valve disease: a retrospective study of 141 cases. PMID- 19645832 TI - Equine herpesvirus-1 consensus statement. AB - Equine herpesvirus-1 is a highly prevalent and frequently pathogenic infection of equids. The most serious clinical consequences of infection are abortion and equine herpesvirus myeloencephalopathy (EHM). In recent years, there has been an apparent increase in the incidence of EHM in North America, with serious consequences for horses and the horse industry. This consensus statement draws together current knowledge in the areas of pathogenesis, strain variation, epidemiology, diagnostic testing, vaccination, outbreak prevention and control, and treatment. PMID- 19645833 TI - Lack of evidence of pregnancy-induced alloantibodies in dogs. AB - BACKGROUND: It is controversial whether or not pregnant bitches become sensitized to red blood cell (RBC) antigens. HYPOTHESIS: Bitches do not develop alloantibodies to RBC antigens during gestation and can be used safely as blood donors. ANIMALS: The study group included 35 healthy female dogs with a prior history of 1 (n = 12), 2 (n = 14), or >or= 3 (n = 9) pregnancies. The control group consisted of 15 healthy female dogs without any history of pregnancy. METHODS: All dogs were blood typed for dog erythrocyte antigens (DEA) 1.1, 1.2, 3, 4, 5, and 7 using ethylenediaminetetraacetic acid blood samples and polyclonal antisera. Antibody screening was performed with serum and canine RBC panels of known blood type. An autocontrol and direct antiglobulin test were performed to rule out the presence of autoantibodies. RESULTS: The only alloantibodies identified were those against DEA 7 and the prevalence of anti-DEA 7 alloantibodies was similar in dogs with known history of pregnancy (11.4%) and in the control group (13.3%). CONCLUSIONS AND CLINICAL IMPORTANCE: These results confirm previous studies and clinical transfusion medicine experience. Naturally occurring anti-DEA 7 alloantibodies have been reported but their clinical relevance has not been shown. Pregnancy does not appear to sensitize dogs to RBC antigens. Consequently, dogs with prior history of pregnancy can be used safely as blood donors. Conversely, no additional pretransfusion compatibility studies would be required should these dogs themselves need to be transfused. PMID- 19645834 TI - Evaluation of a portable meter to measure ketonemia and comparison with ketonuria for the diagnosis of canine diabetic ketoacidosis. AB - BACKGROUND: The diagnosis of canine diabetic ketoacidosis (DKA) usually is based on measurement of urinary acetoacetate (ketonuria). In humans, this test is less sensitive and specific than blood 3-beta-hydroxybutyrate (ketonemia) evaluation. HYPOTHESIS: Ketonemia measurement using a portable meter is more accurate than ketonuria determination with a dipstick to diagnose canine DKA. ANIMALS: Seventy two client-owned diabetic dogs with ketonemia, ketonuria, or both. METHODS: Prospective observational study. Based on blood bicarbonate concentration and anion gap, dogs were divided into 2 groups: patients with DKA (n= 25); patients with diabetic ketosis (n= 47). Sensitivity, specificity, and positive and negative likelihood ratio (LR) at different cut-off points were determined for both ketonemia and ketonuria. Receiver operating characteristic (ROC) analysis was used to assess the accuracy of each diagnostic test to diagnose DKA. RESULTS: With regard to ketonemia, cut-off values of 2.3 and 4.3 mmol/L revealed 100% sensitivity and 100% specificity, respectively, whereas cut-off values of 2.8 and 3.5 mmol/L showed a -LR of 0.05 and a + LR of 13.16, respectively. With regard to ketonuria, a cut-off value of 1+ revealed 92% sensitivity, 40% specificity, and LR of 0.20, whereas a cut-off value of 3+ revealed 44% sensitivity, 94% specificity, and +LR of 6.89. The areas under the ROC curves for the ketonemia and ketonuria tests were significantly different (0.97 and 0.81, respectively, P= .003). CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of ketonemia is accurate and more effective than measurement of ketonuria to diagnose canine DKA. PMID- 19645835 TI - Possible emergence of drug-resistant variants of Babesia gibsoni in clinical cases treated with atovaquone and azithromycin. AB - BACKGROUND: There is no well-established treatment strategy for Babesia gibsoni infection. A new therapeutic protocol using atovaquone (ATV) and azithromycin (AZM) has been proposed, but there is concern about the possible induction of relapse and the emergence of ATV-resistant variants after treatment. OBJECTIVE: To evaluate the clinical use of combination therapy with ATV and AZM as a first line treatment of clinical B. gibsoni infection in dogs, and to investigate the emergence of ATV-resistant variants. ANIMALS: Eight B. gibsoni naturally infected dogs showing signs of acute onset of disease. METHODS: Retrospective case study. Eight clinical cases received combination therapy with ATV and AZM at Kagoshima University Veterinary Teaching Hospital during 2007-2008, and their clinical courses and clinicopathological parameters were evaluated. In addition, alterations in the cytochrome b (CYTb) gene of B. gibsoni were analyzed by polymerase chain reaction and DNA sequencing techniques. RESULTS: All of the dogs responded well to the treatment, with rapid improvement in their clinical condition and hematological parameters. However, 5 of the 8 dogs relapsed after treatment. Analysis of the CYTb gene strongly suggested the emergence of ATV resistant variants after treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: The combination of ATV and AZM can be used as a first-line treatment for dogs with babesiosis, but relapses occur. Attention should be paid to the possible in vivo selection of drug-resistant variants. PMID- 19645836 TI - Combination therapy with digoxin and diltiazem controls ventricular rate in chronic atrial fibrillation in dogs better than digoxin or diltiazem monotherapy: a randomized crossover study in 18 dogs. AB - BACKGROUND: Atrial fibrillation (AF) with excessively high ventricular rates (VR) occurs in dogs with advanced heart disease. Rate control improves clinical signs in these patients. Optimal drug therapy and target VR remain poorly defined. HYPOTHESIS: Digoxin-diltiazem combination therapy reduces VR more than either drug alone in dogs with high VR AF. ANIMALS: Eighteen client-owned dogs (>15 kg) with advanced heart disease, AF, and average VR on 24-hour Holter > 140 beats per minute (bpm). METHODS: After baseline Holter recording, dogs were randomized to digoxin or diltiazem monotherapy, or combination therapy. Repeat Holter evaluation was obtained after 2 weeks; dogs were then crossed over to the other arm (monotherapy or combination therapy) for 2 weeks and a third Holter was acquired. Twenty-four hour average VR, absolute and relative VR changes from baseline, and percent time spent within prespecified VR ranges (>140, 100-140, and <100 bpm) were compared. Correlations between serum drug concentrations and VR were examined. RESULTS: Digoxin (median, 164 bpm) and diltiazem (median, 158 bpm) decreased VR from baseline (median, 194 bpm) less than the digoxin-diltiazem combination (median, 126 bpm) (P < .008 for each comparison). With digoxin diltiazem, VR remained <140 bpm for 85% of the recording period, but remained >140 bpm for 88% of the recording period with either monotherapy. Serum drug concentrations did not correlate with VR. CONCLUSIONS AND CLINICAL IMPORTANCE: At the dosages used in this study, digoxin-diltiazem combination therapy provided a greater rate control than either drug alone in dogs with AF. PMID- 19645837 TI - Comparison of two regimens for the treatment of meningoencephalomyelitis of unknown etiology. AB - BACKGROUND: The optimal treatment for meningoencephalomyelitis of unknown etiology (MUE) remains unknown, despite the widespread use of a variety of immunosuppressive drugs. OBJECTIVE/HYPOTHESIS: To compare the efficacy of prednisolone combined with either vincristine and cyclophosphamide (COP group; n= 10) or with cytosine arabinoside (AraC group; n= 9). ANIMALS: Nineteen dogs with neurological deficits, neuroimaging, and cerebrospinal fluid abnormalities consistent with a diagnosis of MUE. METHODS: Prospective, blinded, and randomized clinical trial. Dogs fulfilling the inclusion criteria were randomly allocated to receive 1 drug regimen. RESULTS: Four of 10 dogs in the COP group and 5/9 in the AraC group survived > 12 months but neither the survival time nor the time-to treatment failure differed between the 2 groups. Treatment with COP resulted in an unacceptable incidence of adverse effects. CONCLUSIONS: The adverse effects of COP make it an unsuitable treatment for MUE. Although survival of animals treated with AraC was broadly similar to that reported in recently published studies describing this treatment, it remains unclear whether it confers any benefit over using prednisolone alone. PMID- 19645838 TI - Magnetic resonance imaging characteristics of necrotizing meningoencephalitis in Pug dogs. AB - BACKGROUND: The magnetic resonance imaging (MRI) characteristics of necrotizing meningoencephalitis (NME) are not well documented. OBJECTIVES: To describe common MRI features of NME, to compare the MRI features to histopathologic findings, and to determine whether or not MRI lesions are predictive of survival time. ANIMALS: Eighteen Pugs with NME. METHODS: Retrospective MRI case study of Pugs identified by a search of medical records at 6 veterinary institutions. Eighteen dogs met inclusion criteria of histopathologically confirmed NME and antemortem MRI exam. MRI lesions were characterized and compared with histopathology with the kappa statistic. Survival times were compared with MRI findings by use of Mann-Whitney U-tests and Spearman's rho. RESULTS: Twelve of 18 lesions were indistinctly marginated with mild parenchymal contrast enhancement. Prosencephalic (17/18) lesion distribution included the parietal (16/18), temporal (16/18), and occipital (16/18) lobes. There were cerebellar (4/18) and brainstem (3/18) lesions. Asymmetric lesions were present in both gray and white matter in all dogs. Falx cerebri shift was common (11/18), and 6 dogs had brain herniation. Leptomeningeal enhancement was present in 9/18 dogs. A moderate positive association was found between parenchymal contrast enhancement and both necrosis (kappa= 0.45; P= .045) and monocytic inflammation (kappa= 0.48; P= .025). Higher MRI lesion burden was correlated with longer time from disease onset to MRI (P= .045). MRI lesion burden did not correlate to survival time. CONCLUSIONS AND CLINICAL IMPORTANCE: Asymmetric prosencephalic grey and white matter lesions with variable contrast enhancement were consistent MRI changes in Pugs with confirmed NME. While not pathognomonic for NME, these MRI characteristics should increase confidence in a presumptive diagnosis of NME in young Pugs with acute signs of neurologic disease. PMID- 19645839 TI - Effects of aging on inner ear morphology in dogs in relation to brainstem responses to toneburst auditory stimuli. AB - BACKGROUND: Age-related hearing loss (ARHL) is the most common form of hearing loss in humans and is increasingly recognized in dogs. HYPOTHESIS: Cochlear lesions in dogs with ARHL are similar to those in humans and the severity of the histological changes is reflected in tone audiograms. ANIMALS: Ten geriatric dogs (mean age: 12.7 years) and three 9-month-old dogs serving as controls for histological analysis. METHODS: Observational study. Auditory thresholds were determined by recording brainstem responses (BERA) to toneburst auditory stimuli (1, 2, 4, 8, 12, 16, 24, and 32 kHz). After euthanasia and perfusion fixation, the temporal bones were harvested and processed for histological examination of the cochleas. The numbers of outer hair cells (OHCs) and inner hair cells (IHCs) were counted and the spiral ganglion cell (SGC) packing density and stria vascularis cross-sectional area (SVCA) were determined. RESULTS: A combination of cochlear lesions was found in all geriatric dogs. There were significant reductions (P .001) in OHC (42%, 95% confidence interval [CI]; 24-64%) and IHC counts (21%, 95% CI; 62-90%) and SGC packing densities (323, 95% CI; 216-290) in the basal turn, SVCA was smaller in all turns. The greatest reduction in auditory sensitivity was at 8-32 kHz. CONCLUSIONS AND CLINICAL IMPORTANCE: ARHL in this specific population of geriatric dogs was comparable histologically to the mixed type of ARHL in humans. The predominance of histological changes in the basal cochlear turn was consistent with the large threshold shifts observed in the middle- to high-frequency region. PMID- 19645841 TI - Relationship among plasma amino acids, C-reactive protein, illness severity, and outcome in critically ill dogs. AB - BACKGROUND: Alterations in circulating amino acids have been documented in animal models and in critically ill people but have not been evaluated in dogs with spontaneously occurring disease. HYPOTHESIS/OBJECTIVES: To compare amino acid concentrations in critically ill dogs and healthy controls and to investigate potential relationships among amino acids, markers of inflammation, illness severity, and clinical outcome. ANIMALS: Forty-eight critically ill dogs and 24 healthy control dogs. METHODS: Plasma was analyzed for amino acids and C-reactive protein (CRP) was measured in serum. The Fischer ratio (the molar ratio of branched chain amino acids [BCAA] to aromatic amino acids [AAA]) and survival prediction index (SPI2) were calculated. RESULTS: Median CRP concentrations were significantly higher in the critically ill dogs compared with controls (P < .001). Critically ill dogs had significantly lower concentrations of alanine (P= .001), arginine (P < .001), citrulline (P < .001), glycine (P < .001), methionine (P < .001), proline (P < .001), and serine (P= .001) but significantly higher concentrations of lysine (P= .02) and phenylalanine (P < .001; Table 1). This pattern resulted in a significantly lower Fischer ratio (P= .001) in the critically ill group. Median SPI2 score was significantly higher in dogs that survived (P= .03). Concentrations of arginine (P= .02), isoleucine (P= .01), leucine (P= .04), serine (P= .04), valine (P= .04), total BCAA (P= .03), and the Fischer ratio (P= .03) were significantly higher in survivors compared with nonsurvivors. CONCLUSIONS AND CLINICAL IMPORTANCE: Critically ill dogs have altered amino acid profiles and additional research to investigate potential benefits of amino acid supplementation is warranted. PMID- 19645840 TI - Hematology and serum biochemistry of feline immunodeficiency virus-infected and feline leukemia virus-infected cats. AB - BACKGROUND: Hematological and biochemical values in cats naturally infected by feline immunodeficiency virus (FIV) or feline leukemia virus (FeLV) are not completely documented. OBJECTIVE: Report differences in laboratory values between FIV- or FeLV-infected and noninfected and between FIV- and FeLV-infected cats. ANIMALS: Three thousand seven hundred and eighty client-owned cats tested for FIV and FeLV. METHODS: Retrospective study. Evaluation of clinicopathologic changes in cats with defined FIV and FeLV status and for which laboratory data were available. RESULTS: FIV-infected cats were more likely to be neutropenic (odds ratio [OR]=3.6, 95% confidence interval [95% CI] 2.1-6.2, P < .0001) and had lower serum activities of aspartate aminotransferase and glutamate dehydrogenase than control cats; serum total protein (8.1 +/- 1.1 versus 7.6 +/- 1.3 g/dL, P < .001) and gamma-globulin concentrations (2.2 +/- 1.1 versus 1.7 +/- 1.3 g/dL, P < .001) were higher than in uninfected cats. Compared with controls, FeLV-infected cats had a higher risk of anemia (OR = 3.8, 95% CI 2.4-6.0, P < .0001), thrombocytopenia (OR = 5.0, 95% CI 3.0-8.4, P < .0001), neutropenia (OR = 3.6, 95% CI 2.1-6.1, P < .0001), lymphocytosis (OR = 2.8, 95% CI 1.6-4.8, P= .0002), and lower erythrocyte counts (6.13 +/- 2.95 x 10(3) versus 8.72 +/- 2.18 x 10(3)/microL, P < .001), thrombocyte counts (253.591 +/- 171.841 x 10(3) versus 333.506 +/- 156.033 x 10(3)/microL, P < .001), hematocrit (28.72 +/- 12.86 versus 37.67 +/- 8.90%, P < .001), hemoglobin and creatinine concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Hematologic abnormalities are common in FeLV-infected but not in FIV-infected cats. Clinicopathologic abnormalities are less frequent in FIV-infected cats and might reflect an unspecific immunologic response. PMID- 19645842 TI - Asparaginase and MOPP treatment of dogs with lymphoma. AB - BACKGROUND: Dogs with multicentric lymphoma are treated with various cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy protocols with variable success. OBJECTIVES: To describe the progression-free survival (PFS) time and overall survival time (OST) of dogs with T-cell lymphoma or hypercalcemic lymphoma treated with L-asparaginase and mechlorethamine, vincristine, prednisone, procarbazine (MOPP). ANIMALS: Fifty dogs with T-cell lymphoma, hypercalcemic lymphoma, or both treated at 3 referral veterinary hospitals. METHODS: Retrospective study. Case were selected based on histologic or cytologic diagnosis of lymphoma; presence of the T-cell phenotype, presence of hypercalcemia or both; and absence of previous chemotherapy. The T cell phenotype was determined by flow cytometry, immunocytochemistry, immunohistochemistry, or polymerase chain reaction of antigen receptor rearrangement. RESULTS: The overall response rate was 98% (78% complete response, 20% partial response). The median PFS for the entire study population was 189 days with 25% PFS at 939 days. The median OST for the entire study population was 270 days with 25% surviving 939 days. Twenty percent of the dogs required hospitalization for treatment related complications. CONCLUSIONS AND CLINICAL IMPORTANCE: L-Asp/MOPP chemotherapy might result in longer PFS and OST for dogs with multicentric T-cell lymphoma, dogs with hypercalcemic lymphoma or both, than achieved with CHOP. PMID- 19645843 TI - Influence of age on surfactant isolated from healthy horses maintained on pasture. AB - BACKGROUND: Surfactant alterations are described in horses after exercise, anesthesia, and prolonged transport, in horses with recurrent airway obstruction, and in neonatal foals. The effect of horse age or bronchoalveolar lavage fluid (BALF) sample characteristics on surfactant is unknown. OBJECTIVES: To evaluate surfactant phospholipid composition and function in healthy horses, and to investigate the influence of age and BALF sample characteristics on surfactant. ANIMALS: Seventeen healthy horses 6-25 years of age maintained on pasture year round. METHODS: BALF was collected by standard procedures and was assessed for recovery volume, nucleated cell count (NCC), and cytology. Cell-free BALF was separated into crude surfactant pellet (CSP) and surfactant supernatant (Supe) by ultracentrifugation. Phospholipid and protein content were determined from both fractions. CSP phospholipid composition was analyzed by high-performance liquid chromatography with an evaporative light scatter detector. Surface tension of CSP was evaluated with a pulsating bubble surfactometer. Regression analysis was used to evaluate associations between age, BALF sample characteristics, and surfactant variables. RESULTS: Results and conclusions were derived from 15 horses. Increasing age was associated with decreased phospholipid content in CSP but not Supe. Age did not affect protein content of CSP or Supe, or surfactant phospholipid composition or function. Age-related surfactant changes were unaffected by BALF recovery percentage, NCC, and cytological profile. CONCLUSIONS AND CLINICAL IMPORTANCE: Older horses have decreased surfactant phospholipid content, which might be because of age-related pulmonary changes. Surfactant composition is unaffected by BALF sample characteristics at a BALF recovery percentage of at least 50%. PMID- 19645844 TI - Lack of detectable equine herpesviruses 1 and 2 in paraffin-embedded specimens of equine sarcoidosis. AB - BACKGROUND: Equine sarcoidosis is a rare, multisystemic, noncaseating, granulomatous and lymphoplasmacytic disease of unknown etiology. A recent report described a horse with granulomatous skin disease displaying histologic, electron microscopic, and polymerase chain reaction (PCR) findings consistent with equine herpesvirus 2 (EHV-2). OBJECTIVE: To investigate the presence of EHV-2 and equine herpesvirus 1 (EHV-1) in 8 horses with sarcoidosis. ANIMALS: Eight horses with sarcoidosis, reported previously. METHODS: Retrospective study. PCR assays of the tissues were performed to detect DNA associated with EHV-1 and EHV-2. For both herpesviruses the target was their respective glycoprotein B gene. Positive controls consisted of DNA from viral cultures of culturettes from naturally occurring respiratory infections of EHV-1 and EHV-2. RESULTS: The PCR analyses for both equine herpesviruses' DNA were negative in all 8 horses. CONCLUSION: The failure to detect DNA from EHV-1 and EHV-2 in paraffin-embedded skin of these 8 horses does not discount EHV-1 or EHV-2 as causing some cases of ES, but lends support to the presumably multifactorial etiologic nature of the disease. PMID- 19645845 TI - Mixed inheritance of equine recurrent airway obstruction. AB - BACKGROUND: Mode of inheritance of equine recurrent airway obstruction (RAO) is unknown. HYPOTHESIS: Major genes are responsible for RAO. ANIMALS: Direct offspring of 2 RAO-affected Warmblood stallions (n = 197; n = 163) and a representative sample of Swiss Warmbloods (n = 401). METHODS: One environmental and 4 genetic models (general, mixed inheritance, major gene, and polygene) were tested for Horse Owner Assessed Respiratory Signs Index (1-4, unaffected to severely affected) by segregation analyses of the 2 half-sib sire families, both combined and separately, using prevalences estimated in a representative sample. RESULTS: In all data sets the mixed inheritance model was most likely to explain the pattern of inheritance. In all 3 datasets the mixed inheritance model did not differ significantly from the general model (P= .62, P= 1.00, and P= .27) but was always better than the major gene model (P < .01) and the polygene model (P < .01). The frequency of the deleterious allele differed considerably between the 2 sire families (P= .23 and P= .06). In both sire families the displacement was large (t= 17.52 and t= 12.24) and the heritability extremely large (h(2)= 1). CONCLUSIONS AND CLINICAL RELEVANCE: Segregation analyses clearly reveal the presence of a major gene playing a role in RAO. In 1 family, the mode of inheritance was autosomal dominant, whereas in the other family it was autosomal recessive. Although the expression of RAO is influenced by exposure to hay, these findings suggest a strong, complex genetic background for RAO. PMID- 19645847 TI - Molecular evidence for persistence of Anaplasma phagocytophilum in the absence of clinical abnormalities in horses after recovery from acute experimental infection. AB - BACKGROUND: Anaplasma phagocytophilum infects several mammalian species, and can persist in sheep, dogs, and calves. However, whether this organism persists in horses or induces long-term clinical abnormalities is not known. OBJECTIVES: To evaluate whether A. phagocytophilum can persist in horses and to document clinical findings for 3 months after complete recovery from acute disease. ANIMALS: Five clinically normal adult horses that had recovered spontaneously from experimentally induced acute disease caused by a Swedish equine isolate of A. phagocytophilum. METHODS: Horses were monitored for up to 129 days post inoculation (PI) by daily clinical examination and at least alternate day blood sampling for evidence of A. phagocytophilum on polymerase chain reaction (PCR) and blood smears. All horses were euthanized and underwent postmortem examination. RESULTS: All horses were periodically PCR positive after recovery from acute infection. Before day 66 PI 2 horses were persistently PCR negative whereas 3 horses were intermittently PCR positive. Subsequently, 4 of 5 horses were intermittently PCR positive, particularly after stress mimicking interventions. One animal was positive immediately before postmortem examination. Clinical abnormalities related to persistence of anaplasma were not observed. No specific changes were found at postmortem examination, and all sampled tissues from all horses were negative on PCR for A. phagocytophilum. CONCLUSIONS AND CLINICAL IMPORTANCE: Infection with A. phagocytophilum can persist in the horse for at least 129 days. However, the continued presence of the organism is not associated with detectable clinical or pathological abnormalities. PMID- 19645846 TI - Reproducibility of airway responsiveness in horses using flowmetric plethysmography and histamine bronchoprovocation. AB - BACKGROUND: Inflammatory airway disease has a high prevalence in horses, but is often a diagnostic challenge. Flowmetric plethysmography and histamine bronchoprovocation (FP/HBP) is a simple and effective tool for diagnosis, but reproducibility of these measurements made over time has not been established. HYPOTHESIS: We hypothesize that the measurement of airway responsiveness in horses using FP/HBP is consistent over both short and long periods of time. ANIMALS: Twenty-nine healthy adult horses from 2 university herds. METHODS: In this prospective experimental study, airway responsiveness was determined in each horse at day 0 (baseline [BL]) with FP/ HBP, using PC35 (provocative concentration of histamine needed to increase Delta(flow) by 35%) as a measure of airway responsiveness. Each horse was re-tested 1-4 weeks after BL (short-term [ST]) and again at 3-12 months after BL (long-term [LT]). RESULTS: In the ST period, 23/27 (85%) of the horses had a PC35 that was within 1 doubling concentration of histamine of their BL value, with a mean change of 0.52 doubling concentrations (95% CI 0.26-0.79, range 0-2.06). For the LT data, 19/26 (73%) of horses were within 1 doubling concentration of their BL value, with a mean change of 0.81 doubling concentrations (95% CI 0.45-1.17, range 0.14-3.10). There was no significant difference in reproducibility between the 2 groups of subjects. CONCLUSIONS AND CLINICAL IMPORTANCE: Repeated measurements of airway responsiveness obtained with FP/HBP show acceptable reproducibility over time periods up to a year. However, caution must be used when testing horses when ambient air temperature is low. PMID- 19645849 TI - Antemortem diagnosis of polyneuritis equi. PMID- 19645848 TI - Methods and reliability of tissue Doppler imaging for assessment of left ventricular radial wall motion in horses. AB - BACKGROUND: Noninvasive assessment of left ventricular (LV) function is incompletely studied in horses. OBJECTIVES: The goals of this study were to investigate the feasibility, techniques, and reliability of tissue Doppler imaging (TDI) for characterization of LV radial wall motion in healthy horses. ANIMALS: Three Standardbreds, 3 Thoroughbreds; age 8-14 years; body weight 517 606 kg. METHODS: Repeated echocardiographic examinations were performed by 2 observers in unsedated horses using TDI. Test reliability was determined by estimating measurement variability, within-day interobserver variability, and between-day interobserver and intraobserver variability of all echocardiographic variables. Variability was expressed as coefficient of variation (CV) and the absolute value below which the difference between 2 measurements will lie with 95% probability. RESULTS: Assessment of LV radial wall motion by TDI was feasible in all horses. Measurement variabilities were very low (CV < 5%) to low (CV 5 15%) for most variables. Within-day interobserver variability as well as between day interobserver and intraobserver variabilities were low to moderate (CV 16 25%) for most variables. All pulsed-wave TDI variables of systolic LV function showed very low to low variability, whereas some of the variables of LV diastolic and LA function showed moderate to high (CV > 25%) variability. Pulsed-wave TDI variables appeared more reliable than color TDI variables. CONCLUSIONS AND CLINICAL IMPORTANCE: Measurement of TDI indices of LV function is feasible and reliable in adult Standardbred and Thoroughbred horses. The clinical relevance of LV function assessment by TDI remains to be determined. PMID- 19645851 TI - Silver-loaded seaweed-based cellulosic fiber improves epidermal skin physiology in atopic dermatitis: safety assessment, mode of action and controlled, randomized single-blinded exploratory in vivo study. AB - BACKGROUND: The epidermal part of the skin is the major interface between the internal body and the external environment. The skin has a specific physiology and is to different degrees adapted for protection against multiple exogenous stress factors. Clothing is the material with the longest and most intensive contact to human skin. It plays a critical role especially in inflammatory dermatoses or skin conditions with an increased susceptibility of bacterial and fungal infections like atopic dermatitis. Previously, we have shown a dose dependent antibacterial and antifungal activity of silver-loaded seaweed-based cellulosic fibres. AIM OF THE STUDY: We studied the mode of action of silver loaded seaweed-based cellulosic fiber and performed a broad safety assessment. The principal aim was to analyse the effects of wearing the textile on epidermal skin physiology in 37 patients with atopic dermatitis in a controlled, randomized single-blinded in vivo study. Furthermore, the sensitization potential was tested in a patch test in 111 panellists. RESULTS: We could demonstrate in vitro a dose dependent scavenging of induced reactive oxygen species by silver-loaded seaweed based cellulosic fibers. Safety assessment of these fibres showed no detectable release of silver ions. Furthermore, ex vivo assessment after 24 h application both in healthy volunteers and patients with atopic dermatitis by sequential tape stripping and subsequently raster electron microscopy and energy dispersive microanalysis analysis revealed no detectable amounts of silver in any of stratum corneum layers. Serum analysis of silver showed no detectable levels. The in vivo patch testing of 111 volunteers revealed no sensitization against different SeaCell Active (SeaCell GmbH, Rudolstadt, Germany) containing fabrics. The in vivo study on 37 patients with known atopic dermatitis and mild-to-moderate eczema on their arms were randomly assigned to either silver-loaded seaweed fibre T-shirts or to cotton T-shirts for 8 weeks. A significant reduction in Staphylococcus aureus colonization was detectable for the silver T-shirts compared with cotton T-shirts without any changes in non-pathogenic surface bacteria colonization. Furthermore, a more pronounced improvement in barrier function (transepidermal water loss) was observed in mildly involved eczema areas during the first 4 weeks of the study. Stratum corneum hydration and surface pH improved in both treatment groups over time. CONCLUSION: The tested silver-loaded seaweed fibre can be regarded as safe and seams to be suited for application in bio-active textiles in atopic dermatitis based on its positive in vivo activity. PMID- 19645852 TI - Does erythropoietin modulate human hair follicle melanocyte activities in situ? AB - Erythropoietin (EPO) is now appreciated for not only drive erythopoiesis, but also to exert additional functions. Since we had previously shown that human hair follicles (HFs) are both an extra-renal source and an extra-medullary target of EPO, we have now studied whether one such function is the regulation of HF pigmentation. Human anagen VI HFs were treated with EPO (100 IU/ml) in serum-free organ culture. Unexpectedly, we noticed greatly divergent pigmentary effects of EPO, since both up- and down-regulation of HF melanin content and tyrosinase activity in situ was seen in HF derived from different individuals. These divergent effects could not be attributed to differences in skin regions, the total HF melanocyte number or specific traits of individual HF donors. Our pilot study provides first evidence suggesting that EPO may modulate normal human melanocyte functions under physiologically relevant conditions in situ. PMID- 19645853 TI - Why do melanomas get so dark? AB - Cutaneous malignant melanomas often exhibit pigmented regions that are darker than the surrounding skin. While melanoma cells are the original source of the melanin, keratinocytes and melanophages also contribute to the tumor colour because they contain melanin obtained from melanoma cells. However, little is known of the origin of darkly pigmented melanoma cells or of the molecular pathways regulating their melanin production. Here we discuss observations that dark melanoma cells emerge from within populations of melanoma in situ and that, in addition to producing abundant dark pigment, they appear to be undergoing autophagy. Moreover, autophagy appears to be a common trait of invasive melanoma cells in the dermis. The underlying cause of this phenomenon may stem from aberrant production of glycosylation structures known as beta1,6-branched oligosaccharides. Our studies of dark cutaneous melanomas were prompted by analyses of experimental mouse macrophage-melanoma hybrids fused in the laboratory. Like melanoma cells in cutaneous malignant melanoma, experimental hybrids also displayed abundant dark pigment and autophagy, and had high levels of beta1,6-branched oligosaccharides. Whether or not darkly pigmented malignant melanoma cells originate from fusion with macrophages in vivo remains to be determined. In any event, pigmentation in melanoma, long considered as a secondary aspect of the malignancy, may be a visible warning that the cells have gained competence for invasion and metastasis. PMID- 19645854 TI - Zileuton prevents the activation of the leukotriene pathway and reduces sebaceous lipogenesis. AB - Arachidonic acid (AA) activates the 5-lipoxygenase, induces leukotriene-B(4) (LTB(4)) synthesis, enhances interleukin-6 (IL-6) release and increases intracellular neutral lipids in human sebocytes. Moreover, the enzymes of LTB(4) biosynthesis are activated in acne-involved sebaceous glands. Zileuton a 5 lipoxygenase inhibitor, reduces the number of inflammatory acne lesions and lipogenesis in patients with acne. In this study, we investigated the activity of zileuton on LTB(4) generation, lipid content and IL-6 and -8 release from human SZ95 sebocytes in vitro. Pretreatment with zileuton partially prevented the AA induced LTB(4) and IL-6 release and increased neutral lipid content. IL-6 release and neutral lipid content were also reduced under long-term zileuton treatment. In conclusion, zileuton prevents the activation of the leukotriene pathway and enhancement of lipogenesis by AA in human sebocytes in vitro. PMID- 19645855 TI - T-lymphocyte-induced, Fas-mediated apoptosis is associated with early keratinocyte differentiation. AB - The development of eczematous lesions is thought to be due in part to a breakdown in skin barrier function as a result of T lymphocytes (T cells) invading the skin causing epidermal keratinocyte apoptosis. In this study, we investigated the interaction of T cells and keratinocytes on apoptosis and terminal differentiation using an in vitro co-culture system. Experiments were performed using the HaCaT keratinocyte cell line or normal human epidermal keratinocytes. Activated human peripheral blood-derived T cells were found to induce Fas dependent keratinocyte apoptosis by up to sixfold. Increased Fas was associated with increased IFN-gamma. The T-cell apoptotic signal was found to target preferentially keratinocytes in the very early stages of terminal differentiation, such as those with low levels of alpha 6-integrin expression, and result in subsequent increased caspase 3 activity. This observation was accompanied by a marked increase in keratinocyte ICAM-1 expression and its ligand LFA-1 on T cells. Our data suggest that T cells may initiate the onset of keratinocyte terminal differentiation making them more susceptible to Fas dependent cell death signals delivered by the T cells. PMID- 19645856 TI - Regression of established subcutaneous B16-F10 murine melanoma tumors after gef gene therapy associated with the mitochondrial apoptotic pathway. AB - Novel treatment modalities, including gene therapy, are needed for patients with advanced melanoma. We evaluated whether the gef gene, a suicide gene from Escherichia coli, had a significant cytotoxic impact on melanoma in vivo. First, we used a non-viral gene delivery approach (pcDNA3.1/gef) to study the inhibition of melanoma cells (B16-F10) proliferation in vitro. Secondly, we used direct intra-tumoral injection of pcDNA3.1/gef complexed with jetPEI to deliver gef cDNA to rapidly growing murine melanomas. We demonstrated that gef gene not only has an antiproliferative effect on B16-F10 cells in vitro, but also induces an important decrease in melanoma tumor volume (77.7% in 8 days) in vivo. Interestingly, after gef gene treatment, melanoma showed apoptosis activation associated with the mitochondrial pathway, suggesting that the induction of this death mechanism may be an effective strategy for its treatment. Our in vivo results indicate that gef gene might become a suitable therapeutic strategy for patients with advanced melanoma. PMID- 19645858 TI - Leukotrienes are auto-/paracrine factors in the bovine corpus luteum: an in vitro study. AB - The aim of this study was to determine leukotrienes (LTs) functions in the bovine corpus luteum (BCL) during the oestrous cycle. In steroidogenic CL cells we examined the effect of luteotropic [LH, prostaglandin E(2) (PGE(2))] and luteolytic (PGF(2alpha), cytokines) factors on: the levels of LTB(4) and C(4), the expression of 5-lipoxygenase (LO), LT receptors type I (LTR-I) and LTR-II, and the effects of LTB(4) and C(4) stimulations on the levels of progesterone (P4), PGE(2), F(2alpha) and nitric oxide (NO) metabolites. Both luteolytic and luteotropic factors stimulated 5-LO expression on days 2-4 and 17-19 of the cycle. Leukotriene receptors type I expression increased after PGE(2) and tumour necrosis factor alpha with interferon gamma (TNF/IFN) stimulation on days 2-4 of the cycle. Leukotriene receptor type II expression increased after PGE(2alpha) and TNF/IFN stimulation on days 2-4 and 17-19 of the cycle, and LTR-II expression on days 8-10 of the cycle was unchanged after cell stimulation with any factor. Leukotriene B(4) level increased after BSC incubation with luteotropic factors during all examined days of the cycle and after cytokine stimulation at early- and mid-luteal stages, whereas luteolytic factors stimulated LTC(4) secretion over the entire cycle. Leukotriene B(4) stimulated P4 secretion at the mid-luteal stage and stimulated NO secretion during all examined phases. Leukotriene B(4) stimulated PGE(2) secretion at the early- and mid-luteal stage. Leukotriene C(4) inhibited P4 secretion at the mid- and regressing-luteal stage, stimulated NO (entire cycle) and PGF(2alpha) at mid- and regressing-luteal phases. Leukotrienes modulate steroidogenic cells functions, depending on the stage of the cycle. Leukotriene B(4) plays a luteotropic role stimulating P4 and PGE(2) secretions; LTC(4) stimulates the secretion of luteolytic factors and enhances the luteolytic cascade within BCL. PMID- 19645857 TI - Expression of oestrogen receptor alpha and oestrogen receptor beta in the uterus of the pregnant swine. AB - The uterus is a well-known target of endocrine, paracrine and autocrine acting molecules among which steroid hormones are of special importance. The objective of our work was to localize oestrogen receptors (ERalpha and ERbeta) mRNA and protein in the pig uterus throughout pregnancy (10, 18, 32, 50, 71, 90 days post coitum) using RT-PCR, Western-blot and immunohistochemistry. The present study is the first one to demonstrate the presence of ERs protein in the porcine uterus not only at the beginning but also at mid- and late pregnancy. In the pregnant swine, ERalpha was immunolocalized in the luminal epithelium (LE) and glandular epithelium (GE) and the myometrium of the uterus with differences in the intensity of staining at different stages of pregnancy studied. The LE and GE of pregnant swine stained for ERbeta regardless of the day of pregnancy examined, whereas only a few cells within the myometrium showed a weak immunoreactivity. Western blot analysis confirmed the presence of ERalpha and ERbeta proteins on all investigated days of gestation. The expression of ERalpha and ERbeta mRNA was detected by RT-PCR in all examined samples corresponding to each of the consecutive stages of pregnancy. The obtained results show that ERalpha is more abundant in comparison to ERbeta within the porcine pregnant uterus. The presence of ERalpha and ERbeta in all compartments of the pig uterus during pregnancy may indicate direct action of oestrogens on proliferation and differentiation of these cells. PMID- 19645860 TI - Short-term undernutrition affects final development of ovulatory follicles in sheep synchronized for ovulation. AB - The objective of this study was to determine, in sheep, the effect of a short term undernutrition on growth dynamics and competence of pre-ovulatory follicles. Synchronization of sexual cycles and induction of ovulation were performed, with progestagens and gonadotrophins, in 14 adult female sheep. Morphological characteristics and developmental competence of ovarian follicles to achieve ovulation were determined by imaging techniques (ultrasonography and laparoscopy) and blood sampling. All the animals ovulated and mean ovulation rates were similar between groups (2.0 +/- 0.6 corpora lutea in control ewes and 2.2 +/- 0.8 in undernourished sheep). However, nutritional restriction, even during a short period, was related to the presence of large follicles in static growing phase which, despite reaching ovulation, persisted static during the induced follicular phase and evidenced functional alterations as there was no inhibition of the development of subordinate follicles. Thus, this study suggests the existence of deleterious effects from short-term undernutrition on functionality of pre ovulatory follicles, which can compromise fertility. PMID- 19645859 TI - Site of intrauterine artificial insemination in the bitch does not affect sperm distribution within the uterus. AB - The aim of this study was to evaluate the distribution of frozen-thawed spermatozoa within the uterine lumen and oviducts following intrauterine laparoscopic deposition at two sites. Twelve bitches of unknown reproductive history were randomly distributed into two groups. Semen (3 ml containing 300 * 10(6) frozen-thawed spermatozoa) was infused at the uterine body (UB group) or at the cranial tip of the left uterine horn. A 22-G catheter was used to access the uterine lumen. Sperm cell distribution was evaluated after ovariohysterectomy performed 3 h after artificial insemination (AI). There was no difference between groups in mean time to perform AI. Spermatozoa were detected in all uterine segments, including the tip of both horns, but none was detected in the oviduct. The 22-G catheter facilitated deposition of semen in the uterine lumen, particularly at the UB site. Sperm cell distribution occurred evenly along both horns, independent of the site of semen deposition. PMID- 19645866 TI - Establishing a diagnosis of pleural effusion due to heart failure. PMID- 19645868 TI - Airway inflammation and anti-protease defences rapidly improve during treatment of an acute exacerbation of COPD. AB - BACKGROUND AND OBJECTIVE: There are few data on the short-term natural history of airway inflammation during severe episodes of acute exacerbation of COPD (AECOPD). An observational study was performed to determine how rapidly conventional treatment improves airway inflammation in patients admitted to hospital with AECOPD. METHODS: Twenty-four consecutive patients with AECOPD were recruited and changes in sputum inflammatory indices were assessed after 2 and 4 days of treatment. The primary end-points included presence of bacteria and viruses, changes in sputum total cell counts (TCC) and polymorphonuclear leukocyte (PMN) differential counts, and levels of secretory leukocyte protease inhibitor (SLPI), IL-8 and TNF-alpha. RESULTS: All patients received oral corticosteroids and 17 (71%) were also treated with oral antibiotics. A bacterial or viral pathogen was isolated from 12 patients (50%), and Aspergillus fumigatus was isolated from one. A positive bacterial culture was associated with increased sputum TCC and PMN count (P < 0.05), as well as higher levels of IL-8 and TNF alpha (P < 0.05), and a trend towards lower sputum SLPI levels (P = 0.06). Sputum PMN numbers fell by 70% within the first 48 h of admission (P < 0.05), accompanied by an increase in sputum SLPI (P < 0.001) and reductions in the levels of TNF-alpha (P < 0.005) and IL-8 (P = 0.06), with no further significant change at 4 days. CONCLUSIONS: Conventional treatment for severe AECOPD is associated with rapid reduction of neutrophilic inflammation and improvement in anti-protease defences. PMID- 19645867 TI - HIV-associated opportunistic pneumonias. AB - Among the HIV-associated pulmonary complications, opportunistic pneumonias are major causes of morbidity and mortality. The spectrum of HIV-associated opportunistic pneumonias is broad and includes bacterial, mycobacterial, fungal, viral and parasitic pneumonias. Bacterial pneumonia is the most frequent opportunistic pneumonia in the United States and Western Europe while tuberculosis is the dominant pathogen in sub-Saharan Africa. With the use of combination antiretroviral therapy and prophylaxis, the incidence of Pneumocystis pneumonia (PCP) has declined. Nevertheless, PCP continues to occur in persons who are unaware of their HIV infection, those who fail to access medical care, and those who fail to adhere to antiretroviral therapy or prophylaxis. Although pneumonias due to Cryptococcus neoformans, Histoplasma capsulatum, Coccidioides immitis, cytomegalovirus and Toxoplasma gondii are less frequent, their presence in the lung is often indicative of disseminated disease and is associated with significant mortality. PMID- 19645869 TI - Protective effects of a superoxide dismutase/catalase mimetic compound against paraquat pneumotoxicity in rat lung. AB - BACKGROUND AND OBJECTIVE: EUK-134 is one of the most promising of the superoxide dismutase (SOD)/catalase mimetic compounds. The antioxidant effects of EUK-134 were tested in a rat model of paraquat pneumotoxicity. METHODS: Male Wistar rats (n = 72) were divided into three groups: group 1, controls; group 2, paraquat alone; group 3, paraquat + EUK-134. Paraquat dichloride was administered per os at a dose of 80 mg/kg. EUK-134 was injected intraperitoneally at 10 mg/kg 2 h before the paraquat and again 4 h later at 5 mg/kg. RESULTS: On days 1, 3 and 5 after treatment with paraquat alone the LDH activity increased (P = 0.0001, P = 0.00001 and P = 0.03, respectively), and the total protein content increased (P = 0.00002, P = 0.001 and P = 0.01, respectively). The levels of acid phosphatase (AcP) in BAL fluid increased on days 1 and 3 (P = 0.006 and P = 0.04). In lung homogenates paraquat alone increased SOD activity on day 1 and decreased it on days 3 and 5. Combined treatment with paraquat and EUK-134 elevated LDH activity on day 3 (significantly less than paraquat alone) and day 5, elevated the total protein content on day 5 only, and did not change AcP activity. The combination of both agents did not alter SOD activity and decreased catalase activity on day 5 significantly less than treatment with paraquat alone (P = 0.05). CONCLUSIONS: EUK-134, a superoxide dismutase/catalase mimetic compound decreased the pneumotoxic effect of paraquat in rats. PMID- 19645870 TI - Patients with mild-to-moderate asthma may develop clinically significant chronic obstructive pulmonary disease. AB - BACKGROUND AND OBJECTIVE: Little is known about the aetiology and clinical characteristics of COPD among people who have never smoked. METHODS: A case control study was conducted to describe the potential risk factors for clinically significant COPD among smokers and people who had never smoked. Medical record reviews and scoring of high-resolution computed tomography (HRCT) findings were performed in patients with clinically significant COPD (defined as having post bronchodilator FEV(1)/FVC < 0.7 and FEV(1) < 60% of the predicted values). Pathological analyses were performed in some patients following autopsy. RESULTS: Among the 9493 subjects screened, 424 (4.5%) were diagnosed with clinically significant COPD. Forty-nine (11.6% of clinically significant COPD) were never smokers (NSCOPD), and a comparative group of 98 smoking patients with COPD was randomly selected (SMCOPD). NSCOPD was characterized by predominantly female sex (87.8%) and a high prevalence of physician-diagnosed asthma (61.2%). Similar levels of reduction in %FEV(1) and %FEF(25-75%) were found in NSCOPD and SMCOPD, but there were higher %DL(CO) values and fewer low attenuation areas on HRCT in NSCOPD. More than half of the NSCOPD patients without a history of asthma had features of asthma. More than one-third of NSCOPD patients with an asthma history had never had a severe attack. At autopsy, both NSCOPD and SMCOPD showed wall thickening and inflammatory cell infiltration in small airways, and the number of CD4(+)-T cells was increased in NSCOPD. CONCLUSION: In elderly Japanese, COPD among never smokers is largely attributable to asthma. Airflow limitation in NSCOPD results from small airway disease (airway predominant phenotype) rather than parenchymal destruction (emphysematous phenotype). PMID- 19645871 TI - Diffuse alveolar haemorrhage due to 5-nitroimidazole treatment. AB - Diffuse alveolar haemorrhage (DAH) is indicated by the presence of red blood cells, fibrin and haemosiderin deposits in the lung parenchyma. We present a case of DAH in a 25-year-old male following 5-nitroimidazole treatment. The first episode of haemoptysis occurred following metronidazole treatment 10 months previously. The second episode of haemoptysis occurred following ornidazole treatment 10 days before admission. During his first admission, the patients haemoglobin concentration decreased to 40 g/L. The CXR was normal, whereas high resolution CT of the lungs revealed a diffuse acinonodular pattern. Serological tests for connective tissue diseases were negative. The haemorrhagic appearance of the BAL fluid obtained during fibreoptic bronchoscopy was consistent with DAH. Microbiological analysis of the BAL fluid showed no evidence for bacterial or mycobacterial infection. Haemosiderin laden macrophages were detected in BAL fluid and lung biopsy specimens. DAH due to use of 5-nitroimidazole was diagnosed on the basis of the patient's previous history and complete recovery following treatment with corticosteroid. This is the first reported case of DAH due to use of 5-nitroimidazole. Physicians should be aware of this side-effect when prescribing this group of drugs to patients. PMID- 19645872 TI - Coccidioidomycosis as a rare cause of pneumonia in non-endemic areas: a short exposure history should not be ignored. AB - Coccidioidomycosis is endemic in the south-western USA. Two cases of infection in travellers returning to Hong Kong are described. A previously healthy patient who had travelled to an endemic area for a short time was successfully treated with fluconazole. A second patient with comorbidities and more prolonged exposure had disseminated and eventually fatal disease, despite prolonged administration of anti-fungal agents. Although coccidioidomycosis is a rare disease in Hong Kong, it should always be considered when there is a relevant travel history. Even a short period of travel to an endemic area should alert clinicians to this possibility when managing patients with severe pneumonia, especially those with multi-organ involvement. On the other hand, in patients with comorbidities, even aggressive and prolonged anti-fungal therapy may not guarantee a successful outcome. PMID- 19645873 TI - Basic and clinical aspects of vertigo and dizziness. Preface. PMID- 19645874 TI - Vestibular and proprioceptive contributions to human balance corrections: aiding these with prosthetic feedback. AB - Movement strategies controlling quiet stance and rapid balance corrections may have common characteristics. We investigated this assumption for lower leg proprioceptive loss (PL), peripheral vestibular loss (VL), and healthy controls. Our underlying hypothesis was that changes in movement-strategy modulation following sensory loss would improve with prosthetic biofeedback. Quiet stance was measured under different sensory conditions and compared to corrections induced by multidirection support-surface tilts. Response synergies were assessed using electromyography recordings from several muscles. Biofeedback of trunk sway during gait and stance tasks used lower trunk rotations to drive head-band mounted vibro-tactile and auditory actuators. Strategies of quiet stance were different for roll and pitch, depending on sensory conditions. Simultaneously acting strategies were observed for low- and high-frequency sway. PL induced strategies different from those of VL and controls. VL strategies were identical to those of controls but with greater amplitudes. Tilt perturbation movement strategies were similar to high-frequency strategies of quiet stance- multisegmental. VL induced increased trunk pitch and roll responses with hypermetric trunk muscle responses and hypometric knee responses but unchanged synergies. Increasing PL up the legs caused changed synergies. Biofeedback reduced stance body sway in VL and elderly subjects. In conclusion, several movement strategies underlie quiet stance with high-frequency strategies being common to those of perturbed stance. PL changes both movement strategies and synergies, whereas VL only causes pathological changes to the modulation depth. Thus, VL is more easily rectified using trunk sway positional biofeedback. PMID- 19645875 TI - The configuration and attachment of the utricular and saccular maculae to the temporal bone. New evidence from microtomography-CT studies of the membranous labyrinth. AB - High-resolution X-ray microtomography (micro-CT) was used to show the spatial configuration of the membranous labyrinth of the fixed guinea pig and human inner ear. Whole temporal bones were en bloc stained in 2% osmium tetroxide for 2 days or more to allow the osmium to attach to the membranes of the inner ear, and then scanned with a Skyscan 1172 micro-CT with highest resolution of 8 microns. The scans were segmented and reconstructed. The findings for guinea pigs and humans are similar. The saccular macula is closely attached to the curved medial wall of the temporal bone, but in both human and guinea pig the utricular macula is attached to the temporal bone only at the anterior region of the macula, and, as others have reported previously, much of the caudal area of the utricular macula is tenuously supported by a thin membrane, just above the dorsal margin of the stapes. This tenuous support may have important consequences for the sensing of forces by the utricular macula. Combining information from a dissected human horizontal canal with CT images allows an estimate of the orientation of the horizontal canal crista in human subjects, data which are necessary for treatment of benign paroyxsmal positional vertigo of the horizontal canal. The very high resolution achieved by micro-CT shows that reconstruction from inadequately sampled CT data produces images that are not anatomically correct, so that canal deformations and aplasias may appear to be present. PMID- 19645876 TI - How vestibular neurons solve the tilt/translation ambiguity. Comparison of brainstem, cerebellum, and thalamus. AB - The peripheral vestibular system is faced by a sensory ambiguity, where primary otolith afferents respond identically to translational (inertial) accelerations and changes in head orientation relative to gravity. Under certain conditions, this sensory ambiguity can be resolved using extra-otolith cues, including semicircular canal signals. Here we review and summarize how neurons in the vestibular nuclei, rostral fastigial nuclei, cerebellar nodulus/uvula, and thalamus respond during combinations of tilt and translation. We focus primarily on cerebellar cortex responses, as nodulus/uvula Purkinje cells reliably encode translation rather than net gravito-inertial acceleration. In contrast, neurons in the vestibular and rostral fastigial nuclei, as well as the ventral lateral and ventral posterior nuclei of the thalamus represent a continuum, with some encoding translation and some net gravito-inertial acceleration. This review also outlines how Purkinje cells use semicircular canal signals to solve the ambiguity problem and how this solution fails at low frequencies. We conclude by attempting to bridge the gap between the proposed roles of nodulus/uvula in tilt/translation discrimination and velocity storage. PMID- 19645877 TI - How actions alter sensory processing: reafference in the vestibular system. AB - Our vestibular organs are simultaneously activated by our own actions as well as by stimulation from the external world. The ability to distinguish sensory inputs that are a consequence of our own actions (vestibular reafference) from those that result from changes in the external world (vestibular exafference) is essential for perceptual stability and accurate motor control. Recent work in our laboratory has focused on understanding how the brain distinguishes between vestibular reafference and exafference. Single-unit recordings were made in alert rhesus monkeys during passive and voluntary (i.e., active) head movements. We found that neurons in the first central stage of vestibular processing (vestibular nuclei), but not the primary vestibular afferents, can distinguish between active and passive movements. In order to better understand how neurons differentiate active from passive head motion, we systematically tested neuronal responses to different combinations of passive and active motion resulting from rotation of the head-on-body and/or head-and-body in space. We found that during active movements, a cancellation signal was generated when the activation of proprioceptors matched the motor-generated expectation. PMID- 19645878 TI - Vestibulo-ocular signal transformation in frequency-tuned channels. AB - Self-generated locomotor activity is accompanied by head movements that cause retinal image displacements with a resultant degradation of visual information processing. To maintain visual acuity, retinal image drift must be counteracted by dynamic compensatory gaze adjustments that derive to a large extent from vestibulo-ocular reflexes (VOR). During head motion, vestibular signals code a wide frequency range from static head position to high acceleration profiles during rapid head turns. This large dynamic range suggests that the sensory-motor transformation occurs in parallel, yet complementary frequency-tuned pathways. In fact, the classic "three-neuronal" VOR pathway is composed of distinct functional subgroups of cells with different intrinsic properties and response dynamics at each synaptic level. This generates sets of neuronal filters that are ideal for particular frequency ranges and signaling patterns, respectively. In second-order vestibular subgroups, different filter functions, and hence a different synaptic processing is facilitated by a coadaptation of intrinsic membrane and emerging network properties. The consecutive assembly and sequential connectivity of pre- and postsynaptic neuronal elements with corresponding physiological properties, generates parallel pathways that allow for separate coding of different dynamic head-motion components during locomotor activity. PMID- 19645879 TI - The Edinger-Westphal nucleus represents different functional cell groups in different species. AB - In all vertebrates, including humans, the Edinger-Westphal nucleus (EW) forms a circumscribed cell group dorsomedial to the oculomotor nucleus (nIII). Traditionally the EW is considered the location of parasympathetic preganglionic neurons of the ciliary ganglion, mediating pupillary constriction and accommodation. In a comparative study in rat, ferret, monkey, and human, the location of cholinergic neurons within and around the nIII, which includes motoneurons of the extra-ocular muscles and the preganglionic neurons of the ciliary ganglion, was compared to the location of urocortin-positive neurons. Irrespective of the species, the cholinergic and urocortin-positive neurons form largely separated cell populations adjacent to each other. Only in monkey, cholinergic putative preganglionic neurons were found within the cytoarchitecturally defined EW, whereas in rat, ferret, and human the EW is almost exclusively composed of urocortin-positive neurons. In humans, the presumed preganglionic neurons are located as an inconspicuous group of choline acetyltransferase-positive neurons dorsal to the urocortin-positive EW. PMID- 19645880 TI - Parallel ascending vestibular pathways: anatomical localization and functional specialization. AB - Information from the vestibular nuclei ascending through the brainstem to the oculomotor and trochlear nuclei (NIII, NIV), the interstitial nucleus of Cajal (INC), the pretectum, or thalamus, is thought to be distributed in at least five different pathways. They include the medial longitudinal fasciculus (MLF), the ascending tract of Deiters (ATD), possibly the brachium conjuctivum (BC), the crossing ventral tegmental tracts (CVTT), and a recently observed ipsilateral pathway close to the medial lemniscus, possibly the equivalent of the ipsilateral vestibulo-thalamic tract (IVTT). This short review describes the location of these ascending tracts, their function with respect to ocular motor control and perception, and their clinical relevance. There is evidence that the MLF carries mainly information from the canals to NIII, NIV, INC, and possibly the thalamus, whereas otolith signals may ascend in the CVTT, along with excitatory anterior canal connections. The evidence for BC as a specific vestibulo-oculomotor pathway is weak and could be the result of the initial observations of CVTT. The ATD carries mostly ipsilateral otolithic information to the medial and inferior recti subgroups in NIII and the Edinger-Westphal nucleus. In the rostral pons an ipsilateral vestibular pathway was seen lying close to the medial lemniscus. This anatomical projection could be the equivalent of the IVTT, bypassing the ocular motor centers and projecting to the thalamus. The IVTT mediates perception of verticality and may be part of a fast three-neuron vestibulo-thalamo-cortical pathway, which provides the multisensory cortical system for spatial orientation and self-motion-perception with information about head acceleration. PMID- 19645881 TI - Modification of the cervico-ocular reflex by canal plugging. AB - The cervico-ocular reflex (COR) has a low gain in normal animals. In this study, we determined whether COR gain increases were specific to the low/midband frequency range, which is the range over which the angular vestibulo-ocular reflex (aVOR) is compromised by plugging. The gain and phase of the yaw and pitch COR and aVOR were compared in normal monkeys and those with all six semicircular canals or only the lateral canal plugged. During experiments animals sat with the body fixed to a chair and the head fixed in space. The body was oscillated about body-yaw and body-pitch axes over a frequency range of 0.05-6 Hz, with amplitude <10 degrees. For normal animals, both yaw and pitch eye velocities were compensatory to the relative velocity of the head with respect to the body. The gains were 0.1-0.2 at frequencies below 1 Hz and decreased to zero as stimulus frequency increased above 1 Hz. Canal-plugged animals had COR gains close to 1.0 at low frequencies, decreasing to approximately 0.6 at 0.5 Hz and to 0.2 for stimulus frequencies above 3 Hz. The phase of eye velocity was 180 degrees relative to head-re-body velocity at frequencies below 0.5 Hz and shifted toward 270 degrees as frequencies were increased to 4 Hz. This study demonstrates that adaptation of COR gain is tuned to a frequency range at which the aVOR is compromised by the canal plugging. PMID- 19645883 TI - Postural compensation for vestibular loss. AB - To what extent can remaining sensory information and/or sensory biofeedback (BF) compensate for loss of vestibular information in controlling postural equilibrium? The primary role of the vestibulospinal system is as a vertical reference for control of the trunk in space, with increasing importance as the surface becomes increasingly unstable. Our studies with patients with bilateral loss of vestibular function show that vision or light touch from a fingertip can substitute as a reference for earth vertical to decrease variability of trunk sway when standing on an unstable surface. However, some patients with bilateral loss compensate better than others, and found that those with more complete loss of bilateral vestibular function compensate better than those with measurable vestibulo-ocular reflexes. In contrast, patients with unilateral vestibular loss (UVL) who reweight sensory dependence to rely on their remaining unilateral vestibular function show better functional performance than those who do not increase vestibular weighting on an unstable surface. Light touch of <100 grams or auditory biofeedback can be added as a vestibular vertical reference to stabilize trunk sway during stance. Postural ataxia during tandem gait in patients with UVL is also significantly improved with vibrotactile BF to the trunk, beyond improvements due to practice. Vestibular rehabilitation should focus on decreasing hypermetria, decreasing an overdependence on surface somatosensory inputs, increasing use of any remaining vestibular function, substituting or adding alternative sensory feedback related to trunk sway, and practicing challenging balance tasks on unstable surfaces. PMID- 19645882 TI - The human vertical translational vestibulo-ocular reflex. Normal and abnormal responses. AB - Geometric considerations indicate that the human translational vestibulo-ocular reflex (tVOR) should have substantially different properties than the angular vestibulo-ocular reflex (aVOR). Specifically, tVOR cannot simultaneously stabilize images of distant and near objects on the retina. Most studies make the tacit assumption that tVOR acts to stabilize foveal images even though, in humans, tVOR is reported to compensate for less than 60% of foveal image motion. We have determined that the compensation gain (eye rotational velocity/required eye rotational velocity to maintain foveal target fixation) of tVOR is held steady at approximately 0.6 during viewing of either near or distant targets during vertical (bob) translations in ambient illumination. We postulate that tVOR evolved not to stabilize the image of the target on the fovea, but rather to minimize retinal image motion between objects lying in different depth planes, in order to optimize motion parallax information. Such behavior is optimized when binocular visual cues of both near and distant targets are available in ambient light. Patients with progressive supranuclear palsy or cerebellar ataxia show impaired ability to increase tVOR responses appropriately when they view near targets. In cerebellar patients, impaired ability to adjust tVOR responses to viewing conditions occurs despite intact ability to converge at near. Loss of the ability to adjust tVOR according to viewing conditions appears to represent a distinct disorder of vestibular function. PMID- 19645884 TI - What the "broken escalator" phenomenon teaches us about balance. AB - Gait adaptation is crucial for coping with varying terrain and biological needs. It is also important that any acquired adaptation is expressed only in the appropriate context. Here we review a recent series of experiments that demonstrate inappropriate expression of gait adaptation. We show that a brief period of walking onto a platform previously experienced as moving results in a large forward sway aftereffect, despite full awareness of the changing context. The adaptation mechanisms involved in this paradigm are extremely fast, just 1-2 discrete exposures to the moving platform result in the motor aftereffect. This aftereffect occurs even if subjects deliberately attempt to suppress it. However, it disappears when the location or method of gait is altered, indicating that aftereffect expression is context dependent. Conversely, making gait self initiated increases sway during the aftereffect. This aftereffect demonstrates a profound dissociation between knowledge and action. The absence of generalization suggests a relatively simple form of motor learning, albeit involving high-level processing by cortical and cerebellar structures. PMID- 19645886 TI - Human bipeds use quadrupedal coordination during locomotion. AB - During evolution, the increased influence of a direct cortical-motoneuronal system in parallel with a more specialized hand function might have replaced phylogenetically older systems that organized locomotor movements. However, recent research indicates that interlimb coordination during human locomotion is organized in a way similar to that in the cat. During locomotion, corticospinal excitation of upper-limb motoneurons is mediated indirectly, via propriospinal neurons in the cervical spinal cord. This allows a task-dependent neuronal linkage of cervical and thoracolumbar propriospinal circuits controlling leg and arm movements during human locomotor activities. During obstacle avoidance steps, an anticipatory quadrupedal limb coordination is up-regulated, with an involvement of proximal arm muscles during the acquisition and performance of this precision locomotor task. PMID- 19645885 TI - Effect of canal plugging on quadrupedal locomotion in monkey. AB - The vestibular system plays an important role in controling gait, but where in the labyrinths relevant activity arises is largely unknown. After the semicircular canals are plugged, low frequency (0.01-2 Hz) components of the angular vestibulo-ocular reflex (aVOR) and angular vestibulo-collic reflex (aVCR) are lost, but high frequency (3-20 Hz) components remain. We determined how loss of low frequency canal afference affects limb and head movements during quadrupedal locomotion. Head, body, and limb movements were recorded in three dimensions (3-D) in a cynomolgus monkey with a motion detection system, while the animal walked on a treadmill. All six canals were plugged, reducing the canal time constants from approximately 4.0 sec to approximately 0.07 sec. Major changes in the control of the limbs occurred after surgery. Fore and hind limbs were held farther from the body, producing a broad-based gait. Swing-phase trajectories were inaccurate, and control of medial-lateral limb movement was erratic. These changes in gait were present immediately after surgery, as well as 15 months later, when the animal had essentially recovered. Thus, control of the limbs in the horizontal plane was defective after loss of the low-frequency semicircular canal input and never recovered. Cycle-averaged pitch and roll head rotations, and 3-D head translations were also significantly larger and more erratic after than before surgery. Head rotations in yaw could not be quantified due to intrusion of voluntary head turns. These findings indicate that the semicircular canals provide critical low frequency information to maximize the accuracy of stepping and stabilize the head during normal quadrupedal locomotion. PMID- 19645887 TI - Structural changes in the human brain following vestibular neuritis indicate central vestibular compensation. AB - Vestibular neuritis (VN) is a sudden unilateral vestibular failure (UVF) with a variable course. Caloric hyporesponsiveness often persists, and it is largely unknown why patients with the same degree of hyporesponsiveness show different functional recovery. As the peripheral vestibular deficit alone does not seem to determine functional recovery, it was the aim of this study to elucidate whether structural (morphological) brain changes (1) contribute to central vestibular compensation, and (2) account for the variability of clinical recovery in VN. Structural global gray-matter volume (GMV) changes in 15 VN patients were compared with age-matched controls. Morphometric changes in multisensory vestibular cortices, which may be related to functional disability scores, were hypothesized. Patients were examined with neuro-otological tests and clinical scores to assess vestibular disability. Using voxel-based morphometry (VBM, SPM2), categorical comparison revealed GMV increase in patients' multisensory vestibular cortices [insula, inferior parietal lobe (IPL), superior temporal gyrus (STG)], cerebellum, and motion-sensitive areas in the middle temporal area (MT). GMV decrease was found in the midline pontomedullary junction. Simple regression analysis revealed (1) GMV increase in insula and retroinsular vestibular cortex and STG with improving clinically assessed vestibular deficits, and (2) GMV increase in insula vestibular cortex and STG with improving self assessed vestibular impairment. For the first time, these data suggest structural cortical plasticity in multisensory vestibular-cortex areas in VN that are related to clinical vestibular function and vertigo. As increase of GMV was related to an improvement of vestibular function, structural alterations may be related to central vestibular compensation. PMID- 19645888 TI - Galvanic vestibular stimulation combines with Earth-horizontal rotation in roll to induce the illusion of translation. AB - Human head rotation in roll around an earth-horizontal axis constitutes a vestibular stimulus that, by its rotational component, acts on the semicircular canals (SCC) and that, by its tilt of the gravity vector, also acts on the otoliths. Galvanic vestibular stimulation (GVS) is thought to resemble mainly a rotation in roll. A superposition of sinusoidal GVS with a natural earth horizontal roll movement was therefore applied in order to cancel the rotation effects and to isolate the otolith activation. By self-adjusting the amplitude and phase of GVS, subjects were able to minimize their sensation of rotation and to generate the perception of a linear translation. The final adjustments are in the range of a model that predicts SCC activation during natural rotations and GVS. This indicates that the tilt-translation ambiguity of the otoliths is resolved by SCC-otolith interaction. It is concluded that GVS might be able to cancel rotations in roll and that the residual tilt of the gravitoinertial force is possibly interpreted as a linear translation. PMID- 19645889 TI - Temporary lesions of the caudal deep cerebellar nucleus in nonhuman primates. Gain, offset, and ocular alignment. AB - The caudal fastigial nucleus (cFN) is one of the main cerebellar areas involved in the control of eye movements. Lesions of this area cause hypermetria of ipsilateral saccades and hypometria of contralateral saccades, as well as cogwheel smooth pursuit. Most studies with nonhuman primates described this dysmetria with a change of the ratio target amplitude to saccade amplitude, whereas in cats this dysmetria was attributed to a static fixation error. The targeting of visually-guided saccades before and after 11 unilateral injections of the inhibitory transmitter muscimol into the caudal fastigial nucleus in 5 monkeys was analyzed. In one monkey, who had eye coils implanted in both eyes, the postsaccadic interocular alignment was also analyzed. The main result is that the dysmetria observed in nonhuman primates can be explained as a combination of (1) hypermetria of the ipsilateral horizontal saccade component, and (2) a horizontal static fixation error of about 1.2 deg toward the side of the lesion. The static postsaccadic alignment of both eyes was only slightly disturbed after unilateral injection. The results suggest that the dysmetria seen after muscimol inactivation of the cFN is due to two distinct processes: one causes a gain change, and the other causes the static fixation error. Unilateral lesions have only a slight influence on binocular postsaccadic alignment. PMID- 19645890 TI - Balance before reason in rats and humans. AB - Considerable clinical and experimental evidence indicates that loss of vestibular function results in cognitive deficits, especially deficits in spatial memory. These studies demonstrate the importance of balance for the most fundamental of cognitive processes and suggest that information about head acceleration and orientation must have been critical to the evolution of brain structures such as the hippocampus. Studies of animals with bilateral vestibular lesions have shown that theta rhythm and the activity of hippocampal place cells are severely disrupted; recent human studies show that bilateral vestibular loss is even associated with hippocampal atrophy. While it is conceivable that the effects of vestibular lesions on the hippocampus are due to chronic stress and increased glucocorticoid levels, at present there is little evidence to support this hypothesis. It is also possible that the hippocampal changes are due to a reduction in exploration and active behavior; however, in rats, at least, bilateral vestibular lesions cause hyperactivity rather than hypoactivity. Alternatively, the hippocampus may have developed a special dependence upon the vestibular system during evolution, since it was the first sensory system to reliably indicate gravitational vertical. PMID- 19645891 TI - Anxiety-related behavior and biogenic amine pathways in the rat following bilateral vestibular lesions. AB - Many clinical studies have reported that patients with vestibular disorders have a high rate of anxiety disorders and depression. By contrast, there have been few studies of affective behavior in animals following vestibular lesions. Recent studies using the vestibular impaired ci2/ci2 mutant rat strain have shown that rather than preferring the closed arm of the elevated plus maze, as rats would normally, they make more open-arm entries and spend more time on the open arms compared to wild-type controls. In the open-field maze, rather than preferring to explore the outer zone near the walls ("thigmotaxis"), ci2/ci2 rats prefer the inner region of the maze. In rats with bilateral vestibular deafferentation (BVD), similar results were obtained. Compared to sham controls, at 3 and 5 months post-op, BVD rats spent more time on the open arms of the elevated plus maze, more time in the inner zone of the open-field maze, and failed to learn inhibitory avoidance in the elevated T maze. They did not display increased hyponeophagia; however, they did exhibit a decrease in social interaction. Blood corticosterone levels were not significantly different from sham controls. At 6 months post-op, BVD rats demonstrated circumscribed changes in the expression of tyrosine hydroxylase, the serotonin transporter, and tryptophan hydroxylase, in various regions of the medial temporal and frontal lobes, suggesting changes in biogenic amine pathways. PMID- 19645892 TI - Estimating the time constants of the rVOR. A model-based study. AB - Single-unit recordings of vestibular afferents from the semicircular canals of squirrel monkeys have shown that the cupular time constant (T(c)) is between 5 and 6 sec. Such recordings obviously cannot be performed in humans, and the corresponding values have thus been inferred to be somewhat longer based on their size and on the cupula-endolymph system. The ocular motor response of the rotational vestibulo-ocular reflex (rVOR) is characterized by longer time constants, typically between 15 and 20 sec, due to the so-called velocity storage mechanism (VSM), which prolongs the time constant of the afferents through central processing. Recent studies have attempted to determine the time constant of the cupula by fitting the slow phase velocity (SPV) of the response to postrotational stimuli using a mathematical model of the rVOR processing. To this goal they considered the processing of head velocity due to the peripheral vestibular organs and to the VSM. The resulting estimates of T(c) are lower than expected, averaging about 4 sec. These modeling approaches, though, neglect both the processing of the final common pathway and the adaptation shown by the discharge of primary vestibular afferents. Here we argue that such an approach may be bound to underestimate the duration of the rVOR time constants. PMID- 19645893 TI - Signal processing and distribution in cortical-brainstem pathways for smooth pursuit eye movements. AB - Smooth pursuit (SP) eye movements are used to maintain the image of a moving object relatively stable on the fovea. Even when tracking a single target over a dark background, multiple areas including frontal eye fields (FEF) and middle temporal (MT) and medial superior temporal (MST) cortex contribute to converting visual signals into initial commands for SP. Signals in the cortical pursuit system reach the oculomotor cerebellum through brainstem centers including the dorsolateral pontine nucleus (DLPN), nucleus reticularis tegmenti pontis (NRTP), and pretectal nucleus of the optic tract (NOT). The relative information carried in these parallel pathways remains to be fully defined. We used multiple linear regression modeling to estimate the relative sensitivities of cortical (MST, FEF), pontine (NRTP, DLPN), and NOT neurons to eye- and retinal-error parameters (position, velocity, and acceleration) during step-ramp SP of macaques (Macaca mulatta). We found that a large proportion of pursuit-related MST and DLPN neurons were most sensitive to eye-velocity or retinal error velocity. In contrast, a large proportion of FEF and rostral NRTP neurons were most sensitive to eye acceleration. Visual neurons in MST, DLPN, and NOT were most sensitive to retinal image velocity. PMID- 19645894 TI - Effect of gravity on vertical eye position. AB - There is growing evidence that gravity markedly influences vertical eye position and movements. A new model for the organization of brainstem upgaze pathways is presented in this review. The crossing ventral tegmental tract (CVTT) could be the efferent tract of an "antigravitational" pathway terminating at the elevator muscle motoneurons in the third nerve nuclei and comprising, upstream, the superior vestibular nucleus and y-group, the flocculus, and the otoliths. This pathway functions in parallel to the medial longitudinal fasciculus pathways, which control vertical eye movements made to compensate for all vertical head movements and may also comprise the "gravitational" vestibular pathways, involved in the central reflection of the gravity effect. The CVTT could provide the upgaze system with the supplement of tonic activity required to counteract the gravity effect expressed in the gravitational pathway, being permanently modulated according to the static positions of the head (i.e., the instantaneous gravity vector) between a maximal activity in the upright position and a minimal activity in horizontal positions. Different types of arguments support this new model. The permanent influence of gravity on vertical eye position is strongly suggested by the vertical slow phases and nystagmus observed after rapid changes in hypo- or hypergravity. The chin-beating nystagmus, existing in normal subjects with their head in the upside-down position, suggests that gravity is not compensated for in the downgaze system. Upbeat nystagmus due to brainstem lesions, most likely affecting the CVTT circuitry, is improved when the head is in the horizontal position, suggesting that this circuitry is involved in the counteraction of gravity between the upright and horizontal positions of the head. In downbeat nystagmus due to floccular damage, in which a permanent hyperexcitation of the CVTT could exist, a marked influence of static positions of the head is also observed. Finally, the strongest argument supporting a marked role of gravity in vertical eye position is that the eye movement alterations observed in the main, typical physiological and pathological conditions are precisely those that would be expected from a direct effect of gravity on the eyeballs, with, moreover, no single alternative interpretation existing so far that could account for all these different types of findings. PMID- 19645895 TI - Some perspectives on saccade adaptation. AB - The saccadic system is an ideal model for the study of how the brain optimizes its motor behavior. Here we review some recent research that points to exciting new areas of investigation relative to the multiple time scales of and the influence of context and consolidation on motor learning. These findings suggest new ways of thinking about the processes that underlie the short-term adaptive mechanisms that maintain accuracy of eye movements and so ensure optimal vision. PMID- 19645896 TI - Respiratory impact on motion sickness induced by linear motion. AB - Motion sickness incidence (MSI) for vertical sinusoidal motion reaches a maximum at 0.167 Hz. Normal breathing frequency is close to this frequency. There is some evidence for synchronization of breathing with this stimulus frequency. If this enforced breathing takes place over a larger frequency range (0.05-0.8 Hz) and whether this contributes to the high MSI at 0.167 Hz was investigated. Sinusoidal motion (amplitude 0.3 g, frequencies 0.05, 0.1, 0.2, 0.4, and 0.8 Hz) was applied. Nausea with the MISC-scores and respiratory parameters, such as tidal volume, respiratory frequency, end-tidal CO(2) (PetCO(2)), and respiratory minute volume, were measured. Control conditions included rest and the hyperventilation provocation test. The nausea scores were highest at 0.2 Hz. With increasing frequencies the respiratory minute volume increased and the PetCO(2) values decreased. The hyperventilation provocation test did not cause nausea. The main conclusion is that the high MSI at 0.167 Hz is not due to enforced breathing, since enforced breathing still increases with higher stimulus frequencies. PMID- 19645897 TI - Vestibular critical period, maturation of central vestibular neurons, and locomotor control. AB - Mutant mice are a good model to study to what extent the postnatal activity of sensory afferents is necessary for the maturation of central neurons. In particular, the question arises whether the signals carried by the first-order vestibular neurons, which encode information on the head movement of pups, are necessary for the maturation of second-order vestibular neurons. To address that question, juvenile and adult transgenic, vestibular-deficient mutants where a null mutation of the KCNE1 potassium-channel gene leads to degeneration of all hair cells of the inner ear just after birth were studied. These KCNE1(-/-) mutants are deaf and show quasi-constant head bobbing and a permanent shaker/waltzer phenotype. This behavior is not due to persistent abnormalities of the membrane properties of central vestibular neurons, because their maturation is delayed but not impaired by the absence of sensory vestibular information. On the other hand, the data shed light on how the membrane properties of vestibular neurons might be modified according to functional requirements or following lesions. The expression levels of the protein calretinin that regulates the intracellular free-calcium concentration in central vestibular neurons could play a major role both in intact animals and following labyrinthectomy. By comparing the KCNE1(-/-) mutant mice to other vestibular-deficient animals, it was concluded that the suppression of vestibular inputs during a "critical period" of postnatal development can induce a permanent circling behavior, but that this phenotype is not always due to congenital vestibular deficiency. PMID- 19645898 TI - Distinct roles for eye and head movements in selecting salient image parts during natural exploration. AB - Humans adjust gaze by eye, head, and body movements. Certain stimulus properties are therefore elevated at the gaze center, but the relative contribution of eye in-head and head-in-world movements to this selection process is unknown. Gaze- and head-centered videos recorded with a wearable device (EyeSeeCam) during free exploration are reanalyzed with respect to responses of a face-detection algorithm. In line with results on low-level features, it was found that face detections are centered near the center of gaze. By comparing environments with few and many true faces, it was inferred that actual faces are centered by eye and head movements, whereas spurious face detections ("hallucinated faces") are primarily centered by head movements alone. This analysis suggests distinct contributions to gaze allocation: head-in-world movements induce a coarse bias in the distribution of features, which eye-in-head movements refine. PMID- 19645899 TI - Reafferent head-movement signals carried by pursuit neurons of the simian frontal eye fields during head movements. AB - The smooth-pursuit system is important to precisely track a slowly moving object and maintain its image on the foveae during movement. During whole-body rotation, the smooth-pursuit system interacts with the vestibular system. The caudal part of the frontal eye fields (FEF) contains smooth pursuit-related neurons that signal eye velocity during pursuit. The majority of them receives vestibular inputs and signal gaze-velocity during passive whole-body rotation. It was asked whether discharge modulation of FEF pursuit neurons during head rotation on the stationary trunk could be accounted for by vestibular inputs only or if both vestibular and neck proprioceptive inputs contributed to the modulation. Discharge modulation during active head pursuit, passive head rotation on the stationary trunk, passive whole-body rotation, and passive trunk rotation against the stationary head were compared. The results indicate that both vestibular and neck proprioceptive inputs contributed to the discharge modulation of FEF pursuit neurons during head movements. PMID- 19645900 TI - The effect of dual tasks in locomotor path integration. AB - Without landmarks, navigation is based on information about self-velocity, which is transformed to position or orientation by a process called path integration. Simple path integration tasks, such as reaching a previously seen goal by blindfolded locomotion, were often considered to be automatic and not influenced by unrelated cognitive activity. However, we recently showed that reproduction of self-motion without landmark cues exhibits systematic dual-task interference. Since these experiments did not exclude that the dual task only interferes with memory for self-motion, we performed two additional experiments testing generic path integration. We show that locomotor homing and reaching predefined goals by active self-motion are affected systematically by a concurrent mental task. The similarity of the effects we found to those reported for duration estimation led us to the hypothesis that subjective time may be used as a temporal basis of path integration. Alternatively, path integration and duration estimation may be based on similar underlying neuronal mechanisms, for example, coincidence detection in neural oscillators. PMID- 19645901 TI - Posture control in vestibular-loss patients. AB - Patients with chronic bilateral loss of vestibular functions normally replace these by visual or haptic referencing to stationary surroundings, resulting in an almost normal stance control. But with eyes closed, they show abnormally large body sway, and may tend to fall when there are external disturbances to the body or when standing on an unstable support surface. Patients' postural responses depend on joint angle proprioception and ground reaction-force cues (occasionally referred to as "somatosensory graviception"). It is asked why the force cues do not allow patients to fully substitute loss of the vestibular cues. In recent years, four sets of observations of experimental situations where patients, eyes closed, show impaired stance control or even may fall were identified: (1) with unstable or compliant support ("inevitable falls"); (2) with large external disturbances such as support surface tilts or pull stimuli impacting on their bodies (leading to abnormally large body movements); (3) with fast body-support tilts (also abnormally large body movements); and (4) with transient support tilt (overshooting body-support stabilization and abnormaly late body-space [BS] stabilization). When patients' data were modeled, it was found that their problems stem mainly from the force cues. It was hypothesized that patients have difficulties decomposing this sensory information into its constituents in order to be able to get rid of an active force component. Normals do not have this difficulty, because the vestibular system performs the decomposition. PMID- 19645902 TI - Spatial neglect: hypothetical mechanisms of disturbed interhemispheric crosstalk for orientation. AB - Schematic drawings are presented of the major anatomical structures involved, along with their functional excitatory and inhibitory connections as the basis of a hypothetical model of visuospatial neglect. It is assumed that multisensory integration centers for attention and orientation (MSO) are represented in the temporo-parietal cortex of both hemispheres, with the dominant MSO being in the right hemisphere (nondominant hemisphere in right-handedness). A lesion of the dominant MSO will cause a left-sided neglect due to a lack of ipsilateral activation of the visual cortex, which is further enhanced by increased inhibition from the contralateral visual cortex. The nondominant MSO in the left hemisphere might be involved in the manifestation of the less frequent and more transient right-sided neglect and in the plastic mechanisms of gradual recovery from a left-sided neglect or extinction. PMID- 19645903 TI - The perception of translational motion: what is vestibular and what is not. AB - In response to translations of the head, the linear vestibulo-ocular reflex (LVOR) produces compensatory eye movements that are high-pass in nature, with a declining response magnitude and an increasing phase lead with declining stimulus frequency. Perception of head translation, however, is reported to be robust at much lower frequency than predicted by the LVOR, causing speculation that the vestibular processing underlying reflex and perceptual responses are different. Direct comparison of these two responses across a large frequency range proves problematic, in part because of difficulties encountered in the assessment of perception at high frequency, and confounding variables at low frequency. We used innovative techniques to measure psychophysical responses to translation, and find strong similarity to the LVOR. These include experiments in which motion cues were limited to those of an inertial nature, and conclude that the vestibular system comprises only one input to perceptual mechanisms related to linear motion, and this is supplemented (particularly at low frequency) by somatic and cognitive cues. PMID- 19645904 TI - Human hippocampal activation during stance and locomotion: fMRI study on healthy, blind, and vestibular-loss subjects. AB - The hippocampal formation, including the parahippocampal gyrus, is known to be involved in different aspects of navigation and spatial orientation. Recently, bilateral parahippocampal activation during mental imagery of walking and running was demonstrated in fMRI. For the current study the question was whether distinct functional regions within the hippocampal formation could be defined from the analysis of brain activity during imagery of stance and locomotion in healthy, blind, and vestibular-loss subjects. Using the same experimental paradigm in all groups (fMRI during mental imagery of stance and locomotion after training of actual performance, regions of interest [ROI] analysis), activations were found in the hippocampal formation, predominantly on the right side, in all subjects. In healthy subjects, standing was associated with anterior hippocampal activation; during locomotion widespread activity was found in the right parahippocampal gyrus. Compared to healthy controls, blind subjects showed less activity in the right dorsal parahippocampal region, whereas vestibular-loss subjects had less activity in the anterior hippocampal formation. The findings show that the hippocampal formation in humans processes visual and vestibular signals in different regions. The data support the assumption that the anterior hippocampus and the entorhinal cortex in the parahippocampal region are input areas for vestibular and somatosensory signals. Posterior parahippocampal and fusiform gyri, which are connected to visual cortical areas, are more important for visually guided locomotion and landmark recognition during navigation. The right-sided dominance reflects the importance of the right hemisphere for spatial orientation. PMID- 19645905 TI - Perceptual encoding of self-motion duration in human posterior parietal cortex. AB - It has been demonstrated previously that repetitive transcranial magnetic stimulation (rTMS) to right or left posterior parietal cortex (PPC) disrupts perceptual encoding of whole-body displacement during an angular path integration task using only vestibular cues for its completion. The effects of rTMS applied to right PPC (and left motor cortex as a control) during a vestibular-cued motion reproduction task (i.e., not requiring path integration) were investigated in 5 subjects. Specifically, subjects were rotated in the dark on a motorized Barany chair with raised cosine velocities of durations 1, 2, and 3 s and peak 30 degrees, 60 degrees, 90 degrees, and 120 degrees/s. Subjects were required to actively reproduce the motion profile after every rotation with a chair-bound joystick. It was found that rTMS applied to the right PPC during the passive (encoding) stimulus phase had no effect on angular velocity reproduction when compared to control (motor-cortex rTMS). In contrast, motion-duration reproduction was significantly worse with right PPC (versus control motor cortex) rTMS. The results imply that vestibular-derived cues of motion duration, but not velocity, are encoded in human PPC. It was inferred from these and previous data that human PPC is involved in human path integration and motion-duration perception, but not angular velocity self-motion perception. PMID- 19645906 TI - Progressive vestibular impairment in patients with polyneuropathy. AB - It is generally assumed that imbalance in patients with polyneuropathy (PNP) results from deficient proprioceptive input arriving from the lower limbs. Polyneuropathic processes, however, may also impair vestibular function. In fact, we observed that two-thirds of patients with PNP show unilateral or bilateral impairment of vestibular function as assessed with search-coil head impulse testing. In the present work, we analyzed the same database of 37 polyneuropathic patients to find out whether the presence of a unilateral or bilateral vestibular deficit reflects a progression of the vestibular impairment. Results suggest that vestibular function in PNP patients deteriorates asymmetrically, first affecting one side and later both sides. PMID- 19645907 TI - Vertigo as a symptom of migraine. AB - Migraine and vertigo are common disorders, affecting about 14% and 10%, respectively, of the general population. If migraine and vertigo were unrelated, the expected comorbidity would be 1%, whereas recent epidemiological studies indicate that 3.2% of the population have both migraine and vertigo. The excess comorbidity may be attributed to two factors: 1) vertigo syndromes (including Meniere's disease, benign paroxysmal positional vertigo, and anxiety-related dizziness) that are more common in migraineurs than in controls and 2) vestibular migraine (VM) (vertigo as a symptom of migraine.) VM presents with attacks of spontaneous or positional vertigo lasting seconds to days. Headaches are often absent during acute attacks, but other migrainous features such as photophobia or auras, may be present. Like migraine headaches, VM triggers include stress, sleep deprivation, and hormonal changes. During acute attacks, there may be central spontaneous or positional nystagmus and, less commonly, unilateral vestibular hypofunction. In the symptom-free interval, vestibular testing shows mostly minor and nonspecific findings. The pathogenesis of VM is uncertain, but migraine mechanisms may interfere with the vestibular system at the labyrinth, brainstem, and cerebral cortex. Treatment includes vestibular suppressants for acute attacks and migraine prophylaxis for patients with frequent recurrences. However, treatment efficacy has not been validated by properly controlled clinical trials. VM does not fit into the 2004 International Headache Society Classification, in which "basilar-type migraine" must have at least two posterior circulation manifestations; isolated vertigo would not satisfy this criterion. PMID- 19645908 TI - Familial episodic ataxia: a model for migrainous vertigo. AB - Familial episodic ataxias are inherited channelopathies that manifest as episodes of vertigo and ataxia triggered by emotional stress and physical exertion. Mutations in two neuronal ion-channel genes KCNA1 and CACNA1A abundantly expressed in the cerebellum account for the majority of the identified cases of episodic ataxia. Overlapping features between episodic ataxia and the more common recurrent vertigo and ataxia syndromes, particularly those associated with migraine, suggest shared underlying mechanisms. Altered neuronal excitability in the brain and inner ear could contribute to the central and peripheral features of migrainous vertigo. Given the familial aggregation of migraine and migrainous vertigo, our objective was to identify predisposing genetic factors. Preliminary findings demonstrate that migrainous vertigo is genetically heterogeneous and complex. Efforts are ongoing to perform genomewide association studies to identify risk alleles for migrainous vertigo, which may also be relevant to migraine in general. PMID- 19645909 TI - Vestibular "PREHAB". AB - A sudden unilateral loss or impairment of vestibular function causes vertigo, dizziness, and impaired postural function. In most occasions, everyday activities supported or not by vestibular rehabilitation programs will promote a compensation and the symptoms subside. As the compensatory process requires sensory input, matching performed motor activity, both motor learning of exercises and matching to sensory input are required. If there is a simultaneous cerebellar lesion caused by the tumor or the surgery of the posterior cranial fossa, there may be a risk of a combined vestibulocerebellar lesion, with reduced compensatory abilities and with prolonged or sometimes permanent disability. On the other hand, a slow gradual loss of unilateral function occurring as the subject continues well-learned everyday activities may go without any prominent symptoms. A pretreatment plan was therefore implemented before planned vestibular lesions, that is, "PREHAB." This was first done in subjects undergoing gentamicin treatment for morbus Meniere. Subjects would perform vestibular exercises for 14 days before the first gentamicin installation, and then continue doing so until free of symptoms. Most subjects would only experience slight dizziness while losing vestibular function. The approach--which is reported here--was then expanded to patients with pontine-angle tumors requiring surgery, but with remaining vestibular function to ease postoperative symptoms and reduce risk of combined cerebellovestibular lesions. Twelve patients were treated with PREHAB and had gentamicin installations transtympanically. In all cases there was a caloric loss, loss of VOR in head impulse tests, and impaired subjective vertical and horizontal. Spontaneous, positional nystagmus, subjective symptoms, and postural function were normalized before surgery and postoperative recovery was swift. Pretreatment training with vestibular exercises continued during the successive loss of vestibular function during gentamicin treatment, and pre-op gentamicin ablation of vestibular function offers a possibility to reduce malaise and speed up recovery. PMID- 19645910 TI - Impact of vertigo and spatial disorientation on concurrent cognitive tasks. AB - Disorientation may draw attention from other activities and its impact on cognition may cause pilot error and problems of concentration in dizzy patients. Tasks used to study the impact of disorientation include number processing, intelligence scales and Brookes matrices (reproduction of 2xD patterns of numbers vs. nonsensical sentences), and Stroop tasks to probe selective effects on spatial versus verbally-loaded tasks. This variety of tasks has been used to evaluate cognitive performance in numerous scenarios, including visual-vestibular mismatch, vection, spinning, coriolis, balancing, and flight maneuvers. A meta analysis provides an overview of how spatial disorientation may affect cognition: Substantial individual differences in managing disorientation are to be expected; errors on cognitive tasks occur during the first few experiences of a disorienting situation and subjects rapidly learn to "quarantine" this "novelty effect"; familiarity with and practice on a test gives protection against disorientation; task performance continues to suffer if the protagonist is unaware of disorientation; with disorientation that demands external resolution (e.g., interpretation of instruments) the subject must learn to switch priority to the cognitive task; there is a moderate preferential impact of disorientation on spatial tasks; anxiety of real situations probably exacerbates the impact of disorientation. PMID- 19645911 TI - Tell me your vestibular deficit, and i'll tell you how you'll compensate. AB - Most patients with unilateral vestibular loss exhibit a similar static and dynamic vestibular syndrome consisting of vestibulo-ocular, posturolocomotor, and perceptive deficits. This vestibular syndrome recovers more or less completely and more or less rapidly over time. One open question is whether recovery mechanisms differ according to vestibular pathology and/or patients. It is reported here (1) data from three different cat models of unilateral vestibular loss reproducing vestibular pathology with sudden (unilateral vestibular neurectomy [UVN] model), gradual (unilateral labyrinthectomy [UL] model), or reversible (tetrodotoxine [TTX]) model) loss of vestibular function, and (2) clinical observations in a population of unilateral vestibular loss patients suffering the same pathology (Meniere's disease). Animal models show that time courses and mechanisms of recovery depend on the type of vestibular deafferentation, and clinical findings show that Meniere's patients compensate their postural and perceptive deficits using different vicarious processes. Taken together, results point to a more complex picture of compensation after unilateral vestibular loss, which cannot be reduced either to a common recovery mechanism or to a single process identical for all individuals. These findings should guide physiotherapists in treatment and rehabilitation for vestibular deficits. PMID- 19645912 TI - Vibrotactile biofeedback improves tandem gait in patients with unilateral vestibular loss. AB - In a crossover design, subjects with unilateral vestibular loss (UVL) practiced tandem gait with eyes closed on two days, two weeks apart, with and without vibrotactile biofeedback (BF) applied to the lateral trunk. Results showed an immediate improvement in postural stability (reduction of lateral center-of-mass displacement, trunk tilt, and medial-lateral step width) that was significantly larger than effects of practice alone. However, BF did not increase the rate of improvement or retention of improved stability during gait. PMID- 19645913 TI - Functional magnetic resonance imaging activations of cortical eye fields during saccades, smooth pursuit, and optokinetic nystagmus. AB - Saccades, smooth pursuit, and optokinetic nystagmus (OKN) are three basic eye movements in our ocular motor repertoire that enable us to explore the visual field. These eye movements are cortically controlled in different cortical eye fields, including the frontal eye fields (FEF) and parietal eye fields (PEF), as well as the motion-sensitive visual area MT+/V5. It is not known if this cortical control is organized in parallel cortico-cortical networks or in adjacent subregions of one system. Nor do we know where the specific eye fields are exactly located. Functional magnetic resonance imaging (fMRI) was used to investigate these open questions about the FEF, PEF, and MT+/V5. Activations of the cortical network of eye-movement control were found in the frontal, parietal, and occipital cortex. While the activation pattern for OKN was not a combination of the patterns for saccades and smooth pursuit, the results suggest that cortical control of OKN occurs in a network parallel to that of saccades and smooth pursuit. Furthermore, a division of the FEF and the PEF into two parts was confirmed for the three ocular motor tasks, as well as a division within each of the three paradigms. MT+/V5 showed two partitions only for saccades, but not for smooth pursuit or OKN. PMID- 19645914 TI - The intensity of downbeat nystagmus during daytime. AB - On the basis of reports by patients with downbeat nystagmus (DBN) that their symptoms were worse during the morning but better during the daytime, we investigated whether the intensity of DBN changes during the daytime. DBN was measured at 9 am, 11 am, and 1 pm. The mean peak slow phase velocity (MPSPV) of DBN was determined in different eye positions, with and without fixation, as well as in three different body positions: sitting upright, lying supine with the nose up, and lying prone with the nose down. Twelve patients with DBN either due to cerebellar degeneration or of idiopathic etiology were examined. The major findings of this study were as follows. First, the intensity of DBN significantly decreased during the daytime. When measured in the sitting upright position and primary eye position, MPSPV decreased from 4.32 deg/sec (+/-SEM 1.02) at 9 am to 2.12 deg/sec (+/- 0.5) at 11 am (P < 0.01) and stayed constant around 1.93 deg/sec (+/- 0.57) at 1 pm (P < 0.01 from 9 am to 1 pm) and 2.08 deg/sec (+/- 0.75) at 3 pm (P < 0.01 from 9 am to 3 pm). Second, this change did not depend on fixation during the measurements. Third, this effect was not influenced by the eye position during the measurements (upward, downward, or straight ahead). Our data show that the intensity of DBN decreases during the daytime. This decrease correlates with the symptoms of the patients. This change during daytime did not depend on visual fixation. Another possible mechanism is the modulation of DBN by head position relative to gravity, that is, by otolith input. This should be evaluated in further studies. PMID- 19645915 TI - The presence of lytic HSV-1 transcripts and clonally expanded T cells with a memory effector phenotype in human sensory ganglia. AB - Herpes simplex virus type 1 (HSV-1) latent persistence in human trigeminal ganglia (TG) is accompanied by a chronic CD8 T-cell infiltration. Thus far, during HSV-1 latency only a single transcript, namely the latency-associated transcript (LAT), has been identified to be synthesized but not translated into a protein. In contrast, the chronic CD8 T-cell infiltration suggests that an antigen trigger must be present. The focus of the current work was to look for HSV-1 transcription activity as a potential trigger of the immune response and to demonstrate whether the immune cells are clonally expanded and have a phenotype that suggests that they have been triggered by viral antigen. By combining in situ hybridization, laser cutting microscopy, and single-cell real time RT-PCR, we demonstrated expression of the HSV-1 immediate early (IE) genes ICP0 and ICP4 in human trigeminal neurons. Using CDR3 spectratyping, we showed that the infiltrating T cells are clonally expanded, indicating an antigen-driven immune response. Moreover, the persisting CD8(+) T cells had prominent features of the memory effector phenotype. Chemokines CCL5 and CXCL10 were expressed by a subpopulation of infiltrating cells and the corresponding chemokine receptors CCR5 and CXCR3 were co-expressed on virtually all T cells bearing the CD8 phenotype. Thus, HSV-1 IE genes are expressed in human TG, and the infiltrating T cells bear several characteristics that suggest viral antigenic stimulation. PMID- 19645916 TI - Effects of acute vestibular lesions on visual orientation and spatial memory, shown for the visual straight ahead. AB - The aim of this study was to investigate the relation between the vestibular system and orientation in space and the role of acute vestibular lesions in spatial memory. In a first step it could be shown that determining the visual straight ahead is systematically influenced by caloric irrigation: deviations up to 10 degrees appeared, which are directed to the slow phase of the simultaneously provoked nystagmus. In a second step, 20 healthy subjects and 20 patients suffering from an acute vestibular disorder were asked to adjust a luminous point visual straight ahead. Whereas the healthy subjects' visual straight ahead was in a range of +/-2 degrees, the vestibular patients showed significantly greater deviations. If healthy subjects and patients were asked to replace a luminous point, which was exposed for a short time, to its original position, young and older healthy subjects showed good performance, with an error not greater than 3 degrees, whereas the vestibular patients showed significantly greater inaccuracy. We conclude that the visual straight ahead is a vestibular dependent parameter of visual orientation and that spatial memory is influenced by acute vestibular lesions. For the first time it is shown that acute vestibular lesions impair spatial memory. This can be explained by the close relationship between the vestibular system and the hippocampus. PMID- 19645917 TI - Applying knowledge--challenges in bringing scientific advances to dizzy patients. AB - Simple diagnostic or therapeutic procedures can produce tremendous benefits for dizzy patients. To see how new ideas in the laboratory evolve into benefits for patients, an attempt to analyze how the corresponding information is distributed was made. To quantify that flow of information, a number of new scientific publications, citation numbers, and a number of new books on relevant subjects were looked at. For vertigo, this approach was facilitated by the fact that the diagnostic procedures for benign paroxysmal positioning vertigo (BPPV) and for canal paresis can be traced back to seminal publications. Results indicate that the current way of disseminating new information used here is working well, and that new ideas on diagnosis and treatment are readily available to practitioners. However, the application of new methods is limited by the availability of the required technology. It is conjectured that the technological requirements have become more complex over time, leading to a slower uptake of new technology. PMID- 19645918 TI - Lateral canal paroxysmal positional vertigo revisited. AB - The first reports of an involvement of the lateral canal (LC) in paroxysmal positional vertigo (PPV), were published in 1985, by Luciano Cipparrone et al., from Italy and Joseph McClure from Canada. The increasing interest of otolaryngologists and neurologists has led to a progressive advance in the knowledge of this labyrinthine disorder regarding its epidemiological, physiopathological, clinical, and therapeutic aspects. According to the most recent data, LC-benign PPV accounts for 17% of all PPV patients, regardless of gender and between the two labyrinths. The LC-PPV syndrome is characterized by intense positional vertigo and direction-changing geotropic horizontal nystagmus, both caused by rotation of the head in the supine position. Less frequently, it presents with apogeotropic nystagmus. In some patients nystagmus is also detectable in the sitting position, mimicking a spontaneous nystagmus. In most cases nystagmus is caused by displaced otoconia floating in the semicircular canal. The pathological side, which must be identified for successful treatment, is usually indicated by nystagmus intensity: the more intense positional nystagmus beats toward the affected ear. In a few cases, where there is no difference in nystgmus intensity, other indicators are necessary to determine the pathological side. Vestibular neuritis and posterior fossa lesions should be considered in the differential diagnosis. Treatment of LC-PPV relies on some physical maneuvers, the objective of which is to allow the otoconial debris to exit from the LC by centrifugal inertia and/or by gravitation. PMID- 19645919 TI - Vestibular-evoked myogenic potentials in "vestibular migraine" and Meniere's disease: a sign of an electrophysiological link? AB - Characterizations of the signs and symptoms of "vestibular migraine" and of Meniere's disease seem to overlap, suggesting that both diseases might be due to a common peripheral vestibular dysfunction. Thus, the aim of the present study was to assess vestibular-evoked myogenic potentials (VEMPs) in both disorders to determine whether there might be an electrophysiological link between the two disorders. The amplitude and latency of VEMPs were measured from the sternocleidomastoid muscle in 63 patients with vestibular migraine (median age 47 years, range 24-70 years) and in 16 patients with Meniere's disease (median age 52 years, range 36-72 years), and compared with those of 63 sex- and age-matched healthy controls (median age 46 years, range 17-73 years). In comparison to the controls, 43 of the 63 patients with vestibular migraine (68%) and 11 patients with Meniere's disease (69%) had reduced electromyography -corrected VEMP amplitudes, whereas no difference was seen in the latencies. Thus, these data provide evidence that the saccule may be affected in both disorders, indicating a possibly related labyrinthine cause for the pathogenesis of vestibular migraine and Meniere's disease. PMID- 19645920 TI - Gait deviations induced by visual motion stimulation in roll depend on head orientation. AB - Locomotion control uses proprioceptive, visual, and vestibular signals. Previously, we analyzed the visual contribution with visual motion stimulation in roll while participants kept their heads in a normal upright orientation. In this study we applied the same visual disturbance in a head-upright and a nose-down condition. Random dot patterns were constantly rotated in roll at +/-15 degrees/sec on a computer-driven binocular head-mounted display, while the participants walked a distance of 6 m. The stimulation effect was more pronounced in the nose-down condition. These results are similar to the results of previous galvanic vestibular stimulation (GVS) studies, suggesting that in terms of the direction of action visual motion stimulation in the roll plane is similar to GVS. PMID- 19645921 TI - Head impulse testing using video-oculography. AB - Head impulses are a routine clinical test of semicircular canal function. At the bedside, they are used to detect malfunctioning of the horizontal semicircular canals. So far, 3-D-search-coil recording is required to reliably test anterior and posterior canal function and to determine the gain of the vestibulo-ocular reflex (VOR). Search-coil recording cannot be done at the bedside. Here we tested whether video-oculography (VOG) is suitable to assess VOR gain for individual canals at the bedside. We recorded head impulses in healthy subjects using a mobile high-frame-rate, head-mounted VOG-device and compared the results with those obtained with standard search-coil recording. Our preliminary results indicate that high-frame-rate VOG is a promising tool to measure and quantify individual semicircular canal function not only at the bedside. PMID- 19645922 TI - Why do subjective vertigo and dizziness persist over one year after a vestibular vertigo syndrome? AB - The overlap and interlinkage of dizzy symptoms in patients with psychiatric and vestibular vertigo/dizziness disorders is the subject of an ongoing debate. In a one-year follow up in 68 patients with vestibular vertigo syndromes, the persistency of vertigo and dizziness symptoms was examined and correlated with vestibular parameters and results from a psychiatric evaluation. Patients with vestibular migraine showed poorest improvement of vertigo and dizziness symptoms over time. In addition, patients who developed anxiety or depressive disorder after the onset of the vestibular disorder showed poor improvement and high persistency of symptoms. PMID- 19645923 TI - Head-shaking nystagmus in central vestibulopathies. AB - Mechanisms of head-shaking nystagmus (HSN) require further exploration in central vestibular disorders. To determine whether impaired uvulonodular inhibition over the velocity storage of the vestibulo-ocular reflex (VOR) is the mechanism of ipsilesional HSN in lateral medullary infarction (LMI), 17 patients with ipsilesional HSN and LMI underwent measurements of the VOR gains during low frequency sinusoidal harmonic accelerations, and the time constants (TC) of the VOR and tilt suppression of the post-otatory nystagmus during step-velocity rotation. Compared with normal controls, the patients showed increased VOR gains without difference between ipsi- and contralesional rotations, while the VOR TCs were decreased without directional asymmetry during step-velocity rotation. In contrast, the patients showed impaired tilt suppression of the postrotatory nystagmus, and the impairment of tilt suppression was more severe after contralesional than ipsilesional rotation. The asymmetric tilt suppression may generate ipsilesional HSN by increasing contralesional velocity storage during head shaking, and may be ascribed to disruption of ipsilesional nodulo-uvular inhibition of the velocity storage mechanism. PMID- 19645924 TI - Testing human otolith function using bone-conducted vibration. AB - Bone-conducted vibration of the forehead, in the midline at the hairline (Fz) causes linear acceleration stimulation of both mastoids and results in an ocular vestibular-evoked myogenic potential (oVEMP), recorded by surface electromyogram (EMG) electrodes just beneath the eyes. The early n10 component of the oVEMP is symmetrical in healthy subjects, absent in patients with bilateral vestibular loss, and in patients after unilateral vestibular loss (uVL) n10 is small or absent on the side contralateral to the uVL, but of normal amplitude on the side contralateral to the healthy ear. The n10 component probably reflects mainly otolithic function, since in the guinea pig, primary otolith irregular neurons are selectively activated by bone-conducted vibration (BCV) at low intensities (0.1 g), whereas semicircular canal primary afferents are not activated even at high intensities (10 g). PMID- 19645925 TI - Displacement of listing's plane by galvanic vestibular stimulation measured by 3 dimensional video-oculography. AB - Saccadic eye movements are located in Listings plane (LP). Activation of the semicircular canals moves the eye positions out of LP, whereas activation of the otolith organs shifts LP. Bipolar galvanic vestibular stimulation (GVS) with DC current stimulates the vestibular periphery, and it is thought to resemble virtual rotations mainly in roll. Eye positions were measured with 3-dimensional (3-D) video-oculography, using sclera markers to determine the ocular torsion. The subjects were seated in darkness, with the head fixed in the upright position, and instructed to perform a saccade when the visual target appeared. GVS was applied in blocks of 10 s. During GVS, subjects showed nystagmus. Eye positions moved out of LP and returned with a torsional offset. Only positions after saccadic eye movements were selected to evaluate that offset. In a group of four healthy subjects, the mean offset to LP was 0.4 degrees (mean current 2.5 mA), with a SD that was greater for GVS (1.0 degrees) than for the control condition (0.4 degrees). PMID- 19645926 TI - Vestibular cortex activation during locomotor imagery in the blind. AB - A previous functional magnetic resonance imaging (fMRI) study in sighted individuals showed deactivations of multisensory vestibular cortex areas in the posterior insula and adjacent temporal sites during locomotor imagery. These vestibular deactivations were suggested to reflect the suppression of vestibular signals during locomotion in order to prevent potentially adverse interactions of these inputs with the optimized automated locomotion pattern. In this fMRI experiment, 10 totally blind subjects and 10 age- and gender-matched sighted controls imagined several locomotor tasks in a first-person perspective (kinesthetic imagery of standing, walking, and running). As opposed to their sighted controls, totally blind individuals activated multisensory vestibular areas in the posterior insula and superior temporal gyrus, with right-sided preponderance during locomotor imagery. These results plausibly suggest that blind subjects rely more on vestibular feedback for locomotor control than do sighted subjects. Thus, this fMRI study provides neuroimaging evidence for distinct cortical processing in the multisensory vestibular system in the blind during locomotor control. PMID- 19645927 TI - Eye-head coordination during free exploration in human and cat. AB - Eye, head, and body movements jointly control the direction of gaze and the stability of retinal images in most mammalian species. The contribution of the individual movement components, however, will largely depend on the ecological niche the animal occupies and the layout of the animal's retina, in particular its photoreceptor density distribution. Here the relative contribution of eye-in head and head-in-world movements in cats is measured, and the results are compared to recent human data. For the cat, a lightweight custom-made head mounted video setup was used (CatCam). Human data were acquired with the novel EyeSeeCam device, which measures eye position to control a gaze-contingent camera in real time. For both species, analysis was based on simultaneous recordings of eye and head movements during free exploration of a natural environment. Despite the substantial differences in ecological niche, photoreceptor density, and saccade frequency, eye-movement characteristics in both species are remarkably similar. Coordinated eye and head movements dominate the dynamics of the retinal input. Interestingly, compensatory (gaze-stabilizing) movements play a more dominant role in humans than they do in cats. This finding was interpreted to be a consequence of substantially different timescales for head movements, with cats' head movements showing about a 5-fold faster dynamics than humans. For both species, models and laboratory experiments therefore need to account for this rich input dynamic to obtain validity for ecologically realistic settings. PMID- 19645928 TI - Adaptation of orientation of central otolith-only neurons. AB - Otolith-only neurons were recorded extracellularly in the vestibular nuclei before and after cynomolgus monkeys were held on-side for up to 3 hr. The aim was to determine whether the polarization vectors of these neurons reorient toward the spatial vertical as do canal-otolith convergent neurons. Otolith input was characterized by tilting the animal 30 degrees from the upright position while positioning the head in different directions in yaw. This determined the response vector orientation (RVO), that is, the projection of the otolith polarization vector onto the head horizontal plane. Changes in the RVO of otolith-only neurons ranged from 2 degrees -16 degrees , which was on average considerably less than the changes previously noted in canal-otolith convergent vestibulo-only (VO) and vestibular plus saccade (VPS) neurons, which ranged up to 109 degrees. Some of the otolith-only neurons had marked sensitivity changes. These findings suggest that otolith-only neurons tend to maintain a head-fixed orientation during prolonged head tilts relative to gravity. In contrast, canal-convergent VO and VPS neurons optimize their response vector orientation to gravity when the head is oriented for prolonged periods. PMID- 19645929 TI - Driving dreams: cortical activations during imagined passive and active whole body movement. AB - It is unclear how subjects perceive and process self-motion cues in virtual reality environments. Movement could be perceived as passive, akin to riding in a car, or active, such as walking down the street. These two very different types of self-motion were studied here using motor imagery in fMRI. In addition, the relative importance of visual and proprioceptive training cues was examined. Stronger activations were found during proprioceptive motor imagery compared with visual motor imagery, suggesting that proprioceptive signals are important for successful imagined movement. No significant activations were found during active movement with proprioceptive training. Passive locomotion, however, was correlated with activity in an occipital-parietal and parahippocampal cortical network, which are the same regions found during navigation with virtual reality stimuli. PMID- 19645930 TI - Modality-dependent indication of the subjective vertical during combined linear and rotational movements. AB - Humans can discriminate whether a change in the direction of gravito-inertial force (GIF) is caused by body tilt or by linear translation. This ability, attributed to vestibular sensory fusion, is often examined by asking subjects to adjust an indicator to match their subjective earth-fixed vertical (SV). We used two different modalities, visual and haptic, to examine continuous adjustment during different combinations of roll rotation and linear translation on a hexapod motion device. We conclude that, in conditions of combined translational and rotational motion, the modality of indication plays a major role for the perception of verticality of the indicator. PMID- 19645931 TI - Handing over a cube: spatial features of physical joint-action. AB - Even though joint action is highly developed in humans, not much is known about motor control in physical joint-action tasks. Here we investigated a physical handover task: one subject sequentially passed wooden cubes to another without communicating verbally. Temporal parameters such as reaction time decreased on a trial-to-trial basis, showing that the efficiency of the task is optimized on line by implicit negotiation between the partners. In contrast, the spatial position of the handover was found to be invariant and trial-independent. Thus, our results suggest that physical joint-action is guided by on-line adaptation and a priori assumptions. PMID- 19645932 TI - Gray-matter atrophy after chronic complete unilateral vestibular deafferentation. AB - It has been shown in blind patients that the abolition of sensory input can lead to changes in white- and cortical gray-matter volumes. Here the white- and gray matter changes found with whole brain voxel-based morphometry in 16 patients with complete chronic unilateral vestibular deafferentation (UVD) due to vestibular schwannoma removal several years prior are reported on. Subtle deficits in spatial memory and navigation were previously shown in patients with right UVD. Images of the brains of right-UVD patients were flipped, standard preprocessing steps were performed, and the data were modulated. Patients showed a gray-matter volume reduction in the cerebellum due to schwannoma removal, in the supramarginal gyrus ipsilateral to the lesion, as well as in the postcentral and superior temporal gyrus, areas involved in the vestibular cortical network, and in the motion-sensitive area MT/V5. There was no correlation with behavioral navigational abilities. No gray-matter atrophy was found in the insular cortical vestibular region or the hippocampus, both of which receive bilateral vestibular projections. The thalamus and tegmentum of the mesencephalon showed gray-matter reduction on the opposite side; this was possibly due to reduced auditory input, which is known to cross at this level. In comparison to healthy controls, no regional increases in gray-matter volume were seen. No white-matter changes were detected at the selected threshold. PMID- 19645933 TI - Vertigo and cerebral hemoglobin changes during unilateral caloric stimulation: a near-infrared spectroscopy study. AB - The aim of the present study using near-infrared spectroscopy (NIRS) is to evaluate the correlation of cerebral (parieto-temporal lobe) hemoglobin changes and vertiginous sensation during unilateral caloric stimulation. During the hot water (44 degrees C) stimulus, cerebral hemoglobin was increased bilaterally, but it was dominant ipsilaterally. During the unilateral cold water (30 degrees C) stimulus, cerebral hemoglobin was decreased on both sides, especially on the ipsilateral side. Vertigious sensation was strong in cases with marked left-right difference of cerebral hemoglobin changes. The usefulness of NIRS to investigate the relationship between peripheral vestibular organ and vestibular cortex was verified. PMID- 19645934 TI - Bilateral vestibular failure as an early sign in Creutzfeldt-Jakob disease. AB - Bilateral vestibular failure causes dysfunction of the vestibulo-ocular reflex with consecutive symptoms like apparent movements of the visual environment during head movements (oscillopsia) and unsteady gait in darkness or on uneven ground. A definite case of Creutzfeldt-Jakob disease in which bilateral vestibular loss was one of the first clinical signs is reported. Further, in a series of 9 consecutive patients with Creutzfeldt-Jakob disease (6 probable, 3 definite), 3 had bilateral vestibular loss at initial presentation. The vestibular nuclei are known to be severely affected in animal spongiform encephalopathies. They might also be a vulnerable target in human prion diseases. PMID- 19645935 TI - Vestibular-neck interaction in cerebellar patients. AB - Vestibulospinal reflexes are important for upright stance and locomotor control. Information from both the vestibular and the proprioceptive system must be combined centrally to guarantee appropriate compensation for a physical disturbance. Recent single-unit recordings from the monkey demonstrated vestibulo proprioceptive interaction in the fastigial nucleus (deep cerebellar nucleus). The present study investigated whether integration of vestibular and proprioceptive signals is compromised in humans with cerebellar degeneration. Control subjects and patients were exposed to binaural, sinusoidal galvanic vestibular stimulation at 0.16 Hz, while their static head-on-trunk position was systematically altered in the head-horizontal plane from 60 degrees left to 60 degrees right. Controls responded to different head-on-trunk positions with fully compensatory changes in the direction of galvanically induced body sway, keeping it aligned with the head-frontal plane. In patients, this compensatory change was lacking. Findings support the assumption that the cerebellum plays a central role in the integration of vestibular and proprioceptive signals in humans. This form of impaired sensory interaction is probably a clinically important component of cerebellar stance and gait ataxia. PMID- 19645936 TI - On-line classification and prediction of eye movements by multiple-model Kalman filtering. AB - An extensible multiple-model Kalman filter framework for eye tracking and video oculography (VOG) applications is proposed. The Kalman filter predicts future states of a system on the basis of a mathematical model and previous measurements. The predicted values are then compared against the current measurements. In a correcting step, the predicted state is enhanced by the measurements. In this work, the Kalman filter is used for smoothing the VOG data, for on-line classification of eye movements, as well as for predictive real-time control of a gaze-driven head-mounted camera (EyeSeeCam). With multiple models running in parallel, it was possible to distinguish between fixations, slow-phase eye movements, and saccades. Under the assumption that each class of eye movement follows a distinct model, one can decide which types of eye movement occurred by evaluating the probability for each model. PMID- 19645937 TI - Influence of uninformative visual cues on gravity perception. AB - The perception of the subjective direction of up (subjective visual zenith, SVZ) is influenced by various sensory cues, such as, vestibular and visual input, and by the idiotropic vector, which acts as prior information about self-orientation with respect to gravity. Here, we tested the influence of a subject-fixed visual cue, which was uninformative with respect to the direction of gravity, on SVZ settings in different pitch angles. Our results show that in most subjects the SVZ was influenced by the gravity-unrelated visual cue in a way suggesting that the cue's orientation was memorized in the first trial and used thereafter as reference. PMID- 19645938 TI - Reversal of initial positioning nystagmus in benign paroxysmal positional vertigo involving the horizontal canal. AB - In benign paroxysmal positional vertigo (BPPV), spontaneous reversal of the initial positioning nystagmus rarely occurs without further position changes. We analyzed the characteristics of spontaneous reversal of the initial head-turning nystagmus in 21 patients with BPPV involving the horizontal semicircular canal. All patients showed initial geotropic nystagmus (first-phase nystagmus) on head turning to either side while supine, which was followed by spontaneous reversal (second-phase nystagmus). The reversal was either unilateral (n = 16) or bilateral (n = 5). The maximal slow phase velocity (SPV) and duration of the first-phase nystagmus were greater and shorter than those of the second-phase nystagmus. The reversal group showed greater maximal SPVs of the initial nystagmus in either ipsi- or contralesional direction than the control group. BPPV resolved after particle repositioning maneuver (PRM) in most patients. However, one patient showed persistent apogeotropic nystagmus after PRM. Short term adaptation of the vestibulo-ocular reflex seems to be the main mechanism of spontaneous reversal of the initial positioning nystagmus. However, coexistence of canalo- and cupulolithiasis should be considered in the patient showing bilateral spontaneous reversal. PMID- 19645939 TI - Head-free gaze control in humans with chronic loss of vestibular function. AB - Healthy subjects use the vestibulo-ocular reflex (VOR) to stabilize gaze. Labyrinthine-defective humans without VOR still are, to some extent, able to maintain gaze stability during active eye-head movements. Here it is investigated whether this stabilization is due to anticipatory mechanisms or proprioceptive feedback. The head inertia was increased in humans who have undergone bilateral vestibulectomy (vestibular subjects) and in healthy controls during large gaze shifts. This leads to head oscillations in both groups. Whereas controls compensate for head oscillations and maintain gaze stability, vestibular subjects display gaze oscillations along with head oscillations. This indicates that vestibular subjects mainly use learned, anticipatory mechanisms, and not proprioception, to stabilize gaze. PMID- 19645940 TI - On-road assessment of driving performance in bilateral vestibular-deficient patients. AB - This study measured on-road driving behavior in subjects with bilateral vestibular loss (BVL). Data included point-of-regard (what the driver is looking at and attending to), gaze stability (the performance of the vestibulo-ocular reflex), and head movement, during complex maneuvers such as changing lanes, cornering, pulling into traffic, and parking. Subjective and objective measures showed few differences between BVL subjects and age-matched controls, and that it is possible to drive well with little or no peripheral vestibular function. This has important implications for driver licensing, road-safety policy, and for the potential successful rehabilitation of vestibular patients. Patients with unilateral vestibular dysfunction may have more difficulty driving than their bilateral counterparts. PMID- 19645942 TI - Long-term follow-up of vestibular neuritis. AB - The long-term outcome of vestibular neuritis was evaluated in 35 patients using 4 bedside tests (head impulse, head heave, head shake, vibration), the caloric test and two surveys that explored the degree of disability (Dizziness Handicap Inventory [DHI]) and the anxiety and depression levels (Hospital Anxiety and Depression Scale [HADS]). Sixty-six percent of patients showed a positive bedside clinical test or calorics abnormalities. DHI scores were significantly higher in the patients group, while HADS scores were comparable between patients and controls. Disability from vestibular neuritis is primarily due to the vestibular disturbance itself, rather than purely psychological factors. PMID- 19645941 TI - Visual search disorders in acute and chronic homonymous hemianopia: lesion effects and adaptive strategies. AB - Patients with homonymous hemianopia due to occipital brain lesions show disorders of visual search. In everyday life this leads to difficulties in reading and spatial orientation. It is a matter of debate whether these disorders are due to the brain lesion or rather reflect compensatory eye movement strategies developing over time. For the first time, eye movements of acute hemianopic patients (n= 9) were recorded during the first days following stroke while they performed an exploratory visual-search task. Compared to age-matched control subjects their search duration was prolonged due to increased fixations and refixations, that is, repeated scanning of previously searched locations. Saccadic amplitudes were smaller in patients. Right hemianopic patients were more impaired than left hemianopic patients. The number of fixations and refixations did not differ significantly between both hemifields in the patients. Follow-up of one patient revealed changes of visual search over 18 months. By using more structured scanpaths with fewer saccades his search duration decreased. Furthermore, he developed a more efficient eye-movement strategy by making larger but less frequent saccades toward his blind side. In summary, visual-search behavior of acute hemianopic patients differs from healthy control subjects and from chronic hemianopic patients. We conclude that abnormal visual search in acute hemianopic patients is related to the brain lesion. We provide some evidence for adaptive eye-movement strategies developed over time. These adaptive strategies make the visual search more efficient and may help to compensate for the persisting visual-field loss. PMID- 19645943 TI - Comparative neurobiology of the optokinetic reflex. AB - A comprehensive overview of the optokinetic reflex (OKR) in vertebrates is given. The main objective is to compare the asymmetry in optokinetic reactions when patterns presented to one eye move horizontally in temporo-nasal or naso-temporal directions. Different hypotheses concerning the evolution of this asymmetry or symmetry in monocular horizontal OKR are discussed. PMID- 19645944 TI - Why do patients with impaired vergence not show "saccadic" vergence? AB - Low gain of the smooth-pursuit system causes correcting saccades that are clinically observed as "saccadic pursuit." In contrast, low gain of the vergence system during tracking does not appear to cause "saccadic tracking." To further evaluate whether this clinical observation is caused by a missing interaction of vergence to step and ramp targets, vergence eye movements to step-ramp, step, and ramp targets in 3-dimensional space were tested. Results show that vergence to a step and a ramp stimulus is additive in the step-ramp paradigm, indicating no interaction of both components. PMID- 19645946 TI - Modeling of intrinsic and synaptic properties to reveal the cellular and network contribution for vestibular signal processing. AB - Computational modeling of cellular and network properties of central vestibular neurons is necessary for understanding the mechanisms of sensory-motor transformation for gaze stabilization. As a first step to mathematically describe vestibular signal processing, the available physiological data of the synaptic and intrinsic properties of frog second-order vestibular neurons (2 degrees VN) were used to create a model that combines cellular and network parameters. With this approach it is now possible to reveal the particular contributions of intrinsic membrane versus emerging network properties in shaping labyrinthine afferent-evoked synaptic responses in 2 degrees VN, to simulate perturbations, and to generate hypotheses that are testable in empiric experiments. PMID- 19645945 TI - Saccadometry of conditional rules in presymptomatic Huntington's disease. AB - The promise of new treatments for Huntington's disease (HD) has intensified interest in markers of preclinical onset and progression. Recent research has shown that elementary saccadic tasks may exhibit subtle preclinical abnormalities. Other studies have shown cognitive dysfunction to be a major component of early-HD phenotype. It was hypothesized that the synergistic combination of an oculomotor response with a cognitively demanding paradigm might therefore offer a functional marker that could be superior both to simpler saccadic paradigms and to conventional cognitive tests. The performance of 12 early-symptomatic HD patients and 17 presymptomatic gene carriers on three saccadic paradigms were studied: prosaccades, color-cued centrally triggered saccades and a second-order conditional rule task on which the direction of the saccade was cued by the combination of central and peripheral cues. Eye movements were recorded using a highly portable, patient-friendly infrared recording device. The analysis of the latency distributions showed that the second-order conditional rule task could discriminate between clinical groups, had a predictive potential within the presymptomatic group and appeared to be more sensitive than easier tasks. The simplicity of portable saccadometry, combined with the sensitivity of a complex oculomotor task, may therefore offer a promising functional marker in HD. PMID- 19645947 TI - Abnormal connection between lateral and posterior semicircular canal revealed by a new modeling process: origin and physiological consequences. AB - We developed a modeling procedure using CT scans or MRI data for exploring the bony and lymphatic canals of vestibular patients. We submitted 445 patients with instability and spatial de-orientation to this procedure. Out of the 445 patients, 95 had scoliosis, some of them, because malformations were suspected also had CT-scan modeling and functional tests. We focused on a never described, abnormal connection between the lymphatic lateral and posterior canal (LPCC) with a frequency of 67/445 (15%). In the scoliosis subgroup, the frequency was 52/95 (55%). Three scoliotic patients had CT scans. For each of them, the modeling revealed that LPCC was present on the bony canals. LPCC has pathognomic signs: no rotatory vertigo but frequent instability, transport sickness head tilt on the side of the anomaly, and spatial disorientation in new environment. We evaluated the functional impact of LPCC by testing the vestibulo-ocular reflex (VOR) in horizontal and vertical planes and found reproducible abnormal responses: in the case of left LPCC, during a counterclockwise horizontal rotation or a post clockwise horizontal rotation, added to the expected horizontal nystagmus, we found an unexpected upbeat nystagmus induced by the ampullofugal displacement of the fluid in the posterior canal. As LPCC was found in CT scans and MRI modeling for a same subject, we suggest that it could be a congenital abnormal process of ossification of the canals. The responses to the vestibular tests highlighting constant unexpected nystagmus underline the potential functional consequences of LPCC on vestibular perception and scoliosis. PMID- 19645948 TI - Visual-motion suppression in congenital pendular nystagmus. AB - Patients with a congenital pendular nystagmus are known not to experience oscillopsia in a normal visual environment. The data of a 31-year-old female patient suffering from a congenital pendular nystagmus are presented. The aim of the fluorodeoxyglucose positron emission tomography (FDG-PET) experiment was to analyze the regional cerebral glucose metabolism (rCGM) during minimal as well as maximal nystagmus. Video-oculography showed a maximum in frequency of the horizontal pendular nystagmus during gaze to the left, whereas the zone of minimal nystagmus was 10 degrees to the right. Two sessions with an 18F fluorodeoxyglucose tracer were performed to analyze cerebral blood-glucose utilization when fixating an object in the areas of maximal and of minimal nystagmus. A structural MRI in a clinical 1.5-T scanner was acquired to superimpose the PET results onto the unique anatomy of the patient. By statistical analysis a significant increase in the rCGM in the cerebellar nodulus and a relative decrease in the area of MT/V5 bilaterally during maximal nystagmus were found. When the patient was looking in her null zone, rCGM was increased in V1 and MT/V5 bilaterally. To the best of the authors' knowledge, this is the first proof by means of functional imaging of a suppression of oscillopsia in higher-order visual cortex areas in a patient with a congenital nystagmus. PMID- 19645949 TI - EyeSeeCam: an eye movement-driven head camera for the examination of natural visual exploration. AB - The prototype of a gaze-controlled, head-mounted camera (EyeSeeCam) was developed that provides the functionality for fundamental studies on human gaze behavior even under dynamic conditions like locomotion. EyeSeeCam incorporates active visual exploration by saccades with image stabilization during head, object, and surround motion just as occurs in human ocular motor control. This prototype is a first attempt to combine free user mobility with image stabilization and unrestricted exploration of the visual surround in a man-made technical vision system. The gaze-driven camera is supplemented by an additional wide-angle, head fixed scene camera. In this scene view, the focused gaze view is embedded with picture-in-picture functionality, which provides an approximation of the foveated retinal content. Such a combined video clip can be viewed more comfortably than the saccade-pervaded image of the gaze camera alone. EyeSeeCam consists of a video-oculography (VOG) device and a camera motion device. The benchmark for the evaluation of such a device is the vestibulo-ocular reflex (VOR), which requires a latency on the order of 10 msec between head and eye (camera) movements for proper image stabilization. A new lightweight VOG was developed that is able to synchronously measure binocular eye positions at up to 600 Hz. The camera motion device consists of a parallel kinematics setup with a backlash-free gimbal joint that is driven by piezo actuators with no reduction gears. As a result, the latency between the rotations of an artificial eye and the camera was 10 msec, which is VOR-like. PMID- 19645951 TI - Stimulus profile and modeling of continuous galvanic vestibular stimulation in functional magnetic resonance imaging. AB - Both direct current (DC) and alternating current (AC) have been used for galvanic vestibular stimulation (GVS) during functional MRI (fMRI). The perceptual effects of apparent rotation persist while the current is being applied, but there is a subjective decay over the entire stimulation period. Particularly during DC-GVS in a supine position, subjects report a strong vestibular sensation related to the onset and offset of the stimulus, and weaker effects during constant DC-GVS stimulation. In the present study, we analyzed DC-GVS fMRI data from a group of volunteers with two different statistical models. In model I, the effects of GVS were modeled as a single regressor that described the periods during which the current was switched on. In model II, an additional regressor describing the onset and offset of the stimulation was included. The activation pattern found by using model I included only a subset of the activation patterns known to respond to vestibular stimulation from previous imaging studies. Model II revealed two different activation maps: block effects similar to the results obtained in model I and additional transient GVS effects with larger activation clusters and higher t-values. This extended activation pattern resembled the results obtained during AC-GVS, including multisensory vestibular projection areas. We show that the major part of the blood oxygenation level dependent (BOLD) responses elicited by DC-GVS is related to the on- and offset of stimulation currents and reflects the perceptual experience just-described. In addition, the separate modeling of transient and persistent effects of DC-GVS can identify distinct cortical correlates of those effects. PMID- 19645950 TI - Changes in dynamic and kinematic properties of saccades in ocular myasthenia following intravenous immunoglobulin treatment. AB - The dynamics and kinematics of saccades in a patient with severe ocular myasthenia were studied before and after treatment with intravenous immunoglobulin (IVIG). Before therapy, horizontal saccades were hypometric, but faster than similar-sized saccades made by normal subjects. During a 5-minute test period, saccades decreased in size (fatigue effect), but remained faster than those of controls. Listing's plane of the eye with greater ophthalmoplegia was increased in thickness. After IVIG treatment, the range of eye movements improved, but saccades remained faster than those of controls. Also, no fatigue was observed and the thickness of Listing's plane was reduced toward the normal range. Increased peak velocity, despite progressive hypometria due to fatigue, supports the hypothesis that the pale global extraocular muscle fibers are relatively spared in myasthenia. Involvement of other extraocular muscle-fiber types leads to limited range of eye movements and an increase in the thickness of Listing's plane. PMID- 19645952 TI - Upbeat-torsional nystagmus and contralateral fourth-nerve palsy due to unilateral dorsal ponto mesencephalic lesion. AB - The central projections of the anterior semicircular canals are thought to be conveyed from the vestibular nuclei to the oculomotor nuclei in the midbrain by three distinct brainstem pathways: the medial longitudinal fasciculus, crossing ventral tegmental tract, and brachium conjunctivum. There is controversy as to whether upbeat nystagmus could result from lesions involving each of these pathways. We report a 52-year-old man who presented with a contralesional fourth nerve palsy and primary-position upbeat-torsional nystagmus due to a small unilateral dorsal pontomesencephalic lymphomatous deposit. It is postulated that the upbeat-torsional nystagmus was caused by involvement of the brachium conjunctivum, which lies adjacent to the fourth-nerve fascicles at the dorsal pontomesencephalic junction, but involvement of the crossing ventral tegmental tract cannot be excluded. These observations suggest that, in humans, excitatory upward-torsional eye movement signals from the anterior semicircular canals could be partly conveyed to the midbrain by the brachium conjunctivum. PMID- 19645953 TI - Prognosis of idiopathic downbeat nystagmus. AB - Downbeat nystagmus (DBN) is a common form of acquired involuntary ocular oscillation overriding fixation. Little is known about the natural evolution of DBN in idiopathic cases. Therefore, eye movements were recorded in seven patients with idiopathic DBN by search-coil technique over a course of up to six years. Neither the slow-phase velocity (SPV) nor the dependency of the SPV on gaze position as an indicator of dysfunction of the oculomotor velocity-to-position integrator changed significantly over the time course investigated in this study. PMID- 19645955 TI - Impulsive testing of semicircular-canal function using video-oculography. AB - The head impulse test (HIT) is a safe, quick way of assessing horizontal semicircular-canal function in patients with peripheral vestibular loss. At the bedside, the clinician identifies "overt" catch-up saccades back to the target after brisk passive head rotation as an indirect sign of canal paresis. However, saccades during head rotation ("covert" saccades) may not be detectable by the naked eye, and so lead to incorrect diagnosis. Up to now, the scleral search coil technique has been the standard for HIT measurement, but that technique is not practical for routine diagnostic use. A new lightweight, nonslip, high-speed video-oculography system (vHIT) that measures eye velocity during horizontal head impulses has been developed. This system is easy to use in a clinical setting, provides an objective measure of the vestibulo-ocular reflex (VOR), and detects both overt and covert catch-up saccades in patients with vestibular loss. PMID- 19645954 TI - Enhancement of the bias component of downbeat nystagmus after lesions of the nodulus and uvula. AB - In two monkeys, we recorded spontaneous eye movements before and after ablation of the cerebellar nodulus and uvula (Nod/Uv). In both monkeys, there was an increase in upward ocular drift (downbeat nystagmus [DBN]) in darkness (M1: 1.5 degrees/s pre, 3.4 degrees/s post; M2: 1.3 degrees/s pre, 7.0 degrees/s post), but not in light. There was little effect of orbital position on drift velocity. These findings suggest that the Nod/Uv may play a role in the bias component of DBN. PMID- 19645956 TI - Electrotactile feedback of sway position improves postural performance during galvanic vestibular stimulation. AB - The purpose of this study was to assess the influence of electrotactile feedback on postural control performance during binaural galvanic vestibular stimulation (GVS). Postural equilibrium was measured with a computerized hydraulic platform in 10 healthy adults (6M, 4F, 24-65 y). Feedback of anterior-posterior (AP) and mediallateral (ML) body sway was derived from a 2-axis linear accelerometer mounted on a torso belt and displayed on a 144-point electrotactile array held against the anterior dorsal tongue. Subjects were trained to use the tongue electrotactile feedback (TEF) by voluntarily swaying to draw figures on their tongue, both with and without GVS. Subjects performed 24 randomized trials (20-s duration with eyes closed, 2 trials per condition), including 4 support surface conditions (fixed, rotational sway-referenced, translating the support surface proportional to AP sway, and combined rotational-translational support-platform sway referencing), and 3 feedback conditions (baseline, GVS, and GVS with TEF). Postural performance was assessed using deviations from upright (peak-to-peak and root-mean-square sway) and convergence toward stability limits (time and distance to limit of support boundaries). Postural stability was impaired (with respect to baseline) during GVS in all platform conditions, with larger decrements in performance during trials with rotation sway-referencing. Electrotactile feedback improved performance with GVS toward non-GVS levels, especially during trials with rotation sway-referencing. These results demonstrate the effectiveness of TEF in providing sensory substitution to maintain postural stability during vestibular disturbances. PMID- 19645957 TI - Effects of the linear vestibulo-ocular reflex on accommodative vergence eye movements. AB - The aim of the study was to determine whether accommodation to the relative motion of a target along the visual axis of one eye during fore-aft movement of the head could induce accurate vergence over a wide range of viewing distances and frequencies of oscillation, despite lack of vision in the second eye. This was compared to the vergence when both eyes viewed the target. Two rhesus monkeys were trained to fixate a visual target located 216-336 mm in front and along the visual axis of one eye, while being sinusoidally translated in the fore-aft direction. There was no movement of the seeing eye while the other eye converged, regardless of whether there was vision in the converged eye. Gain and phase of the convergence were determined based on the ratio of actual versus expected eye position if the target was accurately fixated. During translation at frequencies from 0.05 to 2 Hz, the eye converged on the target with an eye position gain of approximately 1, and a phase close to zero. When vision was occluded in the converging eye, gains of convergence were 0.6-0.8 Hz up to 2 Hz, and the phases remained close to zero. At low frequencies of fore-aft movement, when the acceleration was negligible, convergence was driven by accommodation in the seeing eye. At higher frequencies, vergence could also be driven by the linear vestibulo-ocular reflex (lVOR). Thus, vision in one nonmoving eye and the lVOR combine to generate convergence over a wide range of frequencies and viewing distances. PMID- 19645958 TI - Causative factors, epidemiology, and follow-up of bilateral vestibulopathy. AB - Bilateral vestibulopathy (BV) is characterized by impaired or lost function of both peripheral labyrinths or of the eighth nerves. In a review of 255 patients (mean age +/- SD, 62 +/- 16 years) with BV diagnosed in the authors' dizziness unit between 1988 and 2005, 62% of the patients were male. Previous vertigo attacks had occurred in 36%, indicating a sequential manifestation. The definite cause of BV was determined in 24% and the probable cause in 25%. The most common causes were ototoxic aminoglycosides (13%), Meniere's disease (7%), and meningitis (5%). Strikingly, 25% exhibited cerebellar signs. Cerebellar dysfunction was associated with peripheral polyneuropathy in 32% compared with 18% in BV patients without cerebellar signs. In a follow-up study on 82 BV patients (mean age at the time of diagnosis 56.3 +/- 17.6 years), the frequency and degree of recovery or worsening of vestibular function over time were determined. The patients were reexamined 51 +/- 6 months after the first examination. Electronystagmography with bithermal caloric irrigation was analyzed by measurement of the mean peak slow-phase velocity (SPV) of the induced nystagmus. Statistical analysis of the mean peak SPV revealed a nonsignificant worsening over time (initial mean peak SPV 3.0 +/- 3.5 degrees/s vs. 2.1 +/- 2.8 degrees/s). Only patients with BV due to meningitis exhibited an increasing, but nonsignificant SPV (1.0 +/- 1.4 degrees/s vs. 1.9 +/- 1.6 degrees/s). Forty-three percent of patients subjectively rated the course of their disease as stable, 28% as worsened, and 29% as improved. PMID- 19645959 TI - From sleep duration to mortality: implications of meta-analysis and future directions. PMID- 19645960 TI - Sleep duration and mortality: a systematic review and meta-analysis. AB - Epidemiologic studies have shown that sleep duration is associated with overall mortality. We conducted a systematic review of the associations between sleep duration and all-cause and cause-specific mortality. PubMed was systematically searched up to January, 2008 to identify studies examining the association between sleep duration and mortality (both all-cause and cause-specific) among adults. Data were abstracted serially in a standardized manner by two reviewers and analyzed using random-effects meta-analysis. Twenty-three studies assessing the associations between sleep duration and mortality were identified. All examined sleep duration measured using participant self-report. Among the 16 studies which had similar reference categories and reported sufficient data on short sleep and mortality for meta-analyses, the pooled relative risk (RR) for all-cause mortality for short sleep duration was 1.10 [95% confidence interval (CI): 1.06, 1.15]. For cardiovascular-related and cancer-related mortality, the RRs associated with short sleep were 1.06 (95% CI: 0.94, 1.18) and 0.99 (95% CI: 0.88, 1.13), respectively. Similarly, among the 17 studies reporting data on long sleep duration and mortality, the pooled RRs comparing the long sleepers with medium sleepers were 1.23 (95% CI: 1.17, 1.30) for all-cause mortality, 1.38 (95% CI: 1.13, 1.69) for cardiovascular-related mortality, and 1.21 (95% CI: 1.11, 1.32) for cancer-related mortality. Our findings indicate that both short sleepers and long sleepers are at increased risk of all-cause mortality. Further research using objective measures of sleep duration is needed to fully characterize these associations. PMID- 19645961 TI - Error correction maintains post-error adjustments after one night of total sleep deprivation. AB - Previous behavioral and electrophysiologic evidence indicates that one night of total sleep deprivation (TSD) impairs error monitoring, including error detection, error correction, and posterror adjustments (PEAs). This study examined the hypothesis that error correction, manifesting as an overtly expressed self-generated performance feedback to errors, can effectively prevent TSD-induced impairment in the PEAs. Sixteen healthy right-handed adults (seven women and nine men) aged 19-23 years were instructed to respond to a target arrow flanked by four distracted arrows and to correct their errors immediately after committing errors. Task performance and electroencephalogram (EEG) data were collected after normal sleep (NS) and after one night of TSD in a counterbalanced repeated-measures design. With the demand of error correction, the participants maintained the same level of PEAs in reducing the error rate for trial N + 1 after TSD as after NS. Corrective behavior further affected the PEAs for trial N + 1 in the omission rate and response speed, which decreased and speeded up following corrected errors, particularly after TSD. These results show that error correction effectively maintains posterror reduction in both committed and omitted errors after TSD. A cerebral mechanism might be involved in the effect of error correction as EEG beta (17-24 Hz) activity was increased after erroneous responses compared to after correct responses. The practical application of error correction to increasing work safety, which can be jeopardized by repeated errors, is suggested for workers who are involved in monotonous but attention demanding monitoring tasks. PMID- 19645962 TI - The effect of 40 h constant wakefulness on task-switching efficiency. AB - This study investigated efficiency of switching between different tasks in 12 male participants (19-30 years) during 40 h of constant wakefulness. As index of task-switching efficiency, switch costs in reaction time were assessed every 3 h under controlled behavioural and environmental conditions. Overall reaction times and switch costs showed a temporal pattern consistent with the assumption of a combined influence of a sleep homeostatic and a circadian process. An additional analysis indicated that the variation in switch costs could not be attributed to interference of the current task with persisting activation from preceding tasks. We therefore conclude that sleep loss and the circadian system affect the ability to prepare the current task rather than automatic processing of irrelevant stimulus information. PMID- 19645963 TI - The sensitivity of a PDA-based psychomotor vigilance task to sleep restriction in 10-year-old girls. AB - The impact of sleep restriction on sustained attention in children has not been well quantified. To address this shortcoming, this study tested the sensitivity of a 5-min personal digital assistant-psychomotor vigilance task (PDA-PVT) to sleep restriction in 14 female children [mean (SD) age = 10.6 +/- 0.3 years]. The children underwent PDA-PVT trials at regular intervals both before and after a sleep restriction (5 h time-in-bed) and a control (10 h time-in-bed) condition. Sleep restriction was associated with longer mean response times and increased number of lapses. These results are consistent with findings in the adult literature suggesting an association between inadequate sleep and impaired functioning. In conclusion, the 5-min PDA-PVT is sensitive to sleep restriction in pre-adolescent female children supporting the utility of the PDA-PVT for examining the impact of sleep deprivation on daytime functioning in children. PMID- 19645964 TI - Overnight emotional adaptation to negative stimuli is altered by REM sleep deprivation and is correlated with intervening dream emotions. AB - Rapid eye movement (REM) sleep and dreaming may be implicated in cross-night adaptation to emotionally negative events. To evaluate the impact of REM sleep deprivation (REMD) and the presence of dream emotions on a possible emotional adaptation (EA) function, 35 healthy subjects randomly assigned to REMD (n = 17; mean age 26.4 +/- 4.3 years) and control (n = 18; mean age 23.7 +/- 4.4 years) groups underwent a partial REMD and control nights in the laboratory, respectively. In the evening preceding and morning following REMD, subjects rated neutral and negative pictures on scales of valence and arousal and EA scores were calculated. Subjects also rated dream emotions using the same scales and a 10 item emotions list. REMD was relatively successful in decreasing REM% on the experimental night, although a mean split procedure was applied to better differentiate subjects high and low in REM%. High and low groups differed - but in a direction contrary to expectations. Subjects high in REMD% showed greater adaptation to negative pictures on arousal ratings than did those low in REMD% (P < 0.05), even after statistically controlling sleep efficiency and awakening times. Subjects above the median on EA(valence) had less intense overall dream negativity (P < 0.005) and dream sadness (P < 0.004) than subjects below the median. A correlation between the emotional intensities of the morning dream and the morning picture ratings supports a possible emotional carry-over effect. REM sleep may enhance morning reactivity to negative emotional stimuli. Further, REM sleep and dreaming may be implicated in different dimensions of cross-night adaptation to negative emotions. PMID- 19645965 TI - Arousal in obstructive sleep apnoea patients is associated with ECG RR and QT interval shortening and PR interval lengthening. AB - Sudden cardiac death appears to be more prevalent during the normal sleeping hours in obstructive sleep apnoea (OSA) patients compared with the general population as well as to cardiovascular disease patients. The reasons for this remain unclear, but there are three likely main contributors to nocturnal death in OSA patients; cardiac arrhythmias, stroke/ruptured cerebral aneurism and myocardial infarction. Particularly marked cardiovascular system activation with arousal may play a role in initiating sudden adverse cardiovascular events in OSA. The purpose of this study was to investigate cardiac RR, QT and PR interval changes in the electrocardiogram (ECG) associated with spontaneous and respiratory-related arousals in OSA patients. A detailed observational study of ECG records obtained during conventional diagnostic sleep study with no further interventions was carried out in 20 patients (12 males, age 42.8 +/- 2.1 years, body mass index 35.1 +/- 1.9 kg m(-2), and respiratory disturbance index 51.8 +/- 6.4 events/hour). RR and QT intervals showed significant shortening during arousals. RR interval shortening was found to be greater during respiratory arousals when compared to spontaneous arousals. PR interval showed a trend toward a greater prolongation during respiratory arousal. QT interval shortening was weakly correlated with arterial oxygen saturation levels preceding arousal. In conclusion, these data suggest that despite greater cardiac acceleration following respiratory versus spontaneous arousals from sleep, QT shortening and PR prolongation responses are similar independent of arousal type. These data support that arousals produce quite marked and differential cardiac conduction system activation in OSA and that the degree and pattern of activation may be partly influenced by the presence and severity of preceding respiratory events. PMID- 19645966 TI - Female executives are particularly prone to the sleep-disturbing effect of isolated high-strain jobs: a cross-sectional study in German-speaking executives. AB - This study assessed the main, curvilinear, interactive and gender-dependent effects of job demands, job control and social support in the prediction of sleep quality. Participants were 348 male and 76 female executives and managers from Germany, Austria and Switzerland. A multiple regression controlling for age, occupational hierarchy and various health behaviors was computed. On the level of the main effects of the Job-Demand-Control-Support (JDCS) model, the results indicate a sleep-promoting effect of social support. A significant three-way interaction of job demands, job control and social support was observed. This interaction confirms the buffering effect of high job control and high social support on high job demands. Further, this three-way interaction of the JDCS dimensions is moderated by gender as indicated by a significant four-way interaction. The directions of the significant interactions suggest that female executives are especially prone to react with impaired sleep quality when exposed to isolated high-strain jobs. The study seems to imply that the JDCS model is a suitable framework for the prediction of sleep quality among executives and managers. The results suggest that the JDCS model might contribute to a better understanding of the higher prevalence of poor sleep amongst female executives. Further, the results imply that high job control and high social support might help executives to maintain good sleep quality despite experiencing high job demands. PMID- 19645968 TI - Cortical locations of maximal spindle activity: magnetoencephalography (MEG) study. AB - The aim of this study was to determine the main cortical regions related to maximal spindle activity of sleep stage 2 in healthy individual subjects during a brief morning nap using magnetoencephalography (MEG). Eight volunteers (mean age: 26.1 +/- 8.7, six women) all right handed, free of any medical psychiatric or sleep disorders were studied. Whole-head 148-channel MEG and a conventional polysomnography montage (EEG; C3, C4, O1 and O2 scalp electrodes and EOG, EMG and ECG electrodes) were used for data collection. Sleep MEG/EEG spindles were visually identified during 15 min of stage 2 sleep for each participant. The distribution of brain activity corresponding to each spindle was calculated using a combination of independent component analysis and a current source density technique superimposed upon individual MRIs. The absolute maximum of spindle activation was localized to frontal, temporal and parietal lobes. However, the most common cortical regions for maximal source spindle activity were precentral and/or postcentral areas across all individuals. The present study suggests that maximal spindle activity localized to these two regions may represent a single event for two types of spindle frequency: slow (at 12 Hz) and fast (at 14 Hz) within global thalamocortical coherence. PMID- 19645967 TI - Experimental sleep fragmentation impairs spatial reference but not working memory in Fischer/Brown Norway rats. AB - Sleep fragmentation is a common symptom in sleep disorders and other medical complaints resulting in excessive daytime sleepiness. The present study seeks to explore the effects of sleep fragmentation on learning and memory in a spatial reference memory task and a spatial working memory (WM) task. Fischer/Brown Norway rats lived in custom treadmills designed to induce locomotor activity every 2 min throughout a 24-h period. Separate rats were either on a treadmill schedule that allowed for consolidated sleep or experienced no locomotor activation. Rats were tested in one of two water maze-based tests of learning and memory immediately following 24 h of sleep interruption. Rats tested in a spatial reference memory task (eight massed acquisition trials) with a 24-h follow-up probe trial to assess memory retention showed no differences in acquisition performance but were impaired on the 24 h retention of the platform location. In contrast, the performance of rats tested in a spatial WM task (delayed matching to position task) was not impaired. Therefore, sleep fragmentation prior to testing impairs the ability to retain spatial reference memories but does not impair spatial reference memory acquisition or spatial WM in Fischer-Norway rats. PMID- 19645969 TI - Comparison of subjective and objective assessments of sleep in healthy older subjects without sleep complaints. AB - Older adults have reduced sleep quality compared with younger adults when sleeping at habitual times and greater sleep disruption when their sleep is at adverse times. The purpose of this analysis was to investigate how subjective measures of sleep relate to objectively recorded sleep in older subjects scheduled to sleep at all times of day. We analyzed data from 24 healthy older (55-74 years) subjects who took part in a 32-day inpatient study where polysomnography was recorded each night and subjective sleep was assessed after each scheduled wake time. The study included baseline nights and a forced desynchrony (FD) protocol when the subjects lived on a 20-h rest activity schedule. Our postsleep questionnaire both included quantitative and qualitative questions about the prior sleep. Under baseline and FD conditions, objective and subjective sleep latency were correlated, subjective sleep duration was related to slow-wave sleep and wake after sleep onset, subjective sleep quality was related to stage 1 and 2 sleep, and sleepiness and refreshment at wake time were related to duration of premature awakening. During FD, most measures of objective and subjective sleep varied with circadian phase and many additional correlations between objective and subjective sleep were present. Our findings show that when sleeping at habitual times, these healthy older subjects did not perceive their generally poor sleep quality, but under FD conditions where sleep quality changed from day-to-day their subjective sleep ratings were more associated with their objective sleep. PMID- 19645970 TI - Circadian rhythm in handwriting. AB - The aim of the present study was to determine whether the motor process of handwriting is influenced by a circadian rhythm. Nine healthy young male subjects underwent a 40-h sleep deprivation protocol under constant routine conditions. Starting at 09:00 hours, subjects performed every 3 h two handwriting tasks of different complexity. Handwriting performance was evaluated by writing speed, writing fluency and script size. The frequency of handwriting, as a measure of movement speed, revealed a circadian rhythm, validated by harmonic regression, with a slowing at the time of the onset of melatonin secretion (22:17 hours) and a trough in the very early morning at around 03:30 hours. In the temporal variability of handwriting an effect of task complexity was suggested in the direction of circadian variations in parallel with speed only for the sentence. Despite deficits of speed and temporal variability, writing fluency did not change significantly across sessions indicating that the basic automation of handwriting was preserved at any time. On the second day, daytime levels of the kinematics of handwriting did not reflect impaired performance after sleep deprivation. Our results show for the first time a clear circadian rhythm for the production of handwriting. PMID- 19645971 TI - Benefits of napping in healthy adults: impact of nap length, time of day, age, and experience with napping. AB - Napping is a cross-cultural phenomenon which occurs across the lifespan. People vary widely in the frequency with which they nap as well as the improvements in alertness and well-being experienced. The systematic study of daytime napping is important to understand the benefits in alertness and performance that may be accrued from napping. This review paper investigates factors that affect the benefits of napping such as duration and temporal placement of the nap. In addition, the influence of subject characteristics such as age and experience with napping is examined. The focus of the review is on benefits for healthy individuals with regular sleep/wake schedules rather than for people with sleep or medical disorders. The goal of the review is to summarize the type of performance improvements that result from napping, critique the existing studies, and make recommendations for future research. PMID- 19645973 TI - The place of suxamethonium in pediatric anesthesia. AB - Suxamethonium is a drug that promotes very strong views both for and against its use in the context of pediatric anesthesia. As such, the continuing debate is an excellent topic for a 'Pro-Con' debate. Despite ongoing efforts by drug companies, the popular view still remains that there is no single neuromuscular blocking drug that can match suxamethonium in terms of speed of onset of neuromuscular block and return of neuromuscular control. However, with this drug the balance of benefit vs risk and side effects are pivotal. Suxamethonium has significant adverse effects, some of which can be life threatening. This is particularly relevant for pediatric anesthesia because the spectrum of childhood diseases may expose susceptible individuals to an increased likelihood of adverse events compared with adults. Additionally, the concerns related to airway control in the infant may encourage the occasional pediatric anesthetist to use the drug in preference to slower onset/offset drugs. In the current environment of drug research, surveillance and licensing, it is debatable whether this drug would achieve the central place it still has in pediatric anesthesia. The arguments for and against its use are set out below by our two international experts, Marcin Rawicz from Poland and Barbara Brandom from USA. This will allow the reader an objective evaluation with which to make an informed choice about the use of suxamethonium in their practice. PMID- 19645975 TI - Pediatric airway management: comparing the Berci-Kaplan Video Laryngoscope with direct laryngoscopy. AB - OBJECTIVES: To assess the utility of the Berci-Kaplan Video Laryngoscope (VL) in pediatric anesthesia. BACKGROUND: The VL is designed to improve visualization of the glottis during tracheal intubation of normal and difficult airways in adults. This study was designed to assess the visual quality and the ease of tracheal intubation in children using the VL when compared with direct laryngoscopy (DL). METHODS: Sixty children, aged 2-16 years requiring tracheal intubation, were enrolled in this prospective, randomized clinical trial. Following induction of anesthesia and muscle paralysis, the first laryngoscopy method, using either a DL or the VL, was performed by one anesthetist, and the laryngoscopic view was graded according to the Cormack-Lehane scale. Laryngoscopy and grading of the view in the second method were then performed by a second anesthetist. Tracheal intubation was completed following the second laryngoscopy, and time to intubation was recorded. RESULTS: The average age and weight were 8.9 +/- 3.6 years and 34.9 +/- 16.0 kg respectively. Videolaryngoscopy improved 8/11 grade 2 views to grade 1 (P = 0.02), and one grade 3 to a grade 2. Three grade 2 views remained unchanged from DL to VL. 4/30 VL intubations required two attempts, and 1/30 failed after two attempts, but was easily intubated with DL. Median time (range) was 16.0 s (14.0-20.0 s) and 22.5 s (17.8-35.0 s) for DL and VL respectively (P < 0.001). CONCLUSION: Videolaryngoscopy provides better views than DL at the expense of time to intubate. Although the time taken to intubate is increased with the VL, it is clinically acceptable. PMID- 19645974 TI - Continuous incisional infusion of local anesthetic in pediatric patients following open heart surgery. AB - AIM: To determine the efficacy and safety of a continuous subcutaneous local anesthetic (LA) infusion in pediatric patients following open heart surgery. BACKGROUND: The use of a continuous LA infusion has been shown to be beneficial following adult cardiac surgery. To date there are no studies in the pediatric population. METHODS/MATERIALS: Using a prospective, randomized, and double blind design, we compared LA, either 0.25% levobupivacaine or bupivacaine (Treatment Group) to saline (Placebo Group) delivered subcutaneously via a continuous infusion for 72 h after open heart surgery in 72 patients. Requirements for postoperative analgesics and pain scores were recorded for 72 h and plasma levels of local anesthetic were measured. Secondary outcomes measures included time to first oral intake, time to first bowel movement, time to urinary catheter removal, length of stay, requirements for antiemetics and additional sedation. RESULTS: Total morphine requirements over the first 24 h were less in the Treatment Group than the Placebo Group (0.05 mg x kg(-1) vs 0.2 mg x kg(-1), P = 0.007); this was true for all patient groups except those patients weighing less than 6.3 kg. The number of patients requiring no morphine was greater in the Treatment Group (7/35 vs 1/37, P = 0.02). The Treatment Group also received less midazolam, lorazepam, and ketorolac than the Placebo Group over 72 h due to the reduced clinical need for these agents in patients weighing less than 31 kg. There were no differences in secondary outcomes. CONCLUSIONS: A continuous incisional infusion of LA reduced postoperative analgesic requirement and sedative use in pediatric patients undergoing a median sternotomy incision. Dosed at a maximum rate of 0.4 mg x kg(-1) x h(-1), a continuous incisional infusion of LA is effective and safe for up to 72 h, with plasma levels of local anesthetic well below the toxic threshold. PMID- 19645976 TI - Perioperative cardiac arrests in children at a university teaching hospital of a developing country over 15 years. AB - OBJECTIVE/AIM: To study the incidence, causes, and outcome of perioperative cardiac arrests in children at a university teaching hospital with an aim of improving quality of care. BACKGROUND: Analysis of anesthesia-related complications is routinely performed by most anesthesia departments to make prevention strategies. METHODS: All perioperative cardiac arrests in children up to 18 years from induction of anesthesia to postanesthesia care unit discharge or ICU admission during noncardiac surgery from January 1992 to December 2006 were analyzed. Outcome variable was noted as survival to discharge. Anesthesia-related cardiac arrests were identified and their causes analyzed. RESULTS: Ten cardiac arrests occurred among 20216 patients. Overall incidence was 4.95 per 10000 (95% CI: 1.88-8.01). Six (6.53/10000) were females. Seven (19.44/10000) patients belonged to the classification III-IV of ASA physical status, eight (18.28/10000) were below 1 year, and two (1.26/10000) above 1 year. Three patients (6.53/10000) were undergoing emergency surgery. Anesthesia was primarily responsible in four cases. The causes of anesthesia-related arrests were medication-related (two), airway-related (one), and under-replacement of fluids (one). Seven patients died during the arrest and three were discharged home. The event was considered avoidable in seven (70%) cases. CONCLUSION: Perioperative cardiac arrests were higher in patients with poor physical status, in those under 1 year of age, and in female patients. Anesthesia-related cardiac arrests were mainly due to medication- or airway-related causes. The majority of arrests were avoidable indicating the importance of prevention strategies. PMID- 19645977 TI - Creation of a head and face protection device for children undergoing procedures in prone position. AB - BACKGROUND: Positioning the head of patients undergoing procedures in lateral or prone position remains a difficult task for the anesthesiologists. Associated risks have attracted increasing attention because they range from minor facial soft tissue injuries to catastrophic complications such as stroke or postoperative blindness. Earlier, we reported on the use of a boxing sports helmet for simple and easy positioning of the head. However, as available helmets are limited in sizes and materials, that system is not easily transferable to children. Therefore, we sought to create a face and head protection device for children undergoing procedures in prone position. METHODS/MATERIALS: We re engineered a standard boxing sports helmet making it suitable as an on-head support cushion. By using WHO standard growth charts, various sizes were calculated and prototypes of different foam materials produced. Facial surface pressures were measured in 15 volunteers. RESULTS: A lightweight foam-based face mask was created. Minimum necessary foam thickness was 2.5 cm. Different materials were tested and pressure in different facial zones never exceeded 30 mmHg. CONCLUSION: Bringing a face protection device onto the patient's face instead of placing the face into support cushions is an elegant way of keeping control over airway devices and providing support for facial structures in various positions simultaneously. Skin surface pressure on facial structures remained low due to the specific mask design and choice of foam materials, which could lead to decreased incidences of undesired sequelae of prone position such as skin damage or even more devastating complications. PMID- 19645978 TI - Evaluation of emergence delirium in Asian children using the Pediatric Anesthesia Emergence Delirium Scale. AB - BACKGROUND: Emergence delirium (ED) is a common problem in children recovering from general anesthesia. ED causes disruption in the postanesthetic care unit, making nursing and monitoring more difficult, and is potentially dangerous to the child. The greatest hindrance to understanding ED was the lack of a standardized tool to assess it. The Pediatric Anesthesia Emergence Delirium (PAED) Scale was recently described to measure the degree of ED in children. In this prospective observational study, we sought to evaluate the incidence of ED by grading emergence behavior using the PAED Score in healthy Asian children undergoing outpatient surgery. METHODS: Three hundred sixteen children aged 2-12 years undergoing general anesthesia for elective outpatient surgery were included. No premedication was administered. Induction behavior was graded using the induction compliance checklist, and the presence of any excitation on induction documented. Emergence behavior was recorded using the PAED Scale, and the children were separately assessed for clinical agitation. RESULTS: One hundred and thirty-six children (43%) had PAED Scores >0 and 33 (10.4%) had PAED Scores of >or=10. Only 28 children (8.9%) had clinical agitation consistent with ED, the rest were agitated for other reasons. A score of >or=10 on the PAED Scale was the best discriminator between presence and absence of clinical agitation. The area under the receiver operating characteristic curve for PAED Score of >or=10 was 0.98, with a true-positive rate (sensitivity) of 0.85 and a false-positive rate (1 specificity) of 0.041. Four factors were found to be predictive of ED. These include young age, poor compliance at induction, lack of intraoperative fentanyl use and rapid time to awakening. CONCLUSIONS: The incidence of ED is approximately 10% in our population of healthy, unpremedicated Asian children undergoing day surgery. Young age, poor compliance at induction, lack of intraoperative fentanyl use and rapid time to awakening were predictive risk factors for ED in our population. A PAED Score of >or=10 was correlated with clinically significant ED and appeared to be the ideal cutoff score for ED. PMID- 19645979 TI - Propofol vs pentobarbital for sedation of children undergoing magnetic resonance imaging: results from the Pediatric Sedation Research Consortium. AB - BACKGROUND: Pentobarbital and propofol are commonly used to sedate children undergoing magnetic resonance imaging (MRI). The Pediatric Sedation Research Consortium (PSRC) was created in 2003 to improve pediatric sedation process and outcomes. OBJECTIVE: To use PSRC records to compare the effectiveness, efficiency and adverse events of propofol vs pentobarbital for sedation of children undergoing MRI. METHODS: Pediatric Sedation Research Consortium records of children aged 6 months to 6 years who were primarily sedated with either i.v. pentobarbital or propofol were included. Participating PSRC investigators obtained institutional review board approval before data collection. RESULTS: Of 11 846 sedations for MRI, 7079 met inclusion criteria (propofol: n = 5072; pentobarbital: n = 2007). Demographic details were similar between the two groups. Ideal sedation was produced in 96.45% of the pentobarbital group and in 96.8% of the propofol group (P = 0.478), but pentobarbital was more likely to result in poor sedation cancelling the procedure (OR 5.88; CI 2.24, 15.40). Propofol resulted in physiologic changes more frequently than did pentobarbital (OR 5.69; CI 1.35, 23.97). Pentobarbital was associated with prolonged recovery (OR 16.82; CI 4.98, 56.8), unplanned admission (OR 5.60; CI 1.02, 30.82), vomiting (OR 36.76; CI 4.84, 279.2) and allergic complication (OR 9.15; CI 1.02, 82.34). The incidence of airway complications was not significantly different between the two. The median recovery time for patients receiving propofol was 30 min, whereas for pentobarbital it was 75 min (P < 0.001). CONCLUSION: Among institutions contributing data to the PSRC, it is found that propofol provides more efficient and effective sedation than pentobarbital for children undergoing MRI. Although apnea occurred with a greater frequency in patients who received propofol, the rate of apnea and airway complications for propofol was not statistically different from that seen in patients who received pentobarbital. PMID- 19645980 TI - The anterior to midaxillary line between the 4th or 5th intercostal space (Buelau position) is safe for the use of thoracostomy tubes in preterm and term infants. AB - OBJECTIVES: Thoracostomy tubes are widely used in neonatology. Complications occurred significantly more frequently in infants, especially neonates, than in adults. Principally, the access is the modified Buelau position which takes place in the anterior axillary line at the 4th or 5th intercostal space above the margin of the ribs. AIM: This study seeks to determine the characteristics and topographic conditions of the anatomical structures at the ventral and lateral thoracic wall in the preterm and term neonate. BACKGROUND: Fifteen formalin-fixed stillborns were prepared (nine male, six female, 28-43 weeks gestational age). METHODS/MATERIALS: The anatomical preparation involved the complete thoracic wall region. RESULTS: In all preparations, a venous vessel was detected at the lateral wall and was identified as v. thoracoepigastrica without accompanying artery. Arteria (a.) and vena (v.) thoracica interna were regularly found close to the sternal plate on both sides between rib and fascia. With increasing gestational ages the course of the v. thoracoepigastrica varied significantly between the left and right thoracic wall. It was demonstrated that the v. thoracoepigastrica regularly arose within the abdominal or thoracic subcutaneous fat and drained into the v. subclavia. The variance between its course was almost 5-12 mm to the lateral or medial side. At both thoracic sides, no other organs or organ structures except lung parenchyma could be detected when using the Buelau position. CONCLUSIONS: The anterior to midaxillary line between the 4th or 5th intercostal space (Buelau position) is safe for the use of thoracostomy tubes in preterm and term infants. PMID- 19645981 TI - Sedation of neonates with chloral. PMID- 19645982 TI - Tracheal intubation without neuromuscular blocking drugs. PMID- 19645983 TI - Is transversus abdominis plane block a real alternative to caudal anesthesia? PMID- 19645984 TI - Anesthesia in neonates with large encephaloceles. PMID- 19645985 TI - Duchenne muscular dystrophy: how I do it? Regional or general anesthesia? PMID- 19645986 TI - A case of Rett syndrome with reduced pain sensitivity. PMID- 19645987 TI - Laparoscopic heminephrectomy in a 3-year old with sickle cell disease. PMID- 19645988 TI - Low bispectral index values after treatment for seizures in Dandy-Walker syndrome. PMID- 19645989 TI - Hypercapnia and tachycardia in a 2-year old. PMID- 19645990 TI - Neuropathic pain or somatoform disorder: is the verdict in the differential block? PMID- 19645991 TI - The use of ultrasound guidance to avoid the pinch-off syndrome. PMID- 19645992 TI - Management of outpatient anesthesia in an unusually case with glutaric aciduria type-1. PMID- 19645993 TI - Late eosinophilic pleural effusion after cardiac surgery in a neonate--prompt response to corticosteroid therapy. PMID- 19645994 TI - Airway rescue with an esophageal airway in a child with a huge venous malformation in oral and maxillofacial region--a case report. PMID- 19645995 TI - Safe use of home-made gauze bite blocks in pediatric anesthesia. PMID- 19645996 TI - Use of bite blocks for pediatric anesthesia. PMID- 19645997 TI - Anticipation, planning and execution of airway strategy in McCune-Albright's syndrome. PMID- 19645998 TI - Anesthetic considerations in a teenager with advanced symptoms of Kearns-Sayre syndrome. PMID- 19645999 TI - Lengths of preformed pediatric orotracheal tubes for children with cleft palate. PMID- 19646000 TI - An extraoral fixation method of endotracheal tube during cranio-maxillo-facial surgery. PMID- 19646001 TI - Anesthesia and airway management for children with tonsillar hypertrophy. PMID- 19646002 TI - An uncommon cause of unanticipated difficult airway. PMID- 19646003 TI - The left paraglossal laryngoscopy for orotracheal intubation in children with bilateral cleft lip and palate. PMID- 19646004 TI - Extubation and endotracheal tube exchange using a guidewire sheath in management of difficult pediatric airways. PMID- 19646005 TI - Use of sheath of ureteric stent as a tube exchanger during bronchoscopy. PMID- 19646006 TI - Technique of endotracheal tube fixation. PMID- 19646007 TI - Anesthesia for a child with Hajdu-Cheney syndrome. PMID- 19646008 TI - Journal of Gastroenterology and Hepatology. In this issue. PMID- 19646010 TI - Lipotoxicity: why do saturated fatty acids cause and monounsaturates protect against it? PMID- 19646011 TI - Bile duct injuries associated with cholecystectomy. PMID- 19646012 TI - Who profits from neoadjuvant radiochemotherapy for locally advanced esophageal carcinoma? PMID- 19646013 TI - Necrotizing pancreatitis and antibiotic prophylaxis. To use or not to use ... that is the question. PMID- 19646014 TI - Prevention of hepatocellular carcinoma in nonviral-related liver diseases. AB - Although chronic infection with hepatitis B virus and/or hepatitis C virus are the most important risk factors for hepatocellular carcinoma (HCC) worldwide, other causes of cirrhosis can also lead to HCC. Given the high prevalence of alcoholism and the worldwide obesity epidemic, the relevant importance of nonviral liver disease-related HCC is expected to increase in the future. Some evidence supports mechanistic interactions between host or environmental factors and chronic viral hepatitis in the development of HCC. For example, food- and water-borne carcinogens have contributed to unusually high rates of HCC in parts of China and sub-Saharan Africa. With some of these conditions, appropriate public health measures to reduce the population's exposure to known etiologic agents, or early therapeutic intervention for 'at-risk' individuals before development of cirrhosis (e.g. hereditary hemochromatosis) can prevent HCC. Community-based programs to discourage and deal with excessive alcohol intake, to promote tobacco smoking awareness, to avoid exposure to aflatoxin and other food toxins, and measures to reduce the pandemic of obesity and diabetes are vital for effective interruption of the rising tide of HCC from nonviral liver disease. PMID- 19646015 TI - Epidemiology of esophageal cancer: Orient to Occident. Effects of chronology, geography and ethnicity. AB - Esophageal adenocarcinoma (EAC) has been rapidly increasing in Western countries during the past half century, especially in white men. Esophageal squamous cell carcinoma (ESCC) used to be the dominant type of esophageal malignancy both in Western and Asian countries. The rapid increase of EAC in Western countries has occurred in parallel with an increased prevalence of gastroesophageal reflux disease (GERD) and its major determinant, obesity. Such an increase in EAC has not yet been observed in Asia, despite a recent increase in prevalence of GERD. In this mini-review, we analyze possible factors influencing such east-west ('Orient to Occident') differences, particularly possible roles of ethnicity and environmental factors, such as Helicobacter pylori infection and nutritional factors, and how these might interact with socioeconomic differences. Development of Barrett's esophagus and esophageal adenocarcinoma appears to be strongly affected by ethnic factors, with populations resident at the west end of the Eurasian continent, such as Anglo-Celtics, being more prone to both conditions. On the other hand, ethnic groups from the eastern and southern ends of Eurasia, such as Chinese, Koreans and Japanese, and Africans might be more prone to developing esophageal squamous cell carcinoma. Future trends will also be discussed. PMID- 19646016 TI - Coagulation dynamics and platelet functions in obstructive jaundiced patients. AB - BACKGROUND: All of the body systems are affected by increased levels of bilirubin. The aim of this study is to investigate the function of platelets and clotting dynamics in patients with obstructive jaundice. METHODS: Liver function tests, serum CRP, PT, PTT and hemogram were measured in 23 patients with obstructive jaundice. Thromboelastography (TEG) was done for the evaluation of coagulation dynamics, while platelet function assay (PFA 100) was used to evaluate platelet functions. Blood samples were obtained at two occasions, before the drainage and 3 weeks after the relief of the obstruction. RESULTS: Hypercoagulation was detected in 80% of patients. Maximum strength, elasticity, coagulation indices of the clot were correlated with increased concentrations of direct bilirubin. Although maximum strength of coagulum usually represents increased activity of platelet function, membrane closure times with PFA 100 were found to be prolonged in 30% of patients, reduced values were determined in 17% of patients. No demonstrable effect on coagulation parameters and platelet function were detected after drainage procedures regardless of modality. CONCLUSIONS: Even though there is a general assumption about the increased bleeding tendency in obstructive jaundiced patients, we could not demonstrate reduced clotting activity by measuring with either PFA or TEG. On the contrary we observed tendency for hypercoagulation independent of increased prothrombin times. The most probable cause of this effect is the increased activity of fibrin polymers on platelet membrane. PMID- 19646017 TI - Silicon drain with channels along the sides for internal biliary stenting of hepaticojejunostomy in hepatic hilar malignancies. AB - BACKGROUND: We compared two types of stents in patients who underwent surgery for hepatic hilar malignancies. METHODS: Twenty-one patients with hepatic hilar malignancies who underwent hepatectomy were randomly assigned to one of two groups. A 5-Fr silicon drain with an internal lumen and side holes was used for the hepaticojejunostomy in one group (intraluminal stent group), and a 10-Fr silicon drain with channels along the sides was used in the other (channel stent group). RESULTS: Leakage developed in four patients (36.4%) in the intraluminal stent group versus two (20.0%) in the channel stent group. Cholangitis developed in three patients with leakage (27.3%) in the intraluminal stent group versus no patient in the channel stent group. After operation, the times required for the serum alkaline phosphatase and total bilirubin levels to return to the normal range were significantly shorter in the channel stent group (5.3 +/- 2.9, 3.8 +/- 2.2 days) than in the intraluminal stent group (17.0 +/- 5.8, 9.4 +/- 5.7 days) (P < 0.0001, P = 0.0093). CONCLUSION: A 10-Fr silicon drain with channels is superior to a 5-Fr silicon drain with an internal lumen for internal biliary stenting of hepaticojejunostomy in patients with hepatic hilar malignancies. PMID- 19646018 TI - Prevalence and time trend of intestinal metaplasia in Hong Kong. AB - BACKGROUND AND METHODS: Upper endoscopy records from 1998 to 2003 were reviewed. The demographic data, endoscopic diagnosis, results of rapid urease test and the absence or presence of intestinal metaplasia (IM) in histology were reviewed, to evaluate the prevalence of IM and Helicobacter pylori (Hp) infection over time in Hong Kong. RESULTS: Among 1805 endoscopies performed, 1751 had both rapid urease test and histology available. A significant drop in the prevalence of duodenal ulcers from 17.9% in 1998 to 9.8% in 2003 was found (P = 0.015). Prevalence of IM was 13.9%, 5.9% and 9.4% in Hp positive, Hp negative and overall respectively (P < 0.05). The prevalence of IM increased with age, and the patterns were similar amongst subjects in 1998-2000 and those in 2001-2003. There was progressive decrease in Hp prevalence from 58% in 1998 to 40% in 2001 (P = 0.014), but no further decrease was seen in 2002-3. There was no corresponding decrease in IM prevalence. Instead IM prevalence in 2002-2003 was significantly higher than the prevalence in previous few years (P = 0.04). CONCLUSION: The prevalence of IM did not change in the period from 1998 to 2003 despite a drop in the prevalence of Hp infection since 1994. PMID- 19646019 TI - Education and imaging. Gastrointestinal: Benign cause for pneumatosis intestinalis and portomesenteric venous gas. PMID- 19646021 TI - Education and imaging. Hepatobiliary and pancreatic: Huge hepatic carcinosarcoma. PMID- 19646020 TI - Education and imaging. Gastrointestinal: Dysphagia caused by erosion of a laparoscopic adjustable gastric band. PMID- 19646022 TI - Education and imaging. Hepatobiliary and pancreatic: Large cavernous hemangioma with obstructive jaundice. PMID- 19646023 TI - Education and imaging. Gastrointestinal: Use of a second endoscope to free a jammed stitch cutter. PMID- 19646025 TI - Thermal sensitivity of some plantain micronutrients during deep-fat frying. AB - The impact of deep-fat frying on the micronutrient content of plantain (Musa AAB"barraganete") was evaluated during processing of plantain chips called "tostones." Water content, micronutrients (potassium, L-ascorbic acid, alpha carotene, beta-carotene) content, and the temperature within the food were quantified during the course of frying. A nonisothermal kinetics analysis of the 1st-order reaction (micronutrient degradation) induced by deep-fat frying, particularly in terms of the spatial distribution of temperature, was proposed. The kinetic parameters (pre-exponential factor k(0,) activation energy E(a)) were identified by nonlinear optimization, minimizing the residual variance between the experimental and theoretical micronutrient content. Agreement between model and experimental values was checked. During 1st and 2nd frying, potassium was well retained while carotenoid contents decreased significantly. Moreover, L ascorbic acid contents decreased significantly, just during 2nd frying. k(0) was identified as well as E(a) observed for L-ascorbic acid, alpha-carotene, and beta carotene as 68.4 to 71.5, 79.6 to 84.9, and 85.9 to 88.6 kJ/mol, respectively. beta-carotene appeared to be more heat-resistant than alpha-carotene and L ascorbic acid. The behavior of the nutritional markers appears to be the consequence of the thermal and hydric histories of the crust and of the heart of the plantain disk related to heat transfer during preparation of the "tostones." PMID- 19646026 TI - Physiological and genetic properties of tomato fruits from 2 cultivars differing in chilling tolerance at cold storage. AB - Postharvest tomato fruits are cold-sensitive, and easy to develop chilling injury (CI) at cold storage. Information on physiological and genetic characteristics closely related to CI is necessary because it is significant to realize CI development regular and find sensitive indicators reflecting cultivar cold tolerance, which are the basics to prevent CI. In this study, we used 2 tomato cultivars (Lichun and Santiam) differing in cold tolerance to analyze ion leakage, malondialdehyde (MDA), proline, catalase (CAT), and peroxidase (POD) in postharvest fruits chilled at cold storage. Expression of cold-response gene LeCBF1, a key regulator in cold-response, was also detected. Results showed that ion leakage, with a high correlation coefficient (0.9661) to CI index, exactly reflected injury development phase and degree; sharp increase of MDA and proline content appeared at and before the time of main development phase of CI (10 d); however, fluctuant CAT and POD activities could not sensitively reflect CI development, since their regular changes didn't appear until the main development phase ended. Thus, ion leakage, MDA, and proline content were effective indicators for CI analysis in postharvest tomato fruits. Although physiological analysis was effective in CI analysis, it was complex to be used in judging cold tolerance. Expression of LeCBF1 gene swiftly responded to low temperature within 1 h. In accordance with those physiological parameters, LeCBF1 expression level was positively correlated with cold tolerance and showed a high correlation to CI index (-0.9176). These suggested that LeCBF1 analysis could be effectively used in fast testing the cold tolerance of tomato. PMID- 19646027 TI - Effect of gamma irradiation on molecular structure and physicochemical properties of corn starch. AB - Carboxyl content and amylose leaching of gamma-irradiated corn starch increased and swelling factor decreased with increasing radiation dose. The apparent amylose content decreased gradually from 28.7% for native starch to 20.9% for 50 kGy irradiated starch. The proportion of short amylopectin branch chains (DP 6 to 12) increased, while the proportion of longer branch chains (DP > or = 37) decreased with increasing radiation dose. The relative crystallinity and the degree of granule surface order decreased from 28.5% and 0.631 in native starch to 26.9% and 0.605 in 50 kGy irradiated starch, respectively. Pasting viscosity and gelatinization temperatures decreased with an increase in radiation dose. At a high dose (50 kGy), melting of amylose-lipid complex in DSC thermogram was not observed. The rapidly digestible starch (RDS) content slightly decreased up to 10 kGy but increased at 50 kGy. The resistant starch (RS) content slightly decreased at 2 kGy and then increased up to 50 kGy. The slowly digestible starch (SDS) content showed the opposite trend to RS content. Slower irradiation dose rate reduced carboxyl content, swelling factor, and amylose leaching. The apparent amylose content and amylopectin chain length distribution were not significantly affected by dose rate of gamma irradiation. However, the relative crystallinity and gelatinization enthalpy increased with slower dose rate. Slower dose rate decreased RDS and SDS contents, and increased RS content. PMID- 19646028 TI - Kinetic study of the quenching reaction of singlet oxygen by common synthetic antioxidants (tert-butylhydroxyanisol, tert-di-butylhydroxytoluene, and tert butylhydroquinone) as compared with alpha-tocopherol. AB - Effects of synthetic phenolic antioxidants (BHA, BHT, and TBHQ) on the methylene blue (MB) sensitized photooxidation of linoleic acid as compared with that of alpha-tocopherol have been studied. Their antioxidative mechanism was studied by both ESR spectroscopy in a 2,2,6,6-tetramethylpiperidone (TMPD)-methylene blue (MB) system and spectroscopic analysis of rubrene oxidation induced by a chemical source of singlet oxygen. Total singlet oxygen quenching rate constants (k(ox Q)+k(q)) were determined using a steady state kinetic equation. TBHQ showed the strongest protective activity against the MB sensitized photooxidation of linoleic acid, followed by BHA and BHT. TBHQ (1 x 10(-3) M) exhibited 86.5% and 71.4% inhibition of peroxide and conjugated diene formations, respectively, in linoleic acid photooxidation after 60-min light illumination. The protective activity of TBHQ against the photosensitized oxidation of linoleic acid was almost comparable to that of alpha-tocopherol. The data obtained from ESR and rubrene oxidation studies clearly showed the strong singlet oxygen quenching ability of TBHQ. The k(ox-Q)+k(q) of BHA, BHT, and TBHQ were determined to be 3.37 x 10(7), 4.26 x 10(6), and 1.67 x 10(8) M(-1) s(-1), respectively. The k(ox Q)+k(q) of TBHQ was within the same order of magnitude of that of alpha tocopherol, a known efficient singlet oxygen quencher. There was a high negative correlation (r(2) = -0.991) between log (k(ox-Q)+k(q)) and reported oxidation potentials for the synthetic antioxidants, indicating their charge-transfer mechanism for singlet oxygen quenching. This is the 1st report on the kinetic study on k(ox-Q)+k(q) of TBHQ in methanol as compared with other commonly used commercial synthetic antioxidants and alpha-tocopherol. PMID- 19646029 TI - Seed viability and functional properties of broccoli sprouts during germination and postharvest storage as affected by irradiation of seeds. AB - The viability of broccoli seeds and functional properties, such as ascorbic acid, carotenoid, chlorophyll, and total phenol contents, of broccoli sprouts grown from irradiated seeds were evaluated. The seeds were irradiated using electron beam and gamma ray at doses up to 8 kGy. High germination percentages (>90%) were observed in seeds irradiated at < or =4 kGy, but the yield ratio and sprout length decreased with increased irradiation dose. Irradiation at > or =6 kGy resulted in curling of the sprout roots. Germinated seeds contained higher amounts of nutrients than raw seeds but the nutritional quality of sprouts decreased during postharvest storage. Radiation treatment hampered the growth of irradiated seeds resulting in underdeveloped sprouts with decreased ascorbic acid, carotenoid, and chlorophyll contents. In addition, the decrease in functional content of sprouts was more substantial in samples grown from high dose (5 kGy) irradiated seeds than that of the low-dose (1 kGy) treated ones. Seed irradiation did not negatively affect the total phenol content of sprouts. In general, electron beam and gamma irradiation of broccoli seeds showed similar effects on the viability and functional properties of sprouts. PMID- 19646030 TI - Effect of chelating agents and spice-derived antioxidants on myoglobin oxidation in a lipid-free model system. AB - This study compared myoglobin (Mb) oxidation in lipid-free model systems containing iron and Type I (radical quenching) or Type II (metal chelating) antioxidants. Oxidation was measured as loss of oxymyoglobin (MbO(2)) during 0 to 24 h holding at 22 degrees C. Sodium tripolyphosphate (STPP) demonstrated iron binding ability at all concentrations tested (88% and 21% added iron bound at 1 and 0.05 mg/mL, respectively). Iron chelation was observed for phytic acid only at the highest concentration (9.5% bound at 1 mg/mL phytate). Neither Type I antioxidant (rosmarinate or eugenol) demonstrated any iron chelating ability (<0.5% bound). In presence of iron, Type I antioxidants had a significant (P < 0.05) prooxidant effect (54.7% retention of MbO(2) in control, 9.5% and 37.5% retention in rosmarinate and eugenol samples, respectively). The Type II antioxidants (STPP and phytate) were more effective inhibitors (P < 0.05) of Mb oxidation than Type I antioxidants, (68.7% and 61.1% for STPP and phytate, respectively). Type I antioxidants were capable of rapid reduction of ferric iron to the ferrous form, as measured by the ferrozine assay. This strong reducing ability accounted for the prooxidant effects of rosmarinic acid and eugenol, since ferrous iron is the form associated with generation of oxygen radicals, and subsequent Mb oxidation. Type II antioxidants chelated and thus prevented the oxidizing effect of added ferrous iron. Mb oxidation can proceed rapidly (within 15 min) in the presence of iron and the absence of lipid, especially if reducing compounds such as rosmarinic acid or eugenol are also present to maintain iron in an active ferrous form. PMID- 19646031 TI - Effects of riboflavin photosensitization on the degradation of bisphenol A (BPA) in model and real-food systems. AB - Effects of riboflavin photosensitizations on the stability of bisphenol A (BPA), a well-known endocrine disrupting chemical, were studied in model and real-food systems by high-performance liquid chromatography (HPLC). Concentration of BPA was significantly decreased under light exposure (P < 0.05) as the concentration of riboflavin increased while those without riboflavin under light or those with riboflavin in the dark did not change significantly (P > 0.05). Addition of 50, 100, and 200 microM sodium azide significantly increased the stability of BPA in riboflavin photosensitization with concentration dependent manner (P < 0.05), implying that a singlet oxygen or type II pathway played a role in the photodegradation of BPA. Stability of BPA in riboflavin was significantly increased in the presence of high concentration of tert-butanol, a hydroxyl radical quencher, under light storage for 80 min, indicating hydroxyl radicals were involved and contributed to the degradation of BPA, at least in part. Availability of riboflavin photosensitization on the photodegradation of BPA was tested in 2 canned tea beverages with different phenolic contents. BPA was more stable in the beverage sample with higher total phenolic contents and free radical scavenging ability. The photodegradation of BPA in riboflavin photosensitization can be an efficient way to decrease the concentration of BPA from environmental or food systems. PMID- 19646032 TI - Fourier transform infrared spectroscopy for Kona coffee authentication. AB - Kona coffee, the variety of "Kona typica" grown in the north and south districts of Kona-Island, carries a unique stamp of the region of Big Island of Hawaii, U.S.A. The excellent quality of Kona coffee makes it among the best coffee products in the world. Fourier transform infrared (FTIR) spectroscopy integrated with an attenuated total reflectance (ATR) accessory and multivariate analysis was used for qualitative and quantitative analysis of ground and brewed Kona coffee and blends made with Kona coffee. The calibration set of Kona coffee consisted of 10 different blends of Kona-grown original coffee mixture from 14 different farms in Hawaii and a non-Kona-grown original coffee mixture from 3 different sampling sites in Hawaii. Derivative transformations (1st and 2nd), mathematical enhancements such as mean centering and variance scaling, multivariate regressions by partial least square (PLS), and principal components regression (PCR) were implemented to develop and enhance the calibration model. The calibration model was successfully validated using 9 synthetic blend sets of 100% Kona coffee mixture and its adulterant, 100% non-Kona coffee mixture. There were distinct peak variations of ground and brewed coffee blends in the spectral "fingerprint" region between 800 and 1900 cm(-1). The PLS-2nd derivative calibration model based on brewed Kona coffee with mean centering data processing showed the highest degree of accuracy with the lowest standard error of calibration value of 0.81 and the highest R(2) value of 0.999. The model was further validated by quantitative analysis of commercial Kona coffee blends. Results demonstrate that FTIR can be a rapid alternative to authenticate Kona coffee, which only needs very quick and simple sample preparations. PMID- 19646033 TI - GC/MS method for the determination of adipate plasticizers in ham sausage and its application to kinetic and penetration studies. AB - A GC/MS method was developed and successfully validated for the determination of adipate plasticizers in ham sausage migrated from polyvinylidene chloride (PVDC) packaging film. The sample pretreatment includes liquid extraction, solvent evaporation, and reconstitution before and after solid phase extraction (SPE). For the 5 adipate plasticizers studied, the SPE process with Oasis MAX cartridge showed an extraction efficiency from 85.7% to 106%, and the calibration curves are all linear in the range of 5 to 1000 ng/g with correlation coefficients greater than 0.998. The method proved to be accurate and precise; the average intraday recovery ranges from 85.4% to 114.6% with a %CV value from 2.5 to 11.3, and the average interday recovery from 83.6% to 118.5% with a %CV value from 2.8 to 15.6, respectively, for the adipate plasticizers. The method is sensitive and was effectively applied in the kinetic and penetration studies of the adipate plasticizers migrating from food-grade PVDC packaging film into ham sausage. The experimental data showed that approximately 6.8% of dibutyl adipate (DBA) in the packaging film migrated into the ham sausage in 4 mo and the migration reached the innermost portion of the sausage in 6 mo. PMID- 19646034 TI - Overall quality and shelf life of minimally processed and modified atmosphere packaged 'ready-to-eat' pomegranate arils. AB - Minimally processed ready-to-eat pomegranate arils have become popular due to their convenience, high value, unique sensory characteristics, and health benefits. The objective of this study was to monitor quality parameters and to extend the shelf life of ready-to-eat pomegranate arils packaged with modified atmospheres. Minimally processed pomegranate arils were packed in PP trays sealed with BOPP film under 4 atmospheres including low and super atmospheric oxygen. Packaged arils were stored at 5 degrees C for 18 d and monitored for internal atmosphere and quality attributes. Atmosphere equilibrium was reached for all MAP applications except for high oxygen. As a general trend, slight or no significant change was detected in chemical and physical attributes of pomegranate arils during cold storage. The aerobic mesophilic bacteria were in the range of 2.30 to 4.51 log CFU/g at the end of the storage, which did not affect the sensory quality. Overall, the pomegranate arils packed with air, nitrogen, and enriched oxygen kept quality attributes and were acceptable to sensory panelists on day 18; however, marketability period was limited to 15 d for the low oxygen atmosphere. PP trays sealed with BOPP film combined with either passive or active modified atmospheres and storage at 5 degrees C provided commercially acceptable arils for 18 d with high quality and convenience. PMID- 19646035 TI - Changes in the composition of raw tea leaves from the Korean Yabukida plant during high-temperature processing to pan-fried Kamairi-cha green tea. AB - To develop a better understanding of compositional changes occurring during the production of commercial teas, we determined by high-performance liquid chromatography (HPLC) changes in ingredient levels during each of several manufacturing steps used to produce Kamairi-cha, a premium green tea. Kamairi-cha uses pan-frying instead of the usual blanching technique to inactivate the enzymes responsible for producing traditional black tea. The resulting tea lacks the characteristic bitterness of green tea, producing a green tea that is described as sweet tasting. The processing steps used to produce this pan-fried tea were as follows: 1st roasting, 1st rolling, 2nd roasting, 2nd rolling, 1st firing, and 2nd firing. The results show that during production at temperatures up to 300 degrees C, raw leaves lost (in percent) 97.3 water, 94 two chlorophylls, 14.3 seven catechins, and 2.75 caffeine. A separate analysis showed that the final product contained 21.67 mg/g dry wt of the biologically active amino acid theanine. The results of this 1st report on changes in individual catechins and other tea ingredients in tea leaves during pan-frying make it possible to select production conditions that maximize levels of beneficial tea ingredients. The possible significance of the results for the human diet is discussed. PMID- 19646036 TI - Kinetic study of the combined effect of high hydrostatic pressure and temperature on the activity of Lactobacillus delbrueckii ssp. bulgaricus aminopeptidases. AB - The effect of high hydrostatic pressure (HHP) (100 to 700 MPa) combined with temperature (20 to 40 degrees C) on the activity of 5 aminopeptidases (PepN, PepX, PepY, PepC, and PepA) of Lactobacillus delbrueckii ssp. bulgaricus ACA-DC 0105, used as starter culture for feta cheese production, was studied. Aminopeptidases PepN, PepX, and PepA were activated at pressures up to 200 MPa, at temperatures up to 40 degrees C. PepY and PepC appeared to be more sensitive to pressure and temperature treatment leading to inactivation for pressures above 100 and 200 MPa, respectively, combined with temperature above 30 degrees C. A multi-parameter equation was used for predicting the activation of PepN, PepX, and PepA aminopeptidases in the pressure and temperature domain. Overall, processing at 200 MPa and 20 degrees C may be selected as the optimum conditions for maximum activation of 4 out of 5 aminopeptidases of L. delbrueckii ssp. bulgaricus. A 20-min treatment at these conditions leads to an average 3-fold increase in activity, which could lead to better and faster maturation of white cheese. PMID- 19646037 TI - Influence of extrusion-cooking parameters on some quality aspects of precooked pasta-like products. AB - The present article aims to evaluate some quality parameters and texture characteristics of precooked wheat pasta-like products. Using the methods for pasta and instant noodles the tested parameters were water absorption, starch gelatinization degree, cooking losses, and hardness. The texture profile was characterized using Zwick apparatus by cutting test with the head speed of 10 mm/min and expressed as hardness and firmness of hydrated products. SEM pictures were used to illustrate the internal structure of dry and cooked pasta-like products. Dough moisture content and process conditions influenced all tested quality parameters of the pasta-like products processed on a modified single screw extrusion-cooker TS-45 with L: D = 16: 1. Good organoleptical quality (notes higher than 4 in a 5-point scale) and firm texture were observed for common wheat flour pasta processed at 30% m.c. Hardness and firmness of hydrated products lowered with a longer hydration time in hot water. The firmest texture and low stickiness was observed for products with a highest starch gelatinization degree. PMID- 19646038 TI - Magnetic resonance temperature mapping of microwave-fried chicken fingers. AB - The main objective of this study was to compare the heating patterns of chicken fingers deep-fried conventionally and using a microwave. Two dimensional internal temperature maps of fried chicken fingers with rectangular geometry were measured post frying using magnetic resonance imaging (MRI). Frying was performed in a microwave oven at 365 W power level for 0.5 and 1.5 min after bringing the oil temperature to 180 +/- 1 degrees C. Samples were also fried in a conventional fryer at 180 degrees C for 2 and 5 min for comparison. Variations in internal temperature distribution increased proportionally to frying time in both microwave and conventional frying. Internal thermal equilibrium is reached in all samples after 13 min of holding time. Internal structural changes, void formation, were also visualized in the images. Void formation did not significantly impact cooling rates. PMID- 19646039 TI - Inverse method to estimate kinetic degradation parameters of grape anthocyanins in wheat flour under simultaneously changing temperature and moisture. AB - Thermal and moisture effects on grape anthocyanin degradation were investigated using solid media to simulate processing at temperatures above 100 degrees C. Grape pomace (anthocyanin source) mixed with wheat pastry flour (1: 3, w/w dry basis) was used in both isothermal and nonisothermal experiments by heating the same mixture at 43% (db) initial moisture in steel cells in an oil bath at 80, 105, and 145 degrees C. To determine the effect of moisture on anthocyanin degradation, the grape pomace-wheat flour mixture was heated isothermally at 80 degrees C at constant moisture contents of 10%, 20%, and 43% (db). Anthocyanin degradation followed a pseudo first-order reaction with moisture. Anthocyanins degraded more rapidly with increasing temperature and moisture. The effects of temperature and moisture on the rate constant were modeled according to the Arrhenius and an exponential relationship, respectively. The nonisothermal reaction rate constant and activation energy (mean +/- standard error) were k(80 degrees C, 43% (db) moisture) = 2.81 x 10(-4)+/- 1.1 x 10(-6) s(-1) and DeltaE = 75273 +/- 197 J/g mol, respectively. The moisture parameter for the exponential model was 4.28 (dry basis moisture content)(-1). One possible application of this study is as a tool to predict the loss of anthocyanins in nutraceutical products containing grape pomace. For example, if the process temperature history and moisture history in an extruded snack fortified with grape pomace is known, the percentage anthocyanin loss can be predicted. PMID- 19646040 TI - Osmotic dehydration of tomato in sucrose solutions: Fick's law classical modeling. AB - Osmotic dehydration of tomato was modeled by the classical Fick's law including shrinkage, convective resistance at the interface and the presence of water bulk flow. Tomato slices having 8 mm thickness were osmotically dehydrated in sucrose solutions at 50, 60, and 70 degrees Brix and at 35, 45, and 55 degrees C. Other experiments were done in a 70 degrees Brix sucrose solution at 35 degrees C with tomato slices of 4, 6, and 8 mm thickness and at different motion levels (velocities 0, 0.053, and 0.107 m/s). Tomato weight, water content, and degrees Brix of the products were measured as a function of processing time (20, 40, 80, 160, and 320 min). Results showed that temperature, concentration, thickness, and solution movement significantly influenced water loss and sucrose gain during the osmotic dehydration of tomato. The model predicted the modifications of soluble solid content and water content as a function of time in close agreement with the experimental data. Experimental Sherwood number correlations for sucrose and water were determined as Sh(s) = 1.3 Re(0.5)Sc(s) (0.15) and Sh(w) = 0.11 Re(0.5)Sc(w) (0.5), respectively. The effective diffusion coefficients of water (4.97 10(-11)- 2.10 10(-10) m(2)/s) and sucrose (3.18 10(-11)- 1.69 10(-10) m(2)/s) depended only on temperature through an Arrhenius-type relationship. PMID- 19646041 TI - Foams prepared from whey protein isolate and egg white protein: 1. Physical, microstructural, and interfacial properties. AB - Foams were prepared from whey protein isolate (WPI), egg white protein (EWP), and combinations of the 2 (WPI/EWP), with physical properties of foams (overrun, drainage 1/2 life, and yield stress), air/water interfaces (interfacial tension and interfacial dilatational elasticity), and foam microstructure (bubble size and dynamic change of bubble count per area) investigated. Foams made from EWP had higher yield stress and stability (drainage 1/2 life) than those made from WPI. Foams made from mixtures of EWP and WPI had intermediate values. Foam stability could be explained based on solution viscosity, interfacial characteristics, and initial bubble size. Likewise, foam yield stress was associated with interfacial dilatational elastic moduli, mean bubble diameter, and air phase fraction. Foams made from WPI or WPI/EWP combinations formed master curves for stability and yield stress when normalized according to the above mentioned properties. However, EWP foams were excluded from the common trends observed for WPI and WPI/EWP combination foams. Changes in interfacial tension showed that even the lowest level of WPI substitution (25% WPI) was enough to cause the temporal pattern of interfacial tension to mimic the pattern of WPI instead of EWP, suggesting that whey proteins dominated the interface. The higher foam yield stress and drainage stability of EWP foams appears to be due to forming smaller, more stable bubbles, that are packed together into structures that are more resistant to deformation than those of WPI foams. PMID- 19646042 TI - Foams prepared from whey protein isolate and egg white protein: 2. Changes associated with angel food cake functionality. AB - The effects of sucrose on the physical properties and thermal stability of foams prepared from 10% (w/v) protein solutions of whey protein isolate (WPI), egg white protein (EWP), and their combinations (WPI/EWP) were investigated in wet foams and angel food cakes. Incorporation of 12.8 (w/v) sucrose increased EWP foam stability (drainage 1/2 life) but had little effect on the stability of WPI and WPI/EWP foams. Increased stability was not due to viscosity alone. Sucrose increased interfacial elasticity (E ') of EWP and decreased E' of WPI and WPI/EWP combinations, suggesting that altered interfacial properties increased stability in EWP foams. Although 25% WPI/75% EWP cakes had similar volumes as EWP cakes, cakes containing WPI had larger air cells. Changes during heating showed that EWP foams had network formation starting at 45 degrees C, which was not observed in WPI and WPI/EWP foams. Moreover, in batters, which are foams with additional sugar and flour, a stable foam network was observed from 25 to 85 degrees C for batters made from EWP foams. Batters containing WPI or WPI/EWP mixtures showed signs of destabilization starting at 25 degrees C. These results show that sucrose greatly improved the stability of wet EWP foams and that EWP foams form network structures that remain stable during heating. In contrast, sucrose had minimal effects on stability of WPI and WPI/EWP wet foams, and batters containing these foams showed destabilization prior to heating. Therefore, destabilization processes occurring in the wet foams and during baking account for differences in angel food cake quality. PMID- 19646043 TI - Effects of waxy wheat flour and water on frozen dough and bread properties. AB - The quality of bread made from frozen dough is diminished by changes that occur during freezing. New cultivars of waxy wheat flour (WWF), containing less than 2% amylose, offer unique properties for the production of baked products. In this study, dough properties and bread quality were investigated at various levels of WWF (0% to 45% flour weight) and water (55% to 65%). Dough stickiness increased with higher levels of WWF and water. During frozen storage, dough with greater WWF and lower water had less change in stickiness. Maximum resistance to extension (MRE) decreased with higher WWF and water. Dough with greater WWF and less water had less change in extensibility after frozen storage. Dough with greater WWF and water was more extensible. Nuclear magnetic resonance (NMR) studies showed that frozen dough with higher WWF content had lower transverse relaxation (T(2)) time of 9 to 11ms. After frozen storage, dough with higher WWF still showed lower T(2). Dough with 15% WWF had higher yeast activity. Bread made from 15% and 30% WWF had higher volume in bread made from unfrozen and frozen dough. Bread firmness decreased with higher amounts of WWF and water. This research demonstrated that specific combinations of WWF and water produced a better quality of frozen dough and bread. PMID- 19646044 TI - Characterization and ACE-inhibitory activity of amaranth proteins. AB - Amaranth seeds have been considered as an excellent alternative or complementary source of food protein due to their balanced amino acid composition. However, their potential as a source of bioactive peptides has not been explored. The present study is aimed at characterizing and evaluating the activity of the angiotensin converting enzyme inhibitor of the amaranth protein concentrate and of hydrolysates produced with Alcalase. The protein concentrate, after simulated gastrointestinal digestion, showed lower angiotensin converting enzyme-inhibitory activity (IC(50) of 0.439 +/- 0.018 mg protein/mL and 0.475 +/- 0.021 mg protein/mL, for untreated and heat treated protein concentrate, respectively) than the hydrolysates produced with Alcalase, before and after simulated gastrointestinal digestion (IC(50) 0.118 +/- 0.009, 0.123 +/- 0.007, 0.137 +/- 0.002, and 0.176 +/- 0.014 mg protein/mL, respectively). The simulated gastrointestinal digestion (pepsin-pancreatin) did not significantly alter the angiotensin-converting enzyme inhibiting activity of the Alcalase hydrolysates, suggesting that the peptides of the hydrolysates were resistant to gastrointestinal hydrolysis. These results highlight the angiotensin converting enzyme-inhibitory potential of amaranth proteins, which is an indication of their health-promoting potential. PMID- 19646046 TI - Effect of guava (Psidium guajava L.) leaf extract on glucose uptake in rat hepatocytes. AB - People in oriental countries, including Japan and Taiwan, boil guava leaves (Psidium guajava L.) in water and drink the extract as a folk medicine for diabetes. The present study investigated the enhancement of aqueous guava leaf extract on glucose uptake in rat clone 9 hepatocytes and searched for the active compound. The extract was eluted with MeOH-H(2)O solutions through Diaion, Sephadex, and MCI-gel columns to separate into fractions with different polarities. The uptake test of 2-[1-(14)C] deoxy-D-glucose in rat clone 9 hepatocytes was performed to evaluate the hypoglycemic effect of these fractions. The active compound was identified by nuclear magnetic resonance analysis and high-performance liquid chromatography (HPLC). The results revealed that phenolics are the principal component of the extract, that high polarity fractions of the guava leaf extract are enhancers to glucose uptake in rat clone 9 hepatocytes, and that quercetin is the major active compound. We suggest that quercetin in the aqueous extract of guava leaves promotes glucose uptake in liver cells, and contributes to the alleviation of hypoglycemia in diabetes as a consequence. PMID- 19646045 TI - The beneficial effect of propolis on fat accumulation and lipid metabolism in rats fed a high-fat diet. AB - This study examined whether propolis, which had many biological activities, affected body fat and lipid metabolism. Four-week-old Wistar rats were fed a control or propolis diet for 8 wk. The control group was fed a high-fat diet, the low and the high group were fed a high-fat diet supplemented with 0.5% (w/w) and 0.05% (w/w) propolis, respectively. The weight of total white adipose tissue of the high group was lower than that of the control group. The level of PPARgamma protein in the adipose tissues of the high group was significantly lower than that of the control group. In plasma and the liver, the high group showed a significantly reduced level of cholesterol and triglyceride compared to the control group. The liver PPARalpha protein level of the high group was significantly higher than that of the control group. The liver HMG-CoA reductase protein in the high group was also significantly lower than that in the control group. Results from rats on an olive oil loading test were used to investigate whether propolis inhibited triglyceride absorption. The serum triglyceride level of the group, which received propolis corresponding to the daily dose of the high group, was significantly lower than that of the control group. It is possible that the administration of propolis improves the accumulation of body fat and dyslipidemia via the change of the expression of proteins involved in adipose depot and lipid metabolism. PMID- 19646047 TI - Children's acceptance, nutritional, and instrumental evaluations of whole grain and soluble fiber enriched foods. AB - The Dietary Guidelines for Americans 2005 report recommends 3 or more daily ounce equivalents of whole grains (WG), and the FDA suggests consumption of 25 g of total dietary fiber (TDF) and 6 g of soluble fiber (SF) for a 2000-calorie diet. Efforts to increase the consumption of WG and SF among elementary school-aged children are needed. The objectives of this study were to examine the consumption of WG- and SF-enriched burritos and cookies among elementary school-aged children and to perform a quality evaluation of all products. Children in grades K to 6 from a local elementary school consumed control (CTR) products made with refined flour along with the test products (TRT) over a 13-wk period. TRT burritos and cookies contained 51% and 100% WG, respectively. CTR and TRT products were served on 3 and 4 different Fridays, respectively. Children's consumption was determined via plate waste. Quality parameters such as texture, color, water activity, weight, and product dimensions were also measured. No significant differences in consumption between CTR and TRT burritos and cookies were found (36% and 90%, respectively). Texture (area) was higher for CTR burritos compared with TRT burritos (1.31 and 0.66 kg-s, respectively). CTR burritos were lighter than TRT burritos with L* values of 80.04 and 64.61, respectively. CTR cookies required a higher breaking force (3.14 compared with 0.58 kg), were lighter than TRT cookies (63.18 compared with 50.27), and had lower water activity (0.5 compared with 0.71). PMID- 19646048 TI - Iron, zinc, and protein bioavailability proxy measures of meals prepared with nutritionally enhanced beans and maize. AB - Nutritionally enhanced beans (NEB) with more Fe and Zn than conventional beans (CB) and nutritionally enhanced maize (NEM) with more tryptophan and lysine than conventional maize (CM) were developed as part of a crop-biofortification strategy to improve human nutrition. Proxy measures were used to assess Fe and Zn bioavailability and protein digestibility of a bean recipe (frijol sancochado) and a maize-milk recipe (mazamorra) prepared with enhanced or conventional crops in Colombia. Fe concentration was similar in the cooked NEB and CB and in NEM and CM (P> or = 0.05); in vitro Fe dialyzability was similar in cooked NEB (9.52%) and CB (9.72%) and greater for NEM (37.01%) than CM (32.24%). Zn concentration was higher in the uncooked and cooked NEB than in the CB (P < 0.05); phytate: Zn molar ratios were high in cooked NEB (36: 1) and CB (47: 1), suggesting low Zn bioavailability, and not different from each other (P = 0.07). There were no differences in Zn concentration or phytate: Zn molar ratio in the maize recipes. Nitrogen, tryptophan, and lysine concentrations were higher in the cooked NEM than CM; nitrogen was higher in the cooked NEB than CB (P < 0.05). In vitro protein digestibility was comparable (82% to 83%) for NEM and CM and higher for NEB (84%) than for CB (82%). The higher nutrient concentrations + similar bioavailability (protein in NEM, Zn in NEB), same nutrient concentrations + higher bioavailability (Fe in NEM) or higher nutrient concentrations + higher bioavailability (protein in NEB) can translate into more nutrients absorbed and utilized by the body. PMID- 19646050 TI - Antifungal activity of sodium silicate on Fusarium sulphureum and its effect on dry rot of potato tubers. AB - The antifungal activity of sodium silicate on Fusarium sulphureum and its inhibitory effect on dry rot of potato tubers were investigated. Sodium silicate strongly inhibited spore germination and mycelial growth. Morphological changes in sodium silicate-treated hyphae such as mycelium sparsity and asymmetry, hyphal swelling, curling, and cupped shape were observed by scanning electron microscopy. Ultrastructural alterations were also observed using transmission electron microscopy, including thickening of the hyphal cell walls, cell distortion, cavity, or electron-dense material in hyphal cells. Daughter hyphae and new daughter hyphae inside of the collapsed hyphal cells were often detected in the cytoplasm of sodium silicate-treated hyphae, although the septa of treated hyphae remained uniform. In vivo testing showed that sodium silicate at 100 and 200 mM effectively controlled dry rot of tubers that were challenged by inoculation with a F. sulphureum spore suspension. These findings suggest that sodium silicate has direct fungitoxic activity against the pathogen. PMID- 19646049 TI - Validation of an improved method for detection of Campylobacter jejuni in foods. AB - Campylobacter jejuni ATCC 29428 and 33560 were inoculated separately into beef muscle, ground beef, and chicken skin to yield approximately 10 to 100 CFU/g of food sample. The samples were stored at 4 degrees C for 10 d. On days 0, 3, 7, and 10, enrichment cultures in Bolton broth supplemented with antibiotics, with and without blood supplementation were made for each sample, for 24 and 48 h following the Food and Agricultural Products Center (FAPC) and the Food and Drug Administration (FDA) protocols. Enumeration of the organisms in the enrichment cultures was done on Campylobacter Karmali selective agar after 24 and 48 h of enrichment to compare the extent of growth in both protocols. There were no significant differences between counts recovered using the FDA and the FAPC methods for detection of Campylobacter jejuni for either strain in any of the food products tested (P > 0.05). No significant differences were observed in performance of enrichment broth supplemented with and without blood (P > 0.05). After 48 h of enrichment, the counts recovered were similar for all products. The organisms were detectable on all days of storage in raw chicken skin, beef, and ground beef samples after both 24 and 48 h of enrichment. The results from the FAPC method for detection of C. jejuni from food were not different from the FDA method. While in the proposed method incubation at 37 degrees C was adequate for the strains tested it is recommended that both enrichment temperatures be used for naturally contaminated samples to ensure detection of all strains that might be present. PMID- 19646051 TI - Survival of Listeria monocytogenes, Listeria innocua, and lactic acid bacteria in chill brines. AB - Listeria monocytogenes is the pathogen of concern in ready-to-eat (RTE) meat products. Salt brines are used to chill processed meats. L. monocytogenes and lactic acid bacteria (LAB) can grow under saline conditions, and may compete with each other for nutrients. The objective of this study was to determine the effect of lactic acid bacteria (Enterococcus faecalis, Carnobacterium gallinarum, and Lactobacillus plantarum) on the survival of L. monocytogenes and Listeria innocua in brines stored under low temperatures for 10 d. Sterile tap water (STW) and 2 brine solutions (7.9% and 13.2% NaCl) were inoculated with 1 of 5 cocktails (L. monocytogenes, L. innocua, LAB, L. monocytogenes+ LAB, or L. innocua+ LAB) at initial concentrations of 7 log CFU/mL. Brines were stored for 10 d at 4 or 12 degrees C. Three replications of each brine concentration/cocktail/temperature combination were completed. No significant reductions of L. monocytogenes occurred in 7.9%[w/v] or 13.2%[w/v] brines when LAB were present; however, there were significant reductions after 10 d of L. monocytogenes in the STW solution when LAB were present (1.43 log CFU/mL at 4 degrees C and 3.02 log CFU/mL at 12 degrees C). L. innocua was significantly less resilient to environmental stresses of the brines than L. monocytogenes, both with and without LAB present (P< or = 0.05). These strains of lactic acid bacteria are not effective at reducing L. monocytogenes in brines at low temperatures. Furthermore, use of L. innocua as a model for L. monocytogenes is not appropriate under these environmental conditions. PMID- 19646053 TI - Consumer liking of fruit juices with different acai (Euterpe oleracea Mart.) concentrations. AB - Overall liking, flavor, and perceived healthiness of one newly developed fruit juice with high acai content (40% acai) and 5 commercially available fruit juices with lower (4% to 20%) acai concentrations were evaluated by consumers in Belgium. General trends for the overall sample were examined by means of analysis of variance, whereas individual consumer preferences were evaluated using internal preference mapping and hierarchical cluster analysis. The relative contribution of flavor and perceived health benefits as predictors of consumers' overall liking of the 6 acai-based fruit juices was estimated through linear regression analysis. The results showed a negative relationship between the juices' overall liking and their acai concentrations. Although the vast majority of consumers preferred the juices having a low acai content (4% to 5% acai), a small consumer segment liked the juice with 40% acai. Flavor or taste experience superseded consumers' perceived health benefits as the primary determinant of the fruit juices' overall liking. The impact of perceived health benefits on the overall liking of the acai juices decreased with higher taste dissatisfaction. PMID- 19646052 TI - Nanocomposite edible films from mango puree reinforced with cellulose nanofibers. AB - Cellulose nanoreinforcements have been used to improve mechanical and barrier properties of biopolymers, whose performance is usually poor when compared to those of synthetic polymers. Nanocomposite edible films have been developed by adding cellulose nanofibers (CNF) in different concentrations (up to 36 g/100 g) as nanoreinforcement to mango puree based edible films. The effect of CNF was studied in terms of tensile properties, water vapor permeability, and glass transition temperature (T(g)) of the nanocomposite films. CNF were effective in increasing tensile strength, and its effect on Young's modulus was even more noticeable, especially at higher concentrations, suggesting the formation of a fibrillar network within the matrix. The addition of CNF was also effective to improve water vapor barrier of the films. Its influence on T(g) was small but significant. The study demonstrated that the properties of mango puree edible films can be significantly improved through CNF reinforcement. PMID- 19646054 TI - A method for intercultivar comparison of potato tuber nutrient content using specific tissue weight proportions. AB - Potato tubers are a staple food item in the North American diet. Each potato cultivar has unique tuber appearance and nutritional composition. A method was developed to facilitate better cultivar selection for dietary purposes and obtain a better understanding of the nutrient distribution within specific tissues of potato tubers. This involved a procedure for estimating the percent weight contribution of the 3 major tissue components, including periderm or "skin," cortex, and pith for 20 potato cultivars. Weight determination was based on the volume (calculated through an ellipsoid formula) and density of each component tissue. Calculated percent weight and dry matter data for each tuber tissue provided conversion factor values that were tabulated for all cultivars. An example is provided to illustrate the application of this procedure in facilitating identification of cultivars with significantly greater or lesser protein content. PMID- 19646055 TI - Probiotic cheddar cheese: influence of ripening temperatures on proteolysis and sensory characteristics of cheddar cheeses. AB - Bifidobacterium longum 1941, B. animalis subsp. lactis LAFTI B94, Lactobacillus casei 279, Lb. casei LAFTI L26, Lb. acidophilus 4962, or Lb. acidophilus LAFTI L10 were used as an adjunct in the production of Cheddar cheeses, which were ripened at 4 and 8 degrees C for 24 wk. Effects of ripening temperatures and probiotic adjuncts on proteolysis and sensory evaluation of the cheeses were examined. Higher ripening temperature increased the level of proteolysis in the cheeses. Product of proteolysis and organic acids released during ripening were shown to be important for the flavor of Cheddar cheeses. There were positive and significant correlations between the levels of soluble nitrogen, lactic, acetic, and butyric acids, percentage hydrolysis of alpha(s1)-CN and beta-CN to the scores of cheddary flavor (P < 0.05). Scores for sour-acid and vinegary flavors were higher in cheeses with the addition of Bifidobacterium sp. or Lb. casei 279 ripened at 8 degrees C. The scores were positively and significantly correlated to the level of lactic, acetic, and free amino acids in the cheeses (P < 0.05). The results show that both 4 and 8 degrees C have potential for use in the ripening of probiotic Cheddar cheeses. PMID- 19646056 TI - Characterization and the possible formation mechanism of 2-acetyl-1-pyrroline in aromatic vegetable soybean (Glycine max L.). AB - 2-Acetyl-1-pyrroline (2-AP) was identified as an important aroma compound of aromatic vegetable soybean. The level of 2-AP in 6 aromatic vegetable soybean lines was found to be positively correlated with popcorn-like aroma score. Comparison between aromatic and nonaromatic vegetable soybeans found that aromatic vegetable soybean contains higher concentration of methylglyoxal (MG) and Delta(1)-pyrroline-5-carboxylate (P5C) than a nonaromatic one. For MG formation-related genes, GapC was down-regulated and TPI was up-regulated in aromatic cultivar (Aromatic 7) as compared to nonaromatic control, which may contribute to the increase of MG level. Based on the data presented, a formation mechanism for 2-AP via interaction between MG and P5C in aromatic vegetable soybean was proposed. PMID- 19646057 TI - Effect of several sugars on consumer perception of cured sheepmeat. AB - This article reports the perception of cooked, nitrite-cured sheepmeat sausage that included 1.5% glucose, sucrose, xylose, or no sugar addition. The 4 sugar treatments were dry-cooked, vacuum packed, and stored chilled, and were hedonically assessed after 0, 1, and 2 mo. Consumers were advised that they could be eating any 1 of beef, chicken, lamb, pork, or turkey, in a salted cured preparation. Three-way analysis of variance (ANOVA) showed that liking of appearance, color, and texture were unaffected by sugar treatment, whereas liking of aroma, flavor, sweetness, and overall liking were markedly and significantly increased by xylose. Storage time as a factor had minimal effects on liking. In contrast, all attributes were liked more by male consumers (57%, P < 0.001). When asked to identify the meat species, lamb was correctly identified 50% of the time. With xylose, the observed frequency of lamb's misidentification as beef increased by 50% above the expected Chi-square frequency. This was largely at the expense of observed lamb selection frequency, which was 18% below expectation. When data were segregated by gender, the misidentification remained significant for males (P = 0.002), but was not significant for females (P = 0.32). The misidentification of beef for lamb may be due to the generation of Strecker aldehydes in the Maillard reaction between xylose and meat amino acids, which were shown to be greatly increased in the headspace above xylose-treated sausage. The restriction of significant misidentification to males is less easy to explain but may be associated with the possible greater sensitivity of females to volatile fatty acids, which are components of sweat. PMID- 19646058 TI - Improved determination of phoxim residue in stored wheat by HPLC with DAD. AB - This article presents an improved method to detect the phoxim residual in whole wheat grain (not milled). The authors used petroleum ether (PE) as solvent to extract phoxim in darkness, and then determined it with high-performance liquid chromatography (HPLC) with diode array detector (DAD) at 280 nm. Use of PE improved the extraction efficiency of phoxim from grain samples over those obtained using acetone, recovery of 83.3% and 65.9%, respectively. Light produced more side effect on the extraction of this pesticide than with darkness, recovery of 63.2% and 83.3%, respectively. The combination of PE with darkness yielded a higher recovery of phoxim in liquid-phase extraction. The peak area of phoxim compared with its absolute values of phoxim in standard solution concentration range from 0.005 mg/kg to 0.253 mg/kg showed a good linear calibration (R(2) = 0.9999). Recoveries, at spiked concentrations of 0.02, 0.05, and 0.10 mg/kg, varied between 83.3% and 106.3% with relative standard deviations (RSD) ranging from 6.5% to 8.0%. The present method provides sufficient sensitivity as reflected by the values of limit of detection (LOD) and limit of quantification (LOQ). LOD was 0.002 mg/kg (S/N 3), and the estimated LOQ was 0.006 mg/kg (S/N = 10). Use of the proposed method successfully detected phoxim residue in wheat grain from Beijing and Kunming City of China. PMID- 19646059 TI - Fate of aflatoxin M(1) during manufacture and storage of feta cheese. AB - The effect of feta cheese manufacture on aflatoxin M(1) (AFM(1)) content was studied using an enzyme immunoassay technique. Feta cheese was made from milk spiked with 1 and 2 microg AFM(1) per kilogram milk. Pasteurization at 63 degrees C for 30 min caused <10% destruction of AFM(1). During cheese making, the remaining AFM(1) in milk was partitioned between curd and whey with two-thirds retained in the curd and one-third going into the whey. Cheeses were then stored for 2 mo in 8%, 10%, and 12% brine solutions at 6 and 18 degrees C. There was a 22% to 27% reduction of AFM(1) during the first 10 d of storage, with slightly more loss as salt concentration increased and when the cheese was stored at 18 degrees C. Further storage caused only slight decrease in AFM(1) and after 30 d of brining there was no difference in AFM(1) content of the cheese based upon salt concentration of the brine. At 18 degrees C, no further losses of AFM(1) occurred after 30 d, and at 6 degrees C, there was continued slight decrease in AFM(1) levels until 50 d. After 60 d of brining, there was a total loss of 25% and 29% of the AFM(1) originally present for cheese brined at 6 and 18 degrees C, respectively. Thus, the combination of pasteurization, conversion of milk into feta cheese, and at least 50 d storage of cheese in brine caused a total loss of about 50% of the AFM(1) originally present in the raw milk. PMID- 19646064 TI - Consumer demand for healthy, additive-free foods has led to increased consumption of raw salad vegetables in developed countries. PMID- 19646060 TI - Detection of mustard, egg, milk, and gluten in salad dressing using enzyme-linked immunosorbent assays (ELISAs). AB - Enzyme-linked immunosorbent assay (ELISA) is a commonly used method for the detection of trace amounts of potentially allergenic protein residues in foods. However, food matrices and processing conditions can affect the detection of protein residues. The effects of acidity on the detectability of several allergenic proteins commonly found in salad dressing using ELISAs was investigated. First, recovery experiments were performed on salad dressing formulated with 0 to 1000 ppm mustard flour (mustard). The mean percent recovery for mustard from the salad dressing was only 7.7%+/- 1.6%. When the pH of the salad dressing was adjusted to pH 7 prior to spiking with mustard, recovery improved to 94.1%+/- 7.6%. However, if the pH was adjusted to pH 7 after spiking and extraction, the recovery was only 11.1%+/- 1.7%. When vinegar was spiked with mustard flour at pH 3, 3.5, and 4, detectability of mustard was lowest at pH 3. Basic extraction of mustard proteins from salad dressing did not improve the mustard detection. Acidic salad dressing matrices reduced the detectability of mustard by the mustard ELISA probably because of acid precipitation of mustard proteins that renders them insoluble and nonextractable. Commercial salad dressings containing 100 ppm (mg/kg) of egg, milk, or gluten were analyzed every 2 to 4 d for 90 d using 3 commercially available ELISAs. A decrease in the detection of the egg, milk, and gluten in the salad dressing upon storage was observed. Our study highlighted the importance of evaluating the utility of various ELISAs for specific food matrices and the recovery as a function of product storage. PMID- 19646065 TI - Genes and nitrogen fuel wood formation. PMID- 19646066 TI - On ants, plants and fungi. PMID- 19646067 TI - Nonhost and basal resistance: how to explain specificity? AB - Nonhost resistance to plant pathogens can be constitutive or induced by microbes. Successful pathogens suppress microbe-induced plant defences by delivering appropriate effectors, which are apparently not sufficiently effective on nonhost plant species, as can be concluded from the strong host specificity of many biotroph plant pathogens. Such effectors act on particular plant targets, such as promoters or motifs in expressed sequences. Despite much progress in the elucidation of the molecular aspects of nonhost resistance to plant pathogens, very little is known about the genes that determine whether effectors can or cannot suppress the basal defence. In hosts they can, in nonhosts they cannot. The targets determining the host status of plants can be identified in inheritance studies. Recent reports have indicated that nonhost resistance is inherited polygenically, and exhibits strong similarity and association with the basal resistance of plants to adapted pathogens. PMID- 19646068 TI - Nitric oxide modulates the influx of extracellular Ca2+ and actin filament organization during cell wall construction in Pinus bungeana pollen tubes. AB - Nitric oxide (NO) plays a key role in many physiological processes in plants, including pollen tube growth. Here, effects of NO on extracellular Ca(2+) flux and microfilaments during cell wall construction in Pinus bungeana pollen tubes were investigated. Extracellular Ca(2+) influx, the intracellular Ca(2+) gradient, patterns of actin organization, vesicle trafficking and cell wall deposition upon treatment with the NO donor S-nitroso-N-acetylpenicillamine (SNAP), the NO synthase (NOS) inhibitor N(omega)-nitro-L-arginine (L-NNA) or the NO scavenger 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) were analyzed. SNAP enhanced pollen tube growth in a dose-dependent manner, while L-NNA and cPTIO inhibited NO production and arrested pollen tube growth. Noninvasive detection and microinjection of a Ca(2+) indicator revealed that SNAP promoted extracellular Ca(2+) influx and increased the steepness of the tip-focused Ca(2+) gradient, while cPTIO and L-NNA had the opposite effect. Fluorescence labeling indicated that SNAP, cPTIO and L-NNA altered actin organization, which subsequently affected vesicle trafficking. Finally, the configuration and/or distribution of cell wall components such as pectins and callose were significantly altered in response to L-NNA. Fourier transform infrared (FTIR) microspectroscopy confirmed the changes in the chemical composition of walls. Our results indicate that NO affects the configuration and distribution of cell wall components in pollen tubes by altering extracellular Ca(2+) influx and F-actin organization. PMID- 19646069 TI - Impact of genetic polymorphisms on the pathogenesis of achalasia: an age dependent paradigm? AB - A wealth of evidence supports the concept that achalasia represents an autoimmune disorder in which a triggering factor (probably a virus) is the starter of an uncontrolled myenteric ganglionitis leading to neurodegeneration. The reasons whereby this process occurs only in some individuals and at the oesophageal level are unknown, but it is reasonable to assume that some genetic influence may affect the achalasia phenotype, making some individuals more or less susceptible to the disease. Association studies between achalasia and polymorphisms of genes involved in the regulation of immune responses may help to explain the complexity of achalasia pathogenesis and progression. PMID- 19646072 TI - Aspirin or paracetamol - what's good for you? PMID- 19646073 TI - Hypersensitivity reactions to penicillins: studies in a group of patients with negative benzylpenicillin G skin test. AB - BACKGROUND: Although skin tests are usually employed to evaluate current penicillin allergy status, a negative result does not exclude hypersensitivity. There is a need for accurate in vitro tests to exclude hypersensitivity. A radioallergosorbent test (RAST) is a potentially good supplementary approach, but there is little information on the suitability of this method to diagnose penicillin hypersensitivity in subjects with a negative skin test to benzylpenicillin. METHODS: A total of 133 patients with a negative skin test to benzylpenicillin G (PG) and all of whom developed allergic reactions to PG were studied. RAST was used to detect eight kinds of specific IgE antibodies to penicillins in serum, which included four kinds of major and minor antigenic determinants to four penicillin drugs. The combination sites for the specific IgE antibodies were studied by RAST inhibition test. RESULTS: The rate of positive reactions for the specific IgE antibodies was 59.40% (79/133). Of the eight kinds of antigenic determinants, the positive rates for specific IgE against the major and minor determinants were 39.10% (52) and 42.86% (57) respectively. Of the four drugs, positive cases only to PG were 10 (7.5%), were significantly fewer than the cross-reacting positive cases (36) to PG (P < 0.01). In the RAST inhibition studies all drugs exhibited good inhibitory potencies, and in some instances the side-chain of the penicillins could induce specific responses with a variable degree of cross-reactivity among the different penicillins. CONCLUSION: Radioallergosorbent test is a good complementary test in persons who are skin test negative with PG, and the sensitivity of RAST increases with increasing specificity of IgE antibodies to be detected. 6-APA and the groups, making part of the different side-chains on penicillins, all contributed to the cross reactivity. PMID- 19646074 TI - Poor oral hygiene enhances gingival overgrowth caused by calcineurin inhibitors. AB - AIM: To estimate the prevalence of gingival overgrowth in kidney allograft recipients in southern Switzerland and to determine the factors associated with it. We hypothesized that poor oral hygiene was a risk factor. METHODS: We assessed the level of oral hygiene among renal transplant patients and determined whether a good level of information and regular dental checkups in addition to good oral hygiene could prevent gingival hyperplasia. Seventy-six adults who had undergone kidney transplantation were examined. The level of oral hygiene, gender, age, time elapsed from transplantation, medication and dose were recorded. RESULTS: In general the level of oral hygiene was average. We found a significant association between the severity of gingival overgrowth and the level of oral hygiene. No statistical relationship between gingival hyperplasia and the other recorded variables was detected. Patients on tacrolimus had a tendency to have less gingival hyperplasia. Patient education, along with regular dental checkups and a good level of oral hygiene, should prevent gingival hyperplasia or maintain it at an acceptable level. CONCLUSION: Intensive motivation of patients to maintain good oral hygiene is necessary to reduce the incidence of gingival hyperplasia. PMID- 19646070 TI - Brain imaging approaches to the study of functional GI disorders: a Rome working team report. AB - Progresses in the understanding of human brain-gut interactions in health and disease have been limited by the lack of non-invasive techniques to study brain activity. The advent of neuroimaging techniques has made it possible not only to study the structure and function of the brain, but also to characterize signaling system underlying brain function. This article gives a brief overview of relevant functional neuroanatomy, and of the most commonly used brain imaging techniques. It summarizes published functional brain imaging studies using acute visceral stimulation of the oesophagus, stomach and colon in healthy control subjects and patients with functional GI disorders, and briefly discusses pertinent findings from these studies. The article concludes with a critical assessment of published studies, and with recommendations for improved study paradigms and analysis strategies. PMID- 19646076 TI - Tolerability and safety profile of posaconazole: evaluation of 18 controlled studies in healthy volunteers. AB - BACKGROUND AND OBJECTIVES: Antifungal agent utility can be limited by safety and tolerability concerns. Posaconazole is an extended-spectrum triazole antifungal agent for the treatment and prophylaxis of invasive fungal infection. The aim was to analyse the overall safety profile of posaconazole in healthy volunteers. METHODS: Safety data from all 18 clinical pharmacology single- and multiple-dose trials of posaconazole conducted in healthy volunteers plus 2 additional healthy subsets from other pharmacology trials were pooled and analysed. Four hundred and forty-nine healthy volunteers (354 men; 95 women) were enrolled. Three hundred and twenty-seven were white, and the mean age and weight of subjects were similar across all dosing groups. The population evaluated had no confounding factors of underlying disease or concomitant medications. Safety evaluations included spontaneously reported adverse events, clinical laboratory test results, electrocardiograms and vital sign measurements. RESULTS: A total of 448 subjects received posaconazole, 50-1200 mg/day administered as single or multiple doses for up to 14 days. Two hundred and seventeen subjects received >or=800 mg/day posaconazole, and 188 subjects received multiple doses of posaconazole at 800 mg/day. Two hundred and thirty-one subjects received <800 mg/day. Forty-eight subjects from three studies received placebo. The incidence of treatment-emergent adverse events reported with posaconazole was similar to that seen with placebo (57% vs. 63% respectively) and unrelated to dose. The most common treatment related adverse events (posaconazole vs. placebo) were headache (17% vs. 13%), dry mouth (9% vs. 0%) and dizziness (6% vs. 2%). No clinically significant changes in vital signs or laboratory test parameters were observed, except for transient, mild to moderate elevations in liver function test results. Posaconazole also demonstrated minimal potential to prolong corrected QT interval. CONCLUSIONS: The safety profile analysis found posaconazole to be well tolerated, and results were similar across sex, age and race. PMID- 19646075 TI - An intervention to develop repeat prescribing in community pharmacy. AB - BACKGROUND: Lack of review of patients' medications in repeat prescribing is common. This and other problems in repeat prescribing need to be addressed. Community pharmacists could be more proactive in the review of chronic medications. OBJECTIVE: The purpose of this study was to test the feasibility and effects of pharmacists' interventions in repeat prescribing. METHODS: The normal repeat prescribing process used at Kuopio University Pharmacy and in Kuopio Health Services was developed by an intervention which included a pharmacist's interview and the annual medication data of the patient that were both transferred to the prescribing physician. RESULTS: Physicians in the intervention group identified and solved patients' drug-related problems better than was the case in the comparison group with normal repeat prescribing. Over half the patients receiving repeat prescriptions had at least one drug-related problem. The physicians used more information sources to support repeat prescribing in the intervention system. CONCLUSIONS: Community pharmacists are able to improve the quality of physician's repeat prescribing by providing vital information. PMID- 19646077 TI - Adverse reactions to over-the-counter cough and cold products among children: the cases managed out of hospitals. AB - BACKGROUND AND OBJECTIVE: Prompted by continuing concerns about the safety of over-the-counter (OTC) cough and cold medications, we examined the frequency and severity of pediatric adverse drug reactions (ADRs) to OTC cough and cold products reported to a major poison control center. The goal was to focus on cases that are usually managed out of hospitals and may not be recognized by the traditional adverse events surveillance and reporting programs. METHODS: We conducted a retrospective review of electronic records on ADRs reported to the New Jersey Poison Information and Education System (NJPIES) through the National Poison Data System. Analyses included ADRs involving a single OTC cough and cold product. The number and proportion of reported ADRs to OTC cough and cold medicines were examined and compared by severity level between children <2 years of age, and children from 2 through 11 years of age. RESULTS: A total of 91 pediatric ADRs to OTC cough and cold products were reported to the NJPIES from 2000 through 2007. Of these, 61 cases (67%) were of minor severity. A larger proportion of the children 2-11 years of age (21.2%), compared with children <2 years of age (8.0%), experienced a reaction of moderate to major severity. CONCLUSIONS: While we found fewer ADR cases of moderate to major severity in younger children, our results call for a further review of the safety of OTC cough and cold medicines in children 2 years of age and older. PMID- 19646078 TI - Assessment of the clinical and economic outcomes of pharmacy interventions in drug-related problems. AB - BACKGROUND AND OBJECTIVE: Due to drug-related problems (DRPs) that cause both unnecessary suffering and huge costs to society, many patients do not receive the intended beneficial effects of their treatment. Pharmacy practitioners have a key responsibility to respond to these problems, but more knowledge about the expected outcomes of their interventions is needed. The objective of the study was to assess the clinical and economic outcomes of community pharmacy interventions in patient DRPs. METHODS: Drug-related problems in 13 different patient groups were identified and classified, according to the Westerlund System, by pharmacy practitioners from 89 Swedish pharmacies in 2006. The cases were documented in the pharmacy software and transferred to the national DRP database. An assessment model was developed and applied by the researchers (a pharmacist and a physician). This assessment was used to conduct a retrospective review by analysing the DRP and intervention documentation, in particular case descriptions from free text fields. Expected clinical patient outcomes of pharmacy interventions were judged in terms of improved therapeutic effects and prevented or relieved adverse drug reactions (ADRs). The review also assessed the expected patient outcomes with regard to initiated or avoided primary care contacts or avoided hospitalisations. The resulting hypothetically avoided direct societal costs and the estimated pharmacy personnel costs were calculated for the study and extrapolated to the Swedish nationwide level on an annual basis, to demonstrate the potential of national cost savings by pharmacy DRP-interventions. RESULTS AND DISCUSSION: In 358 cases (68%), the pharmacy interventions were judged to have produced an improved therapeutic effect in the patient, and in 172 cases (32%) to have prevented or relieved ADRs. Primary care contacts were initiated for 151 patients (29%), and pharmacy interventions were assessed to have saved 68 (13%) primary care contacts and 16 (3%) future hospitalisations. The potential societal cost savings extrapolated to Sweden at the national level were estimated at euro 358 million. This is 37 times the expected pharmacy personnel costs for identifying and responding to the DRPs. CONCLUSION: Our study demonstrates that community pharmacy interventions in patient DRPs are most likely to lead to favourable clinical and economic outcomes. The convincing cost benefit ratio should be presented to health care politicians and decision makers to encourage appropriate remuneration for these services. PMID- 19646079 TI - Effect of obesity on serum amiodarone concentration in Japanese patients: population pharmacokinetic investigation by multiple trough screen analysis. AB - OBJECTIVE: To evaluate the influence of obesity on pharmacokinetics of amiodarone (AMD) using Non-Linear Mixed Effects Modelling (NONMEM) in Japanese patients treated with oral therapy. METHOD: Serum concentrations of AMD were determined by high performance liquid chromatography. One hundred and fifty-one trough concentrations from 23 patients receiving repetitive oral AMD were collected. Body mass index (BMI) and body fat percentage were measured. RESULTS: Estimates generated using NONMEM indicated that the clearance of AMD was influenced by BMI, age and daily dosage of AMD. The final pharmacokinetic model was CL (L/h) = 0*16 * TBW * 0.53(AGE >or= 65 ) * 0*78(BMI >or= 25) * DD(0.51), V(d) (L) = 10*2 * TBW, where CL is total body clearance, TBW is total body weight (kg), DD (mg/kg/day) is daily dosage of AMD, AGE (years) >or=65 = 1 for patient was 65 years old or over and 0 otherwise, BMI (kg/m(2)) >or=25 = 1 for patient was 25 kg/m(2) or over and 0 otherwise and V(d) is apparent volume of distribution. The clearance of AMD decreased significantly by 22.3% with a BMI higher than 25 kg/m(2). The clearance of AMD also decreased significantly by 46.9% when patient age was more than 65 years. CONCLUSION: Population pharmacokinetic analysis confirms that obesity affects the pharmacokinetics of AMD. PMID- 19646080 TI - Population pharmacokinetics of intravenous itraconazole in patients with persistent neutropenic fever. AB - PURPOSE: Empirical use of intravenous (IV) itraconazole (ITZ) for febrile neutropenic patients has recently been introduced in Korea. This study was designed to investigate the population pharmacokinetics (PK) of IV-ITZ. METHODS: Sparse PK data were collected from febrile neutropenic patients undergoing empirical ITZ therapy at 200 mg/day after loading doses. NONMEM (Version. 5.1.1) was used to estimate population PK parameters. RESULTS: Forty-two patients were enrolled in the study. Mean population CL and V of IV-ITZ were 10 L/h and 1050 L, respectively. Body weight was the only contributing covariate of CL. The median simulated trough concentration of ITZ after 10 days was predicted to be about 700 ng/mL. CONCLUSIONS: In this study, we explored the population PK profile of ITZ given in IV formulation. We found that the current dosage regimen of IV-ITZ (200 mg/day) was appropriate to obtain therapeutic trough concentrations for neutropenic patients in Korea. PMID- 19646081 TI - Pharmacokinetic profile of talipexole in healthy volunteers is not altered when it is co-administered with Madopar (co-beneldopa). AB - OBJECTIVES: To investigate the pharmacokinetics of talipexole hydrochloride tablets and the potential influence of Madopar (benserazide and levodopa combination; co-beneldopa) tablets on talipexole's pharmacokinetics when the two tablets are co-administered orally to healthy Chinese volunteers. METHODS: A sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to measure talipexole concentration in human plasma in an open-label, randomized, two-way crossover, single-dose study, with 1-week washout period. Healthy Chinese volunteers were randomized to receive talipexole tablets either alone or together with Madopar tablets by oral administration after an overnight fast. Serial blood samples were collected for a period of 36 h after the administration. Pharmacokinetic parameters C(max), t(max), t(1/2z), mean residence time (MRT), AUC(0-tau), AUC(0-infinity), CL(z)/F and V(z)/F were determined under the non-compartmental model. Pharmacokinetic values of talipexole administered alone to the subjects were compared with those administered simultaneously with Madopar to determine whether or not the differences were statistically significant. RESULTS: The subjects experienced mild gastrointestinal irritation when talipexole was administered alone as well as together with Madopar. For talipexole hydrochloride, there were no significant differences in the pharmacokinetic values between the two administrations. No pharmacokinetic differences based on gender were observed either. CONCLUSION: A single oral dose of Madopar co-administered with talipexole does not significantly change talipexole's pharmacokinetics in human. PMID- 19646082 TI - Hypertriglyceridaemia-induced acute pancreatitis due to patient non-compliance. AB - A 34-year-old woman presented with acute and progressive pain in the upper abdomen with worsening nausea, vomiting and diarrhoea. Her pain was described as severe, sharp and stabbing, with radiation to her chest and back. The patient's amylase and lipase levels were only mildly elevated. However, triglyceride levels (10,039 mg/dL) were markedly elevated upon presentation and no other causes of acute pancreatitis (e.g. obstruction, alcohol and medication) were identified. The patient was treated with opioids to control her pain and gemfibrozil was initiated to reduce her triglycerides. In addition, the patient received enoxaparin for deep vein thrombosis prevention and insulin for hyperglycaemia which also have been shown to decrease elevated triglycerides. The patient subsequently required antibiotic therapy with piperacillin-tazobactam after developing fever and an elevated white blood cell count. We review the role of adjunctive therapy with heparin and insulin in a patient with recurrent pancreatitis probably because of hypertriglyceridaemia and medication non compliance. PMID- 19646083 TI - Multiple oral dosing of valacyclovir in horses and ponies. AB - The aim of the current study was to investigate whether multiple oral dosing of valacyclovir could result in plasma concentrations exceeding the EC(50)-value of acyclovir against equine herpesvirus 1 (EHV1) during the majority of the treatment period. Additionally, we wanted to determine the concentration of acyclovir in nasal mucus and cerebrospinal fluid (CSF). Valacyclovir was administered to four horses and two ponies, three times daily, at a dosage of 40 mg/kg, for four consecutive days. Blood was collected prior to each administration and 1 h after dosing. Nasal mucus samples and CSF were collected once during treatment; 1 h after the last administration. This dosage regimen resulted in plasma concentrations that were higher than the EC(50)-value of 1.7 microg/mL, i.e. EC(50) of an isolate highly susceptible to acyclovir, for 80% of the treatment period; and higher than the EC(50)-value of 3.0 microg/mL, i.e. EC(50) of an isolate less susceptible to acyclovir, for 60% of the treatment period. Concentration in nasal mucus samples and CSF was 0.36-1.17 microg/mL and 0.11-0.23 microg/mL, respectively. This study illustrates that multiple dosing of valacyclovir may result in a therapeutic benefit as plasma concentrations could be maintained above the EC(50)-value of acyclovir against EHV1 for more than 50% of the treatment period. Acyclovir could be detected in both nasal mucus samples and CSF. However, these concentrations were lower than the EC(50). PMID- 19646084 TI - Pharmacokinetics of cimetidine in dogs after oral administration of cimetidine tablets. AB - Long-term oral treatment with cimetidine is recommended to reduce vomiting in dogs with chronic gastritis. Despite this, few studies have specifically examined the plasma disposition and pharmacokinetics of cimetidine in dogs, particularly following repeated oral administration. The pharmacokinetics of cimetidine following oral administration as tablets was investigated in healthy dogs. Cimetidine was absorbed rapidly post-treatment (t(max) = 0.5 h). A mean absolute bioavailability of 75% was calculated following a single oral administration of 5 mg cimetidine/kg body weight. After intravenous administration, a plasma half life of 1.6 h was calculated. Repeated oral administration at the recommended dose rate and regime (5 mg/kg body weight three times daily) for 30 consecutive days did not lead to any accumulation of cimetidine in plasma. Food intake concomitant with oral administration of cimetidine delayed (t(max) = 2.25 h) and decreased the rate and extent of absorption (AUC) by about 40%. Cimetidine was well absorbed in fasted dogs. Administration of food decreased the bioavailability of cimetidine by 40%. Cimetidine does not accumulate over time in plasma when administered long term to dogs. PMID- 19646085 TI - Pharmacokinetics and pharmacokinetic/pharmacodynamic integration of orbifloxacin in Korean Hanwoo cattle. AB - The pharmacokinetics and pharmacodynamics of orbifloxacin were studied in six clinically healthy Hanwoo cows after intravenous (i.v.) and intramuscular (i.m.) administration at a dose of 3 mg/kg. Orbifloxacin concentrations were determined by high performance liquid chromatography with fluorescence detection. Steady state volume of distribution and clearance of orbifloxacin after i.v. administration were 0.92 L/kg and 0.24 L/h x kg, respectively. Following i.m. administration, a slow and complete absorption with absolute bioavailability of 101.4%, and a maximum concentration (C(max)) of 1.17 microg/mL at 1.04 h were observed. The in vitro serum protein binding was 14.76%. The in vitro antibacterial activity of orbifloxacin against a pathogenic strain of Mannheimia haemolytica (M. haemolytica), Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was determined. The ex vivo activity of orbifloxacin against M. haemolytica strain was also determined, and these data were integrated with the ex vivo bacterial counts to establish AUC(24h)/MIC values producing bacteriostatic action, bactericidal action and elimination of bacteria. Mean values were 32.7, 51.6 and 102.6 h, respectively. From these data, we predict that orbifloxacin, when administered i.m. at a dosage of 2.5-5 mg/kg once a day, would be effective against bovine pathogens, such as M. haemolytica. Additional studies may be needed to confirm its efficacy in a clinical setting, and to evaluate the penetration of the drug in diseased tissues. PMID- 19646086 TI - Dispositions and residue depletion of enrofloxacin and its metabolite ciprofloxacin in muscle tissue of giant freshwater prawns (Macrobrachium rosenbergii). AB - Fates and residue depletion of enrofloxacin (ER) and its metabolite ciprofloxacin (CP) were examined in giant freshwater prawns, Macrobrachium rosenbergii, following either single oral (p.o.) administration of ER at a dosage of 10 mg/kg body weight (b.w.) or medicated-feed treatment at the feeding concentration of 5 g/kg of feed for five consecutive days. The concentrations of ER and CP in prawn muscle tissues were measured simultaneously using high-performance liquid chromatography (HPLC) equipped with a fluorescence detector. Muscle tissue concentrations of ER and CP were below the detection limit (LOD, 0.015 microg/g for ER; 0.025 microg/g for CP) after 360 and 42 h, following single p.o. administration respectively. Peak muscle concentration (C(max)) of ER was 1.98 +/ 0.22 microg/g whereas CP was measurable at concentrations close to the detection limit of the analytical method after p.o. administration at a single dosage of 10 mg/kg b.w. The concentration of ER in prawn muscle tissue with respect to time was analyzed with a non-compartmental pharmacokinetic model. The elimination half life and area under the curve of ER were 39.33 +/- 7.27 h and 168.7 +/- 28.7 microg x h/g after p.o. administration at a single dose of 10 mg/kg x b.w. respectively. In medicated-feed treated group, ER was detectable in prawn muscle tissue 11 days postdosing at the dose of 5 g/kg of feed for five consecutive days, which is the value corresponding to the maximum residue limit (MRL) of ER in animal products. The maximum concentrations of ER and CP were 2.77 +/- 0.91 and 0.06 +/- 0.006 microg/g during medicated-feed treatment and postdosing respectively. The values of elimination half-life and absorption half-life of ER after single p.o. administration at a dosage of 10 mg/kg b.w. corresponded well with the values determined from medicated-feed treated group, showing 41.01 +/- 6.62 and 11.36 +/- 3.15 h respectively in M. rosenbergii. Based on data derived from this study, to avoid the ER residue in prawn muscle, it should take at least 11 days postcessation of medicated feed containing ER at the dose concentration of 5 g/kg of feed twice a day at a rate of 1% of total body weight for five consecutive days to wash out the drug from the muscle of M. rosenbergii. PMID- 19646087 TI - Pharmacokinetics of voriconazole after single dose intravenous and oral administration to alpacas. AB - Voriconazole is a new antifungal drug that has shown effectiveness in treating serious fungal infections and has the potential for being used in large animal veterinary medicine. The objective of this study was to determine the plasma concentrations and pharmacokinetic parameters of voriconazole after single-dose intravenous (i.v.) and oral administration to alpacas. Four alpacas were treated with single 4 mg/kg i.v. and oral administrations of voriconazole. Plasma voriconazole concentrations were measured by a high-performance liquid chromatography method. The terminal half-lives following i.v. and oral administration were 8.01 +/- 2.88 and 8.75 +/- 4.31 h, respectively; observed maximum plasma concentrations were 5.93 +/- 1.13 and 1.70 +/- 2.71 microg/mL, respectively; and areas under the plasma concentration vs. time curve were 38.5 +/- 11.1 and 9.48 +/- 6.98 mg.h/L, respectively. The apparent systemic oral availability was low with a value of 22.7 +/- 9.5%. The drug plasma concentrations remained above 0.1 microg/mL for at least 24 h after single i.v. dosing. The i.v. administration of 4 mg/kg/day voriconazole may be a safe and appropriate option for antifungal treatment of alpacas. Due to the low extent of absorption in alpacas, oral voriconazole doses of 20.4 to 33.9 mg/kg/day may be needed. PMID- 19646088 TI - Influence of administration route on the biotransformation of amoxicillin in the pig. AB - A comparison was made in the plasma concentration of the major metabolites of amoxicillin (AMO), i.e. amoxicilloic acid (AMA) and amoxicillin diketopiperazine 2',5'-dione (DIKETO) in portal and jugular venous plasma after oral (p.o.) and intravenous (i.v.) AMO administration to pigs, in order to study a possible presystemic degradation of AMO in the gastro-intestinal tract and liver. Almost identical plasma concentration-time curves were obtained for AMO and its metabolites in portal and jugular venous plasma, both after p.o. and i.v. AMO administration. Almost immediately after i.v. AMO administration, high AMA and DIKETO concentrations were measured in plasma, while after p.o. dosing, the metabolites appeared in plasma after almost complete absorption of AMO. No significant differences in pharmacokinetic parameters of AMO, AMA and DIKETO, derived from the concentration-time profiles in portal and jugular venous plasma were calculated, both after i.v. and p.o. AMO administration (P > 0.05). After p.o. administration, the half-life of elimination (t(1/2(el))) for AMA is at least two or three times the t(1/2(el)) of AMO (0.75 h for AMO vs. 2.69 h for AMA), indicating the slower clearance of the metabolite. It could be hypothesized that AMA is only eliminated by glomerular filtration, as its open beta-lactam structure might not be recognized by the transport carrier in the proximal tubule of the kidney. The results of the study indicate that AMO is not substantially metabolized presystemically in the gut and liver. Therefore, it may be assumed that the kidney may be the major organ for AMO biotransformation. Future in vivo and in vitro experiments should be performed to state this hypothesis. PMID- 19646089 TI - Bioavailability of veterinary drugs in vivo and in silico. AB - The physical and chemical properties of a drug determine the behaviour of its molecule in a living organism. In this paper, the relationship between selected physical and chemical parameters and drug bioavailability in vivo was investigated. Data sets from 75 compounds, which can be administered per os to 11 various animal species were analyzed. The selected parameters for the prediction of the in vivo bioavailability were the lipophilicity (LogP) and the polar surface area (PSA) or apolar surface area (aPSA) of a molecule. It was shown that the calculation of the hybrid parameters aPSA/PSA and LogP + (aPSA/PSA) allows to estimate the oral bioavailability of a drug and its allocation to clusters with either an oral bioavailability of <70% or >70%. The performed analysis also showed that an extreme low value of the PSA of a molecule (<40 square angstroms) combined with the extreme high value of LogP (>4) is associated with a lower oral bioavailability (<50%). The results obtained indicate the existence of a relationship between the mean LogP value and aPSA/PSA in silico, and the bioavailability of veterinary drugs as determined in vivo. PMID- 19646090 TI - Pharmacokinetics and bioavailability of sulfadiazine and trimethoprim following intravenous, intramuscular and oral administration in ostriches (Struthio camelus). AB - A pharmacokinetic and bioavailability study of sulfadiazine combined with trimethoprim (sulfadiazine/trimethoprim) was carried out in fifteen healthy young ostriches after intravenous (i.v.), intramuscular (i.m.) and oral administration at a total dose of 30 mg/kg body weight (bw) (25 and 5 mg/kg bw of sulfadiazine and trimethoprim, respectively). The study followed a single dose, three periods, cross-over randomized design. The sulfadiazine/trimethoprim combination was administered to ostriches after an overnight fasting on three treatment days, each separated by a 2-week washout period. Blood samples were collected at 0 (pretreatment), 0.08, 0.25, 0.50, 1, 2, 4, 6, 8, 12, 24 and 48 h after drug administration. Following i.v. administration, the elimination half-life (t(1/2beta)), the mean residence time (MRT), volume of distribution at steady state (V(d(ss))), volume of distribution based on terminal phase (V(d(z))), and the total body clearance (Cl(B)) were (13.23 +/- 2.24 and 1.95 +/- 0.19 h), (10.06 +/- 0.33 and 2.17 +/- 0.20 h), (0.60 +/- 0.08, and 2.35 +/- 0.14 L/kg), (0.79 +/- 0.12 and 2.49 +/- 0.14 L/kg) and (0.69 +/- 0.03 and 16.12 +/- 1.38 mL/min/kg), for sulfadiazine and trimethoprim, respectively. No significant difference in C(max) (35.47 +/- 2.52 and 37.50 +/- 3.39 microg/mL), t(max) (2.47 +/- 0.31 and 2.47 +/- 0.36 h), t((1/2)beta) (11.79 +/- 0.79 and 10.96 +/- 0.56 h), V(d(z))/F (0.77 +/- 0.06 and 0.89 +/- 0.07 L/kg), Cl(B)/F (0.76 +/- 0.04 and 0.89 +/- 0.07) and MRT (12.39 +/- 0.40 and 12.08 +/- 0.36 h) were found in sulfadiazine after i.m. and oral dosing, respectively. There were also no differences in C(max) (0.71 +/- 0.06 and 0.78 +/- 0.10 microg/mL), t(max) (2.07 +/- 0.28 and 3.27 +/- 0.28 h), t((1/2)beta) (3.30 +/- 0.25 and 3.83 +/- 0.33 h), V(d(z))/F (6.2 +/- 0.56 and 6.27 +/- 0.77 L/kg), Cl(B)/F (21.9 +/- 1.46 and 18.83 +/- 1.72) and MRT (3.68 +/- 0.19 and 4.34 +/- 0.14 h) for trimethoprim after i.m. and oral dosing, respectively. The absolute bioavailability (F) was 95.41% and 86.20% for sulfadiazine and 70.02% and 79.58% for trimethoprim after i.m. and oral administration, respectively. PMID- 19646091 TI - Characterization of bradykinin-induced endothelium-independent contraction in equine basilar artery. AB - We investigated the effect of bradykinin (BK) on isolated equine basilar arterial rings with and without endothelium. BK induced concentration-dependent contraction of resting arterial rings and no relaxation when the rings were precontracted by prostaglandin F(2alpha). The maximal response and pD(2) value were 161.2 +/- 28.1% (to 60 mm KCl-induced contraction) and 8.24 +/- 0.25 respectively. The cumulative concentration-response curve for BK was not shifted to the right by des-Arg(9)-[Leu(8)]-BK (a B(1)-receptor antagonist), HOE140 (a B(2)-receptor antagonist) or NPC567 (another B(2)-receptor antagonist). In four of six basilar arteries, NPC567 induced concentration-dependent contraction. Indomethacin (a cyclooxygenase inhibitor), nordihydroguaiaretic acid (a lipoxygenase inhibitor), quinacrine (a phospholipase A(2) inhibitor), tetrodotoxin (a selective blocker of Na(+) channels), guanethidine (a nor adrenergic neuron blocking drug), phentolamine (an alpha-adrenoceptor antagonist), Nomega-nitro-L-arginine (L-NNA, a nitric oxide (NO) synthase inhibitor) and endothelial denudation did not affect the BK-induced contraction. L-NNA and indomethacin induced contraction and relaxation under resting vascular tone respectively. These results suggest that endothelial cells are not involved in BK-induced contraction and that the contraction is not mediated via activation of known B(1) and B(2) receptors. Arachidonic acid metabolites and neurotransmitters like norepinephrine and NO might not play a role in BK-induced contraction in equine basilar artery. PMID- 19646092 TI - Nonsteroidal anti-inflammatory agents and musculoskeletal injuries in Thoroughbred racehorses in Kentucky. AB - Injuries sustained by horses during racing have been considered as an unavoidable part of horse racing. Many factors may be associated with the musculoskeletal injuries of Thoroughbred race horses. This study surveyed the amounts of nonsteroidal anti-inflammatory agents (NSAIDs) in injured horse's biological system (plasma) at Kentucky racetracks from January 1, 1995 through December 31, 1996. During that period, there were 84 catastrophic cases (euthanized horses) and 126 noncatastrophic cases. Plasma concentrations of NSAIDs were determined by High Performance Liquid Chromatography in injured and control horses. The possible role of anti-inflammatory agents in musculoskeletal injuries of Thoroughbred race horses was investigated by comparing the apparent concentrations of NSAIDs in injured horses to concentrations in control horses. The plasma concentrations of phenylbutazone and flunixin were higher in injured horses than in control horses. Most injured and control horses did not have a detectable level of naproxen in their plasma samples. Further studies must be carried out to determine whether horses with higher plasma concentrations of NSAIDs have an altered risk of musculoskeletal injuries compared with other horses. PMID- 19646093 TI - Detection, quantifications and pharmacokinetics of toltrazuril sulfone (Ponazuril) in cattle. AB - Toltrazuril sulfone (Ponazuril) is a triazine-based anti-protozoal agent with highly specific actions against apicomplexan group of organisms, which are undergoing intensive investigation. Toltrazuril sulfone may have clinical application in the treatment of Neospora. caninum and other protozoal infections in cattle. To evaluate absorption, distribution, and elimination characteristics of toltrazuril sulfone in cattle, a sensitive validated quantitative high pressure liquid chromatography method for toltrazuril sulfone in bovine biological fluids was developed. After a single oral dose of toltrazuril sulfone at 5 mg/kg (as 150 mg/g of Marquis; Bayer HealthCare, Shawnee Mission, KS, USA), samples from six cows showed good plasma concentrations of toltrazuril sulfone, which peaked at 4821 ng/mL +/- 916 (SD) at 48 h postadministration. Thereafter, plasma concentration declined to 1950 ng/mL +/- 184 (SD) at 192 h after administration with an average plasma elimination half-life of approximately 58 h. Following oral dose of toltrazuril sulfone, the observed peak plasma concentrations were in relatively close agreement ranging from the lowest 3925 ng/mL to the highest of 6285 ng/mL with the mean peak plasma concentration being 4821 ng/mL. This study shows that toltrazuril sulfone is relatively well absorbed after oral dose in cattle. These results are therefore entirely consistent with and support the reported clinical efficacy of toltrazuril sulfone in the treatment of experimentally induced clinical cases of N. caninum and other protozoal-mediated bovine diseases. PMID- 19646095 TI - Pharmacokinetics of levofloxacin in male camels (Camelus dromedarius). PMID- 19646094 TI - Kinetics and residues after intraperitoneal procaine penicillin G administration in lactating dairy cows. AB - This paper describes the pharmacokinetic profile of procaine penicillin G after intraperitoneal (IP) administration in eight lactating dairy cows. Procaine pencillin G (PPG, 21 000 IU/kg) was deposited into the abdominal cavity of each cow following an incision in the right paralumbar fossa. Blood and milk samples were taken over the following 10 days, at which point the cows were euthanized. Plasma, milk, muscle, liver, and kidney penicillin concentrations were determined by HPLC, with a limit of quantification of 5 ng/mL for plasma and milk and 40 ng/g for tissue samples. A noncompartmental method was used to analyze plasma kinetics. The mean pharmacokinetic parameters (+/-SD) were: C(max), 5.5 +/- 2.6 microg/mL; T(max), 0.75 +/- 0.27 h; AUC(0-infinity), 10.8 +/- 4.9 microg x h/mL; MRT, 2.2 +/- 0.9 h. All milk from treated cows contained detectable penicillin residues for a minimum of three milkings (31 h) and maximum of five milkings (52 h) after administration. Concentrations of penicillin in all muscle, liver, and kidney samples taken 10 days postadministration were below the limit of quantification. Necropsy examinations revealed foci of hemorrhage on the rumenal omentum of most cows but peritonitis was not observed. Systemic inflammation as determined by change in leukogram or plasma fibrinogen was noted in one cow. The results of this study demonstrate that IP PPG is absorbed and eliminated rapidly in lactating dairy cows. PMID- 19646096 TI - Pharmacokinetics and clinical efficacy of lidocaine in cattle after intranasal administration during rhinotracheobronchoscopy. PMID- 19646097 TI - Animal safety report on intravaginal progesterone controlled internal drug releasing devices in sheep and goats. PMID- 19646098 TI - Pharmacokinetic behaviour of perphenazine in sheep after intramuscular administration of a long-acting formulation. PMID- 19646099 TI - Autonomy in relation to health among people with intellectual disability: a literature review. AB - BACKGROUND: Since the 1990s, individualisation, participation, normalisation and inclusion have been the main principles of care for people with intellectual disability (ID). Autonomy has become an important issue for these people. This review of the literature tried to answer the question: how do people with ID exercise autonomy in relation to health? METHOD: Searches in Cochrane, Medline and PsycINFO were based on the following aspects of autonomy: self-determination, independence, self-regulation and self-realisation. RESULTS: Thirty-nine of 791 articles met our criteria, including 14 on self-determination, seven on independence, 15 on self-regulation and three on self-realisation. CONCLUSIONS: In spite of decades of promoting autonomy, the exercise of autonomy in relation to health has so far rarely been an issue in the literature. PMID- 19646102 TI - Glucose, epithelium, and enteric nervous system: dialogue in the dark. AB - The gastrointestinal epithelium is in close contact with the various components of the chymus, including nutrients, bacteria and toxins. The epithelial barrier has to decide which components are effectively absorbed and which components are extruded. In the small intestine, a nutrient like glucose is mainly absorbed by the sodium linked glucose cotransporter 1 (SGLT1) and the glucose transporter 2 (GLUT2). The expression and activity of both transport proteins is directly linked to the amount of intraluminal glucose. Besides the direct interaction between glucose and the enterocytes, glucose also stimulates different sensory mechanisms within the intestinal wall. The most important types of cells involved in the sensing of intraluminal contents are enteroendocrine cells and neurones of the enteric nervous system. Regarding glucosensing, a distinct type of enteroendocrine cells, the enterochromaffine (EC) cells are involved. Excitation of EC cells by intraluminal glucose results in the release of serotonin (5-HT), which modulates epithelial functions and activates enteric secretomotorneurones. Enteric neurones are not only activated by 5-HT, but also directly by glucose. The activation of different cell types and the subsequent crosstalk between these cells may trigger appropriate absorptive and secretory processes within the intestine. PMID- 19646103 TI - Electrophysiological characterization of electrolyte and nutrient transport across the small intestine in horses. AB - The aim of this study was to characterize the transport mechanisms of electrolytes and nutrients across the jejunum of nine healthy horses electrophysiologically. The stripped mucosa was mounted in Ussing chambers and tissue conductances (G(t)) and short circuit currents (I(sc)) were continuously monitored. After blocking the sodium and potassium channels with amiloride, tetraethylammonium chloride (TEA) and barium, chloride secretion was stimulated by carbachol and forskolin. Subsequently, chloride channels were inhibited by 4,4'-diisothiocyanato-stilbene-2,2'-disulfonic acid, 5-nitro-2-(3 phenylpropylamino)benzoic acid, CFTR(inh)-172, N-(2-naphtalenyl)-(3.5-dibromo-2.4 dihydroxyphenyl)methylene glycine hydrazide (GlyH-101) and glibenclamide and their dose-response effect was investigated. The response to glucose, l-alanine and glycyl-l-glutamine was determined at two different mucosal pH values (pH 7.4 and 5.4 respectively). Mean basal I(sc) was -0.47 +/- 0.31 microEq/cm(2)h and mean G(t) was 22.17 +/- 1.78 mS/cm(2). Amiloride and TEA did not alter the baseline I(sc). Barium, carbachol and forskolin significantly increased I(sc). Irrespective of the dose, none of the chloride inhibitors changed I(sc). All nutrients induced a significant increase in I(sc) with the increase being significantly higher at pH 7.4 than at pH 5.4. In conclusion, there is evidence that chloride secretion in horses may be different from respective transport mechanisms in other species. The glucose absorption is suggestive of a sodium dependent glucose cotransporter 1. However, a decrease in luminal pH did not stimulate current response to peptides as shown for other mammals. PMID- 19646104 TI - Lysine requirement studies in modern genotype barrows dependent on age, protein deposition and dietary lysine efficiency. AB - N balance experiments were conducted to derive age-dependent model parameters for modelling of lysine (Lys) requirements in growing pigs. Modern genotype barrows from 16 litters were utilized (four piglets/litter) at 15, 30, 50, 70, 90 and 110 kg body weight respectively. Six diets provided graded dietary protein supply (40 to 320 g/kg) by a constant mixture of barley, wheat, potato protein, wheat gluten, soybean protein concentrate and crystalline amino acids. Lys was set as the first limiting dietary amino acid. Each age period provided 24 N balance data (n = 4) to derive N maintenance requirement (NMR) and theoretical maximum for daily N retention (NR(max)T) by non-linear regression analysis. At high dietary Lys efficiency, 17-18 g daily Lys intake was required for 170 g daily protein deposition. To achieve similar daily protein deposition, pigs need 21-23 g Lys if the Lys efficiency is 20% lower. For higher daily protein deposition (195-200 g) and varying dietary Lys efficiency, between 22 and 29 g Lys was required. The Lys requirement data yielded by modelling were in line with current recommendations. Further developments of the approach are discussed to improve age-independent applications. PMID- 19646105 TI - In vitro fermentation characteristics of different carbohydrate sources in two dog breeds (German shepherd and Neapolitan mastiff). AB - Few studies have been published on the normal intestinal biota of canines unlike the wealth of information regarding livestock animal species. The in vitro gas production technique (IVGPT) including measurements of accumulating gas during fermentation and end-product determinations allows obtaining a complete picture of microbial activity kinetics. The aim of this study was to study the in vitro fermentation characteristics of different carbohydrate sources using inocula from two dog breeds (German Shepherd and Neapolitan mastiff). Faeces sampled from rectum of two GS and NM adult dogs, fed the same dry food, were used as inocula. The samples, diluted and filtered, were incubated at 39 degrees C under anaerobic condition with nine substrates different for carbohydrate composition (rice, corn, potato, spelt, pure cellulose, beet pulp, wheat bran, inulin and fructo oligosaccharide). Gas production was recorded 17 times using a manual pressure transducer. After 48 h, the fermentation was stopped and fermenting liquor was analysed for pH and volatile fatty acids (VFA). Organic matter digestibility (OMD) was calculated as difference after burning the residuals. OMD, gas production and end-products were significantly correlated with chemical composition of substrates, in particular carbohydrate fractions (total dietary fibre and starch), confirming the effectiveness of the IVGPT in evaluating dog feeds. Concerning the comparison between breeds significant differences (p < 0.01) were found for OMD, gas production, fermentation kinetic parameters and end products, suggesting a different pathway of fermentation and consequently, a different anaerobic population. PMID- 19646106 TI - Investigation into selenium requirement of growing turkeys offered a diet supplemented with two levels of vitamin E. AB - To evaluate dietary selenium (Se) requirement in turkeys offered a diet supplemented with two levels of vitamin E (VE), 96 newly hatched male BIG 6 chicks (58.4 +/- 4.12 g) were divided into eight groups of 12 animals each and fed maize soya diets containing 0.05, 0.10, 0.20 and 0.30 mg Se/kg from sodium selenate in combination either with the natural VE content (approximately 10 IU/kg) or with a VE addition of 50 IU/kg. Animals from all the groups were highly performant and their final body weights (1746 +/- 190 g) after 35 days on experiment were not significantly different. According to its dietary supply, Se concentration in the liver and plasma increased dose dependently. Independent of dietary VE, the activities of GPx3 in plasma and of GPx1 in liver and breast muscle increased to a larger extent in turkeys supplemented with 0.10 and 0.20 mg Se/kg in relation to animals with low marginal Se supply (0.05 mg/kg). Supplementation of 0.30 mg Se/kg only slightly increased further selenoprotein activities. 2-Thiobarbituric acid reactive substances in the liver were strongly reduced by dietary VE, but not by Se. Plasma aspartate aminotransferase (AST) and creatine kinase (CK) activities did not show muscular lesions in none of the groups. Although there were no signs of muscular lesions even in turkeys with marginal Se and moderate VE supply, the activity of selenoproteins in various organs increased up to 0.30 mg Se/kg diet, independent of VE supply. It was concluded that for growing turkeys the Se supply should meet at least a level of 0.20 mg/kg diet as currently recommended by the National Research Council and Gesellschaft fur Ernahrungsphysiologie. Vitamin E addition confirmed the particular function of the vitamin as a lipid antioxidant and should be taken into consideration when diets with high PUFA concentrations are fed. PMID- 19646107 TI - Dietary incorporation of feedstuffs naturally high in organic selenium for racing pigeons (Columba livia): effects on plasma antioxidant markers after a standardised simulation of a flying effort. AB - Selenium is a trace element of importance for animal health. It is essential for adequate functioning of many enzymes such as, the antioxidant enzyme, glutathione peroxidase, which protects the cell against free radicals. A muscular effort induces a rise in reactive oxygen species production which, in turn, can generate an oxidative stress. Two groups of eight racing pigeons were fed respectively with a diet containing 30.3 (control group) and 195.3 (selenium group) microg selenium/kg diet. The pigeons were submitted to a standardised simulation of a flying effort during 2 h. Blood was taken before and after the effort to measure antioxidant markers and blood parameters related to muscle metabolism. Plasma selenium concentration and glutathione peroxidase activity were significantly higher in the selenium group. There were no significant differences for the other measured parameters. As a consequence of the effort, the pigeons of the selenium group showed a higher increase of glutathione peroxidase activity and a smaller increase of plasma lactate concentration. Variations because of the effort in the other markers were not significantly different between the two groups. It is concluded that the selenium status was improved with the feeding of feedstuffs high in Selenium. PMID- 19646109 TI - Effect of starch gelatinisation on nutrient digestibility and plasma metabolites in pigeons. AB - Feed manufacturing exerts physical and chemical changes in ingredients, including the gelatinisation of starch. Studies on the effect of the degree of starch gelatinisation on nutrient digestibility, metabolism and subsequent performance show inconsistent results, and no data are available in pigeons. In a cross-over trial, fourteen adult pigeons were randomly divided into two groups, in which two extruded pellet diets were tested. Both the diets were similar in ingredient composition and nutrient content, but differed in extrusion conditions, resulting in a different degree of starch gelatinisation: pellets with high gelatinisation degree (HG; 73.6% gelatinisation) and low gelatinisation degree (LG; 53.1% gelatinisation). After a 14-day adaptation period, all excreta were gathered per bird during a 5-day collection period. Coefficients of apparent digestibility of dry matter (DM), crude protein (CP), ether extract (EE), crude fibre (CF), crude ash (CA) and nitrogen free extract (NFE) as well as apparent nitrogen retention were calculated from proximate analyses of feed and excreta. Further, excreta consistency was subjectively scored. Blood samples were taken at the end of each period and plasma samples were analysed for glucose, fructosamine and triglycerides. Feed intake and body weight changes were recorded weekly. The apparent digestibility coefficients (ADCs) of DM, OM, CP, EE, CA and NFE were significantly higher in the LG group (p < or = 0.05). The ADC of crude fibre was numerically higher in the LG group but not significant, and no significant differences were found in starch digestibility. Excreta consistency score tended to be higher in the LG diet group. Neither plasma glucose nor plasma fructosamine values were significantly different between the two test diets. The results of this study show that lower degree of starch gelatinisation in extruded diets can enhance digestibility in pigeons. PMID- 19646108 TI - Risk factors of colic in horses in Austria. AB - A hospital-based case study was conducted at the University of Veterinary Medicine Vienna for a 1-year period. The purpose of this study was to determine possible alterable and non-alterable risk factors of equine colic in Austria. The investigated parameters were obtained from hospital medical records (individual factors, duty of the horse, deworming, change in diet and water intake), from questionnaires (feed intake, watering types, housing and pasture practices) and from http://www.orf.at (weather-related factors). Moreover, 221 collected feed samples were investigated through hygienic quality sensory evaluation and mould, yeast and bacteria presumptive samples were confirmed by microbiological investigation. Variables that were observed from the hospital medical records and found to be significantly associated with colic in a univariate analysis were included in multivariate analysis and the only remaining risk factor was decreased water consumption (p < 0.001, OR = 5.025). Consequently, a total of 2743 horses and 366 cases of colic were observed during the study period. The risk factors for colic in Austria were identified for the first time in this study and these increased risk factors were decreased water consumption, high amount of concentrate intake (p = 0.037), low hygienic quality of hay (p = 0.027) and high temperature on the arrival date (p = 0.003). Results suggest that the occurrence of colic may not stop, but may decrease with better feed management practices in Austria. PMID- 19646110 TI - Prediction of digestible protein content of dry extruded dog foods: comparison of methods. AB - The aim of this study was to check the accuracy of laboratory methods to predict the apparent protein digestibility (CPd, %) and digestible protein content (DP, g/kgDM) of dog foods, avoiding the use of experimental animals in digestion trials. Twenty-eight commercial dry extruded dog foods were tested by three different methodologies: an adaptation of the in vitro incubation method described by Hervera et al. (J Anim Physiol Anim Nutr 2007, 91: 205) for estimation of digestible energy of commercial dog foods, a modification of the pH drop methodology proposed by Hsu et al. (J Food Sci 1977, 42: 1269) for protein evaluation of human foods and the Near Infra Red Spectroscopy (NIRS) technology. All the methods assessed revealed very good, similar accuracy in the prediction of DP content either using the in vitro method (r = 0.99; RSD = 6.76; CV = 2.31%), the pH drop method (r = 0.99; RSD = 6.94; CV = 3.02%) or the NIRS (R2 = 0.96; SECV = 10.50) method, although the in vitro digestion method showed the highest accuracy approach of in vivo crude protein apparent digestibility: CPd in vitro (r = 0.81; RSD = 2.01; CV = 2.41%); CPd pH-drop (r = 0.78; RSD = 2.48; CV = 2.98%) and NIRS (r(2)cv = 0.53; SECV = 2.37). PMID- 19646112 TI - Editorial: JCN continues to 'go global'. PMID- 19646111 TI - Integrity of gastric mucosa in reared piglets--effects of physical form of diets (meal/pellets), pre-processing grinding (coarse/fine) and addition of lignocellulose (0/2.5%). AB - The aim of the present study was to investigate the potential effects of different particle fractions in non-pelleted (meal) and pelleted diets on the development of pre-ulcerative gastric alterations. Furthermore, the effect of increased crude fibre supply (lignocellulose) on the integrity of gastric mucosa were investigated. For that purpose, 49 piglets were divided into eight feeding groups and fed pelleted diets differing in grinding intensity (very coarse/coarse/fine/very fine) and addition of lignocellulose (0/2.5%) for 6 weeks. A coarsely ground meal was used as control diet. Mucosal integrity of the pars non-glandularis was characterised by macroscopical and histological score and basal epithelial conductance. Feed structure was assessed by sieve analysis (wet/dry). The use of coarsely ground meal (25% >2 mm, 29% <0.4 mm) had almost no negative effects on the gastric wall: three of seven pigs had slight histological and none had macroscopical lesions. Irrespective of the original grinding intensity before pelleting, offering pelleted diets led to mucosal changes similar in severity (one out of seven pigs fed coarsely ground and pelleted diets had no macroscopical alterations, whereas all pigs fed finely ground and pelleted diets showed altered tissues). Increasing the proportion of coarse particles in the pellet (from 25 to 29% >2 mm) did not show any ulceroprotective effect. An increase of crude fibre content (42-54 g/kg dm) by adding lignocellulose did not result in a decreased ulcerogenity. Unpelleted diets are recommended as more favourable for alleviating the problem of gastric ulcers in pigs as the pelleting process is equal to a secondary grinding process. According to our results, an upper level of fine particles seems to be reasonable (a minimum level of coarse particles is not ulceroprotective). In this study, an amount of 30% <0.4 mm resulted in higher risks for ulcerations. PMID- 19646113 TI - A critical view of how nursing has defined spirituality. AB - AIMS: To offer a detailed discussion of the issue of 'lack of critique' in the literature on spirituality in nursing. The discussion will include the limited use of sources from theology and religious studies and the demand to separate spirituality and religion and will go on to examine the consequences of the resulting approach. The drive for unique knowledge to further professionalisation and the demands of inclusiveness are suggested as possible reasons for the development of the current model. The dangers and pitfalls of definition are explored. The paper suggests that theology could provide insights into explaining spirituality. BACKGROUND: The last four decades have seen a proliferation of definitions of spirituality in the nursing literature. Recently, in response to their own concerns and prompts from outside the 'spirituality' community authors have suggested that we revisit this literature with a more critical stance. This paper is in response to that suggestion. During the course of a PhD supervised from a department of practical theology I have critically analysed the literature from several perspectives and this paper is one result of that review. DESIGN: Literature review. METHODS: Critical reflection on how spirituality has been defined. CONCLUSION: The lack of critique has produced a bias in the literature towards broad, generic, existential definitions which, together with the intentional divorce from religion and theology have led to definitions which have the tendency to result in a type of spiritual care which is indistinguishable from psychosocial care, hard to explain to patients and difficult to put into practice. RELEVANCE TO CLINICAL PRACTICE: The acceptance of a diverse range of understandings of spirituality and a greater focus on practical ways of using it in nursing care are the direction the profession should be moving into. PMID- 19646114 TI - Identifying trajectories of birth-related fatigue of expectant fathers. AB - AIMS AND OBJECTIVES: The objectives of this prospective study were to identify birth-related fatigue trajectories in expectant fathers with the progress of labour and the physiological, psychological and situational factors related to specific trajectory patterns. BACKGROUND: An increasing number of fathers participate in their partner's labour; however, their fatigue experience remains unclear. Previous studies have focused on overall groups without considering the possibility of between-subject heterogeneity. With an advanced data-analytic strategy, it is feasible to identify subgroup variation within the population over time. DESIGN: A prospective, repeated measures design was used. METHOD: A convenience sample of 108 Taiwanese expectant fathers was followed throughout the labour process. Data were collected by visual analogue scales and self administered questionnaires. The repeated measures of fatigue were analysed by using semi-parametric, group-based modelling. RESULTS: Two distinct groups of individual trajectories among the expectant fathers were identified; the persistent low-fatigue group (49.2%) and the persistent high-fatigue group (50.8%). After birth, a moderate level of fatigue persisted in the high-fatigue group. The fastest period of increasing level in the persistent high-fatigue group was in the latent phase. The persistent high-fatigue group also experienced significantly more sleep difficulties prior to labour and more anxiety than the persistent low-fatigue group. CONCLUSIONS: Identifying and characterising meaningful clusters of trajectories could provide a better understanding of the birth-related fatigue experience of fathers and contributes to recognising the target client and timing for early intervention. RELEVANCE TO CLINICAL PRACTICE: There are points in time at which professional caregiver actions may have an effect on the birth-related fatigue of fathers. Caregivers should prevent high levels of fatigue, which could accumulate as fathers accompany the women entering the labour phase. Fathers who present with high fatigue at onset of labour should receive early intervention, especially in the rapid-increasing fatigue period. PMID- 19646115 TI - Family experience of waiting for living donor liver transplantation: from parental donor perspective. AB - AIMS AND OBJECTIVES: The aim of this study was to investigate from the perspectives of the donor parents of children with biliary atresia, the essence of family experiences during the period when waiting for a living donor liver transplant. BACKGROUND: Living donor liver transplantation is a new hope for children and families when the child suffers from biliary atresia. It is obvious, during the waiting period, for a family with a child undergoing living donor liver transplantation, that the process has a serious impact and there is a need for them to be well-prepared. DESIGN: A descriptive phenomenological design was used in this study. METHODS: Nine donor parents from a medical centre in Taiwan participated in this study. The inclusion criteria were that the parent had a child with biliary atresia, that the child had received living donor liver transplantation over the last year and a half and that the parent was the living donor for child's liver transplantation. An open in-depth interview technique encouraged the parents to reflect on their experiences as the process raised their feelings to a conscious level. The data were analysed using the Colaizzi's approach. RESULTS: This study explores the essence of families undergoing the waiting period for living donor liver transplantation surgery from the point of view of the donating parents. Five themes emerged: (1) surgery as hope of rebirth, (2) negotiating the decision to have surgery, (3) the selection of the donor to achieve family welfare, (4) preparing and planning for the surgery and (5) worry over the impact of the surgery. CONCLUSIONS: The results demonstrate that the parents' experiences included a variety of domains: hope of rebirth, mental negotiation while deciding on surgery and choice of donor, coping with the preparation for surgery and the possible impact on the family of the surgery. RELEVANCE TO CLINICAL PRACTICE: The findings indicated that nursing professionals should provide family-centred care to assist the family with the steps needed to move toward surgery. PMID- 19646116 TI - Living with type 1 diabetes: perceptions of children and their parents. AB - AIM: To explore and describe the experiences of children and their parents living with type 1 diabetes mellitus from diagnosis onwards. BACKGROUND: Type 1 diabetes mellitus is a psychologically and behaviourally demanding chronic condition that necessitates children and their parents taking extensive responsibility for managing the condition. Diabetes management involves maintaining a highly effective level of treatment to reduce the risks of short- and long-term complications. Treatment is carried out in the context of daily life, but little research evidence is available about this experience. DESIGN: A phenomenological study using conversational interview. METHOD: A purposive sample of 10 children, (aged 4-17) living with type 1 diabetes mellitus and their parents participated in this study. Participants were from different ethnic backgrounds and at differing lengths of time since diagnosis. Data were generated through conversational interviews and analysed using thematic analysis. RESULTS: The central theme that was identified was 'normal'. This was underpinned by four subthemes: transition, attachment, loss and meaning. The notion of 'normal' is dominant in the lives of these children and their parents because diabetes not only makes these families different, but also makes their pursuit of 'normal' more visible. CONCLUSION: These findings highlight that, despite different cultures, ages and lengths of time since diagnosis, families living with diabetes share very similar experiences. Understanding how children and parents create meaning and how this meaning influences their actual and potential health problems, is important if the provision of healthcare is to be effective in meeting their needs. RELEVANCE TO CLINICAL PRACTICE: Conducting child- and parent centred qualitative research allows exploration of the perceptions and understanding of type 1 diabetes mellitus and the meaning ascribed by children and their parents who live with the condition. Diabetes is a lifelong, life threatening condition that has a significant impact on children's and parents' lives. Developing a deeper understanding of their lives and experiences will enable the delivery of nursing care to meet their specific needs. PMID- 19646117 TI - Helping adolescents who self-mutilate: parental descriptions. AB - AIM: The purpose of this qualitative descriptive study was to explore parental views on how to help adolescents who self-mutilate. BACKGROUND: Self-harm, including self-mutilation, is common among adolescents. However, parental conceptions of helping adolescents who self-mutilate have rarely been investigated in nursing science. DESIGN: Qualitative descriptive design. METHOD: Four parents of self-mutilating adolescents were interviewed in depth. Qualitative content analysis was applied. RESULTS: Three main categories emerged: a description of an adolescent who self-mutilates and descriptions of ways to help self-mutilating adolescents and ways to help their parents and family. An adolescent who self-mutilates appears externally to feel very well, but inside feels lonely and inferior to others. Help may include an adolescent helping herself by performing some activities alone or in relation to other people and an adolescent receiving help from a safe and trusting human relationship. Such a relationship can be with anyone who knows about the self-mutilation and is of utmost importance, but a caring attitude is particularly expected from adults. Factors that facilitate helping were identified as well as those considered help hindering or helpful. Help that had been provided to parents and the family included factors considered helpful and unhelpful. CONCLUSION: Adolescents who self-mutilate try to help themselves, but are in need of external, probably professional help. Parents are in need of information about self-mutilation as a phenomenon to be able to help their children. Help for self-mutilating adolescents as perceived by their parents also includes help for the whole family. RELEVANCE TO CLINICAL PRACTICE: The findings of this study could assist health care professionals in approaching and helping both self-mutilating adolescents and their parents. PMID- 19646118 TI - Nurse staffing, quality of nursing care and nurse job outcomes in intensive care units. AB - AIM: To examine the relationship between nurse staffing and nurse-rated quality of nursing care and job outcomes. BACKGROUND: Nurse staffing has been reported to influence patient and nurse outcomes. DESIGN: A cross-sectional study with a survey conducted August-October 2007. METHODS: The survey included 1365 nurses from 65 intensive care units in 22 hospitals in Korea. Staffing was measured using two indicators: the number of patients per nurse measured at the unit level and perception of staffing adequacy at the nurse level. Quality of care and job dissatisfaction were measured with a four-point scale and burnout measured by the Maslach Burnout Inventory. Multilevel logistic regression models were used to determine the relationships between staffing and quality of care and job outcomes. RESULTS: The average patient-to-nurse ratio was 2.8 patients per nurse. A fifth of nurses perceived that there were enough nurses to provide quality care, one third were dissatisfied, half were highly burnt out and a quarter planned to leave in the next year. Nurses were more likely to rate quality of care as high when they cared for two or fewer patients (odds ratio, 3.26; 95% confidence interval, 1.14-9.31) or 2.0-2.5 patients (odds ratio, 2.44; 95% confidence interval, 1.32-4.52), compared with having more than three patients. Perceived adequate staffing was related to a threefold increase (odds ratio, 2.97; 95% confidence interval, 2.22-3.97) in the odds of nurses' rating high quality and decreases in the odds of dissatisfaction (odds ratio, 0.30; 95% confidence interval, 0.23-0.40), burnout (odds ratio, 0.50; 95% confidence interval, 0.34-0.73) and plan to leave (odds ratio, 0.40; 95% confidence interval, 0.28-0.56). CONCLUSIONS: Nurse staffing was associated with quality of care and job outcomes in the context of Korean intensive care units. RELEVANCE TO CLINICAL PRACTICE: Adequate staffing must be assured to achieve better quality of care and job outcomes. PMID- 19646119 TI - Developing relationships in long term care environments: the contribution of staff. AB - AIMS AND OBJECTIVES: The aim of this study was to consider how relationships in care homes influence the experience of older people, their families and staff. The main objective reported in this paper considers how these relationships are developed and the contribution that staff make to this process through the routines of care. BACKGROUND: Relationships have been found to be integral to experiences of residents, families and staff in care homes but little is known about how these relationships develop. Few studies consider relationships in care homes as their main focus and there is a dearth of studies that consider relationships from the perspective of residents, families and staff within the same care home. DESIGN: The study employed a constructivist design where the different perspectives held by participants were explored and shared to develop a joint construction of how relationships influenced their experiences. METHODS: Data were collected from three care homes in England over two years between 2003 2005. Participant observation and interviews enabled a hermeneutic circle to be created between residents, families and staff. Data collection and analysis were conducted concurrently using a constant comparative method. RESULTS: Staff adopted three approaches to care delivery and these influenced the type of relationships that were developed between residents, families and staff. The three approaches were described as individualised task-centred, resident-centred and relationship-centred. CONCLUSION: This study progresses our understanding of the development of relationships between staff, residents and families in care homes by considering how the staff may support or constrain these relationships through their approach to care delivery. RELEVANCE TO CLINICAL PRACTICE: These findings have implications for developing practice in care homes to improve the experience of older people and their families by encouraging staff to develop a relationship-based approach to care routines. PMID- 19646120 TI - The experiences of people with an intersex condition: a journey from silence to voice. AB - AIM AND OBJECTIVES: The aim of this research was to explore the experiences of people with intersex conditions. The main objective was to contribute to knowledge of the condition by giving voice to a group of people who are invisible in society. BACKGROUND: Medical management of intersex conditions has historically focused on erasing visual bodily difference through gender assignation and medical/surgical intervention to ensure congruent body appearance. People with intersex conditions require support to live free from shame in a normalising society and need particularly sensitive care when engaged with the health system. DESIGN: A small-scale qualitative study was undertaken. Recruitment of participants was difficult because of barriers created by invisibility and marginalisation. After extensive and careful negotiation with one contact, three people in New Zealand agreed to participate in the research. METHODS: In-depth interviews were undertaken and thematic analysis used to develop themes that were common across participants' experiences. RESULTS: Three themes emerged from the data: managing silence, coping with difference and development of acceptance. These themes highlight: the negative impact of societal ignorance, lack of acceptance of body difference and the journey from silence to disclosure and acceptance of individuality and choice in gender identification. CONCLUSION: These findings highlight the need for nurses to be knowledgeable and skilled communicators to ensure age-appropriate information and support is provided to enable individual choice in gender identification and normalisation for people with intersex conditions. RELEVANCE TO CLINICAL PRACTICE: Many nurses will be unaware of the condition of being intersex and have little knowledge of the challenges faced by this group yet are likely to be involved in their care. People with intersex conditions require particularly sensitive care and nurses can provide appropriate, supportive and 'safe' care if they are aware of the condition and its challenges. PMID- 19646121 TI - Older people's views of dignity and how it can be promoted in a hospital environment. AB - AIM: The study investigated the lived experiences of older patients who had been in hospital, to explore their views on dignity and the factors which promote dignity. BACKGROUND: The UK government's new ambition for old age (New Ambition for Old Age: Next Steps in implementing the National Service Framework for Older People: A Report from Professor Ian Philip, DH) states that older people should be treated with dignity. The dignity in Care Campaign ('Dignity in Care'Public Survey, October 2006: Report of the Survey, DH) highlighted the need to raise staff's awareness and understanding of dignity. DESIGN: A purposive sample of older people took part in semi- structured interviews which focussed on their recent experiences of hospital admission. Qualitative data analysis was used. METHOD: Ten participants aged 73-83 were interviewed by a nurse researcher at home. All of the participants had an unplanned admission and were discharged home. RESULTS: The participants although generally satisfied with their care had strong views on dignity. The following factors had the potential to promote dignity; privacy for the body, cleanliness, independence and being able to exert control, sufficient time from staff, attitudes to older people and communication. CONCLUSIONS: This study suggests that independence and effective communication are of central importance in maintaining dignity through achieving control of their situation. The participants observed that factors such as speaking inappropriately and waiting for personal care undermined older people's perceptions of dignity. Several participants feared for their own dignity should they have cognitive problems later in their lives. RELEVANCE TO CLINICAL PRACTICE: Staff need to be aware that communicating in a way that conveys empathy and responds to the individual as a valued person is an important factor in maintaining dignity. Nurses on hospital wards particularly need to take measures to safeguard the dignity of older people with cognitive problems who have difficulty in making their needs known. PMID- 19646122 TI - The impact of stroke consequences on spousal relationships from the perspective of the person with stroke. AB - AIMS AND OBJECTIVES: This paper aims to provide a subjective insight into the experience of stroke recovery within spousal relationships. The aftermath of stroke and its impact on the physical, emotional, psychological and social effects of spousal relationships are explored. BACKGROUND: Many studies have examined observable functional recovery following stroke from the perspective of health care professionals. Longer-term effects of stroke such as changes in role and perception of self can alter significantly the dynamics of spousal relationships. Despite this, little attention has been given to the subjective impact of stroke on spousal relationships. DESIGN: A qualitative study design was adopted. Individual, audio-taped interviews were carried out over three months. METHODS: A convenience sample of 16 stroke survivors was recruited from the Stroke Nurse Specialist Register. All participants were over 18 years old and had been discharged from hospital following a diagnosis of stroke. Transcribed interviews were analysed using content data analysis to code and categorise emerging themes. RESULTS: Poststroke, spousal relationships altered significantly in terms of sexuality, sexual desire and sexual functioning. Within their role of husband or wife, stroke survivors described a lack of control and dramatic changes in their perception of self. CONCLUSIONS: Survivors of stroke experience profound, complex and multi-faceted difficulties in many areas of their spousal relationships, which are distressing to both them and their spouses. These have a significant impact on each individual's quality of life particularly in the longer term. RELEVANCE TO CLINICAL PRACTICE: Health care professionals and service providers need to understand and recognise the subjective experience of stroke and the complex difficulties that stroke survivors experience within their spousal relationships. It would appear that current service provision does not adequately address the range of needs that the stroke survivors described in this study. PMID- 19646123 TI - Commentary on Hewison A, Badger F, Clifford C & Thomas K (2009) Delivering 'Gold Standards' in end-of-life care in care homes: a question of teamwork? Journal of Clinical Nursing 18, 1757-1766. PMID- 19646125 TI - Is it worth the wait? PMID- 19646128 TI - Individual variations of serum testosterone in patients with prostate cancer receiving androgen deprivation therapy. Commentary. PMID- 19646129 TI - The significance of syndecan-1 expression in patients treated with radical prostatectomy. Commentary. PMID- 19646130 TI - Robot-assisted ascending-descending laparoscopic nerve-sparing prostatectomy. PMID- 19646134 TI - Bathing and cleansing in newborns from day 1 to first year of life: recommendations from a European round table meeting. AB - BACKGROUND: Development of the skin barrier continues up to 12 months after birth; therefore, care must be taken when cleansing and bathing infants' skin. Available guidelines for skin care in newborns are, however, limited. In 2007, the 1st European Round Table meeting on 'Best Practice for Infant Cleansing' was held, at which a panel of expert dermatologists and paediatricians from across Europe aimed to provide a consensus on infant bathing and cleansing. OUTCOMES: Based on discussions at the meeting and a comprehensive literature review, the panel developed a series of recommendations relating to several aspects of infant skin care, including initial and routine bathing, safety while bathing, and post bathing procedures. The panel also focused on the use of liquid cleansers in bathing, particularly relating to the benefits of liquid cleansers over water alone, and the criteria that should be used when choosing an appropriate liquid cleanser for infants. Alkaline soaps have numerous disadvantages compared with liquid cleansers, with effects on skin pH and lipid content, as well as causing skin drying and irritation. Liquid cleansers used in newborns should have documented evidence of their mildness on skin and eyes, and those containing an emollient may have further benefits. Finally, the panel discussed seasonal differences in skin care, and issues relating to infants at high risk of atopic dermatitis. The panel further discussed the need of clinical studies to investigate the impact of liquid cleansers on skin physiology parameters on newborns' and infants' skin. CONCLUSIONS: Bathing is generally superior to washing, provided basic safety procedures are followed, and has psychological benefits for the infant and parents. When bathing infants with a liquid cleanser, a mild one not altering the normal pH of the skin surface or causing irritation to skin or eyes should be chosen. PMID- 19646136 TI - Superficial basal cell carcinoma treated with imiquimod 5% topical cream for a 4 week period: a case series. AB - Basal cell carcinoma (BCC) is a malignant cutaneous neoplasm with a tendency to spread locally and with several clinical and histological subsets. We studied 82 patients with a clinical diagnosis of superficial BCC on different anatomical locations, to whom imiquimod 5% cream was administered on a low-frequency regime (three times a week for 4 weeks), and who were followed up 2 years after completion of treatment. Clinical clearance rate at 1 and 2 years were 89% and 85%, respectively. We conclude that imiquimod seems to be an appropriate therapeutic alternative for the treatment of superficial BCC in patients with associated comorbidities. PMID- 19646135 TI - Melasma in Latin America: options for therapy and treatment algorithm. AB - OBJECTIVE/AIM: To examine approaches to therapy for melasma in Latin Americans and to propose treatment algorithms for patients with mild, moderate and severe melasma. BACKGROUND: Melasma is prevalent in up to 10% of the Latin American population. It is found in all racial groups and is more common in subjects with darker skin phototypes. A number of topical treatments and procedures have been used for melasma. Topical treatments containing hydroquinone are the most popular. Care must be taken when treating melasma to avoid inducing post inflammatory hyperpigmentation and ochronosis. Determination of the severity of melasma (using the Melasma Area Severity Index and/or Physician's Global Assessment) and choice of the most effective and suitable treatment and/or procedure for individual patients is therefore essential. Sun protection is mandatory for all melasma patients. METHODS: Thirty-one clinical studies of topical treatments, chemical peels and laser and other therapies used for treating melasma were assessed for the level and quality of clinical evidence, by the Latin American Pigmentary Disorders Academy. The results of this analysis were combined with differential diagnosis guidelines and methods for assessing treatment success to establish algorithms for treating mild and moderate-to severe melasma. RESULTS: The most appropriate first-line treatment for mild melasma is hydroquinone 4%, triple combination cream containing hydroquinone 4%, tretinoin 0.05% and fluocinolone acetate 0.01%, double combination (e.g. 4% hydroquinone and 0.1% tretinoin) or non-phenolic therapy where there is an allergy to compounds. In moderate-to-severe melasma, triple combination cream is the recommended first-line treatment. Second-line treatment is double combination or hydroquinone 4% where triple therapy is not available or if allergic to compounds. Sun avoidance measures and broad spectrum sunscreens with high SPF are fundamental for the successful management of the disease. PMID- 19646138 TI - Tumour lysis syndrome induced by corticosteroid in metastatic melanoma presenting with initial hyperkalemia. PMID- 19646137 TI - Palmoplantar pustulosis with arthro-osteitis: successful treatment with etanercept and acitretin. PMID- 19646139 TI - Paradoxical postoperative hyperpigmentation from Q-switched YAG laser treatment of pigmented lesions in children with fair skin types. PMID- 19646140 TI - Increased serum levels of interleukin-22 in patients affected by pityriasis rosea. PMID- 19646142 TI - Commentary: the epilepsy diathesis. PMID- 19646143 TI - Letter: Antiepileptogenic and neuroprotective effects of erythropoietin: recent data. PMID- 19646145 TI - An animal breeder on Darwin's birthday. PMID- 19646146 TI - Predictive ability of models for calving difficulty in US Holsteins. AB - The performance of alternative threshold models for analyzing calving difficulty (CD) in Holstein cows was evaluated in terms of predictive ability. Four models were considered, with CD classified into either three or four categories and analysed either as a single trait or jointly with gestation length (GL). The data contained GL and CD records from 90 393 primiparous cows, sired by 1122 bulls and distributed over 935 herd-calving year classes. Predictive ability of each model was evaluated using four criteria: mean squared error of the difference between observed and predicted CD scores; a Kullback-Leibler divergence measure between the observed and predicted distributions of CD scores; Pearson's correlation between observed and predicted CD scores and ability to correctly classify bulls as above or below average for incidence of CD. In general, the four models had similar predictive abilities. The joint analysis of CD with GL produced little, if any, improvement in predictive ability over univariate models. In light of the small difference in predictive ability between models treating CD with three or four categories and considering that a greater number of categories can provide more information, analysis of CD classified into four categories seems warranted. PMID- 19646147 TI - Genetic description of a divergent selection experiment in Angora rabbits with overlapping generations. AB - The chief aims of this paper were the following: (i) to describe the demography and genetic structure in two divergent selected lines for total fleece weight (TFW) of French Angora rabbits with overlapping generations; (ii) to describe the effects of inbreeding during an experiment of divergent selection. A study of longevity with the survival kit showed that there was no significant difference in the risk of death or culling between the low line (LL) and high line (HL). A significant effect of inbreeding (p < 0.05) was observed with a 30% higher risk factor in the highest class of inbreeding coefficient compared with the other classes. The means of generation interval were 562 and 601 days in LL and HL, respectively. The numbers of generations for LL and HL were 3.90 and 3.64, respectively. Generation intervals decreased significantly from 1995 to 2000 (p < 0.05). The number of daughters in HL was very variable. The number of animals per generation was higher in HL than in LL. Each buck left nearly three daughters to the next generation (2.52 in LL, 3.24 in HL). In both lines, the effective number of ancestor genomes still present in the genetic pool of the generation was around eight from the reference population of 1995 to that of 2001. Inbreeding in HL was always higher than in LL. The effect of inbreeding was also significant (p < 0.05) on TFW and live weight. The animals with the lowest inbreeding category produced a higher TFW (p < 0.05) than the others. The observed selection differentials were lower than that expected owing to the breeding animal management rules in order to control inbreeding increase. PMID- 19646148 TI - Variation in direct and maternal genetic effects for meat production traits in Egyptian Zaraibi goats. AB - Multi-trait analyses were carried out to quantify the (co)variation in meat production traits in Zaraibi goats. The data were obtained from a research station. There were birth weight records on 6610 kids, of which 5970 and 5237 had also pre-and postweaning gain record, respectively. The kids were progeny of 115 bucks and 1387 does, which had altogether 3603 litter size and milk yield records in different parities and which were daughters of 109 sires and 721 dams. Single trait analyses were carried out as preliminary to a three-trait (litter size, birth weight, early growth) and five-trait (litter size, milk and growth traits) analyses. The analyses containing birth weight data required the highest number of iteration rounds in estimating the variance components using AI REML. The maternal genetic component was important for the genetic variation of birth weight and preweaning gain. In general, direct heritability was low (0.03-0.12) for growth traits, possibly due to the low-input environment. The estimates on genetic correlation between direct and maternal effects within these traits indicated mostly favourable relationship. Genetic antagonism was found between birth weight and early growth. Heritability (repeatability) for 90-day and total milk yield was 0.16-0.23 and 0.23-0.24 (0.28 and 0.39-0.40), respectively and 0.04-0.05 (0.10-0.11) for litter size. The genetic correlation between 90-day (total) milk yield and litter size was 0.45 (0.22). The correlation between the milk yield and the maternal genetic effects for the preweaning gain was very high (0.94). Selection schemes aiming to improve meat (litter size and growth) and milk production simultaneously are feasible. The increased milk production serves also for the acceleration of early growth in kids. PMID- 19646149 TI - Genetic evaluation of Australian dairy cattle for somatic cell scores using multi trait random regression test-day model. AB - A multi-trait (MT) random regression (RR) test day (TD) model has been developed for genetic evaluation of somatic cell scores for Australian dairy cattle, where first, second and third lactations were considered as three different but correlated traits. The model includes herd-test-day, year-season, age at calving, heterosis and lactation curves modelled with Legendre polynomials as fixed effects, and random genetic and permanent environmental effects modelled with Legendre polynomials. Residual variance varied across the lactation trajectory. The genetic parameters were estimated using asreml. The heritability estimates ranged from 0.05 to 0.16. The genetic correlations between lactations and between test days within lactations were consistent with most of the published results. Preconditioned conjugate gradient algorithm with iteration on data was implemented for solving the system of equations. For reliability approximation, the method of Tier and Meyer was used. The genetic evaluation system was validated with Interbull validation method III by comparing proofs from a complete evaluation with those from an evaluation based on a data set excluding the most recent 4 years. The genetic trend estimate was in the allowed range and correlations between the two sets of proofs were very high. Additionally, the RR model was compared to the previous test day model. The correlations of proofs between both models were high (0.97) for bulls with high reliabilities. The correlations of bulls decreased with increasing incompleteness of daughter performance information. The correlations between the breeding values from two consecutive runs were high ranging from 0.97 to 0.99. The MT RR TD model was able to make effective use of available information on young bulls and cows, and could offer an opportunity to breeders to utilize estimated breeding values for first and later lactations. PMID- 19646150 TI - A whole genome scan to map QTL for milk production traits and somatic cell score in Canadian Holstein bulls. AB - The detection and mapping of genetic markers linked to quantitative trait loci (QTL) can be utilized to enhance genetic improvement of livestock populations. With the completion of the bovine genome sequence assembly, single nucleotide polymorphisms (SNP) assays spanning the whole bovine genome and research work on large scale identification, validation and analysis of genotypic variation in cattle has become possible. The objective of the present study was to perform a whole genome scan to identify and map QTL affecting milk production traits and somatic cell scores using linkage disequilibrium (LD) regression and 1536 SNP markers. Three and 18 SNP were found to be associated with only milk yield (MY) at a genome and chromosome wise significance (p < 0.05) level respectively. Among the 21 significant SNP, 16 were in a region reported to have QTL for MY in other dairy cattle populations and while the rest five were new QTL finding. Four SNP out of 21 are significant for the milk production traits (MY, fat yield, protein yield (PY), and milk contents) in the present study. Six and nine SNP were associated with PY at a genome and chromosome wise significant (p < 0.05) level respectively. Three and 17 SNP were found to be associated with FY at a genome and chromosome wise significant (p < 0.05) level. Five and seven SNP were mapped with somatic cell score at a genome and chromosome wise significant (p < 0.05) level respectively. The results of this study have revealed QTL for MY, PY, protein percentage, FY, fat percentage, somatic cell score and persistency of milk in the Canadian dairy cattle population. The chromosome regions identified in this study should be further investigated to potentially identify the causative mutations underlying the QTL. PMID- 19646151 TI - An evaluation of four candidate genes for use in selection programmes aimed at increased intramuscular fat in Duroc swine. AB - A sufficient level of intramuscular fat (IMF) is needed to enhance consumer acceptance of pork products, and is currently receiving greater attention within swine genetic improvement programmes. An examination of previously described and novel genetic variants within candidate genes for IMF deposition was performed to evaluate potential use of genetic markers in marker-assisted selection (MAS). Biological candidate genes implicated to play a role in adipogenesis were investigated within two different lines of purebred Duroc pigs. These included MC4R, FABP3, DLK1, and TCF7L2. Significant variation in IMF within the control line was described by the MC4R genotype and a novel BsrfI single nucleotide polymorphism within the FABP3 gene. Genetic markers for DLK1 and TCF7L2 evaluated in this population are not currently recommended for selection in Duroc swine. Existence of MC4R and FABP3 mutations may be useful markers in MAS aimed at IMF improvement, provided that gene effects are segregating and the presence of an association is detected within the population. However, additional work to confirm the use of the investigated genetic markers in selection programmes is needed. PMID- 19646152 TI - Association of parathyroid hormone-like hormone (PTHLH) and its receptor (PTHR1) with the number of functional and inverted teats in pigs. AB - Parathyroid hormone-like hormone gene (PTHLH) and its receptor, parathyroid hormone/ parathyroid hormone-like hormone receptor 1 (PTHR1), play a role in epithelial mesenchymal interactions during growth and differentiation of different tissues and anatomic structures, including teats. Therefore, PTHLH and PTHR1 were evaluated as functional candidate genes for their effects on number and shape of teats in pigs. In particular, focus was on the occurrence and number of inverted teats, the most frequent and economically relevant teat developmental defect in pigs. For this purpose, association and linkage of the PTHLH gene and the PTHR1 gene with inverted teat defect and the total number of teats and inverted teats were studied in an experimental Duroc and Berlin Miniature pig (DUMI) population. Polymorphism C1819T of PTHR1 was significantly associated with inverted teat phenotype (p = 0.014), total number of teats (p = 0.047) and was close to significance with the number of inverted teats (p = 0.078). Polymorphism C375T of PTHLH was close to significance with the inverted teat phenotype (p = 0.122) and showed no significant association with the total number of teats (p = 0.621) and the number of inverted teats (p = 0.256) in the DUMI population. Association analyses were also performed for combined effects of PTHLH and PTHR1 in order to address potential interaction, however, revealed no indication of effects of interaction. The function, position and the association shown here promote PTHR1 as a candidate gene for number of teats and in particular for affection by and number of inverted teats. PMID- 19646153 TI - Role of selection and inbreeding on the incidence of cutaneous malignant melanoma in Sinclair swine. AB - This paper reports the quantitative analysis of the historical database of a herd of Sinclair swine affected by cutaneous malignant melanoma. The herd was under partial and non-systematic selection for melanoma susceptibility (animals having at least one tumour during the first 6 weeks of life). Weighted selection differentials for the number of tumours at birth and the number of tumours at 6 weeks were generally positive and between -0.43 and 4.76 tumours for the number of tumours at 6 weeks. Estimates of the heritability for number of tumours at birth and at 6 weeks using 1934 animals were 0.27 (+/-0.03) and 0.25 (+/-0.03), respectively. The estimate of the genetic correlation between these two traits was 0.95 (+/-0.03). Genetic trends were positive for the number of tumours at birth and at 6 weeks. In spite of positive selection differentials and a moderate heritability, there was a negative phenotypic trend in the number of tumours. Natural selection might be acting in a direction opposite to artificial selection in the Sinclair herd. The slopes of the regression of the number of tumours at birth, at 6 weeks, and melanoma susceptibility on individual inbreeding coefficients were non-significant, indicating no evidence of dominance. The number of live-born pigs was lower in litters from parents susceptible to the disease (p < 0.01). PMID- 19646154 TI - Effects of incomplete pedigree on genetic management of the Dutch Landrace goat. AB - Genetic diversity in the Dutch Landrace goat was investigated based on information from the pedigree with about 6500 animals. Annual inbreeding rate after 1985 was below 0.5% and after 1987 close to 0%. However, pedigree information was incomplete, and 350 animals had unknown parents, while for the majority the real parents must have been in the pedigree. To determine the influence of unknown parents, 20 new pedigrees were created by random assignment of animals, alive at the time of birth, as parents to individuals with unknown parents. Only 12 founders remained for these pedigrees, and inbreeding levels varied considerably between these 20 pedigrees. However, inbreeding rates were remarkably constant. They increased to about 0.2%, indicating that the population is not endangered by inbreeding. The optimal contribution theory was used to evaluate possibilities of decreasing the average relationship in the population and thus to increase the genetic diversity of the breed. Optimal contribution decreased the average relationship in the population whether randomly assigned parents were used or not. However, individuals selected as parents for the resampled pedigrees differed from the original pedigree, and only a few animals were selected for all pedigrees. Candidates for inclusion in the genebank were also selected using optimal contribution. Adding animals to the genebank increased the conserved genetic diversity substantially, but as the lists differed between the analysed pedigrees it was not clear which animals were best added to the genebank. PMID- 19646156 TI - International collaboration in the pursuit of patient safety. PMID- 19646157 TI - INR aims to be a truly international journal. PMID- 19646158 TI - Adapting nurse education in the face of nurse migration. PMID- 19646163 TI - Economics, health and nursing. PMID- 19646160 TI - Spanish nurse leader receives nursing's top international award. PMID- 19646164 TI - Electronic theses and dissertations: a review of this valuable resource for nurse scholars worldwide. AB - OVERVIEW: A worldwide repository of electronic theses and dissertations (ETDs) could provide worldwide access to the most up-to-date research generated by masters and doctoral students. Until that international repository is established, it is possible to access some of these valuable knowledge resources. BACKGROUND: ETDs provide a technologically advanced medium with endless multimedia capabilities that far exceed the print and bound copies of theses and dissertations housed traditionally in individual university libraries. CURRENT USE: A growing trend exists for universities worldwide to require graduate students to submit theses or dissertations as electronic documents. However, nurse scholars underutilize ETDs, as evidenced by perusing bibliographic citation lists in many of the research journals. SOURCES: ETDs can be searched for and retrieved through several digital resources such as the Networked Digital Library of Theses and Dissertations (http://www.ndltd.org), ProQuest Dissertations and Theses (http://www.umi.com), the Australasian Digital Theses Program (http://adt.caul.edu.au/) and through individual university web sites and online catalogues. BENEFITS: An international repository of ETDs benefits the community of nurse scholars in many ways. The ability to access recent graduate students' research electronically from anywhere in the world is advantageous. For scholars residing in developing countries, access to these ETDs may prove to be even more valuable. LIMITATIONS: In some cases, ETDs are not available for worldwide access and can only be accessed through the university library from which the student graduated. Public access to university library ETD collections is not always permitted. CONCLUSIONS: Nurse scholars from both developing and developed countries could benefit from ETDs. PMID- 19646165 TI - Childhood obesity: current literature, policy and implications for practice. AB - THE PROBLEM: In most of the industrialized world, a childhood obesity epidemic is evident, with the numbers rising each year. PURPOSE: To discuss the current literature in relation to childhood obesity and to provide health practitioners, especially nurses, with the fundamental knowledge that is imperative in the recognition of children who are at risk and thereby tailor appropriate interventions. METHOD: Databases that were accessed for current literature included CINAHL, Science Direct and ProQuest. Keywords used in the search included obesity, childhood, health, relevant national statistics, policy and health risks. The literature was confined to the past 10 years with emphasis on the past 5 years. The 50 most pertinent papers from a variety of countries were chosen, and 35 papers that represented key areas of relevance were selected as the basis of this article. This selection of papers dictated the key areas of discussion such as the acknowledged factors in childhood obesity. FINDINGS: Although childhood obesity may be related to specific cultural and national circumstances, universal themes emerged from the literature review. These include social factors, exercise, advertising, public policy and the importance of partnerships in policy. CONCLUSION: Any country that has a high rate or increasing rate of childhood obesity must acknowledge core factors that contribute to this serious health problem. Furthermore, public policy and community partnerships that include all health professionals have a responsibility in the prevention of childhood obesity. This can be implemented through education, research and advocacy of all nurses involved with children and families. PMID- 19646166 TI - Facilitators and barriers to adjustment of international nurses: an integrative review. AB - BACKGROUND: There is a scarcity of research focusing on issues encountered by international nurses (INs) in their adjustment to foreign health-care environments. Increasingly, INs are relied upon to address staffing shortages in many Western countries. As such, it is vital to identify what facilitates and what the barriers are to the successful adjustment in order to assist their integration into new workplace environments. AIM: This integrative review identifies facilitators and barriers encountered by INs as they adjust to foreign health-care environments. METHOD: Based on Cooper's Five Stages of Integrative Research Review, a systematic search of eight electronic databases was conducted, combined with hand and ancestral searches. Two authors independently reviewed each qualified study for relevance and significance. Subsequently, facilitators and barriers were identified and categorized into themes and subthemes. FINDINGS: Twenty-nine studies conducted in Australia, Canada, Iceland, UK and the USA were included in this review. Findings indicated that positive work ethic, persistence, psychosocial and logistical support, learning to be assertive and continuous learning facilitated the adjustment of INs to their new workplace environments. In contrast, language and communication difficulties, differences in culture-based lifeways, lack of support, inadequate orientation, differences in nursing practice and inequality were barriers. CONCLUSION: The review findings provide the basis for the development and testing of an evidence-informed programme to facilitate the successful adjustment of INs to their new work environments. PMID- 19646167 TI - Ontario's internationally educated nurses and waste in human capital. AB - AIM: To analyse critically the waste in human capital of Ontario's internationally educated nurses resulting from unemployment or underemployment. BACKGROUND: Globalization of the nursing workforce is resulting in more and more internationally educated nurses migrating to Canada every year. In Ontario, internationally educated nurses represent 11% of the total nursing workforce but many are unable to become registered in Ontario. According to the College of Nurses of Ontario (CNO), 40% of internationally educated nurse applicants never complete the application process and thus never become Registered Nurses in Ontario. Systemic barriers that prevent registration in Ontario can result from any of the seven requirements for completing the application process. The inability of internationally educated nurses to become registered is significant, considering the national and global nursing shortage. In addition, the inability to become registered results in tremendous waste of human capital, especially in developing countries that have invested financially in educating nurses. Although several programmes have been implemented in Ontario for internationally educated nurses, barriers exist in the design and administration of these programmes, and these are described. DATA SOURCE: An opinion piece of international interest and a human interest piece. CONCLUSION: Internationally educated nurses face significant barriers, which prevent their integration into the Ontario healthcare system. Several policy and management strategies are outlined that could be implemented to ease their integration into the Ontario healthcare system. PMID- 19646168 TI - Internationally educated nurses: profiling workforce diversity. AB - AIM: Nurses with diverse educational and cultural backgrounds are likely to adapt differently to new workforces. The aim of this study was to provide a profile of nurses educated in different countries who are employed in a major settlement jurisdiction. BACKGROUND: Despite difficulties in measuring its magnitude, it is evident that nurse migration has increased as a result of globalization. Major destinations for internationally educated nurses (IENs) include the USA, Canada, the UK, Australia and the Gulf States. Chief donor countries include the Philippines, India and other South Asian countries. Half of all IENs registered in Canada work in the province of Ontario. METHODS: Published literature and secondary data were used to profile cohorts of nurses educated in different countries who are employed in the Ontario workforce. FINDINGS: Statistics available on IENs in Ontario reveal a largely urban settlement pattern. There are major differences among IEN cohorts in terms of age, gender, work status, and type and place of employment. DISCUSSION AND CONCLUSIONS: Although IENs resident in Ontario could not be quantified, a relatively detailed description of IENs in the workforce was possible. Comparison of nurse cohorts indicated that generalizations about IENs should be made with caution. Changes in regulatory conditions have a significant effect on IEN employment. Difficulties associated with international educational and regulatory differences illustrate the need to create global nursing standards. Further investigation of differences in workforce profiles should provide insights leading to improved utilization of IENs. PMID- 19646169 TI - Is the grass any greener? Canada to United States of America nurse migration. AB - AIM: Little or no attempt has been made to determine why nurses leave Canada, remain outside of Canada, or under what circumstances might return to Canada. The purpose of this study was to gain an understanding of Canadian-educated registered nurses working in the USA. DATA SOURCES: Data for this study include the 1996, 2000 and 2004 USA National Sample Survey of Registered Nurses and reports from the same time period from the Canadian Institute for Health Information. FINDINGS: This research demonstrates that full-time work opportunities and the potential for ongoing education are key factors that contribute to the migration of Canadian nurses to the USA. In addition, Canada appears to be losing baccalaureate-prepared nurses to the USA. DISCUSSION: These findings underscore how health care policy decisions such as workforce retention strategies can have a direct influence on the nursing workforce. Policy emphasis should be on providing incentives for Canadian-educated nurses to stay in Canada, and obtain full-time work while continuing to develop professionally. CONCLUSION: Findings from this study provide policy leaders with important information regarding employment options of interest to migrating nurses. STUDY LIMITATIONS: This study describes and contrasts nurses in the data set, thus providing information on the context of nurse migration from Canada to the USA. Data utilized in this study are cross-sectional in nature, thus the opportunity to follow individual nurses over time was not possible. PMID- 19646170 TI - Evaluating the impact of a new pay agreement on New Zealand nursing. AB - AIM: This paper examines the labour market impact of a new national pay award for nurses implemented in New Zealand in 2004/5 - the Multi-Employer Collective Agreement (MECA). BACKGROUND: The health system in New Zealand is unusual in that, while retaining a public sector system, the focus of pay determination for nurses over the last 20 years has shifted first from national to local pay determination, and then more recently reversed this trend, moving back to a national level pay determination. The shift back to a national pay determination approach in 2004/5 is therefore worthy of examination, both in terms of its labour market impact, and as a case study in the use of national level pay determination. METHODS: The research was conducted in 2007-8. A rapid appraisal method was used, based on key stakeholder interviews, a document and literature review and a review and analysis of available data on the New Zealand nurse labour market, and trends in application rates to schools of nursing were assessed. In addition, interviews with managers of two District Health Boards, and interviews with five non-government employers of nurses, were conducted. RESULTS: Indicators pointing to improvements included: steady (though not rapid) growth in staff numbers; reduced difficulty in recruiting; reduced vacancy rates; and increased application rates to schools of nursing. Managers interviewed in the study supported these positive indications, but some health-care employers not covered by the pay award reported negative knock-on effects (e.g. needing to match DHB rates, increased retention and recruitment difficulties). CONCLUSIONS: Available nurse labour market data provide an incomplete but compelling picture of the positive impacts of the MECA in a period of a very tight labour market. While much of the content of the 2004/5 agreement could be characterized as a 'normal' pay bargaining contract, there were also issues that differentiated it from the norm. In particular, it included an agreement to establish a safe staffing commission to assess the impact and implications of low staffing levels, nursing workload, and to establish guidelines on safe staffing and healthy workplaces. PMID- 19646171 TI - Developing a valid and reliable Self-Efficacy in Clinical Performance scale. AB - AIM: This paper describes the development and testing of the Self-Efficacy in Clinical Performance (SECP) instrument for nursing students. BACKGROUND: Accurate measurement of self-efficacy can be used to predict nursing students' clinical performance. The literature review indicated there is no existing self-efficacy in clinical performance instrument for Iranian nursing students. METHODS: To clarify the concept of self-efficacy in clinical performance, 28 semi-structured interviews and three focus groups were conducted. A self-efficacy framework with well-developed theoretical constructs was formed. A review of literature and content analysis of the interview transcripts identified subscales and items to be included in the instrument. Then, a methodological design was used. The SECP was developed into 69 Likert-format items, which were evaluated by 20 nursing experts in the form of content validity index. The scale's validity and reliability were tested in a randomized sample of 207 final year nursing students. FINDINGS: The final scale consists of four dimensions with 37 items. The overall scale internal reliability had alpha = 0.96; the dimensions Cronbach's alpha ranged from 0.90 to 0.92. Test-retest reliability with a 2-week time interval was: r = 0.94. In addition, concurrent validity was obtained (r = 0.73, P = 0.01). CONCLUSIONS: The SECP has demonstrated evidence of content validity, construct validity, concurrent validity, internal consistency reliability and stability. Statistical analysis provided an objective tool for assessing nursing students' self-efficacy in clinical performance. It may have been fruitful to further test the instrument with students from other years of their education. PMID- 19646172 TI - Swedish student nurses' knowledge of health statutes: a descriptive survey. AB - BACKGROUND: The nurse's function, no matter the working area, is guided by ethical approaches, grounded in science and well-tried experiences, and has to be conducted according to national laws, statutes and instructions. AIM: To survey newly graduated Swedish nurses' knowledge about current statutes and laws that govern their healthcare system. METHOD: A questionnaire was developed from facts in relevant statutes and laws presented and used in the nursing education programmes. Following a pilot study testing the items, a 20-item questionnaire, with mostly open-ended questions, was distributed to student nurses in the last semester of their nursing education programme before graduation. RESULTS: One hundred and seventy-eight participants answered the questionnaire (response rate 59%). Only 29% of responses on all questions showed correct knowledge about the different statutes and laws that regulate their work as nurses. The best knowledge was found in the area of documentation (range 35-86%) and in the area of information (range 16-54%) on group scores. CONCLUSION: This survey concerning novice nurses' knowledge about statutes and laws showed great deficiencies. It was surprising to find that, on existing demands regarding nurses delegating medical tasks, not a single respondent presented a correct answer. Evidence-based knowledge was difficult to recognize. Nurses will be more conscious of their own limitations and more prepared to meet the reality of practice if there is emphasis on relevant statutes and laws during their education. PMID- 19646173 TI - Smoking prevalence among qualified nurses in the Republic of Ireland and their role in smoking cessation. AB - BACKGROUND: Smoking is the leading preventable cause of premature mortality, killing approximately 6000 people in Ireland each year. On 29 March 2004, the Republic of Ireland became the first country in the world to ban smoking in all workplaces, including bars and restaurants. This study took place after the introduction of this smoking ban. An admission to hospital provides an opportunity to help people stop smoking. Nurses' role and wide availability puts them in a prime position to encourage people to quit smoking. AIM: To examine the smoking prevalence among qualified nurses at a large university teaching hospital in Cork Southern Ireland and their role in smoking cessation. METHODS: This was a descriptive cross-sectional study using a calculated sample of 430 qualified nurses (with a 70% response rate). A structured questionnaire was used. FINDINGS: It was found that 21% (n = 63) of nurses were smokers, 23% (n = 70) were ex smokers and 56% (n = 167) were non-smokers. The highest prevalence of smokers was found in the age groups 20-25 years (28%, n = 17) and 26-30 years (34%, n = 21). Nurses working within psychiatric care (47.4%) and coronary care (33.3%) had the highest smoking prevalence among the nurses who smoked. The study found that there was a significant difference between the attitudes of smokers and non smokers, 89% (n = 211) of non-smokers strongly agreed that cigarette smoke represents a major risk to health in comparison with only 65% (n = 41) of smokers. Only 14% (n = 43) of the nurses surveyed had received training in smoking cessation. Lack of time (74%) and lack of training (65%) were the two main reasons given by nurses for not giving smoking cessation advice to patients. CONCLUSION: Nurses' potential in preventive health care has been largely under utilized. Lack of time and training are major factors inhibiting nurses' role in smoking cessation with their patients. PMID- 19646174 TI - Turkish nurses' perspectives on a programme to reduce burnout. AB - BACKGROUND: Burnout is a serious problem among nurses. Programmes to prevent and reduce burnout have been described, but nurses report that they have difficulty attending such programmes and the dropout rate is substantial. AIM: To investigate the perspectives of nurses on burnout and the barriers and facilitators affecting attendance at a burnout reduction programme offered in their institution. METHODS: A qualitative study using semi-structured interviews was conducted with 18 nurses who had volunteered to attend a burnout intervention programme at a University Hospital in Izmir, Turkey. Six of the nurses had not attended any sessions, six attended four or less of the seven and six attended all sessions. Data were analysed using thematic analysis. RESULTS: Nurses attributed burnout to their heavy workload and a lack of recognition for their work. Most stated that they need work-directed rather than person-directed interventions to reduce stress and burnout. Attendance at the intervention programme was impeded by such issues as a perceived lack of institution support and the possibility of being seen by other nurses as unable to cope with stress. CONCLUSION: Researchers planning burnout intervention programmes should consider ways of increasing cooperation between the administration and the staff that facilitate attendance at such programmes. A holistic approach involving work directed and person-directed interventions is recommended. PMID- 19646175 TI - Nurse-patient communication barriers in Iranian nursing. AB - BACKGROUND: Providing effective communication with patients is an essential aspect of nursing care. Understanding the barriers that inhibit nurse-patient communication can provide an opportunity to eliminate them. AIM: To investigate nurse-patient and environment-related communication barriers perceived by patients and nurses in Iranian nursing. METHODS: A descriptive survey was carried out in three randomly selected educational hospitals in a large urban city in Iran. Data were collected by questionnaire; the study sample consisted of 61 patients and 75 nurses. Participants were asked to rate the importance of each communication barriers item. Finally, data were analysed using descriptive statistics, and to compare the perceived importance of communication barriers between patients and nurses, item means were calculated and the t-test for independent samples was applied. RESULTS: Similarities and differences between the two groups were identified. According to nurses' views, 'heavy nursing workload', 'hard nursing tasks' and 'lack of welfare facilities for nurses' were the main communication barriers. From patients' views, 'unfamiliarity of nurses with dialect', 'having contagious diseases' and 'sex differences between nurses and patients' were determined as the main communication barriers. The shared communication barriers were 'age difference', 'social class difference' and 'having contagious diseases'. CONCLUSION: It can be concluded that nursing managers and healthcare system planners should focus on eliminating or modifying the barriers stated by the two groups, particularly the shared ones. It is suggested that understanding the cultural aspects of nurse-patient communication barriers in various contexts can help nurses. LIMITATIONS: The study relied on self-report by a limited sample of nurses and patients. The responses should now be tested by a larger sample and then by empirical research into actual practice in order to test whether the nurses' and patients' perceived ideas of communication barriers are substantiated. PMID- 19646176 TI - Pregnant women's knowledge and attitudes about stem cells and cord blood banking. AB - AIM: This study was to determine pregnant women's knowledge and attitudes towards stem cells and cord blood banking in Istanbul, Turkey. BACKGROUND: Stem cell research is one of the most important and, at the same time, the most controversial topics of science and technology today. Nurses need to understand stem cell research so they can enter the debate on this issue. They can become important sources of information in order to help parents understand the issues. METHODS: This exploratory descriptive study was conducted in two antenatal outpatient clinics in Istanbul. The sample consisted of 334 pregnant women during routine prenatal visits. Data were collected in interviews by using an interview form developed by the researchers according to the literature. The form included demographic characteristics of participants and 20 questions about stem cells, storing cord blood and banking and 10 independent attitude statements. RESULTS: The majority of the participants had a lack of knowledge about stem cells and cord blood banking and wanted more information. Before pregnancy, they received some information through the media (newspaper, Internet, television, etc.), but unintentionally. It was determined that they wanted information before becoming pregnant, more from their obstetrician but also from nurses and midwives. The majority also wanted to store their infants' cord blood and stated that they would be more likely to choose a public cord blood bank. CONCLUSION: Those giving ante- and perinatal care need to offer accurate and scientific counselling services on this subject to parents who need to be informed. PMID- 19646177 TI - The experience of puberty in adolescent boys: an Iranian perspective. AB - BACKGROUND: The process of puberty is a normal physiological event for adolescents. Studies show that there is not enough knowledge about boys' puberty experiences. In spite of physiological similarities of puberty characteristics in different societies, social, cultural and religious factors have an important influence on puberty process. AIM: To begin to explore the experiences of adolescents and parents about puberty within the Iranian cultural context. METHODS: Qualitative research was adopted using thematic analysis of semi structured interviews carried out with 16 adolescent boys (13-17 years old) and 12 parents. All studies were transcribed verbatim and analysed. FINDINGS: The analysis of the transcripts showed four main themes including shame and embarrassment, anxiety, transition, puberty orientation and management. CONCLUSION: Development of knowledge about puberty issues is important; additionally meeting health and educational needs of this transient period is one of the main priorities of the healthcare system and society. Knowledge of puberty is important for nurses and counsellors who work with adolescents for planning primary prevention programmes related to sexual health education and adolescent mental health. LIMITATIONS: Boy's embarrassment about describing puberty changes was a hindrance to their full engagement in the interviews; therefore in some situations the interviews were not as deep as was wished. This limitation is related to the subject itself, not the method used for data gathering. PMID- 19646178 TI - The education of Romany health and social assistants in the Czech Republic. AB - AIM: This paper presents the Czech national pilot project - the first educational course of Romany health and social assistants for community work with the Romany population in excluded communities. BACKGROUND: The Romany people are the biggest minority in the Czech Republic. The number is ever increasing because of the migration from South-East Europe. At the same time, the health and social problems of the Romany population are rising, too. To begin to address some of the health problems of this population, a pilot community project entitled Romany Health and Social Assistant was implemented in the years 2002-2004 in Ostrava. Ostrava is the third largest city and has the largest Romany population. Based on the outcomes of this project and as part of the national project SASTIPEN - Reduction of Health Inequalities in the Romany Community, the systematic education of selected Romany health and social assistants was carried out in 2005 2007. CONCLUSIONS: These trained Romany assistants are now working in the regions of the Czech Republic where inhabitants live in large Romany communities. The project evaluation was based on a questionnaire investigation of 170 clients living in Romany communities and on the statements of Romany health assistants. They found positive outcomes in several areas: obtaining information on health, motivation to healthy lifestyle, concrete changes in lifestyle and boosting trust towards doctors. Following the end of the project and its evaluation, an educational course will be accredited and certified, and the education of Romany assistants will be widespread across the whole country. PMID- 19646179 TI - Developing the scope of practice and education for advanced practice nurses in Finland. AB - BACKGROUND: The reorganization of Finnish healthcare services has required a restructuring of the areas of responsibility between healthcare professionals. AIM: To describe the need for Advanced Practice Nurses in Finland and the development process of a Master's programme in Health Promotion, Advanced Clinical Care. METHODS: The study consisted of a survey of nurse managers (24) and focus group interviews with clinical nurse specialists (46). FINDINGS: The expanded role includes advanced clinical skills and responsibility for health prevention and promotion, education, supervision, leadership, research and development. CONCLUSIONS: The legislation, scope and models have to be supported and further developed to promote the full scope of advanced practice. PMID- 19646180 TI - Identification of the transcription factor responsible for L-malate-dependent regulation in the marine Antarctic bacterium Pseudoalteromonas haloplanktis TAC125. AB - Two-component systems are widespread in nature and constitute the most common mechanism of transmembrane signal transduction in bacteria. Recently, a functionally active two-component system consisting of malS and malR genes possibly involved in the expression of a C4-dicarboxylate transporter system (dctAB operon) was identified in the marine Antarctic bacterium Pseudoalteromonas haloplanktis TAC125. In this paper, we performed a functional analysis of the two component system and demonstrated its involvement in the regulation of the expression of C4-dicarboxylate transporter genes. The expression of the C4 dicarboxylate transporter genes was induced by l-malate with the promoter element located upstream of the dctA gene being active only in the presence of the inducer. A sigma(54) promoter responsible for the l-malate dependent transcription regulation was identified and functionally characterized. The molecular mechanism involves an inverted repeat sequence located upstream the sigma(54) promoter that was shown to bind regulatory proteins only in the presence of l-malate. The protein factor responsible for the induction of the dctAB operon expression was eventually identified as the transcriptional regulatory protein MalR. MalR is the first transcriptional factor identified in P. haloplanktis TAC125 and one of the few transcriptional modulators reported so far in cold adapted bacteria. PMID- 19646181 TI - Role of a serine-type D-alanyl-D-alanine carboxypeptidase on the survival of Ochrobactrum sp. 11a under ionic and hyperosmotic stress. AB - The plant growth-promoting rhizobacterium, Ochrobactrum sp. 11a displays a high intrinsic salinity tolerance and has been used in this work to study the molecular basis of bacterial responses to high concentrations of NaCl. A collection of Ochrobactrum sp. 11a mutants was generated by Tn5-B21 mutagenesis and screened for sensitivity to salinity. One clone, designated PBP and unable to grow on glutamate mannitol salt agar medium supplemented with 300 mM NaCl was selected and further characterized. The PBP mutant carries a single transposon insertion in a gene showing a high degree of identity to the serine-type d-alanyl d-alanine carboxypeptidase gene of Ochrobactrum anthropi. Interestingly, the expression of this gene was shown to be upregulated by salt in the PBP mutant. Moreover, evidence is presented for the requirement of the gene product for adaptation to high-salt conditions as well as to overcome the toxicity of LiCl, KCl, sucrose, polyethylene glycol (PEG), AlCl(3), CuSO(4), and ZnSO(4). In addition to the altered tolerance to both ionic and osmotic stresses, the PBP mutant exhibited changes in colony and cell morphology, exopolysaccharide production, and an increased sensitivity to detergents. PMID- 19646182 TI - Metabolic syndrome: collapsing under its own weight? PMID- 19646183 TI - The Y402H variant of complement factor H is associated with age-related macular degeneration but not with diabetic retinal disease in the Go-DARTS study. AB - AIMS: The Y402H variant of complement factor H (CFH) is associated with risk of age-related macular degeneration (ARMD). In common with ARMD, diabetic retinal disease also appears to involve complement activation. The aim was to investigate the impact of Y402H on both retinal pathologies in patients with Type 2 diabetes (T2DM) undergoing systematic eye screening. METHODS: Patients with T2DM (n = 2350) were genotyped for the CFH Y402H variant. The association of genotype with retinal disease was determined in both retrospective and prospective models. RESULTS: The retrospective study demonstrated that the HH genotype was associated with an age-adjusted odds ratio of 7.4 for ARMD (P = 2.9 x 10(-11)). In a longitudinal study in the disease-free cohort, the age-adjusted hazard ratio was 2.8 (P = 2.4 x 10(-7)). The life-time hazard ratio was 3.4 (P = 2.1 x 10(-16)). We found no association of Y402H with development of referable diabetic retinal disease. CONCLUSION: The ARMD-associated Y402H variant in CFH does not appear to be associated with diabetic retinal disease, although complement activation is involved in the pathoaetiology of both conditions. PMID- 19646184 TI - Phenotypical aspects of maturity-onset diabetes of the young (MODY diabetes) in comparison with Type 2 diabetes mellitus (T2DM) in children and adolescents: experience from a large multicentre database. AB - AIMS: To analyse and compare clinical characteristics in young patients with maturity-onset diabetes of the young (MODY) and Type 2 diabetes mellitus (T2DM). METHODS: We conducted an observational investigation using the DPV-Wiss database containing clinical data on 40 757 diabetic patients < 20 years of age from Germany and Austria. RESULTS: Three hundred and thirty-nine cases were clinically categorized as MODY (0.83%); 562 patients were diagnosed as T2DM (1.4%). In 20% of cases, the diagnosis of MODY was based on clinical findings only. Of the 272 subjects where genetic testing was available, 3% did not carry mutations in the three examined MODY genes. Glucokinase-MODY was commoner than HNF1A-MODY and HNF4A-MODY. Age at diagnosis was younger in MODY patients. The body mass index of T2DM was significantly higher compared with all MODY subgroups. Macrovascular risk factors such as dyslipidaemia and hypertension were commoner in T2DM, but 23% of MODY patients had dyslipidaemia and 10% hypertension. Glycaemic control was within the therapeutic target (HbA(1c) < 7.5%) in 86% of MODY and 70% of T2DM patients. CONCLUSIONS: The prevalence of MODY in children and adolescents in Germany and Austria is lower than that of T2DM in this age group. Dyslipidaemia and hypertension are less frequent in MODY compared with T2DM patients, but do occur. PMID- 19646185 TI - Abnormal screening glucose challenge test in pregnancy and future risk of diabetes in young women. AB - AIMS: Pregnant women commonly undergo screening for gestational diabetes mellitus (GDM) using a 50-g glucose challenge test (GCT), followed by a diagnostic oral glucose tolerance test (OGTT) in those women in whom the GCT is abnormal. Although it has long been recognized that GDM is associated with subsequent Type 2 diabetes, it has recently emerged that any degree of abnormal antepartum glucose homeostasis predicts an increased risk of postpartum glucose intolerance. Thus, in this context, we sought to determine whether women who have a pregnancy complicated by an abnormal GCT, but who do not have GDM, are at increased risk of subsequent diabetes, compared with their peers with an abnormal GCT. METHODS: A population-based, retrospective cohort study was conducted. Women referred for an antepartum OGTT indicative of an abnormal GCT (n = 15 381), but without GDM, were matched (for age, region, socioeconomic status, and year of delivery) with up to four other women without such referral (n = 61 237). The two cohorts were followed over a median 6.4 years for the development of diabetes. RESULTS: The rate of incident diabetes was 5.04 cases per 1000 person-years in the cohort of women who underwent an antepartum OGTT, compared with 1.74 cases per 1000 person years in women without an OGTT. The hazard ratio for subsequent diabetes in women with an antepartum OGTT was 2.56 (95% confidence interval 2.28, 2.87) (P < 0.0001). CONCLUSIONS: Even in the absence of GDM, abnormal screening GCT in pregnancy is associated with an increased future risk of diabetes in young women. PMID- 19646186 TI - Modification of diet in renal disease and Cockcroft-Gault formulas do not predict mortality (ZODIAC-6). AB - AIMS: An inverse relationship between estimates of renal function, with formulas such as the Modification of diet in renal disease (MDRD) study equation or the Cockcroft-Gault formula, and mortality has been suggested. These formulas both contain the variables sex, serum creatinine and age and the latter also contains body weight. We investigated whether these formulas predict mortality better than the variables they contain together in patients with Type 2 diabetes. METHODS: In 1998, 1143 primary care patients with Type 2 diabetes participated in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) Study, in the Netherlands. Clinical and laboratory data were collected at baseline. Life status was assessed after 6 years. We used Cox proportional hazard modelling to investigate the association between estimates of renal function (continuous data) and the variables they contain and mortality, adjusting for confounders. Both formulas were compared with models consisting of the variables present in the formulas. Predictability was assessed using Bayesian information criterion (BIC) and Harrell's C statistics. RESULTS: At follow-up, 335 patients had died. All variables, except sex, influenced mortality. Predictive capability, indicated by lower BIC values and higher Harrell's C values, was up to 10% better for models containing the separate variables as compared with Cockcroft-Gault or MDRD. CONCLUSIONS: Using estimates of renal function to assess mortality risk decreases predictability as compared with the combination of the risk factors they contain. These formulas, therefore, could be used to estimate renal function; however, they should not be used as a tool to predict mortality risk. PMID- 19646187 TI - Relationship of Type 2 diabetes to the prevalence, incidence and progression of age-related hearing loss. AB - AIMS: Type 2 diabetes and associated microvascular abnormalities are postulated to affect hearing. Our study reports on the relationship between Type 2 diabetes and the prevalence, 5-year incidence and progression of hearing impairment in a representative, older, Australian population. METHODS: The Blue Mountains Hearing Study is a population-based survey of age-related hearing loss conducted in a defined suburban area, west of Sydney. Hearing loss was defined as the pure-tone average of frequencies 0.5, 1.0, 2.0 and 4.0 kHz > 25 decibels hearing level (dB HL) in the better ear (bilateral hearing loss). Type 2 diabetes was defined from reported physician-diagnosed diabetes or fasting blood glucose > or = 7.0 mmol/l. RESULTS: Age-related hearing loss was present in 50.0% of diabetic participants (n = 210) compared with 38.2% of non-diabetic participants (n = 1648), odds ratio (OR) 1.55 [95% confidence interval (CI) 1.11-2.17], after adjusting for multiple risk factors. A relationship of diabetes duration with hearing loss was also demonstrated. After 5 years, incident hearing loss occurred in 18.7% of participants with, and 18.0% of those without diabetes, adjusted OR 1.01 (CI 0.54 1.91). Progression of existing hearing loss (> 5 dB HL), however, was significantly greater in participants with newly diagnosed diabetes (69.6%) than in those without diabetes (47.8%) over this period, adjusted OR 2.71 (CI 1.07 6.86). CONCLUSIONS: Type 2 diabetes was associated with prevalent, but not incident hearing loss in this older population. Accelerated hearing loss progression over 5 years was more than doubled in persons newly diagnosed with diabetes. These data explore further reported links between Type 2 diabetes and age-related hearing loss. PMID- 19646188 TI - Long-term impact of retinal screening on significant diabetes-related visual impairment in the working age population. AB - AIMS: Diabetic retinopathy has long been regarded as the commonest preventable cause of blindness in the working age population. The aim was to determine if consistent annual screening for treatable retinopathy decreased the incidence of new blindness. METHODS: We collated the causes of blindness for a 5-year period between 2001 and 2005 for the 16- to 64-year age group in a district that had operated systematic retinal screening in diabetes since 1986. RESULTS: Diabetic retinopathy was found to be the second commonest cause of blindness, with optic atrophy being the commonest cause in Newcastle District. This differs from national data showing diabetic retinopathy to be the commonest cause. Diabetic retinopathy was also the second commonest cause of partial sightedness registrations, with stroke being the commonest cause. Overall, stroke disease accounted for 16.2% and diabetic retinopathy for 15.4% of registrations. The annual incidence of blindness was 0.22 per 1000 with diabetes and of partial sightedness 0.43 per 1000 with diabetes. CONCLUSIONS: In a district that has operated retinal screening since 1986, diabetic retinopathy was not the commonest cause of blindness in the working age population, consistent with an effect of systematic annual screening. PMID- 19646189 TI - Investigation of quality of life and family burden issues during insulin pump therapy in children with Type 1 diabetes mellitus--a large-scale multicentre pilot study. AB - AIMS: To investigate psychosocial aspects of continuous subcutaneous insulin infusion (CSII) therapy in children with Type 1 diabetes and to identify relevant and sensitive measures. METHODS: We performed a multi-centre prospective pre /post-study with children (53 girls, 64 boys, age 10.5 +/- 3.7 years, mean +/- sd) with Type 1 diabetes and their main carer from 18 German diabetic centres. Twenty-five children aged 8-11 years and 63 adolescents aged 12-16 years and their parents, plus 29 parents of children aged 4-7 years completed standardized questionnaires on generic and diabetes-specific quality of life (QOL), generic parenting stress, mealtime behaviour, fear of hypoglycaemia and family conflict immediately before and 6 months after transition to CSII. RESULTS: After transition to CSII, diabetes-specific QOL of children increased significantly (P < 0.001) in all age groups, with moderate to large effect sizes (children aged 4 7 years: Cohen's effect sized = 1.3; 8-11 years: d = 0.9, adolescents 12-16 years: d = 0.6). Parents reported reduced frequency (P < 0.01, d = 0.4-0.7) and difficulty (P < 0.01, d = 0.3-0.6) of overall parenting stress and decreased worries about hypoglycaemia (P < 0.01, d = 0.4-0.6). Parents of younger children (4-7 years) reported reduced problems with nutrition management (frequency: P < 0.001, d = 1.1; difficulty: P < 0.05, d = 0.7). CONCLUSIONS: CSII may have substantial psychosocial benefits. Controlled studies are needed. PMID- 19646190 TI - Communication skills of healthcare professionals in paediatric diabetes services. AB - AIMS: To identify training needs in communication skills and to assess training preferences of staff working in paediatric diabetes services, which will inform the development of a learning programme in behaviour change counselling for healthcare professionals. METHODS: Three hundred and eighty-five staff in 67 UK paediatric diabetes services were sent questionnaires to determine their previous communication skills training, to measure their self-reported view of the importance of and confidence in addressing common clinical problems and to assess the perceived feasibility of training methods to improve skillfulness. RESULTS: Two hundred and sixty-six questionnaires (69%) were returned from 65 services. Sixteen per cent of doctors, nurses and dietitians reported no previous training in communication skills and 47% had received no training since graduating. Respondents rated psychosocial issues as more important to address than medical issues within consultations (t = 8.93, P < 0.001), but felt less confident addressing such issues (t = 15.85, P < 0.001). One-day workshops and monthly team meetings were the most popular of the training options considered (65% and 77%, respectively). CD ROM and web-based learning were considered feasible for 54% and 56% of respondents, respectively, although lack of time (55%) and privacy (34%) were potential barriers. CONCLUSIONS: Addressing psychosocial issues is an important component of consultations involving young people with diabetes, but healthcare professionals find it easier to address medical issues. This represents a key training need in communication skills for diabetes professionals. The survey will inform the development of a tailored learning programme for health professionals in UK paediatric diabetes clinics. PMID- 19646191 TI - Individual and contextual factors associated with follow-up use of diabetes self management education programmes: a multisite prospective analysis. AB - AIMS: Although a considerable body of research supports the efficacy of diabetes self-management education (DSME), these programmes are often challenged by high attrition rates. Little is known about factors influencing follow-up use of DSME services, thus the aim of this study was to identify these factors. METHODS: In this multisite prospective analysis, adults with Type 2 diabetes (n = 268) who attended one of two diabetes management centres (DMCs) were followed over a 1 year period from their initial visit. The influence of individual and contextual factors on the number of contacts with DMC providers was examined. Data were analysed within the context of the Health Behavioral Model of Health Services Utilization. RESULTS: In a multivariable negative binomial regression model, the number of contacts over 1 year was greater for those who were female, non smokers, unemployed, self-referred to the DMC, lived closer to the DMC, had a lower body mass index, or had a longer known duration of diabetes. Follow-up use of services differed significantly between the two sites. Provider contacts were greater at the centre that offered flexible hours of services and a variety of optional educational modules. CONCLUSIONS: Healthcare professionals need to encourage ongoing use of DSME, particularly for individuals prone to lower follow up use of these services. Providing services that are accessible, convenient, and can easily fit into patients' schedules may increase follow-up use. Further exploration into how operations and delivery of these services influence utilization patterns is strongly recommended. PMID- 19646192 TI - Socioeconomic factors related to attendance at a Type 2 diabetes screening programme. AB - AIMS: The prevalence of diabetes is increasing, and screening of high-risk populations is recommended. A low attendance rate has been observed in many Type 2 diabetes screening programmes, so that an analysis of factors related to attendance is therefore relevant. This paper analyses the association between socioeconomic factors and attendance for Type 2 diabetes screening. METHODS: Persons aged 40-69 years (n = 4603) were invited to participate in a stepwise diabetes screening programme performed in general practitioners' offices in the county of Aarhus, Denmark in 2001. The study was population-based and cross sectional with follow-up. The association between screening attendance in the high-risk population and socioeconomic factors was analysed by odds ratio. RESULTS: Forty-four percent of the estimated high-risk population attended the screening programme. In those with known risk for Type 2 diabetes, attenders were more likely to be older, to be unemployed and to live in the countryside than non attenders. The risk for Type 2 diabetes was unknown for 21% of the study population; this group was younger and less likely to be cohabitant, skilled, or employed and to have middle or high income than the study population with known risk score for diabetes. CONCLUSIONS: A low attendance rate was found in this screening programme for Type 2 diabetes. No substantial socioeconomic difference was found between attenders and non-attenders in the high-risk population. Further research is needed to uncover barriers to screening of Type 2 diabetes in socioeconomically deprived persons. PMID- 19646193 TI - Effects of grape seed extract in Type 2 diabetic subjects at high cardiovascular risk: a double blind randomized placebo controlled trial examining metabolic markers, vascular tone, inflammation, oxidative stress and insulin sensitivity. AB - OBJECTIVE: Current research has focused upon the potential links between novel markers of vascular risk such as endothelial dysfunction, oxidative stress, inflammation and insulin resistance in the pathogenesis of Type 2 diabetes and its complications. Grape seed extract (GSE), a flavonoid-rich product, is a potential moderator of these markers. This study aimed to test the hypothesis that GSE may improve these markers in high-risk cardiovascular subjects with Type 2 diabetes. RESEARCH DESIGN AND METHODS: Thirty-two Type 2 diabetes mellitus patients, prescribed diet or oral glucose-lowering agents, received GSE (600 mg/day) or placebo for 4 weeks in a double-blinded randomized crossover trial. Markers of endothelial function (measured by photoplethysmography), oxidative stress [total antioxidant status (TAOS), reduced glutathione (GSH)/oxidized glutathione (GSSG)], inflammation [highly sensitive C-reactive protein (hsCRP), urinary albumin : creatinine ratio), insulin resistance [homeostasis model assessment-insulin resistance (HOMA-IR)] and metabolism (fructosamine, lipid profile) was measured at baseline and after intervention with GSE or placebo. RESULTS: Baseline characteristics (16 male and 16 female): age 61.8 +/- 6.36 years; body mass index 30.2 +/- 5.92 kg/m2; diabetes duration 5.9 +/- 2.14 years. Following GSE (but not placebo), significant changes were noted in fructosamine (282 +/- 40.9 vs. 273 +/- 50.2 mmol/l; P = 0.0004); whole blood GSH (2359 +/- 823 vs. 3595 +/- 1051 mmol/l; P < 0.01) and hsCRP (3.2 +/- 3.65 vs. 2.0 +/- 2.2 mg/l; P = 0.0006). Total cholesterol concentration also decreased (4.5 +/- 0.96 vs. 4.3 +/- 0.99 mmol/l; P = 0.05). No statistically significant changes were shown in endothelial function, HOMA-IR or TAOS. CONCLUSION: GSE significantly improved markers of inflammation and glycaemia and a sole marker of oxidative stress in obese Type 2 diabetic subjects at high risk of cardiovascular events over a 4 week period, which suggests it may have a therapeutic role in decreasing cardiovascular risk. PMID- 19646194 TI - Effects of rosiglitazone and pioglitazone on lipoprotein metabolism in patients with Type 2 diabetes and normal lipids. AB - AIMS: Previous studies have suggested that plasma lipids are affected differently by the peroxisome proliferators-activated receptor (PPAR)-gamma agonists pioglitazone and rosiglitazone. The aim of this study was to perform a quantitative lipoprotein turnover study to determine the effects of PPAR-gamma agonists on lipoprotein metabolism. METHODS: Twenty-four subjects with Type 2 diabetes treated with diet and/or metformin were randomized in a double-blind study to receive 30 mg pioglitazone, 8 mg rosiglitazone or placebo once daily for 3 months. Before and after treatment, absolute secretion rate (ASR) and fractional catabolic rate (FCR) of very low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL) and low-density lipoprotein (LDL) apolipoprotein B100 were measured with a 10-h infusion of 1-13C leucine. RESULTS: There was a significant decrease in glycated haemoglobin (HbA(1c)) and non esterified fatty acids with pioglitazone (P = 0.01; P = 0.02) and rosiglitazone (P = 0.04; P = 0.003), respectively, but no change in plasma triglyceride or high density lipoprotein (HDL) cholesterol. Following rosiglitazone, there was a significant reduction in VLDL apolipoprotein B100 (apoB) ASR (P = 0.01) compared with baseline, a decrease in VLDL triglyceride/apoB (P = 0.01), an increase in LDL2 cholesterol (P = 0.02) and a decrease in LDL3 cholesterol (P = 0.02). There was a decrease in VLDL triglyceride/apoB (P = 0.04) in the pioglitazone group. There was no significant difference in change in VLDL ASR or FCR among the three groups. CONCLUSIONS: In patients with Type 2 diabetes and normal lipids, treatment with rosiglitazone or pioglitazone had no significant effect on lipoprotein metabolism compared with placebo. PMID- 19646195 TI - Randomized controlled trial to assess the impact of continuous glucose monitoring on HbA(1c) in insulin-treated diabetes (MITRE Study). AB - AIMS: To determine whether continuous glucose information provided through use of either the GlucoWatch G2 Biographer or the MiniMed continuous glucose monitoring system (CGMS) results in improved glycated haemoglobin (HbA(1c)) for insulin treated adults with diabetes mellitus, relative to an attention control and standard care group. METHODS: Four hundred and four adults taking at least two daily insulin injections and with two consecutive HbA(1c) values > or = 7.5% were recruited to this randomized controlled trial (RCT). All were trained at baseline to use the same monitor for traditional capillary glucose testing throughout the 18-month study. The CGMS group were asked to wear the device three times during the first 3 months of the trial and on another three occasions thereafter. The GlucoWatch group wore the device a minimum of four times per month and a maximum of four times per week during the first 3 months and as desired for the remainder of the trial. Trained diabetes research nurses used downloaded data to guide therapy adjustments. Proportional reduction in HbA(1c) from baseline to 18 months was the primary outcome measure. RESULTS: Neither an intention-to-treat nor per protocol analysis showed improvement in HbA(1c) in the device groups compared with standard care. For the intention-to-treat analysis, when the standard care group was compared with each of the other groups, this equated to differences in mean relative HbA(1c) reduction (95% confidence interval) from baseline to 18 months of 3.5% (-1.3 to 8.3; GlucoWatch), 0.7% (-4.1 to 5.5; CGMS), and -0.1% ( 4.6 to 4.3; attention control). CONCLUSIONS: The additional information provided by these devices did not result in improvements in HbA(1c) in this population. PMID- 19646196 TI - Fungal foot infection, cellulitis and diabetes: a review. AB - AIMS: To review the current evidence for the presence of fungal foot infection (tinea pedis and toenail onychomycosis) as a risk factor for the development of cellulitis within the lower limb, particularly for those individuals with diabetes. METHODS: A structured review of medline, embase and cinahl databases was undertaken to identify publications investigating fungal foot infection as a risk factor for the development of cellulitis. RESULTS: Sixteen studies were identified. Eight studies adopted a case-control methodology, with the remainder being cross-sectional surveys. The majority of studies established the presence of tinea infection by clinical rather than established microbiological methods. Although the majority of papers suggested a link, only two case-control studies employed microbiological diagnosis to demonstrate that fungal foot infection was a risk for the development of lower limb cellulitis, particularly when infection was located between the toes. There were insufficient data to suggest that fungal foot infection posed an increased risk to patients with diabetes. CONCLUSION: There is some evidence to suggest that fungal infection of the foot is a factor in the development of lower limb cellulitis, but further robust research is needed to confirm these findings and quantify the risk that fungi pose, particularly to the diabetic foot. Meanwhile, improved surveillance and treatment of tinea infections on the foot by healthcare professionals should be encouraged to reduce potential complications. PMID- 19646197 TI - Are diabetic foot ulcers complicated by MRSA osteomyelitis associated with worse prognosis? Outcomes of a surgical series. AB - AIMS: The aim of this study was to compare the outcomes of surgical treatment of osteomyelitis caused by methicillin-resistant Staphylococcus aureus (MRSA) with cases caused by methicillin-sensitive Staphylococcus aureus (MSSA). METHODS: We abstracted data of a series of 185 consecutive patients with diabetes and foot osteomyelitis undergoing surgery within the first 12 h after admission at a single hospital. Bone infection was confirmed by histopathological studies. Only cases where Staphylococcus aureus was isolated from bone specimens were included in this analysis. We analysed several variables between the two groups: MRSA vs. MSSA. RESULTS: MRSA bone infection was associated with higher body temperature (P = 0.02) and white blood cell count (P = 0.02) than MSSA. Patients with MRSA infections underwent a greater number of surgical procedures (P = 0.03). Limb salvage was achieved in 93.6% of the patients, with no statistically significant difference in limb salvage rates between MRSA and MSSA-related osteomyelitis. CONCLUSIONS: From our experience, where treatment is based on early and aggressive surgical treatment, MRSA bone infections are not associated with worse prognosis. PMID- 19646198 TI - Alkalinization of urine samples preserves albumin concentrations during prolonged frozen storage in patients with diabetes mellitus. AB - BACKGROUND: In epidemiological studies in patients with diabetes, urine samples are often stored frozen prior to assessment of urinary albumin concentration (UAC). However, prolonged frozen storage may result in a falsely low UAC. In the current study, we investigated whether adjustment of urinary pH to alkaline values prior to frozen storage can prevent this problem. METHODS: Urine samples were collected in 90 patients from our diabetes outpatient clinic and divided into two portions. One portion was first adjusted to pH > 8.0 with 0.1 m sodium hydroxide, the other was left unprocessed. Both portions were divided into aliquots. UAC was assessed in fresh samples and after 7 days, 1, 6 and 12 months of storage at -20 and -80 degrees C. RESULTS: Until 1 month of storage there were no significant changes in UAC. After longer storage, UAC fell significantly in pH unadjusted samples stored at -20 degrees C, with a -7.6% (27.8) and -13.6% (31.7) change after 6 and 12 months storage, respectively. No significant change in UAC occurred in pH adjusted samples stored at -20 degrees C or when samples were stored at -80 degrees C, both with and without pH adjustment. Variation in UAC assessed after 12 months of storage was larger for samples stored at -20 degrees C without adjustment of pH than for the samples stored with pH adjustment or stored at -80 degrees C. CONCLUSIONS: Urine alkalinization to pH > 8.0 prevents the decline in UAC associated with 12 months of frozen storage at -20 degrees C and results in lower variation between samples after storage. PMID- 19646199 TI - Diabetes specialist nurses and role evolvement: a survey by Diabetes UK and ABCD of specialist diabetes services 2007. AB - AIMS: To review the working practices of UK diabetes specialist nurses (DSNs), specific clinical roles, and to examine changes since 2000. METHODS: Postal questionnaires were sent to lead DSNs from all identifiable UK diabetes centres (n = 361). Quantitative and qualitative data were collected on the specific clinical roles, employment, and continual professional development of hospital and community DSNs, Nurse Consultants and Diabetes Healthcare Assistants. RESULTS: 159 centres (44%) returned questionnaires. 78% and 76% of DSNs plan and deliver education sessions compared with 13% in 2000 with a wider range of topics and with less input from medical staff. 22% of DSNs have a formal role in diabetes research compared with 48% in 2000. 49% of Hospital DSNs, 56% of Community DSNs and 66% of Nurse Consultants are involved in prescribing. 55% of DSNs carry out pump training, 72% participate in ante-natal and 27% renal clinics. 90% of services have independent diabetes nurse-led clinics. 93% of services have a dedicated Paediatric DSN. The mean number of children under the care of each PDSN is 109 (mode 120), which exceeds Royal College of Nursing recommendations. 48% of DSNs have protected time for continuing professional development of staff and 15% have a protected budget. One third of DSNs are on short-term contracts funded by external sources. CONCLUSIONS: The DSN role has evolved since 2000 to include complex service provision and responsibilities including specialist clinics, education of healthcare professionals and patients. The lack of substantive contracts and protected study leave may compromise these roles in the future. PMID- 19646200 TI - Pneumorrhachis: a rare complication of diabetic ketoacidosis. PMID- 19646201 TI - Glibenclamide treatment in relapsed transient neonatal diabetes as a result of a KCNJ11 activating mutation (N48D). PMID- 19646202 TI - Variants in the isoform-specific coding regions of the HNF1A, HNF4A and HNF1B genes are not a common cause of familial, young-onset diabetes or renal cysts and diabetes (RCAD). PMID- 19646203 TI - Effects of splenectomy for hereditary spherocytosis on glycated haemoglobin in a woman with Type 2 diabetes. PMID- 19646206 TI - Immunopathogenic competences of Leishmania (V.) braziliensis and L. (L.) amazonensis in American cutaneous leishmaniasis. AB - The immunopathogenic competences of Leishmania (V.) braziliensis and L. (L.) amazonensis were reviewed in the light of more recent features found in the clinical and immunopathological spectrum of American cutaneous leishmaniasis. It was shown a dichotomy in the interaction between these Leishmania species and human T-cell immune response; while L. (V.) braziliensis shows a clear tendency to lead infection from the localized cutaneous leishmaniasis (LCL), a moderate T cell hypersensitivity form at the centre of the spectrum, toward to the mucocutaneous leishmaniasis (MCL) at the T-cell hypersensitivity pole and with a prominent Th1-type immune response, L. (L.) amazonensis shows an opposite tendency, leading infection to the anergic diffuse cutaneous leishmaniasis (ADCL) at the T-cell hyposensitivity pole and with a marked Th2-type immune response. Between the central LCL and the two polar MCL and ADCL, the infection can present an intermediary form known as borderline disseminated cutaneous leishmaniasis, characterized by an incomplete inhibition of T-cell hypersensitivity but with a evident supremacy of Th1 over Th2 immune response (Th1 > or = Th2). These are probably the main immunopathogenic competences of L. (V.) braziliensis and L. (L.) amazonensis regarding the immune response dichotomy that modulates human infection outcome by these Leishmania parasites. PMID- 19646207 TI - Recruitment of CD8(+) T cells expressing granzyme A is associated with lesion progression in human cutaneous leishmaniasis. AB - Human infection with Leishmania braziliensis leads to the establishment of cutaneous leishmaniasis (CL), characterized by the appearance of skin lesions that progress from nonulcerated to ulcerated forms. Our goal was to characterize the immunological kinetics associated with this progression, comparing the cellular composition, cytokines and granzyme expression between lesions of patients with early (E-CL) and late stages (L-CL) of CL. Histopathological analysis showed that lesions from L-CL had more exuberant inflammatory infiltrate as compared to E-CL. Although E-CL and L-CL lesions were predominantly mononuclear, lesions from E-CL patients presented higher neutrophil and eosinophil counts than L-CL. While percentages of CD4(+) and of CD68(+) cells were slightly higher in L-CL, a fivefold increase of CD8(+) cells was observed in L-CL, as compared to E-CL. Moreover, CD8(+) T-cells from L-CL expressed significantly higher levels of granzyme A than E-CL. Interestingly, granzyme A expression was positively correlated with intensity of the inflammatory infiltrate in L-CL but not E-CL. Lastly, percentages of IFN-gamma(+) and IL-10(+) cells were higher in L-CL as compared to E-CL, with CD4(+) T-cells and CD68(+) monocytes as the main sources of these cytokines, respectively. These results suggest that recruitment of CD8(+) granzyme A(+) T cells is involved in lesion progression in human CL. PMID- 19646208 TI - Relative imbalance between T regulatory cells and activated T cells in mice with differential morbidity in chronic Schistosoma mansoni infections. AB - Chronic (20-week) Schistosoma mansoni infections of CBA/J male mice present as two distinct forms of morbidity. Most mice develop moderate splenomegaly syndrome (MSS) resembling the intestinal form of chronic human schistosomiasis mansoni, while approximately 20% of mice develop hypersplenomegaly syndrome (HSS), more consistent with the severe hepatosplenic form of chronic human schistosomiasis mansoni. Here, we report the relative proportions of natural T regulatory cells (Treg) and activated CD4(+) T cells (Tact) for both splenic and granulomatous cell populations of MSS and HSS mice. Proportions of both Treg and Tact are greater in HSS than MSS mice. However, the ratios of Treg to Tact in both splenic and granulomatous cell populations from MSS mice are significantly higher than those of HSS mice. For both HSS and MSS mice, in vitro proliferation of their CD3(+) splenic cells induced by soluble egg antigens is inversely correlated with the ratio of Treg to Tact. Also, spleen or granuloma cells from MSS mice produced higher mean levels of IFN-gamma than those from HSS mice. Differential IFN-gamma productive capacities dictated by Treg : Tact ratios may contribute to the development of differential morbidities in this model of chronic experimental schistosomiasis mansoni. PMID- 19646209 TI - Gonadectomy inhibits development of experimental amoebic liver abscess in hamsters through downregulation of the inflammatory immune response. AB - Incidence of amoebic liver abscess (ALA) in human males is considerably higher than in females, suggesting a role for sex hormones in this parasite infection. We describe here the effect of hamster gonadectomization on the development of ALA. After monitoring the decrease of oestradiol in females and testosterone in males to undetectable levels by ELISA and Radio Immuno Assay (RIA) in serum, hamsters were intraportally infected with Entamoeba histolytica trophozoites and killed 7 days later. ALA was absent in 50% of male and 15% of female gonadectomized (Gdx) hamsters, in comparison with 100% infection in non-Gdx controls. This protection against ALA in Gdx hamsters was concomitant to a comparatively scarce inflammatory infiltrate and necrosis surrounding clusters of trophozoites in the liver tissue, as well as to a lack of response of spleen cells to Con A, evaluated in proliferation assays. As tissue damage in ALA has been associated with a local inflammatory Th1 response, we determined the profile of response in hamsters by immunohistochemistry on liver sections. In contrast to strong Th1 responses in non-Gdx animals, Gdx females and males exhibited Th2 and Th3 profiles of cytokines, respectively, suggesting that protection against ALA following gonadectomization, could be related to downregulation of liver Th1 response during amoebic infection. PMID- 19646210 TI - Depleted intestinal goblet cells and severe pathological changes in SCID mice infected with Heligmosomoides polygyrus. AB - To determine the role of T cells and mast cells in intestinal pathology and immune expulsion of intestinal nematodes, worm burdens, goblet cell responses and villus structures were analysed in T- and B-cell-deficient severe combined immunodeficiency (SCID) mice, athymic nu/nu mice and mast cell deficient W/W(v) mice after infection with the nematode Heligmosomoides polygyrus. SCID and nu/nu mice showed significantly higher worm burdens at week 9 post-infection compared with the wild-type controls. SCID and nu/nu mice showed compromised goblet cell hyperplasia and/or Muc 2 expression, indicating that both events are T-cell dependant. On the other hand, the SCID mice showed increased pathology (villus atrophy and crypt hyperplasia) and increased numbers of proliferating cell nuclear antigen positive cells compared to the wild-type controls. W/W(v) mice, conversely, were able to expel the worms normally, had normal goblet cell hyperplasia, and did not demonstrate the changes in mucosal architecture seen in SCID mice, confirming that a normal mast cell response is not necessarily required for these changes. These results suggest that a functional T-cell response, but not a mast cell response, is necessary for anti-parasite responses, goblet cell function, and maintaining normal mucosal architecture. PMID- 19646211 TI - Inhibitory role of toll-like receptors agonists in Plasmodium yoelii liver stage development. AB - It is well known that innate immune plays an important role in controlling the development of Plasmodium liver stage. However, little is known about the role of toll-like receptors (TLR) signalling in the pre-erythrocytic immunity against Plasmodium. Here, we found that pre-treatment with individual TLR agonist pam3CSK4 (TLR2), poly(I:C) (TLR3), LPS (TLR4) and CpG (TLR9) could decrease significantly the liver malaria parasite load in mice for 58%, 63%, 75% and 88% respectively. Moreover, no parasitaemia was observed within 14 days in CpG group mice challenged with 100 sporozoites. At 24 h prior to CpG injection, administration of gadolinium chloride (GdCl(3)) led to the rebound of liver Plasmodium load through inhibiting selectively Kupffer cells (KC) phagocytosis capacity but failed to neutralize completely CpG-induced immunity against malaria liver stage. Compared with the control, pre-treatment of CpG up-regulated hepatic pro-inflammatory cytokines IL-12, IFN-gamma and TNF-alpha, but down-regulated anti-inflammatory cytokines IL-10 and TGF-beta. Hence, our data demonstrated the inhibitory role of diverse TLR agonists in the Plasmodium development during pre erythrocytic stage. As the most robust agonist, CpG might inhibit the development of Plasmodium liver stage through regulation of intrahepatic inflammatory cytokines and enhancement of KC cells phagocytosis capacity. PMID- 19646212 TI - Humoral and cell-mediated immunity to MSP3 peptides in adults immunized with MSP3 in malaria endemic area, Burkina Faso. AB - We performed a single-blind, randomized phase 1 trial of the long synthetic peptide (LSP) of merozoite surface protein-3 (MSP3) in adults living in Burkina Faso. Thirty eligible volunteers were randomized to receive either the MSP3-LSP candidate vaccine or tetanus toxoid vaccine as a control. A dose of each vaccine was administered on days 0, 28 and 112 and the vaccine was formulated with aluminium hydroxide. Humoral immune responses were assessed by ELISA at days 0, 28, 56, 112, 140, 252 and 365 and cell-mediated immune responses by lymphoproliferation assay and by ELISA on days 0, 56 and 140. IgG responses to four peptides of MSP3 were similar in both vaccine groups. Higher IgG concentrations were recorded after the beginning of malaria high transmission season in both vaccine groups. The lymphocyte proliferation and the production of IFN-gamma in response to stimulation with the four overlapping peptides increased following vaccination in the MSP3-LSP vaccine group, but did not change appreciably in the control group. In contrast to natural infection, MSP3-LSP did not boost humoral responses to the four overlapping peptides of MSP3 to any detectable degree in our semi-immune adult. MSP3-LSP may be more immunogenic in young children with little or no acquired immunity. PMID- 19646213 TI - Galbeta1-6Gal, antigenic epitope which accounts for serological cross-reaction in diagnosis of Echinococcus multilocularis infection. AB - Parasitic helminths express various antigenic carbohydrates, which often account for serological cross-reactions. In serodiagnosis, it is essential to inspect cross-reactivity between the target parasite and other parasites in order to assess diagnostic performance. Our previous study showed that the Galbeta1-6Gal sequence was a common epitope between Echinococcus multilocularis (Em) and E. granulosus (Eg). Furthermore, compounds with this sequence from Fasciola hepatica (Fh) reportedly were recognized by sera with Eg infection. Our aim is to investigate whether this sequence is one of the widely common epitopes in many kinds of parasites. For various parasites, sera with Fh infection cross-reacted at the highest frequency (71.4%) against Em antigen. In patients with other parasitic infections, sera showed cross-reactions against Fh antigen bound to Em antigen with a high frequency (23.7%). Binding inhibition tests with commercial Galbeta1-6Gal disaccharide showed that Galbeta1-6Gal was the common epitope between not only Em, Eg and Fh, but also between various other parasites. Furthermore, the presence of the Galbeta1-6Gal epitope in Em antigen was confirmed by immunoblot testing with the specific antibody for this sequence. This study showed that the Galbeta1-6Gal sequence is one of the antigenic epitopes that accounts for serological cross-reactivity between Em and various other parasites. PMID- 19646214 TI - Abstracts of the 34th FEBS Congress. July 4-9, 2009. Prague, Czech Republic. PMID- 19646220 TI - A dry lab for medical engineers? AB - INTRODUCTION: We describe a teaching and training method with objective evaluation to improve medical engineering students' knowledge and analysis skills about Minimally Invasive Surgery (MIS) instrumentation and techniques through hands-on experience. Training has been scheduled during a three-month course. METHODS: Twenty medical engineering students were trained to perform three times on a pelvic trainer a sequence of standardized drills connected with the selected MIS techniques, in order to improve their dexterity. The time required to perform each dexterity drill was recorded in seconds.Then, the participants were divided into groups and asked to write an essay about an instrument they chose, analyzing and criticizing the instrument itself. RESULTS: All the trainees showed steady improvement in skill acquisition on the laparoscopic simulator and discussed their essays, making proposals in order to improve the instrument they tested. CONCLUSION: Significant improvement in performance with increasing skillness has been measured; during the course and during their discussion the participants showed deep knowledge of the instrument, ability to analyze and criticize it and ability to make improvement proposals.Dry lab experience for medical engineering students is useful for teaching and improving analysis and management of laparoscopic devices, allowing identification of problems and developing better devices. PMID- 19646221 TI - Hospital variation in transfusion and infection after cardiac surgery: a cohort study. AB - BACKGROUND: Transfusion practices in hospitalised patients are being re evaluated, in part due to studies indicating adverse effects in patients receiving large quantities of stored blood. Concomitant with this re-examination have been reports showing variability in the use of specific blood components. This investigation was designed to assess hospital variation in blood use and outcomes in cardiac surgery patients. METHODS: We evaluated outcomes in 24,789 Medicare beneficiaries in the state of Michigan, USA who received coronary artery bypass graft surgery from 2003 to 2006. Using a cohort design, patients were followed from hospital admission to assess transfusions, in-hospital infection and mortality, as well as hospital readmission and mortality 30 days after discharge. Multilevel mixed-effects logistic regression was used to calculate the intrahospital correlation coefficient (for 40 hospitals) and compare outcomes by transfusion status. RESULTS: Overall, 30% (95 CI, 20% to 42%) of the variance in transfusion practices was attributable to hospital site. Allogeneic blood use by hospital ranged from 72.5% to 100% in women and 49.7% to 100% in men. Allogeneic, but not autologous, blood transfusion increased the odds of in-hospital infection 2.0-fold (95% CI 1.6 to 2.5), in-hospital mortality 4.7-fold (95% CI 2.4 to 9.2), 30-day readmission 1.4-fold (95% CI 1.2 to 1.6), and 30-day mortality 2.9-fold (95% CI 1.4 to 6.0) in elective surgeries. Allogeneic transfusion was associated with infections of the genitourinary system, respiratory tract, bloodstream, digestive tract and skin, as well as infection with Clostridium difficile. For each 1% increase in hospital transfusion rates, there was a 0.13% increase in predicted infection rates. CONCLUSION: Allogeneic blood transfusion was associated with an increased risk of infection at multiple sites, suggesting a system-wide immune response. Hospital variation in transfusion practices after coronary artery bypass grafting was considerable, indicating that quality efforts may be able to influence practice and improve outcomes. PMID- 19646222 TI - Does blood transfusion harm cardiac surgery patients? AB - Over recent years there has been a substantial body of evidence demonstrating strong associations between transfusion and adverse outcomes, including myocardial, neurological and renal injury, in a range of clinical settings where transfusion is administered for reasons other than life-threatening bleeding. The strength of these associations across a range of clinical settings suggests that confounding and bias, the chief limitations of all observational studies, are unlikely to account for all of these observations. Given the wide range in transfusion rates in cardiac centres, with up to 100% of patients in some centres exposed to allogenic blood components, this evidence, albeit circumstantial, presents a strong argument for prospective randomised trials to attempt to determine, firstly, if transfusion causes adverse outcomes, and secondly, in which patient groups does the benefit of transfusion outweigh these risks? These issues are discussed in the context of an article published this month in BMC Medicine. PMID- 19646223 TI - A possibilistic framework for constraint-based metabolic flux analysis. AB - BACKGROUND: Constraint-based models allow the calculation of the metabolic flux states that can be exhibited by cells, standing out as a powerful analytical tool, but they do not determine which of these are likely to be existing under given circumstances. Typical methods to perform these predictions are (a) flux balance analysis, which is based on the assumption that cell behaviour is optimal, and (b) metabolic flux analysis, which combines the model with experimental measurements. RESULTS: Herein we discuss a possibilistic framework to perform metabolic flux estimations using a constraint-based model and a set of measurements. The methodology is able to handle inconsistencies, by considering sensors errors and model imprecision, to provide rich and reliable flux estimations. The methodology can be cast as linear programming problems, able to handle thousands of variables with efficiency, so it is suitable to deal with large-scale networks. Moreover, the possibilistic estimation does not attempt necessarily to predict the actual fluxes with precision, but rather to exploit the available data--even if those are scarce--to distinguish possible from impossible flux states in a gradual way. CONCLUSION: We introduce a possibilistic framework for the estimation of metabolic fluxes, which is shown to be flexible, reliable, usable in scenarios lacking data and computationally efficient. PMID- 19646224 TI - Improved efficacy of a gene optimised adenovirus-based vaccine for venezuelan equine encephalitis virus. AB - BACKGROUND: Optimisation of genes has been shown to be beneficial for expression of proteins in a range of applications. Optimisation has increased protein expression levels through improved codon usage of the genes and an increase in levels of messenger RNA. We have applied this to an adenovirus (ad)-based vaccine encoding structural proteins (E3-E2-6K) of Venezuelan equine encephalitis virus (VEEV). RESULTS: Following administration of this vaccine to Balb/c mice, an approximately ten-fold increase in antibody response was elicited and increased protective efficacy compared to an ad-based vaccine containing non-optimised genes was observed after challenge. CONCLUSION: This study, in which the utility of optimising genes encoding the structural proteins of VEEV is demonstrated for the first time, informs us that including optimised genes in gene-based vaccines for VEEV is essential to obtain maximum immunogenicity and protective efficacy. PMID- 19646225 TI - GPs' reasons for referral of patients with chest pain: a qualitative study. AB - BACKGROUND: Prompt diagnosis of an acute coronary syndrome is very important and urgent referral to a hospital is imperative because fast treatment can be life saving and increase the patient's life expectancy and quality of life. The aim of our study was to identify GPs' reasons for referring or not referring patients presenting with chest pain. METHODS: In a semi-structured interview, 21 GPs were asked to describe why they do or do not refer a patient presenting with chest pain. Interviews were taped, transcribed and qualitatively analysed. RESULTS: Histories of 21 patients were studied. Six were not referred, seven were referred to a cardiologist and eight to the emergency department. GPs' reasons for referral were background knowledge about the patient, patient's age and cost benefit estimation, the perception of a negative attitude from the medical rescue team, recent patient contact with a cardiologist without detection of a coronary disease and the actual presentation of signs and symptoms, gut feeling, clinical examination and ECG results. CONCLUSION: This study suggests that GPs believe they do not exclusively use the 'classical' signs and symptoms in their decision making process for patients presenting with chest pain. Background knowledge about the patient, GPs' personal ideas and gut feeling are also important. PMID- 19646226 TI - A 44 year-old lady with chronic renal disease and intractable ulcers: a case report. AB - Calciphylaxis is a rare but potentially fatal condition occurring in patients with end stage renal disease on dialysis. Due to interplay of various factors, disturbances occur in the metabolism of calcium and phosphate leading to calcification within the vessel walls. The net result is tissue ischemia and necrosis. Clinically this presents as painful non-healing skin ulcers, which contribute to significant morbidity and mortality due to septic progression of the lesion. In this case report, we highlight the rapidly progressive nature of this disease, its etiopathogenesis and the role of early diagnosis in preventing life-threatening complications. PMID- 19646227 TI - Differences in risk factors for children with special health care needs (CSHCN) receiving needed specialty care by Socioeconomic Status. AB - BACKGROUND: The purpose of this study is to identify factors affecting CSHCN's receiving needed specialty care among different socioeconomic levels. Previous literature has shown that Socioeconomic Status (SES) is a significant factor in CHSHCN receiving access to healthcare. Other literature has shown that factors of insurance, family size, race/ethnicity and sex also have effects on these children's receipt of care. However, this literature does not address whether other factors such as maternal education, geographic location, age, insurance type, severity of condition, or race/ethnicity have different effects on receiving needed specialty care for children in each SES level. METHODS: Data were obtained from the National Survey of Children with Special Health Care Needs, 2000-2002. The study analyzed the survey which studies whether CHSCN who needed specialty care received it. The analysis included demographic characteristics, geographical location of household, severity of condition, and social factors. Multiple logistic regression models were constructed for SES levels defined by federal poverty level: < 199%; 200-299%; >or= 300%. RESULTS: For the poorest children (,199% FPL) being uninsured had a strong negative effect on receiving all needed specialty care. Being Hispanic was a protective factor. Having more than one adult in the household had a positive impact on receipt of needed specialty care but a larger number of children in the family had a negative impact. For the middle income group of children (200-299% of FPL severity of condition had a strong negative association with receipt of needed specialty care. Children in highest income group (> 300% FPL) were positively impacted by living in the Midwest and were negatively impacted by the mother having only some college compared to a four-year degree. CONCLUSION: Factors affecting CSHCN receiving all needed specialty care differed among socioeconomic groups. These differences should be addressed in policy and practice. Future research should explore the CSHCN population by income groups to better serve this population. PMID- 19646230 TI - Bipolar hip hemiarthroplasty in a patient with an above knee amputation: a case report. AB - The treatment of an above knee amputee who has sustained a fracture of femoral neck is a challenge for both the orthopaedic surgeon and the rehabilitation team. We present a case of such a patient and discuss different difficulties in his treatment. PMID- 19646229 TI - School children sufficiently apply life supporting first aid: a prospective investigation. AB - INTRODUCTION: The usefulness of CPR training in schools has been questioned because young students may not have the physical and cognitive skills needed to correctly perform such complex tasks correctly. METHODS: In pupils, who received six hours of CPR training from their teachers during a standard school semester at four months post training the following outcome parameters were assessed: CPR effectiveness, AED deployment, accuracy in checking vital signs, correctness of recovery position, and whether the ambulance service was effectively notified. Possible correlations of age, gender, body mass index (BMI), and outcome parameters were calculated. RESULTS: Of 147 students (mean age 13 +/- 2 years), 86% performed CPR correctly. Median depth of chest compressions was 35 mm (inter quartile range (IQR) 31 to 41), and the median number of compressions per minute was 129 bpm (IQR 108 to 143). Sixty nine percent of the students tilted the mannequin head sufficiently for mouth to mouth resuscitation, and the median air volume delivered was 540 ml (IQR 0 to 750). Scores on other life supporting techniques were at least 80% or higher. Depth of chest compressions showed a correlation with BMI (r = 0.35; P < 0.0001), body weight (r = 0.38; P < 0.0001), and body height (r = 0.31; P = 0.0002) but not with age. All other outcomes were found to be unrelated to gender, age, or BMI. CONCLUSIONS: Students as young as 9 years are able to successfully and effectively learn basic life support skills including AED deployment, correct recovery position and emergency calling. As in adults, physical strength may limit depth of chest compressions and ventilation volumes but skill retention is good. PMID- 19646228 TI - Zebrafish reward mutants reveal novel transcripts mediating the behavioral effects of amphetamine. AB - BACKGROUND: Addiction is a pathological dysregulation of the brain's reward systems, determined by several complex genetic pathways. The conditioned place preference test provides an evaluation of the effects of drugs in animal models, allowing the investigation of substances at a biologically relevant level with respect to reward. Our lab has previously reported the development of a reliable conditioned place preference paradigm for zebrafish. Here, this test was used to isolate a dominant N-ethyl-N-nitrosourea (ENU)-induced mutant, no addiction (nad(dne3256)), which fails to respond to amphetamine, and which we used as an entry point towards identifying the behaviorally relevant transcriptional response to amphetamine. RESULTS: Through the combination of microarray experiments comparing the adult brain transcriptome of mutant and wild-type siblings under normal conditions, as well as their response to amphetamine, we identified genes that correlate with the mutants' altered conditioned place preference behavior. In addition to pathways classically involved in reward, this gene set shows a striking enrichment in transcription factor-encoding genes classically involved in brain development, which later appear to be re-used within the adult brain. We selected a subset of them for validation by quantitative PCR and in situ hybridization, revealing that specific brain areas responding to the drug through these transcription factors include domains of ongoing adult neurogenesis. Finally, network construction revealed functional connections between several of these genes. CONCLUSIONS: Together, our results identify a new network of coordinated gene regulation that influences or accompanies amphetamine-triggered conditioned place preference behavior and that may underlie the susceptibility to addiction. PMID- 19646231 TI - sscMap: an extensible Java application for connecting small-molecule drugs using gene-expression signatures. AB - BACKGROUND: Connectivity mapping is a process to recognize novel pharmacological and toxicological properties in small molecules by comparing their gene expression signatures with others in a database. A simple and robust method for connectivity mapping with increased specificity and sensitivity was recently developed, and its utility demonstrated using experimentally derived gene signatures. RESULTS: This paper introduces sscMap (statistically significant connections' map), a Java application designed to undertake connectivity mapping tasks using the recently published method. The software is bundled with a default collection of reference gene-expression profiles based on the publicly available dataset from the Broad Institute Connectivity Map 02, which includes data from over 7000 Affymetrix microarrays, for over 1000 small-molecule compounds, and 6100 treatment instances in 5 human cell lines. In addition, the application allows users to add their custom collections of reference profiles and is applicable to a wide range of other 'omics technologies. CONCLUSION: The utility of sscMap is two fold. First, it serves to make statistically significant connections between a user-supplied gene signature and the 6100 core reference profiles based on the Broad Institute expanded dataset. Second, it allows users to apply the same improved method to custom-built reference profiles which can be added to the database for future referencing. The software can be freely downloaded from http://purl.oclc.org/NET/sscMap. PMID- 19646232 TI - In vitro, but not in vivo, reversibility of peritoneal macrophages activation during experimental acute pancreatitis. AB - BACKGROUND: Systemic inflammatory response syndrome is one of the major pathobiologic processes underlying severe acute pancreatitis and the degree of macrophage activation could be one of the factors that finally determine the severity of the disease. We evaluated the activation phenotype in peritoneal macrophages during the progression of an experimental model of acute pancreatitis induced in rats by intraductal administration of 5% sodium taurocholate and the effect of IL-4 and IL-13 to modulate this activation. Samples of pancreas, lung and adipose tissue as well as plasma were also obtained. In some animals IL4 and IL13 were injected 1 h after induction in order to modulate macrophage activation. The expressions of TNFalpha and Mannose Receptor, as indicators of classical and alternative macrophage activation, were evaluated. Levels of myeloperoxidase and plasma lipase were determined to evaluate the severity of the inflammatory process. The stability of IL-4 in ascitic fluid and plasma was evaluated. RESULTS: Peritoneal macrophages showed a classical M1 activation clearly induced 3 h after pancreatitis induction and maintained until 18 h. Treatment with IL-4 and IL-13 reversed the activation of macrophages from a classical M1 to alternative M2 in vitro, but failed to modulate the response of peritoneal macrophages in vivo despite a reduction in inflammation was observed in lung and adipose tissue. Finally, IL-4 shows a short half-live in ascitic fluid when compared with plasma. CONCLUSION: Peritoneal macrophages adopt a pro inflammatory activation early during acute pancreatitis. Treatment with M2 cytokines could revert in vitro the pancreatitis-induced activation of macrophages but fails to modulate its activation in vivo. This treatment has only a moderate effect in reducing the systemic inflammation associated to acute pancreatitis. Hydrolytic enzymes presents in ascitic fluid could be involved in the degradation of cytokines, strongly reducing its utility to modulate peritoneal macrophages in pancreatitis. PMID- 19646233 TI - Partial isolated rupture of the popliteus tendon in a professional soccer player: a case report. AB - The complete isolated rupture of the popliteus tendon has been described as a rare injury and this report describes the case of a 31-year-old soccer player who sustained a partial rupture of the popliteus tendon during a game. The injury was suspected clinically and at MRI but confirmed only by the arthroscopic examination. The treatment consisted in open debridment with no tendon repair or augmentation. Seven weeks post-operation the patient was symptom-free and returned to competitive professional soccer at the same preinjury level. The clinical and arthroscopic findings of the case reported suggest a possible overuse disease with degenerative expression. PMID- 19646235 TI - Polymorphism FXII 46C>T and cardiovascular risk: additional data from Spanish and Tunisian patients. AB - BACKGROUND: Previous studies showed an association between Coagulation Factor XII 46C>T polymorphism and variation in FXII plasma levels, as 46C>T seems to affect the translation efficiency. Case-control studies in Spanish samples indicated that genotype T/T is an independent risk factor for venous thrombosis, ischemic stroke and acute coronary artery disease. In this study, we tried to reaffirm the importance of 46C>T in two samples from Spain and Tunisia. FINDINGS: A Transmission Disequilibrium Test (TDT) based on 101 family trios from Barcelona with one offspring affected by ischemic heart disease and a classical case control study based on 76 patients with IHD and 118 healthy individuals from North and Centre-South Tunisia were conducted. Subjects were genotyped for 46C>T and data were analyzed accordingly, revealing no association in any of the two samples (TDT: P = 0.16, relative risk 1.17; case-control study: P = 0.59, odds ratio 1.36). CONCLUSION: The results suggest that 46C>T is not a risk factor for ischemic heart disease in any of the two analyzed samples and therefore the polymorphism seems not to be a universal risk factor for cardiovascular diseases. PMID- 19646234 TI - Association between community health center and rural health clinic presence and county-level hospitalization rates for ambulatory care sensitive conditions: an analysis across eight US states. AB - BACKGROUND: Federally qualified community health centers (CHCs) and rural health clinics (RHCs) are intended to provide access to care for vulnerable populations. While some research has explored the effects of CHCs on population health, little information exists regarding RHC effects. We sought to clarify the contribution that CHCs and RHCs may make to the accessibility of primary health care, as measured by county-level rates of hospitalization for ambulatory care sensitive (ACS) conditions. METHODS: We conducted an ecologic analysis of the relationship between facility presence and county-level hospitalization rates, using 2002 discharge data from eight states within the US (579 counties). Counties were categorized by facility availability: CHC(s) only, RHC(s) only, both (CHC and RHC), and neither. US Agency for Healthcare Research and Quality definitions were used to identify ACS diagnoses. Discharge rates were based on the individual's county of residence and were obtained by dividing ACS hospitalizations by the relevant county population. We calculated ACS rates separately for children, working age adults, and older individuals, and for uninsured children and working age adults. To ensure stable rates, we excluded counties having fewer than 1,000 residents in the child or working age adult categories, or 500 residents among those 65 and older. Multivariate Poisson analysis was used to calculate adjusted rate ratios. RESULTS: Among working age adults, rate ratio (RR) comparing ACS hospitalization rates for CHC-only counties to those of counties with neither facility was 0.86 (95% Confidence Interval, CI, 0.78-0.95). Among older adults, the rate ratio for CHC-only counties compared to counties with neither facility was 0.84 (CI 0.81-0.87); for counties with both CHC and RHC present, the RR was 0.88 (CI 0.84-0.92). No CHC/RHC effects were found for children. No effects were found on estimated hospitalization rates among uninsured populations. CONCLUSION: Our results suggest that CHCs and RHCs may play a useful role in providing access to primary health care. Their presence in a county may help to limit the county's rate of hospitalization for ACS diagnoses, particularly among older people. PMID- 19646236 TI - Increased OXPHOS activity precedes rise in glycolytic rate in H-RasV12/E1A transformed fibroblasts that develop a Warburg phenotype. AB - BACKGROUND: The Warburg phenotype in cancer cells has been long recognized, but there is still limited insight in the consecutive metabolic alterations that characterize its establishment. We obtained better understanding of the coupling between metabolism and malignant transformation by studying mouse embryonic fibroblast-derived cells with loss-of-senescence or H-RasV12/E1A-transformed phenotypes at different stages of oncogenic progression. RESULTS: Spontaneous immortalization or induction of senescence-bypass had only marginal effects on metabolic profiles and viability. In contrast, H-RasV12/E1A transformation initially caused a steep increase in oxygen consumption and superoxide production, accompanied by massive cell death. During prolonged culture in vitro, cell growth rate increased gradually, along with tumor forming potential in in vitro anchorage-independent growth assays and in vivo tumor formation assays in immuno-deficient mice. Notably, glucose-to-lactic acid flux increased with passage number, while cellular oxygen consumption decreased. This conversion in metabolic properties was associated with a change in mitochondrial NAD+/NADH redox, indicative of decreased mitochondrial tricarboxic acid cycle and OXPHOS activity. CONCLUSION: The high rate of oxidative metabolism in newly transformed cells is in marked contrast with the high glycolytic rate in cells in the later tumor stage. In our experimental system, with cells growing under ambient oxygen conditions in nutrient-rich media, the shift towards this Warburg phenotype occurred as a step-wise adaptation process associated with augmented tumorigenic capacity and improved survival characteristics of the transformed cells. We hypothesize that early-transformed cells, which potentially serve as founders for new tumor masses may escape therapies aimed at metabolic inhibition of tumors with a fully developed Warburg phenotype. PMID- 19646237 TI - Mantle cell lymphoma of the gastrointestinal tract presenting with multiple intussusceptions--case report and review of literature. AB - BACKGROUND: Mantle cell lymphoma (MCL) is an aggressive type of B-cell non Hodgkin's lymphoma that originates from small to medium sized lymphocytes located in the mantle zone of the lymph node. Extra nodal involvement is present in the majority of cases, with a peculiar tendency to invade the gastro-intestinal tract in the form of multiple lymphomatous polyposis. MCL can be accurately diagnosed with the use of the highly specific marker Cyclin D1. Few cases of mantle cell lymphoma presenting with intussuception have been reported. Here we present a rare case of multiple intussusceptions caused by mantle cell lymphoma and review the literature of this disease. CASE PRESENTATION: A 68-year-old male presented with pain, tenderness in the right lower abdomen, associated with nausea and non bilious vomiting. CT scan of abdomen revealed ileo-colic intussusception. Laparoscopy confirmed multiple intussusceptions involving ileo-colic and ileo ileal segments of gastrointestinal tract. A laparoscopically assisted right hemicolectomy and extended ileal resection was performed. Postoperative recovery was uneventful. The histology and immuno-histochemistry of the excised small and large bowel revealed mantle cell lymphoma with multiple lymphomatous polyposis and positivity to Cyclin D1 marker. The patient was successfully treated with Rituximab-CHOP chemotherapy and remains in complete remission at one-year follow up. CONCLUSION: This is a rare case of intestinal lymphomatous polyposis due to mantle cell lymphoma presenting with multiple small bowel intussusceptions. Our case highlights laparoscopic-assisted bowel resection as a potential and feasible option in the multi-disciplinary treatment of mantle cell lymphoma. PMID- 19646238 TI - The functional magnetic resonance imaging (fMRI) procedure as experienced by healthy participants and stroke patients--a pilot study. AB - BACKGROUND: An important aspect in functional imaging research employing magnetic resonance imaging (MRI) is how participants perceive the MRI scanning itself. For instance, the knowledge of how (un)comfortable MRI scanning is perceived may help institutional review boards (IRBs) or ethics committees to decide on the approval of a study, or researchers to design their experiments. METHODS: We provide empirical data from our lab gained from 70 neurologically healthy mainly student subjects and from 22 mainly elderly patients suffering from motor deficits after brain damage. All participants took part in various basic research fMRI studies using a 3T MRI scanner. Directly after the scanning, all participants completed a questionnaire assessing their experience with the fMRI procedure. RESULTS: 87.2% of the healthy subjects and 77.3% of the patients rated the MRI procedure as acceptable to comfortable. In healthy subjects, males found the procedure more comfortable, while the opposite was true for patients. 12.1% of healthy subjects considered scanning durations between 30 and 60 min as too long, while no patient considered their 30 min scanning interval as too long. 93.4% of the healthy subjects would like to participate in an fMRI study again, with a significantly lower rate for the subjects who considered the scanning as too long. Further factors, such as inclusion of a diffusion tensor imaging (DTI) scan, age, and study duration had no effect on the questionnaire responses. Of the few negative comments, the main issues were noise, the restriction to keep still for the whole time, and occasional feelings of dizziness. CONCLUSION: MRI scanning in the basic research setting is an acceptable procedure for elderly and patient participants as well as young healthy subjects. PMID- 19646239 TI - Transcriptome analysis of Taenia solium cysticerci using Open Reading Frame ESTs (ORESTES). AB - BACKGROUND: Human infection by the pork tapeworm Taenia solium affects more than 50 million people worldwide, particularly in underdeveloped and developing countries. Cysticercosis which arises from larval encystation can be life threatening and difficult to treat. Here, we investigate for the first time the transcriptome of the clinically relevant cysticerci larval form. RESULTS: Using Expressed Sequence Tags (ESTs) produced by the ORESTES method, a total of 1,520 high quality ESTs were generated from 20 ORESTES cDNA mini-libraries and its analysis revealed fragments of genes with promising applications including 51 ESTs matching antigens previously described in other species, as well as 113 sequences representing proteins with potential extracellular localization, with obvious applications for immune-diagnosis or vaccine development. CONCLUSION: The set of sequences described here will contribute to deciphering the expression profile of this important parasite and will be informative for the genome assembly and annotation, as well as for studies of intra- and inter-specific sequence variability. Genes of interest for developing new diagnostic and therapeutic tools are described and discussed. PMID- 19646240 TI - Space-time variation of malaria incidence in Yunnan province, China. AB - BACKGROUND: Understanding spatio-temporal variation in malaria incidence provides a basis for effective disease control planning and monitoring. METHODS: Monthly surveillance data between 1991 and 2006 for Plasmodium vivax and Plasmodium falciparum malaria across 128 counties were assembled for Yunnan, a province of China with one of the highest burdens of malaria. County-level Bayesian Poisson regression models of incidence were constructed, with effects for rainfall, maximum temperature and temporal trend. The model also allowed for spatial variation in county-level incidence and temporal trend, and dependence between incidence in June-September and the preceding January-February. RESULTS: Models revealed strong associations between malaria incidence and both rainfall and maximum temperature. There was a significant association between incidence in June-September and the preceding January-February. Raw standardised morbidity ratios showed a high incidence in some counties bordering Myanmar, Laos and Vietnam, and counties in the Red River valley. Clusters of counties in south western and northern Yunnan were identified that had high incidence not explained by climate. The overall trend in incidence decreased, but there was significant variation between counties. CONCLUSION: Dependence between incidence in summer and the preceding January-February suggests a role of intrinsic host-pathogen dynamics. Incidence during the summer peak might be predictable based on incidence in January-February, facilitating malaria control planning, scaled months in advance to the magnitude of the summer malaria burden. Heterogeneities in county-level temporal trends suggest that reductions in the burden of malaria have been unevenly distributed throughout the province. PMID- 19646241 TI - Prolonged QT interval in a man with anorexia nervosa. AB - Anorexia nervosa is an eating disorder characterized by the avoidance of food intake, which usually leads to a weight loss. Cardiac co-morbility is common and we can find sometimes a mass loss from the left ventricle, which can be seen by echocardiography. But the commonest complications are rhythm variations, typically bradycardia with a prolonged QT interval in up to a 40% of the cases, which altogether elevates ventricular tachycardia and sudden death risk. We present the case of a male who was diagnosed with anorexia nervosa and developed asthenia, a long QT interval and also a severe both hypokalaemia and hypomagnesaemia. We intend to discuss the pathogenic paths as well as prophylactic and therapeutic measures to this potentially-lethal pathology. PMID- 19646243 TI - ColorTree: a batch customization tool for phylogenic trees. AB - BACKGROUND: Genome sequencing projects and comparative genomics studies typically aim to trace the evolutionary history of large gene sets, often requiring human inspection of hundreds of phylogenetic trees. If trees are checked for compatibility with an explicit null hypothesis (e.g., the monophyly of certain groups), this daunting task is greatly facilitated by an appropriate coloring scheme. FINDINGS: In this note, we introduce ColorTree, a simple yet powerful batch customization tool for phylogenic trees. Based on pattern matching rules, ColorTree applies a set of customizations to an input tree file, e.g., coloring labels or branches. The customized trees are saved to an output file, which can then be viewed and further edited by Dendroscope (a freely available tree viewer). ColorTree runs on any Perl installation as a stand-alone command line tool, and its application can thus be easily automated. This way, hundreds of phylogenic trees can be customized for easy visual inspection in a matter of minutes. CONCLUSION: ColorTree allows efficient and flexible visual customization of large tree sets through the application of a user-supplied configuration file to multiple tree files. PMID- 19646242 TI - Characterization of the Zoarces viviparus liver transcriptome using massively parallel pyrosequencing. AB - BACKGROUND: The teleost Zoarces viviparus (eelpout) lives along the coasts of Northern Europe and has long been an established model organism for marine ecology and environmental monitoring. The scarce information about this species genome has however restrained the use of efficient molecular-level assays, such as gene expression microarrays. RESULTS: In the present study we present the first comprehensive characterization of the Zoarces viviparus liver transcriptome. From 400,000 reads generated by massively parallel pyrosequencing, more than 50,000 pieces of putative transcripts were assembled, annotated and functionally classified. The data was estimated to cover roughly 40% of the total transcriptome and homologues for about half of the genes of Gasterosteus aculeatus (stickleback) were identified. The sequence data was consequently used to design an oligonucleotide microarray for large-scale gene expression analysis. CONCLUSION: Our results show that one run using a Genome Sequencer FLX from 454 Life Science/Roche generates enough genomic information for adequate de novo assembly of a large number of genes in a higher vertebrate. The generated sequence data, including the validated microarray probes, are publicly available to promote genome-wide research in Zoarces viviparus. PMID- 19646244 TI - Role of subtyping in detecting Salmonella cross contamination in the laboratory. AB - BACKGROUND: With the exception of M. tuberculosis, little has been published on the problems of cross-contamination in bacteriology laboratories. We performed a retrospective analysis of subtyping data from the National Salmonella Reference Laboratory (Ireland) from 2000-2007 to identify likely incidents of laboratory cross contamination. METHODS: Serotyping and antimicrobial susceptibility testing was performed on all Salmonella isolates received in the NSRL. Phage typing was performed on all S. Typhimurium and S. Enteritidis isolates while multi-locus variance analysis (MLVA) was performed on selected S. Typhimurium isolates. Pulsed field gel electrophoresis (PFGE) using the PulseNet standard protocol was performed on selected isolates of various serovars. RESULTS: Twenty-three incidents involving fifty-six isolates were identified as likely to represent cross contamination. The probable sources of contamination identified were the laboratory positive control isolate (n = 13), other test isolates (n = 9) or proficiency test samples (n = 1). CONCLUSION: The scale of laboratory cross contamination in bacteriology is most likely under recognized. Testing laboratories should be aware of the potential for cross-contamination, regularly review protocols to minimize its occurrence and consider it as a possibility when unexpected results are obtained. PMID- 19646245 TI - Evaluation of selective embolization of thyroid arteries (SETA) as a preresective treatment in selected cases of toxic goitre. AB - BACKGROUND: in recent years, an increasing interest in the application of selective embolization of thyroid arteries (SETA) in the treatment of thyroid diseases is observed. In the present report, we analyse the value, safety and possible indications for preresective SETA in cases of large toxic goitres. PATIENTS AND METHOD: the study group comprised 10 patients with large toxic goitre (thyroid volume 254 +/- 50 mL), including one patient with cervicomediastinal goitre and one patient with anti-thyroid drug intolerance in state of overt thyrotoxicosis. All the patients underwent SETA of the superior and/or inferior thyroid arteries, followed by thyroidectomy, performed up to thirty-six hours after SETA (23.1 +/- 11 h). After embolization, selective angiographies of thyroid arteries were performed to ensure that the targeted arteries had been completely occluded. RESULTS AND CONCLUSION: in all the patients, SETA decreased blood flow through the thyroid. Preresective SETA reduced blood loss during and after thyroidectomy and decreased the operating time, but the differences were too small to justify routine applications of preresective SETA as an adjunct to surgical treatment of toxic goitre. On the other hand, SETA is a safe and minimally-invasive technique, which may become an attractive option for quick preparation to surgery in selected patients with toxic goitre, who present anti-thyroid drug intolerance or refuse radioactive iodine treatment. PMID- 19646246 TI - Threat-responsiveness and the decision to obtain free influenza vaccinations among the older adults in Taiwan. AB - BACKGROUND: Although older adults are encouraged by government agencies to receive influenza vaccinations, many do not obtain them. In Taiwan, where universal health care coverage has significantly reduced the barriers of access to care, the health care system has provided free influenza vaccinations for people 65 years or older since 2001. Nevertheless, the numbers of people who use this service are much fewer than expected. The aim of this study was to explore major factors that might affect the decision to receive influenza vaccinations among older adults in Taiwan. METHODS: Using national representative health insurance medical claims from the National Health Insurance Research Database between 2002 and 2004, we investigated the role of threat-responsiveness, represented by prior vaccinations and prior physician visits for flu-like respiratory conditions, in the decisions of older adults to obtain vaccinations in Taiwan. RESULTS: Among the sample of 23,023 older adults, the overall yearly vaccination rates in this study were 38.6%, 44.3% and 39.3% for 2002, 2003, and 2004, respectively. Adjusting for covariates of individual and health care facility characteristics, the multivariate logistic regression revealed that older adults who had had prior vaccinations were ten times more likely to be vaccinated during the following influenza season than those who had not (OR=10.22, 95%CI: 9.82-10.64). The greater the frequency of prior physician visits for flu-like respiratory conditions, the greater the likelihood that one would decide to be vaccinated. Visits during prior interim (non-epidemic) season exerted a stronger positive influence than prior influenza season on this likelihood (OR=1.59, 95% CI: 1.46-1.73 vs. OR=1.11 95% CI: 1.01-1.22, respectively). CONCLUSION: Threat-responsiveness, or perceived risk, greatly influences influenza vaccination rates among the older adults in Taiwan. These findings can be used to help design public health campaigns to increase the influenza vaccination rate in this vulnerable group of citizens. Particularly, older adults who never had influenza vaccinations can be identified, educated, and encouraged to participate. PMID- 19646247 TI - A class of DNA-binding peptides from wheat bud causes growth inhibition, G2 cell cycle arrest and apoptosis induction in HeLa cells. AB - BACKGROUND: Deproteinized DNA from eukaryotic and prokaryotic cells still contains a low-molecular weight peptidic fraction which can be dissociated by alkalinization of the medium. This fraction inhibits RNA transcription and tumor cell growth. Removal from DNA of normal cells causes amplification of DNA template activity. This effect is lower or absent in several cancer cell lines. Likewise, the amount of active peptides in cancer cell DNA extracts is lower than in DNA preparation of the corresponding normal cells. Such evidence, and their ubiquitous presence, suggests that they are a regulatory, conserved factor involved in the control of normal cell growth and gene expression. RESULTS: We report that peptides extracted from wheat bud chromatin induce growth inhibition, G2 arrest and caspase-dependent apoptosis in HeLa cells. The growth rate is decreased in cells treated during the S phase only and it is accompanied by DNA damage and DNA synthesis inhibition. In G2 cells, this treatment induces inactivation of the CDK1-cyclin B1 complex and an increase of active chk1 kinase expression. CONCLUSION: The data indicate that the chromatin peptidic pool inhibits HeLa cell growth by causing defective DNA replication which, in turn, arrests cell cycle progression to mitosis via G2 checkpoint pathway activation. PMID- 19646249 TI - Neonatal diabetes mellitus due to pancreatic agenesis and pervasive developmental disorder. AB - Recent studies suggested a link between type 1 diabetes mellitus and pervasive developmental disorder. Moreover, permanent neonatal diabetes mellitus due to pancreatic agenesis can be associated with neurological deficit involving cerebellar functions, but no association with pervasive developmental disorder has been described so far. Clinical and neuropsychological evaluation of a child with pancreatic agenesis, mental retardation and pervasive developmental disorder is reported. PMID- 19646248 TI - Vasodilator factors in the systemic and local adaptations to pregnancy. AB - We postulate that an orchestrated network composed of various vasodilatory systems participates in the systemic and local hemodynamic adaptations in pregnancy. The temporal patterns of increase in the circulating and urinary levels of five vasodilator factors/systems, prostacyclin, nitric oxide, kallikrein, angiotensin-(1-7) and VEGF, in normal pregnant women and animals, as well as the changes observed in preeclamptic pregnancies support their functional role in maintaining normotension by opposing the vasoconstrictor systems. In addition, the expression of these vasodilators in the different trophoblastic subtypes in various species supports their role in the transformation of the uterine arteries. Moreover, their expression in the fetal endothelium and in the syncytiotrophoblast in humans, rats and guinea-pigs, favour their participation in maintaining the uteroplacental circulation. The findings that sustain the functional associations of the various vasodilators, and their participation by endocrine, paracrine and autocrine regulation of the systemic and local vasoactive changes of pregnancy are abundant and compelling. However, further elucidation of the role of the various players is hampered by methodological problems. Among these difficulties is the complexity of the interactions between the different factors, the likelihood that experimental alterations induced in one system may be compensated by the other players of the network, and the possibility that data obtained by manipulating single factors in vitro or in animal studies may be difficult to translate to the human. In addition, the impossibility of sampling the uteroplacental interface along normal pregnancy precludes obtaining longitudinal profiles of the various players. Nevertheless, the possibility of improving maternal blood pressure regulation, trophoblast invasion and uteroplacental flow by enhancing vasodilation (e.g. L-arginine, NO donors, VEGF transfection) deserves unravelling the intricate association of vasoactive factors and the systemic and local adaptations to pregnancy. PMID- 19646250 TI - The cellulose synthase superfamily in fully sequenced plants and algae. AB - BACKGROUND: The cellulose synthase superfamily has been classified into nine cellulose synthase-like (Csl) families and one cellulose synthase (CesA) family. The Csl families have been proposed to be involved in the synthesis of the backbones of hemicelluloses of plant cell walls. With 17 plant and algal genomes fully sequenced, we sought to conduct a genome-wide and systematic investigation of this superfamily through in-depth phylogenetic analyses. RESULTS: A single copy gene is found in the six chlorophyte green algae, which is most closely related to the CslA and CslC families that are present in the seven land plants investigated in our analyses. Six proteins from poplar, grape and sorghum form a distinct family (CslJ), providing further support for the conclusions from two recent studies. CslB/E/G/H/J families have evolved significantly more rapidly than their widely distributed relatives, and tend to have intragenomic duplications, in particular in the grape genome. CONCLUSION: Our data suggest that the CslA and CslC families originated through an ancient gene duplication event in land plants. We speculate that the single-copy Csl gene in green algae may encode a mannan synthase. We confirm that the rest of the Csl families have a different evolutionary origin than CslA and CslC, and have proposed a model for the divergence order among them. Our study provides new insights about the evolution of this important gene family in plants. PMID- 19646252 TI - Caecal diverticulitis presenting as acute appendicitis: a case report. AB - Solitary caecal diverticulum is an uncommon entity and therefore difficult to diagnose except at surgery. Caecal diverticulitis is an infrequent cause of acute abdomen and usually presents in a manner similar to acute appendicitis. It is extremely difficult to differentiate it preoperative from acute appendicitis and such distinction is usually made in the operating room. The optimal management of this clinical condition is still controversial, ranging from conservative treatment with antibiotics to aggressive surgical resections.We report a case of a 61 year old Caucasian who presented with acute onset right iliac fossa pain indistinguishable from acute appendicitis. The true diagnosis of a perforated acute caecal diverticulitis with an abscess mass was only made at operation in the presence of a macroscopically normal appendix. We reviewed the literature to highlight the difficulty of a preoperative diagnosis and the need for a high index of suspicion especially in the older age group presenting in manner similar to acute appendicitis. PMID- 19646251 TI - Development and diversity of Andean-derived, gene-based microsatellites for common bean (Phaseolus vulgaris L.). AB - BACKGROUND: Gene-based (genic) microsatellites are a useful tool for plant genetics and simple sequence repeat loci can often be found in coding regions of the genome. While EST sequencing can be used to discover genic microsatellites, direct screening of cDNA libraries for repeat motifs can save on overall sequencing costs. The objective of this research was to screen a large cDNA library from and Andean common bean genotype for six di-nucleotide and tri nucleotide repeat motifs through a filter hybridization approach and to develop microsatellite markers from positive clones. RESULTS: Robotics were used for high throughput colony picking and to create a high-density filter of 18,432 double spotted cDNA clones which was followed by hybridization with repeat motif containing probes based on GA, CA, AAT, CAG, CAA and ACG repeats. A total of 1203 positive clones were identified by their addresses and sequenced from 5' ends and if required from 3' ends to confirm repeat motif and length. Out of 886 high quality sequences, 497 had complete microsatellite loci that were not truncated by the sequencing reaction and of these tri-nucleotide repeats were more common than di-nucleotide repeats. Different motifs were found in different frequencies in the 5' and 3' ends of the cDNAs. In a microsatellite development program, primers were designed for 248 SSR loci which were tested on a panel of 18 common bean genotypes to determine their potential as genetic markers finding higher average polymorphism information content for di-nucleotide repeat markers (0.3544) than for tri-nucleotide repeat markers (0.1536). CONCLUSION: The present study provides a set of validated gene-based markers for common bean that are derived from G19833, an Andean landrace that is an important source of disease and abiotic stress tolerance which has been used for physical map development and as a mapping parent. Gene-based markers appear to be very efficient at separating divergent wild and cultivated accessions as well as Andean and Mesoamerican gene pools and therefore will be useful for diversity analyses and for comparative and transcript mapping in common bean. PMID- 19646253 TI - An archived activation tagged population of Arabidopsis thaliana to facilitate forward genetics approaches. AB - BACKGROUND: Functional genomics tools provide researchers with the ability to apply high-throughput techniques to determine the function and interaction of a diverse range of genes. Mutagenized plant populations are one such resource that facilitate gene characterisation. They allow complex physiological responses to be correlated with the expression of single genes in planta, through either reverse genetics where target genes are mutagenized to assay the affect, or through forward genetics where populations of mutant lines are screened to identify those whose phenotype diverges from wild type for a particular trait. One limitation of these types of populations is the prevalence of gene redundancy within plant genomes, which can mask the affect of individual genes. Activation or enhancer populations, which not only provide knock-out but also dominant activation mutations, can facilitate the study of such genes. RESULTS: We have developed a population of almost 50,000 activation tagged A. thaliana lines that have been archived as individual lines to the T3 generation. The population is an excellent tool for both reverse and forward genetic screens and has been used successfully to identify a number of novel mutants. Insertion site sequences have been generated and mapped for 15,507 lines to enable further application of the population, while providing a clear distribution of T-DNA insertions across the genome. The population is being screened for a number of biochemical and developmental phenotypes, provisional data identifying novel alleles and genes controlling steps in proanthocyanidin biosynthesis and trichome development is presented. CONCLUSION: This publicly available population provides an additional tool for plant researcher's to assist with determining gene function for the many as yet uncharacterised genes annotated within the Arabidopsis genome sequence http://aafc-aac.usask.ca/FST. The presence of enhancer elements on the inserted T DNA molecule allows both knock-out and dominant activation phenotypes to be identified for traits of interest. PMID- 19646254 TI - Photodynamic therapy inhibits P-glycoprotein mediated multidrug resistance via JNK activation in human hepatocellular carcinoma using the photosensitizer pheophorbide a. AB - BACKGROUND: Multidrug resistance (MDR) is frequently observed after prolonged treatment in human hepatoma with conventional anti-tumor drugs, and photodynamic therapy (PDT) is a recently suggested alternative to overcome MDR. The therapeutic potential of PDT was evaluated in a multidrug resistance (MDR) human hepatoma cell line R-HepG2 with photosensitizer pheophorbide a (Pa). RESULTS: Our results demonstrated that intracellular accumulation of Pa was not reduced by the overexpression of P-glycoprotein. Pa-based PDT (Pa-PDT) significantly inhibited the growth of R-HepG2 cells with an IC50 value of 0.6 microM. Mechanistic study demonstrated that genomic DNA fragmentation and phosphatidylserine externalization occurred where increase of intracellular singlet oxygen level triggers the phosphorylation of c-Jun N-terminal Kinase (JNK) and leads to activation of intrinsic apoptotic caspases cascade during the Pa-PDT treatment. The cytotoxicity of Pa-PDT, accumulation of sub-G1 population, and depolarization of mitochondrial membrane could be inhibited by JNK inhibitor in the Pa-PDT treated cells. Interestingly, the Pa-PDT induced JNK activation showed inhibitory effect on MDR by the down-regulation of P-glycoprotein in R-HepG2 cells in a dose dependent manner. In addition, significant reduction of tumor size was obtained in Pa-PDT treated R-HepG2-bearing nude mice with no significant damages in liver and heart. CONCLUSION: In summary, our findings provided the first evidence that PDT could inhibit the MDR activity by down-regulating the expression of P glycoprotein via JNK activation using pheophorbide a as the photosensitizer, and our work proved that Pa-PDT inhibited the growth of MDR hepatoma cells by mitochondrial-mediated apoptosis induction. PMID- 19646255 TI - Drug choice, spatial distribution, HIV risk, and HIV prevalence among injection drug users in St. Petersburg, Russia. AB - BACKGROUND: The HIV epidemic in Russia has been driven by the unsafe injection of drugs, predominantly heroin and the ephedrine derived psychostimulants. Understanding differences in HIV risk behaviors among injectors associated with different substances has important implications for prevention programs. METHODS: We examined behaviors associated with HIV risk among 900 IDUs who inject heroin, psychostimulants, or multiple substances in 2002. Study participants completed screening questionnaires that provided data on sociodemographics, drug use, place of residence and injection- and sex-related HIV risk behaviors. HIV testing was performed and prevalence was modeled using general estimating equation (GEE) analysis. Individuals were clustered by neighborhood and disaggregated into three drug use categories: Heroin Only Users, Stimulant Only Users, and Mixed Drug Users. RESULTS: Among Heroin Only Users, younger age, front/backloading of syringes, sharing cotton and cookers were all significant predictors of HIV infection. In contrast, sharing needles and rinse water were significant among the Stimulant Only Users. The Mixed Drug Use group was similar to the Heroin Only Users with age, front/back loading, and sharing cotton significantly associated with HIV infection. These differences became apparent only when neighborhood of residence was included in models run using GEE. CONCLUSION: The type of drug injected was associated with distinct behavioral risks. Risks specific to Stimulant Only Users appeared related to direct syringe sharing. The risks specific to the other two groups are common to the process of sharing drugs in preparation to injecting. Across the board, IDUs could profit from prevention education that emphasizes both access to clean syringes and preparing and apportioning drug with these clean syringes. However, attention to neighborhood differences might improve the intervention impact for injectors who favor different drugs. PMID- 19646256 TI - CRYSTALP2: sequence-based protein crystallization propensity prediction. AB - BACKGROUND: Current protocols yield crystals for <30% of known proteins, indicating that automatically identifying crystallizable proteins may improve high-throughput structural genomics efforts. We introduce CRYSTALP2, a kernel based method that predicts the propensity of a given protein sequence to produce diffraction-quality crystals. This method utilizes the composition and collocation of amino acids, isoelectric point, and hydrophobicity, as estimated from the primary sequence, to generate predictions. CRYSTALP2 extends its predecessor, CRYSTALP, by enabling predictions for sequences of unrestricted size and provides improved prediction quality. RESULTS: A significant majority of the collocations used by CRYSTALP2 include residues with high conformational entropy, or low entropy and high potential to mediate crystal contacts; notably, such residues are utilized by surface entropy reduction methods. We show that the collocations provide complementary information to the hydrophobicity and isoelectric point. Tests on four datasets show that CRYSTALP2 outperforms several existing sequence-based predictors (CRYSTALP, OB-score, and SECRET). CRYSTALP2's accuracy, MCC, and AROC range between 69.3 and 77.5%, 0.39 and 0.55, and 0.72 and 0.79, respectively. Our predictions are similar in quality and are complementary to the predictions of the most recent ParCrys and XtalPred methods. Our results also suggest that, as work in protein crystallization continues (thereby enlarging the population of proteins with known crystallization propensities), the prediction quality of the CRYSTALP2 method should increase. The prediction model and the datasets used in this contribution can be downloaded from http://biomine.ece.ualberta.ca/CRYSTALP2/CRYSTALP2.html. CONCLUSION: CRYSTALP2 provides relatively accurate crystallization propensity predictions for a given protein chain that either outperform or complement the existing approaches. The proposed method can be used to support current efforts towards improving the success rate in obtaining diffraction-quality crystals. PMID- 19646257 TI - Physical activity and risk of metabolic syndrome in an urban Mexican cohort. AB - BACKGROUND: In the Mexican population metabolic syndrome (MS) is highly prevalent. It is well documented that regular physical activity (PA) prevents coronary diseases, type 2 diabetes and MS. Most studies of PA have focused on moderate-vigorous leisure-time activity, because it involves higher energy expenditures, increase physical fitness, and decrease the risk of MS. However, for most people it is difficult to get a significant amount of PA from only moderately-vigorous leisure activity, so workplace activity may be an option for working populations, because, although may not be as vigorous in terms of cardio respiratory efforts, it comprises a considerable proportion of the total daily activity with important energy expenditure. Since studies have also documented that different types and intensity of daily PA, including low-intensity, seem to confer important health benefits such as prevent MS, we sought to assess the impact of different amounts of leisure-time and workplace activities, including low-intensity level on MS prevention, in a sample of urban Mexican adults. METHODS: The study population consisted of 5118 employees and their relatives, aged 20 to 70 years, who were enrolled in the baseline evaluation of a cohort study. MS was assessed according to the criteria of the National Cholesterol Education Program, ATP III and physical activity with a validated self administered questionnaire. Associations between physical activity and MS risk were assessed with multivariate logistic regression models. RESULTS: The prevalence of the components of MS in the study population were: high glucose levels 14.2%, high triglycerides 40.9%, high blood pressure 20.4%, greater than healthful waist circumference 43.2% and low-high density lipoprotein 76.9%. The prevalence of MS was 24.4%; 25.3% in men and 21.8% in women. MS risk was reduced among men (OR 0.72; 95%CI 0.57-0.95) and women (OR 0.78; 95%CI 0.64-0.94) who reported an amount of >or=30 minutes/day of leisure-time activity, and among women who reported an amount of >or=3 hours/day of workplace activity (OR 0.75; 95%CI 0.59-0.96). CONCLUSION: Our results indicate that both leisure-time and workplace activity at different intensity levels, including low-intensity significantly reduce the risk of MS. This finding highlights the need for more recommendations regarding the specific amount and intensity of leisure-time and workplace activity needed to prevent MS. PMID- 19646258 TI - Evaluation of DNA ploidy in relation with established prognostic factors in patients with locally advanced (unresectable) or metastatic pancreatic adenocarcinoma: a retrospective analysis. AB - BACKGROUND: Most patients with ductal pancreatic adenocarcinoma are diagnosed with locally advanced (unresectable) or metastatic disease. The aim of this study was to evaluate the prognostic significance of DNA ploidy in relation with established clinical and laboratory variables in such patients. METHODS: Two hundred and twenty six patients were studied retrospectively. Twenty two potential prognostic variables (demographics, clinical parameters, biochemical markers, treatment modality) were examined. RESULTS: Mean survival time was 38.41 weeks (95% c.i.: 33.17-43.65), median survival 27.00 weeks (95% c.i.: 23.18 30.82). On multivariate analysis, 10 factors had an independent effect on survival: performance status, local extension of tumor, distant metastases, ploidy score, anemia under epoetin therapy, weight loss, pain, steatorrhoea, CEA, and palliative surgery and chemotherapy. Patients managed with palliative surgery and chemotherapy had 6.7 times lower probability of death in comparison with patients without any treatment. Patients with ploidy score > 3.6 had 5.0 times higher probability of death in comparison with patients with ploidy score < 2.2 and these with ploidy score 2.2-3.6 had 6.3 times higher probability of death in comparison with patients with ploidy score < 2.2. CONCLUSION: According to the significance of the examined factor, survival was improved mainly by the combination of surgery and chemotherapy, and the presence of low DNA ploidy score. PMID- 19646259 TI - The use of group dynamics strategies to enhance cohesion in a lifestyle intervention program for obese children. AB - BACKGROUND: Most research pertaining to childhood obesity has assessed the effectiveness of preventative interventions, while relatively little has been done to advance knowledge in the treatment of obesity. Thus, a 4-week family- and group-based intervention utilizing group dynamics strategies designed to increase cohesion was implemented to influence the lifestyles and physical activity levels of obese children. METHODS/DESIGN: This paper provides an overview of the rationale for and implementation of the intervention for obese children and their families. Objectives of the intervention included the modification of health behaviors and cohesion levels through the use of group dynamics strategies. To date, a total of 15 children (7 boys and 8 girls, mean age = 10.5) and their families have completed the intervention (during the month of August 2008). Physiological and psychological outcomes were assessed throughout the 4-week intervention and at 3-, 6-, and 12-month follow-up periods. DISCUSSION: It is believed that the information provided will help researchers and health professionals develop similar obesity treatment interventions through the use of evidence-based group dynamics strategies. There is also a need for continued research in this area, and it is our hope that the Children's Health and Activity Modification Program (C.H.A.M.P.) will provide a strong base from which others may build. PMID- 19646261 TI - A generic method for assignment of reliability scores applied to solvent accessibility predictions. AB - BACKGROUND: Estimation of the reliability of specific real value predictions is nontrivial and the efficacy of this is often questionable. It is important to know if you can trust a given prediction and therefore the best methods associate a prediction with a reliability score or index. For discrete qualitative predictions, the reliability is conventionally estimated as the difference between output scores of selected classes. Such an approach is not feasible for methods that predict a biological feature as a single real value rather than a classification. As a solution to this challenge, we have implemented a method that predicts the relative surface accessibility of an amino acid and simultaneously predicts the reliability for each prediction, in the form of a Z score. RESULTS: An ensemble of artificial neural networks has been trained on a set of experimentally solved protein structures to predict the relative exposure of the amino acids. The method assigns a reliability score to each surface accessibility prediction as an inherent part of the training process. This is in contrast to the most commonly used procedures where reliabilities are obtained by post-processing the output. CONCLUSION: The performance of the neural networks was evaluated on a commonly used set of sequences known as the CB513 set. An overall Pearson's correlation coefficient of 0.72 was obtained, which is comparable to the performance of the currently best public available method, Real SPINE. Both methods associate a reliability score with the individual predictions. However, our implementation of reliability scores in the form of a Z score is shown to be the more informative measure for discriminating good predictions from bad ones in the entire range from completely buried to fully exposed amino acids. This is evident when comparing the Pearson's correlation coefficient for the upper 20% of predictions sorted according to reliability. For this subset, values of 0.79 and 0.74 are obtained using our and the compared method, respectively. This tendency is true for any selected subset. PMID- 19646260 TI - The sea lamprey Petromyzon marinus genome reveals the early origin of several chemosensory receptor families in the vertebrate lineage. AB - BACKGROUND: In gnathostomes, chemosensory receptors (CR) expressed in olfactory epithelia are encoded by evolutionarily dynamic gene families encoding odorant receptors (OR), trace amine-associated receptors (TAAR), V1Rs and V2Rs. A limited number of OR-like sequences have been found in invertebrate chordate genomes. Whether these gene families arose in basal or advanced vertebrates has not been resolved because these families have not been examined systematically in agnathan genomes. RESULTS: Petromyzon is the only extant jawless vertebrate whose genome has been sequenced. Known to be exquisitely sensitive to several classes of odorants, lampreys detect fewer amino acids and steroids than teleosts. This reduced number of detectable odorants is indicative of reduced numbers of CR gene families or a reduced number of genes within CR families, or both, in the sea lamprey. In the lamprey genome we identified a repertoire of 59 intact single exon CR genes, including 27 OR, 28 TAAR, and four V1R-like genes. These three CR families were expressed in the olfactory organ of both parasitic and adult life stages. CONCLUSION: An extensive search in the lamprey genome failed to identify potential orthologs or pseudogenes of the multi-exon V2R family that is greatly expanded in teleost genomes, but did find intact calcium-sensing receptors (CASR) and intact metabotropic glutamate receptors (MGR). We conclude that OR and V1R arose in chordates after the cephalochordate-urochordate split, but before the diversification of jawed and jawless vertebrates. The advent and diversification of V2R genes from glutamate receptor-family G protein-coupled receptors, most likely the CASR, occurred after the agnathan-gnathostome divergence. PMID- 19646262 TI - Sensitivities of conventional and new electrophysiological techniques in carpal tunnel syndrome and their relationship to body mass index. AB - The purpose of this study is to evaluate prospectively the sensitivities of conventional and new electrophysiological techniques and to investigate their relationship with the body mass index (BMI) in a population of patients suspected of having carpal tunnel syndrome (CTS). In this study, 165 hands of 92 consecutive patients (81 female, 11 male) with clinical diagnosis of CTS were compared to reference population of 60 hands of 30 healthy subjects (26 female and 4 male). Extensive sensory and motor nerve conduction studies (NCSs) were performed in the diagnosis of subtle CTS patients. Also, the patients were divided into subgroups and sensitivities were determined according to BMI. The mean BMI was found to be significantly higher in the CTS than in the control group (p < 0.001). The sensitivity of the median sensory nerve latency (mSDL) and median motor distal latency (mMDL) were 75.8% and 68.5%, respectively. The most sensitive parameters of sensory and motor NCSs were the difference between median and ulnar sensory distal latencies to the fourth digit [(D4M-D4U), (77%)] and the median motor terminal latency index [(mTLI), (70.3%)], while the median-to-ulnar sensory action potential amplitude ratio (27%) and the median-thenar to ulnar hypothenar motor action potential amplitude ratio (15%) were least sensitive tests. Sensory tests were more sensitive than motor NCSs. Combining mSDL with D4M D4U, and mMDL with mTLI allowed for the detection of abnormalities in 150 (91%) and 132 (80%) hands, respectively. Measurements of all NCSs parameters were abnormal in obese than in non-obese patients when compared to the BMI. The newer nerve conduction techniques and combining different NCSs tests are more sensitive than single conventional NCS test for the diagnosis of suspected CTS. Meanwhile, CTS is associated with increasing BMI. PMID- 19646264 TI - Redefining the expressed prototype SICAvar gene involved in Plasmodium knowlesi antigenic variation. AB - BACKGROUND: The SICAvar gene family, expressed at the surface of infected erythrocytes, is critical for antigenic variation in Plasmodium knowlesi. When this family was discovered, a prototypic SICAvar gene was characterized and defined by a 10-exon structure. The predicted 205-kDa protein lacked a convincing signal peptide, but included a series of variable cysteine-rich modules, a transmembrane domain encoded by the penultimate exon, and a cytoplasmic domain encoded by the final highly conserved exon. The 205 SICAvar gene and its family with up to 108 possible family members, was identified prior to the sequencing of the P. knowlesi genome. However, in the published P. knowlesi database this gene remains disjointed in five fragments. This study addresses a number of structural and functional questions that are critical for understanding SICAvar gene expression. METHODS: Database mining, bioinformatics, and traditional genomic and post-genomic experimental methods including proteomic technologies are used here to confirm the genomic context and expressed structure of the prototype 205 SICAvar gene. RESULTS: This study reveals that the 205 SICAvar gene reported previously to have a 10-exon expressed gene structure has, in fact, 12 exons, with an unusually large and repeat-laden intron separating two newly defined upstream exons and the bona fide 5'UTR from the remainder of the gene sequence. The initial exon encodes a PEXEL motif, which may function to localize the SICA protein in the infected erythrocyte membrane. This newly defined start of the 205 SICAvar sequence is positioned on chromosome 5, over 340 kb upstream from the rest of the telomerically positioned SICAvar gene sequence in the published genome assembly. This study, however, verifies the continuity of these sequences, a 9.5 kb transcript, and provides evidence that the 205 SICAvar gene is located centrally on chromosome 5. CONCLUSION: The prototype 205 SICAvar gene has been redefined to have a 12-exon structure. These data are important because they 1) address questions raised in the P. knowlesi genome database regarding SICAvar gene fragments, numbers and structures, 2) show that this prototype gene encodes a PEXEL motif, 3) emphasize the need for further refinement of the P. knowlesi genome data, and 4) retrospectively, provide evidence for recombination within centrally located SICAvar sequences. PMID- 19646263 TI - Depletion of intrinsic expression of Interleukin-8 in prostate cancer cells causes cell cycle arrest, spontaneous apoptosis and increases the efficacy of chemotherapeutic drugs. AB - BACKGROUND: The progression of all cancers is characterized by increased-cell proliferation and decreased-apoptosis. The androgen-independent prostate cancer (AIPC) is the terminal stage of the disease. Many chemokines and cytokines are suspects to cause this increased tumor cell survival that ultimately leads to resistance to therapy and demise of the host. The AIPC cells, but not androgen responsive cells, constitutively express abundant amount of the pro-inflammatory chemokine, Interleukin-8 (IL-8). The mechanism of IL-8 mediated survival and therapeutic resistance in AIPC cells is unclear at present. The purpose of this report is to show the pervasive role of IL-8 in malignant progression of androgen independent prostate cancer (AIPC) and to provide a potential new therapeutic avenue, using RNA interference. RESULTS: The functional consequence of IL-8 depletion in AIPC cells was investigated by RNA interference in two IL-8 secreting AIPC cell lines, PC-3 and DU145. The non-IL-8 secreting LNCaP and LAPC 4 cells served as controls. Cells were transfected with RISC-free siRNA (control) or validated-pool of IL-8 siRNA. Transfection with 50 nM IL-8 siRNA caused >95% depletion of IL-8 mRNA and >92% decrease in IL-8 protein. This reduction in IL-8 led to cell cycle arrest at G1/S boundary and decreases in cell cycle-regulated proteins: Cyclin D1 and Cyclin B1 (both decreased >50%) and inhibition of ERK1/2 activity by >50%. Further, the spontaneous apoptosis was increased by >43% in IL 8 depleted cells, evidenced by increases in caspase-9 activation and cleaved PARP. IL-8 depletion caused significant decreases in anti-apoptotic proteins, BCL 2, BCL-xL due to decrease in both mRNA and post-translational stability, and increased levels of pro-apoptotic BAX and BAD proteins. More significantly, depletion of intracellular IL-8 increased the cytotoxic activity of multiple chemotherapeutic drugs. Specifically, the cytotoxicity of Docetaxel, Staurosporine and Rapamycin increased significantly (>40% at IC50 dose) in IL-8 depleted cells as compared to that in C-siRNA transfected cells. CONCLUSION: These results show the pervasive role of IL-8 in promoting tumor cell survival, and resistance to cytotoxic drugs, regardless of the cytotoxic mechanism of antiproliferative drugs, and point to potential therapeutic significance of IL-8 depletion in men with AIPC. PMID- 19646265 TI - Stretches of alternating pyrimidine/purines and purines are respectively linked with pathogenicity and growth temperature in prokaryotes. AB - BACKGROUND: The genomic fractions of purine (RR) and alternating pyrimidine/purine (YR) stretches of 10 base pairs or more, have been linked to genomic AT content, the formation of different DNA helices, strand-biased gene distribution, DNA structure, and more. Although some of these factors are a consequence of the chemical properties of purines and pyrimidines, a thorough statistical examination of the distributions of YR/RR stretches in sequenced prokaryotic chromosomes has to the best of our knowledge, not been undertaken. The aim of this study is to expand upon previous research by using regression analysis to investigate how AT content, habitat, growth temperature, pathogenicity, phyla, oxygen requirement and halotolerance correlated with the distribution of RR and YR stretches in prokaryotes. RESULTS: Our results indicate that RR and YR-stretches are differently distributed in prokaryotic phyla. RR stretches are overrepresented in all phyla except for the Actinobacteria and beta Proteobacteria. In contrast, YR tracts are underrepresented in all phyla except for the beta-Proteobacterial group. YR-stretches are associated with phylum, pathogenicity and habitat, whilst RR-tracts are associated with phylum, AT content, oxygen requirement, growth temperature and halotolerance. All associations described were statistically significant with p < 0.001. CONCLUSION: Analysis of chromosomal distributions of RR/YR sequences in prokaryotes reveals a set of associations with environmental factors not observed with mono- and oligonucleotide frequencies. This implies that important information can be found in the distribution of RR/YR stretches that is more difficult to obtain from genomic mono- and oligonucleotide frequencies. The association between pathogenicity and fractions of YR stretches is assumed to be linked to recombination and horizontal transfer. PMID- 19646267 TI - Online assessment of patients' views on hospital performances using Rasch model's KIDMAP diagram. AB - BACKGROUND: To overcome the drawback of individual item-by-item box plots of disclosure for patient views on healthcare service quality, we propose to inspect interrelationships among items that measure a common entity. A visual diagram on the Internet is developed to provide thorough information for hospitals. METHODS: We used the Rasch rating scale model to analyze the 2003 English inpatient questionnaire data regarding patient satisfactory perception, which were collected from 169 hospitals, examined model-data fit, and developed a KIDMAP diagram on the Internet depicting the satisfaction level of each hospital and investigating aberrant responses with Z-scores and MNSQ statistics for individual hospitals. Differential item functioning (DIF) analysis was conducted to verify construct equivalence across types of hospitals. RESULTS: 18 of the 45 items fit to the model's expectations, indicating they jointly defined a common construct and an equal-interval logit scale was achieved. The most difficult aspect for hospitals to earn inpatients' satisfaction were item 29 (staff told you about any medication side effects to watch when going home). No DIF in the 18-item questionnaire was found between types of hospitals, indicating the questionnaire measured the same construct across hospitals. Different types of hospitals obtained different levels of satisfaction. The KIDMAP on the Internet provided more interpretable and visualized message than traditional item-by-item box plots of disclosure. CONCLUSION: After removing misfit items, we find that the 18-item questionnaire measures the same construct across types of hospitals. The KIDMAP on the Internet provides an exemplary comparison in quality of healthcare. Rasch analysis allows intra- and inter-hospital performances to be compared easily and reliably with each other on the Internet. PMID- 19646266 TI - A catalytically and genetically optimized beta-lactamase-matrix based assay for sensitive, specific, and higher throughput analysis of native henipavirus entry characteristics. AB - Nipah virus (NiV) and Hendra virus (HeV) are the only paramyxoviruses requiring Biosafety Level 4 (BSL-4) containment. Thus, study of henipavirus entry at less than BSL-4 conditions necessitates the use of cell-cell fusion or pseudotyped reporter virus assays. Yet, these surrogate assays may not fully emulate the biological properties unique to the virus being studied. Thus, we developed a henipaviral entry assay based on a beta-lactamase-Nipah Matrix (betala-M) fusion protein. We first codon-optimized the bacterial betala and the NiV-M genes to ensure efficient expression in mammalian cells. The betala-M construct was able to bud and form virus-like particles (VLPs) that morphologically resembled paramyxoviruses. betala-M efficiently incorporated both NiV and HeV fusion and attachment glycoproteins. Entry of these VLPs was detected by cytosolic delivery of betala-M, resulting in enzymatic and fluorescent conversion of the pre-loaded CCF2-AM substrate. Soluble henipavirus receptors (ephrinB2) or antibodies against the F and/or G proteins blocked VLP entry. Additionally, a Y105W mutation engineered into the catalytic site of betala increased the sensitivity of our betala-M based infection assays by 2-fold. In toto, these methods will provide a more biologically relevant assay for studying henipavirus entry at less than BSL 4 conditions. PMID- 19646268 TI - Cardiomyopathy in offspring of diabetic rats is associated with activation of the MAPK and apoptotic pathways. AB - BACKGROUND: Maternal diabetes affects the developing fetal cardiovascular system. Newborn offspring of diabetic mothers can have a transient cardiomyopathy. We hypothesized that cardiomyopathic remodeling is associated with activation of the mitogen activated protein kinase (MAPK) signaling and apoptotic pathways. METHODS: To evaluate the effects of moderate and severe maternal hyperglycemia, pregnant rats were made diabetic with an injection of 50 mg/kg of streptozotocin. Moderately well controlled maternal diabetes was achieved with twice daily glucose checks and insulin injections. No insulin was given to severely diabetic dams. Offspring of moderate and severe diabetic mothers (OMDM and MSDM, respectively) were studied on postnatal days 1 (NB1) and 21 (NB21). Echocardiograms were performed to evaluate left ventricular (LV) dimensions and function. Myocardial MAPK and apoptotic protein levels were measured by Western blot. RESULTS: OMDM had increased cardiac mass at NB1 compared to controls that normalized at NB21. OSDM demonstrated microsomia with relative sparing of cardiac mass and a dilated cardiomyopathy at NB1. In both models, there was a persistent increase in the HW:BW and significant activation of MAPK and apoptotic pathways at NB21. CONCLUSION: The degree of maternal hyperglycemia determines the type of cardiomyopathy seen in the offspring, while resolution of both the hypertrophic and dilated cardiomyopathies is associated with activation of MAPK signaling and apoptotic pathways. PMID- 19646269 TI - A survey of factors associated with the successful recognition of agonal breathing and cardiac arrest by 9-1-1 call takers: design and methodology. AB - BACKGROUND: Cardiac arrest victims most often collapse at home, where only a modest proportion receives life-saving bystander cardiopulmonary resuscitation. As many as 40% of all sudden cardiac arrest victims have agonal or abnormal breathing in the first minutes following cardiac arrest. 9-1-1 call takers may wrongly interpret agonal breathing as a sign of life, and not initiate telephone cardiopulmonary resuscitation instructions. Improving 9-1-1 call takers' ability to recognize agonal breathing as a sign of cardiac arrest could result in improved bystander cardiopulmonary resuscitation and survival rates for out-of hospital cardiac arrest victims. METHODS/DESIGN: The overall goal of this study is to design and conduct a survey of 9-1-1 call takers in the province of Ontario to better understand the factors associated with the successful identification of cardiac arrest (including patients with agonal breathing) over the phone, and subsequent administration of cardiopulmonary resuscitation instructions to callers. This study will be conducted in three phases using the Theory of Planned Behaviour. In Phase One, we will conduct semi-structured qualitative interviews with a purposeful selection of 9-1-1 call takers from Ontario, and identify common themes and belief categories. In Phase Two, we will use the qualitative interview results to design and pilot a quantitative survey. In Phase Three, a final version of the quantitative survey will be administered via an electronic medium to all registered call takers in the province of Ontario. We will perform qualitative thematic analysis (Phase One) and regression modelling (Phases Two and Three), to determine direct and indirect relationship of behavioural constructs with intentions to provide cardiopulmonary resuscitation instructions. DISCUSSION: The results of this study will provide valuable insight into the factors associated with the successful recognition of agonal breathing and cardiac arrest by 9-1-1 call takers. This will guide future interventional studies, which may include continuing education and protocol changes, in order to help increase the number of callers appropriately receiving cardiopulmonary resuscitation instructions, and save the lives of more cardiac arrest victims. PMID- 19646270 TI - Antagonistic actions of boron against inhibitory effects of aluminum toxicity on growth, CO2 assimilation, ribulose-1,5-bisphosphate carboxylase/oxygenase, and photosynthetic electron transport probed by the JIP-test, of Citrus grandis seedlings. AB - BACKGROUND: Little information is available on the amelioration of boron (B) on aluminum (Al)-induced photosynthesis inhibition. Sour pummelo (Citrus grandis) seedlings were irrigated for 18 weeks with nutrient solution containing 4 B levels (2.5, 10, 25 and 50 microM H3BO3) x 2 Al levels (0 and 1.2 mM AlCl3.6H2O). The objectives of this study were to determine how B alleviates Al-induced growth inhibition and to test the hypothesis that Al-induced photosynthesis inhibition can be alleviated by B via preventing Al from getting into shoots. RESULTS: B had little effect on plant growth, root, stem and leaf Al, leaf chlorophyll (Chl), CO2 assimilation, ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), Chl a fluorescence (OJIP) transient and related parameters without Al stress except that root, stem and leaf B increased with increasing B supply and that 50 muM B decreased slightly root dry weight. Al-treated roots, stems and leaves displayed a higher or similar B. B did not affect root Al under Al stress, but decreased stem and leaf Al level. Shoot growth is more sensitive to Al stress than root growth, CO2 assimilation, Chl, Rubisco, OJIP transient and most related parameters. Al-treated leaves showed decreased CO2 assimilation, but increased or similar intercellular CO2 concentration. Both initial and total Rubisco activity in Al-treated leaves decreased to a lesser extent than CO2 assimilation. Al decreased maximum quantum yield of primary photochemistry and total performance index, but increased minimum fluorescence, K-band, relative variable fluorescence at J- and I-steps. B could alleviate Al-induced increase or decrease for all these parameters. Generally speaking, the order of B effectiveness was 25 microM > 10 microM >or= 50 microM (excess B) > 2.5 microM. CONCLUSION: We propose that Al-induced photosynthesis inhibition was mainly caused by impaired photosynthetic electron transport chain, which may be associated with growth inhibition. B induced amelioration of root inhibition was probably caused by B-induced changes in Al speciation and/or sub-cellular compartmentation. However, B-induced amelioration of shoot and photosynthesis inhibition and photoinhibitory damage occurring at both donor and acceptor sides of photosystem II could be due to less Al accumulation in shoots. PMID- 19646271 TI - Targeted suppression of heme oxygenase-1 by small interference RNAs inhibits the production of bilirubin in neonatal rat with hyperbilirubinemia. AB - BACKGROUND: Excessive accumulation of bilirubin contributes to neonatal hyperbilirubinemia in rats. Heme oxygenase (HO) is one of the rate-limiting enzymes in catabolizing heme to bilirubin. In the present study, we investigated whether suppression of rat HO-1 (rHO-1) expression by small interference RNAs (siRNAs) reduces bilirubin levels in hyperbilirubinemic rats. RESULTS: Four pairs of siRNA targeting rHO-1 mRNA were introduced into BRL cells and compared for their inhibitory effect on the expression of rHO-1 gene and production of rHO-1 protein. The siRNA exhibiting the most potent effect on HO-1 expression and activity was then administered intraperitoneally to 7 to 9-day-old rats with hyperbilirubinemia. The siRNA distributed mostly in the liver and spleen of neonatal rat. Serum bilirubin levels and hepatic HO-1 expression were further evaluated. Systemic treatment of siRNA targeting rHO-1 reduced hepatic HO-1 expression and decreased the serum bilirubin levels in a time- and dose-dependent manner, and siRNA decreased the indirect bilirubin levels more effectively than Sn-protoporphyrin (SnPP), an HO-1 inhibitor. CONCLUSION: siRNA targeting rHO-l attenuates hepatic HO-1 expression and serum bilirubin levels. Thus this study provides a novel therapeutic rationale for the prevention and treatment of neonatal hyperbilirubinemia. PMID- 19646273 TI - Translation and validation study of the Persian version of the Arthritis Impact Measurement Scales 2 (AIMS2) in patients with osteoarthritis of the knee. AB - BACKGROUND: The Arthritis Impact Measurement Scales 2 (AIMS2) has not been translated and validated for Persian-speaking patients with osteoarthritis of the knee. This was to provide a validated instrument to measure functional disability and health-related quality of life in patients with osteoarthritis of the knee in Iran. The aim of this study was to culturally adapt and validate the AIMS2 for Persian-speaking patients with osteoarthritis of the knee in Iran. METHODS: A consecutive sample of patients with knee osteoarthritis were asked to complete the AIMS2, the Short Form Health Survey (SF-36) and four visual analog scales for pain, joint stiffness, patient's and physician's global assessment. Internal consistency and convergent validity were applied to examine psychometric properties of the AIMS2. In addition, 30 randomly selected patients were asked to complete the questionnaire two days later for the second time for test-retest reliability. Finally factor structure of the Persian AIMS2 was performed using the principal component factor analysis. RESULTS: In all 230 patients were entered into the study. The mean (SD) age of the participants was 56.9 (8.7) years and the mean (SD) duration of disease was 7.2 (3.5) years. Cronbach's alpha coefficient and intraclass correlation coefficient (ICC) for the Persian AIMS2 scales ranged from 0.74 to 0.92 and 0.85 to 0.96, respectively. The correlation between most of the Persian AIMS2 scales and the physical and mental summary scores of the SF-36 and the visual analogue scales for pain, joint stiffness, patient's and physician's global assessment were statistically significant indicating a good convergent validity (p < 0.05). The results obtained from factor analysis indicated three latent factors that jointly accounted for 67.5% of the total variance. CONCLUSION: The results showed that the Persian AIMS2 had reasonably good internal consistency, test-retest reliability, and convergent validity in patients with osteoarthritis of the knee. It is simple and easy to use and now can be applied in the future studies in Iran. However, its sensitivity to change needs still to be studied. PMID- 19646272 TI - Comparison of next generation sequencing technologies for transcriptome characterization. AB - BACKGROUND: We have developed a simulation approach to help determine the optimal mixture of sequencing methods for most complete and cost effective transcriptome sequencing. We compared simulation results for traditional capillary sequencing with "Next Generation" (NG) ultra high-throughput technologies. The simulation model was parameterized using mappings of 130,000 cDNA sequence reads to the Arabidopsis genome (NCBI Accession SRA008180.19). We also generated 454-GS20 sequences and de novo assemblies for the basal eudicot California poppy (Eschscholzia californica) and the magnoliid avocado (Persea americana) using a variety of methods for cDNA synthesis. RESULTS: The Arabidopsis reads tagged more than 15,000 genes, including new splice variants and extended UTR regions. Of the total 134,791 reads (13.8 MB), 119,518 (88.7%) mapped exactly to known exons, while 1,117 (0.8%) mapped to introns, 11,524 (8.6%) spanned annotated intron/exon boundaries, and 3,066 (2.3%) extended beyond the end of annotated UTRs. Sequence based inference of relative gene expression levels correlated significantly with microarray data. As expected, NG sequencing of normalized libraries tagged more genes than non-normalized libraries, although non-normalized libraries yielded more full-length cDNA sequences. The Arabidopsis data were used to simulate additional rounds of NG and traditional EST sequencing, and various combinations of each. Our simulations suggest a combination of FLX and Solexa sequencing for optimal transcriptome coverage at modest cost. We have also developed ESTcalc http://fgp.huck.psu.edu/NG_Sims/ngsim.pl, an online webtool, which allows users to explore the results of this study by specifying individualized costs and sequencing characteristics. CONCLUSION: NG sequencing technologies are a highly flexible set of platforms that can be scaled to suit different project goals. In terms of sequence coverage alone, the NG sequencing is a dramatic advance over capillary-based sequencing, but NG sequencing also presents significant challenges in assembly and sequence accuracy due to short read lengths, method specific sequencing errors, and the absence of physical clones. These problems may be overcome by hybrid sequencing strategies using a mixture of sequencing methodologies, by new assemblers, and by sequencing more deeply. Sequencing and microarray outcomes from multiple experiments suggest that our simulator will be useful for guiding NG transcriptome sequencing projects in a wide range of organisms. PMID- 19646274 TI - Robo-Lector - a novel platform for automated high-throughput cultivations in microtiter plates with high information content. AB - BACKGROUND: In industry and academic research, there is an increasing demand for flexible automated microfermentation platforms with advanced sensing technology. However, up to now, conventional platforms cannot generate continuous data in high-throughput cultivations, in particular for monitoring biomass and fluorescent proteins. Furthermore, microfermentation platforms are needed that can easily combine cost-effective, disposable microbioreactors with downstream processing and analytical assays. RESULTS: To meet this demand, a novel automated microfermentation platform consisting of a BioLector and a liquid-handling robot (Robo-Lector) was sucessfully built and tested. The BioLector provides a cultivation system that is able to permanently monitor microbial growth and the fluorescence of reporter proteins under defined conditions in microtiter plates. Three examplary methods were programed on the Robo-Lector platform to study in detail high-throughput cultivation processes and especially recombinant protein expression. The host/vector system E. coli BL21(DE3) pRhotHi-2-EcFbFP, expressing the fluorescence protein EcFbFP, was hereby investigated. With the method 'induction profiling' it was possible to conduct 96 different induction experiments (varying inducer concentrations from 0 to 1.5 mM IPTG at 8 different induction times) simultaneously in an automated way. The method 'biomass-specific induction' allowed to automatically induce cultures with different growth kinetics in a microtiter plate at the same biomass concentration, which resulted in a relative standard deviation of the EcFbFP production of only +/- 7%. The third method 'biomass-specific replication' enabled to generate equal initial biomass concentrations in main cultures from precultures with different growth kinetics. This was realized by automatically transferring an appropiate inoculum volume from the different preculture microtiter wells to respective wells of the main culture plate, where subsequently similar growth kinetics could be obtained. CONCLUSION: The Robo-Lector generates extensive kinetic data in high-throughput cultivations, particularly for biomass and fluorescence protein formation. Based on the non-invasive on-line-monitoring signals, actions of the liquid-handling robot can easily be triggered. This interaction between the robot and the BioLector (Robo-Lector) combines high-content data generation with systematic high-throughput experimentation in an automated fashion, offering new possibilities to study biological production systems. The presented platform uses a standard liquid-handling workstation with widespread automation possibilities. Thus, high-throughput cultivations can now be combined with small-scale downstream processing techniques and analytical assays. Ultimately, this novel versatile platform can accelerate and intensify research and development in the field of systems biology as well as modelling and bioprocess optimization. PMID- 19646275 TI - Implementation of a novel PCR based method for detecting malaria parasites from naturally infected mosquitoes in Papua New Guinea. AB - BACKGROUND: Detection of Plasmodium species in mosquitoes is important for designing vector control studies. However, most of the PCR-based detection methods show some potential limitations. The objective of this study was to introduce an effective PCR-based method for detecting Plasmodium vivax and Plasmodium falciparum from the field-caught mosquitoes of Papua New Guinea. METHODS: A method has been developed to concurrently detect mitochondrial cytochrome b (Cyt b) of four human Plasmodium species using PCR (Cytb-PCR). To particularly discriminate P. falciparum from P. vivax, Plasmodium ovale and Plasmodium malariae, a polymerase chain reaction-repeated fragment length polymorphism (PCR-RFLP) has further been developed to use with this method. However, due to limited samples number of P. ovale and P. malariae; this study was mainly confined to P. vivax and P. falciparum. The efficiency of Cytb-PCR was evaluated by comparing it with two 'gold standards' enzyme linked immunosorbent assay specific for circumsporozoite protein (CS-ELISA) using artificially infected mosquitoes; and nested PCR specific for small subunit ribosomal RNA (SSUrRNA) using field caught mosquitoes collected from three areas (Kaboibus, Wingei, and Jawia) of the East Sepic Province of Papua New Guinea. RESULTS: A total of 90 mosquitoes were artificially infected with three strains of Plasmodium: P. vivax-210 (n = 30), P. vivax-247 (n = 30) and P. falciparum (n = 30). These infected mosquitoes along with another 32 unfed mosquitoes were first checked for the presence of Plasmodium infection by CS-ELISA, and later the same samples were compared with the Cytb-PCR. CS-ELISA for P. vivax-210, P. vivax-247 and P. falciparum detected positive infection in 30, 19 and 18 mosquitoes respectively; whereas Cytb-PCR detected 27, 16 and 16 infections, respectively. The comparison revealed a close agreement between the two assays (kappa = 0.862, 0.842 and 0.894, respectively for Pv-210, Pv-247 and P. falciparum groups). It was found that the eight CS-ELISA-positive mosquitoes detected negative by Cytb PCR were false-positive results. The lowest detection limit of this Cytb-PCR was 10 sporozoites. A highly concordance result was also found between nested PCR and Cytb-PCR using 107 field caught mosquitoes, and both tests concordantly detected P. falciparum in an Anopheles punctulatus mosquito collected from Kaboibus. Both tests thus suggested an overall sporozoite rate of 0.9% (1/107) in the study areas. Subsequently, PCR-RFLP efficiently discriminated P. falciparum from P. vivax for all of the Cytb-PCR positive samples. CONCLUSION: A single step PCR based method has been introduced here that is highly sensitive, efficient and reliable for identifying P. vivax and P. falciparum from mosquitoes. The reliability of the technique was confirmed by its ability to detect Plasmodium as efficiently as those of CS-ELISA and nested PCR. Application of the assay offers the opportunity to detect vector species of Papua New Guinea and may contribute for designing further vector control programmes. PMID- 19646276 TI - Acute effect of electroacupuncture at the Zusanli acupoints on decreasing insulin resistance as shown by lowering plasma free fatty acid levels in steroid background male rats. AB - BACKGROUND: Insulin sensitivity has been enhanced by electroacupuncture (EA) in rats, but the EA phenomenon in an insulin resistant state is still unclear. This study reports the use of a large dose of prednisolone to evaluate the effects of EA in a state of insulin resistance. METHODS: The plasma levels of free fatty acids (FFAs) were estimated in steroid-background rats (SBRs) and compared with those in healthy rats treated with normal saline. In addition, plasma glucose and endogenous insulin levels were assayed to calculate the homeostasis model assessment (HOMA) index. Intravenous glucose tolerance test (IVGTT) was carried out to compare glucose tolerance. The SBRs were randomly divided into EA treatment and non-EA treatment groups and 15-Hz EA was applied to the bilateral Zusanli acupoints to investigate its effects on insulin resistance. In addition to an insulin challenge test (ICT) and IVGTT, the plasma levels of FFAs were measured and western blot was performed to help determine the effects of EA on the insulin resistant state. RESULTS: The plasma levels of FFAs increased markedly in SBRs, the HOMA index was markedly higher, and glucose tolerance was impaired. EA improved glucose tolerance and insulin sensitivity by decreasing the plasma levels of FFAs. Further, the insulin signaling proteins (IRS1) and glucose transporter isoform protein (GLUT4) in skeletal muscle inhibited by prednisolone recovered after EA. CONCLUSION: Insulin resistance was successfully induced by a large dose of prednisolone in male rats. This insulin resistance can be improved by 15 Hz EA at the bilateral Zusanli acupoints, as shown by decreased plasma levels of FFAs. PMID- 19646277 TI - 13-cis-retinoic acid re-differentiation therapy and recombinant human thyrotropin aided radioiodine treatment of non-Functional metastatic thyroid cancer: a single center, 53-patient phase 2 study. AB - In 30-50% of patients with metastatic non-medullary thyroid cancer the metastases are not radioiodine-avid and so there is no effective treatment. Retinoids have demonstrated inhibition of thyroid tumor growth and induction of radioiodine uptake. The aim of our study was to assess benefits of the retinoic acid (RA) treatment to re-differentiate non-functional NMTC metastases. PATIENTS AND METHODS: In this prospective study, 53 patients with radioiodine non avid metastatic disease (45) or hyperthyroglobulinemia (8) were treated with 13-cis retinoic acid (13-CRA) [1.0 mg/kg/day over 1st week and then 1.5 mg/kg] for six weeks prior to I-131 treatment performed under rhTSH stimulation. The re differentiating effect of RA was evaluated by serum thyroglobulin (Tg) monitoring before and after cessation of RA treatment and by qualitative analysis of iodine uptake on the post-therapeutic whole body scan (rxWBS). RESULTS: 13-CRA induced radioiodine uptake in 9 (17%) of patients. In the univariate analysis neither the patient's gender, age, tumor histopathology, uptake in thyroid bed nor time since thyroid cancer diagnosis was associated with results of rxWBS.41 (77%) patients were evaluable for Tg response before and after to 13-CRA treatment. There was a statistically significant increase in median Tg level (60 v. 90 ng/ml, p < 0.05). There was no difference in Tg increase between scintigraphic responders and non responders.13-CRA and RIT was repeated at least once in 8 of 9 scintigraphic responders. None of them showed tumor regression by radiological imaging within 12 months after the first treatment, 4/9 (44%) of them had disease progression.13 CRA treatment was well-tolerated. All but one patient complained of at least one side effect the most prevalent being lip dryness (98%). All side effects were transient and resolved within 2 weeks after 13-CRA cessation. CONCLUSION: Our results show that in patients with non-functional metastases from NMTC, 13-CRA is able to exert some re-differentiation effect by induction of radioiodine uptake in <20% of patients and increase of Tg serum level in about 30% of them. Nevertheless, this does not transfer into clinical benefit as it neither induces measurable tumor response nor prevents disease progression. PMID- 19646279 TI - Post-consent assessment of dental subjects' understanding of informed consent in oral health research in Nigeria. AB - BACKGROUND: Research participants may not adequately understand the research in which they agree to enroll. This could be due to a myriad of factors. Such a missing link in the informed consent process contravenes the requirement for an "informed" consent prior to the commencement of research. This study assessed the post consent understanding of Nigerian study participants of the oral health research they were invited to join. METHODS: A descriptive cross sectional study with research participants who had just consented to one of three ongoing research studies on oral health. Study sites included two centers, one in the northern and one in the southern part of Nigeria. Data were collected using a combination of quantitative and qualitative methods. RESULTS: A total of 113 research participants were interviewed. The southern part of the country had 58 respondents with the north having 55. The age range was 21 - 80 years. Mean age was 46.1 (SD16.3). The sample was predominantly male (69.9%) and married (64.6%). There was poor understanding of some key elements of the informed consent process such as involvement in research, benefits, contacts, confidentiality and voluntariness. Some identified factors potentially compromising understanding were poverty, illiteracy, therapeutic misconception and confusion about the dual roles of the Dentist and the researcher. CONCLUSION: The participants recruited into the oral health research in Nigeria did not adequately understand the studies they were invited to join nor do they understand their rights as research participants. Measures should be taken to include research bioethics into the curricula of Dental schools and to train oral health researchers in the country on research ethics. PMID- 19646278 TI - Gastrointestinal stromal tumor. AB - BACKGROUND: GISTs are a subset of mesenchymal tumors and represent the most common mesenchymal neoplasms of GI tract. However, GIST is a recently recognized tumor entity and the literature on these stromal tumors has rapidly expanded. METHODS: An extensive review of the literature was carried out in both online medical journals and through Athens University Medical library. An extensive literature search for papers published up to 2009 was performed, using as key words, GIST, Cajal's cells, treatment, Imatinib, KIT, review of each study were conducted, and data were abstracted. RESULTS: GIST has recently been suggested that is originated from the multipotential mesenchymal stem cells. It is estimated that the incidence of GIST is approximately 10-20 per million people, per year. CONCLUSION: The clinical presentation of GIST is variable but the most usual symptoms include the presence of a mass or bleeding. Surgical resection of the local disease is the mainstay therapy. However, therapeutic agents, such as Imatinib have now been approved for the treatment of advanced GISTs and others, such as everolimus, rapamycin, heat shock protein 90 and IGF are in trial stage demonstrate promising results for the management of GISTs. PMID- 19646280 TI - A phase 1 trial of pharmacologic interactions between transdermal selegiline and a 4-hour cocaine infusion. AB - BACKGROUND: The selective MAO-B inhibitor selegiline has been evaluated in clinical trials as a potential medication for the treatment of cocaine dependence. This study evaluated the safety of and pharmacologic interactions between 7 days of transdermal selegiline dosed with patches (Selegiline Transdermal System, STS) that deliver 6 mg/24 hours and 2.5 mg/kg of cocaine administered over 4 hours. METHODS: Twelve nondependent cocaine-experienced subjects received deuterium-labeled cocaine-d5 intravenously (IV) 0.5 mg/kg over 10 minutes followed by 2 mg/kg over 4 hours before and after one week of transdermal selegiline 6 mg/24 hours. Plasma and urine were collected for analysis of selegiline, cocaine, catecholamine and metabolite concentrations. Pharmacodynamic measures were obtained. RESULTS: Selegiline did not change cocaine pharmacokinetic parameters. Selegiline administration increased phenylethylamine (PEA) urinary excretion and decreased urinary MHPG-sulfate concentration after cocaine when compared to cocaine alone. No serious adverse effects occurred with the combination of selegiline and cocaine, and cocaine induced physiological effects were unchanged after selegiline. Only 1 peak subjective cocaine effects rating changed, and only a few subjective ratings decreased across time after selegiline. CONCLUSION: No pharmacological interaction occurred between selegiline and a substantial dose of intravenous cocaine, suggesting the combination will be safe in pharmacotherapy trials. Selegiline produced few changes in subjective response to the cocaine challenge perhaps because of some psychoactive neurotransmitters changing in opposite directions. PMID- 19646281 TI - Periodontal treatment to improve glycaemic control in diabetic patients: study protocol of the randomized, controlled DIAPERIO trial. AB - BACKGROUND: Periodontitis is a common, chronic inflammatory disease caused by gram-negative bacteria leading to destruction of tissues supporting the teeth. Epidemiological studies have consistently shown increased frequency, extent and severity of periodontitis among diabetic adults. More recently, some controlled clinical trials have also suggested that periodontal treatment could improve glycaemic control in diabetic patients. However current evidence does not provide sufficient information on which to confidently base any clinical recommendations. The main objective of this clinical trial is to assess whether periodontal treatment could lead to a decrease in glycated haemoglobin levels in metabolically unbalanced diabetic patients suffering from chronic periodontitis. METHODS: The DIAPERIO trial is an open-label, 13-week follow-up, randomized, controlled trial. The total target sample size is planned at 150 participants, with a balanced (1:1) treatment allocation (immediate treatment vs delayed treatment). Periodontal treatment will include full mouth non-surgical scaling and root planing, systemic antibiotherapy, local antiseptics (chlorhexidine 0.12%) and oral health instructions. The primary outcome will be the difference in change of HbA1c between the two groups after the 13-weeks' follow-up. Secondary outcomes will be the difference in change of fructosamine levels and quality of life between the two groups. DISCUSSION: The DIAPERIO trial will provide insight into the question of whether periodontal treatment could lead to an improvement in glycaemic control in metabolically unbalanced diabetic patients suffering from periodontitis. The results of this trial will help to provide evidence-based recommendations for clinicians and a draft framework for designing national health policies. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15334496. PMID- 19646282 TI - Surgical outcome after spinal fractures in patients with ankylosing spondylitis. AB - BACKGROUND: Ankylosing spondylitis is a rheumatic disease in which spinal and sacroiliac joints are mainly affected. There is a gradual bone formation in the spinal ligaments and ankylosis of the spinal diarthroses which lead to stiffness of the spine.The diffuse paraspinal ossification and inflammatory osteitis of advanced Ankylosing spondylitis creates a fused, brittle spine that is susceptible to fracture. The aim of this study is to present the surgical experience of spinal fractures occurring in patients suffering from ankylosing spondylitis and to highlight the difficulties that exist as far as both diagnosis and surgical management are concerned. METHODS: Twenty patients suffering from ankylosing spondylitis were operated due to a spinal fracture. The fracture was located at the cervical spine in 7 cases, at the thoracic spine in 9, at the thoracolumbar junction in 3 and at the lumbar spine in one case. Neurological defects were revealed in 10 patients. In four of them, neurological signs were progressively developed after a time period of 4 to 15 days. The initial radiological study was negative for a spinal fracture in twelve patients. Every patient was assessed at the time of admission and daily until the day of surgery, then postoperatively upon discharge. RESULTS: Combined anterior and posterior approaches were performed in three patients with only posterior approaches performed on the rest. Spinal fusion was seen in 100% of the cases. No intra operative complications occurred. There was one case in which superficial wound inflammation occurred. Loosening of posterior screws without loss of stability appeared in two patients with cervical injuries. Frankel neurological classification was used in order to evaluate the neurological status of the patients. There was statistically significant improvement of Frankel neurological classification between the preoperative and postoperative evaluation. 35% of patients showed improvement due to the operation performed. CONCLUSION: The operative treatment of these injuries is useful and effective. It usually succeeds the improvement of the patients' neurological status. Taking into consideration the cardiovascular problems that these patients have, anterior and posterior stabilization aren't always possible. In these cases, posterior approach can be performed and give excellent results, while total operation time, blood loss and other possible complications are decreased. PMID- 19646283 TI - Optimized surgical techniques and postoperative care improve survival rates and permit accurate telemetric recording in exercising mice. AB - BACKGROUND: The laboratory mouse is commonly used as a sophisticated model in biomedical research. However, experiments requiring major surgery frequently lead to serious postoperative complications and death, particularly if genetically modified mice with anatomical and physiological abnormalities undergo extensive interventions such as transmitter implantation. Telemetric transmitters are used to study cardiovascular physiology and diseases. Telemetry yields reliable and accurate measurement of blood pressure in the free-roaming, unanaesthetized and unstressed mouse, but data recording is hampered substantially if measurements are made in an exercising mouse. Thus, we aimed to optimize transmitter implantation to improve telemetric signal recording in exercising mice as well as to establish a postoperative care regimen that promotes convalescence and survival of mice after major surgery in general. RESULTS: We report an optimized telemetric transmitter implantation technique (fixation of the transmitter body on the back of the mouse with stainless steel wires) for subsequent measurement of arterial blood pressure during maximal exercise on a treadmill. This technique was used on normal (wildtype) mice and on transgenic mice with anatomical and physiological abnormalities due to constitutive overexpression of recombinant human erythropoietin. To promote convalescence of the animals after surgery, we established a regimen for postoperative intensive care: pain treatment (flunixine 5 mg/kg bodyweight, subcutaneously, twice per day) and fluid therapy (600 microl, subcutaneously, twice per day) were administrated for 7 days. In addition, warmth and free access to high energy liquid in a drinking bottle were provided for 14 days following transmitter implantation. This regimen led to a substantial decrease in overall morbidity and mortality. The refined postoperative care and surgical technique were particularly successful in genetically modified mice with severely compromised physiological capacities. CONCLUSION: Recovery and survival rates of mice after major surgery were significantly improved by careful management of postoperative intensive care regimens including key supportive measures such as pain relief, administration of fluids, and warmth. Furthermore, fixation of the blood pressure transmitter provided constant reliable telemetric recordings in exercising mice. PMID- 19646284 TI - Mental health first aid for Indigenous Australians: using Delphi consensus studies to develop guidelines for culturally appropriate responses to mental health problems. AB - BACKGROUND: Ethnic minority groups are under-represented in mental health care services because of barriers such as poor mental health literacy. In 2007, the Mental Health First Aid (MHFA) program implemented a cultural adaptation of its first aid course to improve the capacity of Indigenous Australians to recognise and respond to mental health issues within their own communities. It became apparent that the content of this training would be improved by the development of best practice guidelines. This research aimed to develop culturally appropriate guidelines for providing first aid to an Australian Aboriginal or Torres Strait Islander person who is experiencing a mental health crisis or developing a mental illness. METHODS: A panel of Australian Aboriginal people who are experts in Aboriginal mental health, participated in six independent Delphi studies investigating depression, psychosis, suicidal thoughts and behaviours, deliberate self-injury, trauma and loss, and cultural considerations. The panel varied in size across the studies, from 2024 participants. Panellists were presented with statements about possible first aid actions via online questionnaires and were encouraged to suggest additional actions not covered by the survey content. Statements were accepted for inclusion in a guideline if they were endorsed by > or = 90% of panellists as essential or important. Each study developed one guideline from the outcomes of three Delphi questionnaire rounds. At the end of the six Delphi studies, participants were asked to give feedback on the value of the project and their participation experience. RESULTS: From a total of 1,016 statements shown to the panel of experts, 536 statements were endorsed (94 for depression, 151 for psychosis, 52 for suicidal thoughts and behaviours, 53 for deliberate self-injury, 155 for trauma and loss, and 31 for cultural considerations). The methodology and the guidelines themselves were found to be useful and appropriate by the panellists. CONCLUSION: Aboriginal mental health experts were able to reach consensus about culturally appropriate first aid for mental illness. The Delphi consensus method could be useful more generally for consulting Indigenous peoples about culturally appropriate best practice in mental health services. PMID- 19646286 TI - Development and experimental verification of a genome-scale metabolic model for Corynebacterium glutamicum. AB - BACKGROUND: In silico genome-scale metabolic models enable the analysis of the characteristics of metabolic systems of organisms. In this study, we reconstructed a genome-scale metabolic model of Corynebacterium glutamicum on the basis of genome sequence annotation and physiological data. The metabolic characteristics were analyzed using flux balance analysis (FBA), and the results of FBA were validated using data from culture experiments performed at different oxygen uptake rates. RESULTS: The reconstructed genome-scale metabolic model of C. glutamicum contains 502 reactions and 423 metabolites. We collected the reactions and biomass components from the database and literatures, and made the model available for the flux balance analysis by filling gaps in the reaction networks and removing inadequate loop reactions. Using the framework of FBA and our genome-scale metabolic model, we first simulated the changes in the metabolic flux profiles that occur on changing the oxygen uptake rate. The predicted production yields of carbon dioxide and organic acids agreed well with the experimental data. The metabolic profiles of amino acid production phases were also investigated. A comprehensive gene deletion study was performed in which the effects of gene deletions on metabolic fluxes were simulated; this helped in the identification of several genes whose deletion resulted in an improvement in organic acid production. CONCLUSION: The genome-scale metabolic model provides useful information for the evaluation of the metabolic capabilities and prediction of the metabolic characteristics of C. glutamicum. This can form a basis for the in silico design of C. glutamicum metabolic networks for improved bioproduction of desirable metabolites. PMID- 19646285 TI - Proteomic-based identification of maternal proteins in mature mouse oocytes. AB - BACKGROUND: The mature mouse oocyte contains the full complement of maternal proteins required for fertilization, reprogramming, zygotic gene activation (ZGA), and the early stages of embryogenesis. However, due to limitations of traditional proteomics strategies, only a few abundantly expressed proteins have yet been identified. Our laboratory applied a more effective strategy: one dimensional sodium dodecyl sulfate polyacrylamide gel electrophoresis (1D SDS PAGE) and reverse-phase liquid chromatography tandem mass spectrometry (RP-LC MS/MS) were employed to analyze the mature oocyte proteome in depth. RESULTS: Using this high-performance proteomic approach, we successfully identified 625 different proteins from 2700 mature mouse oocytes lacking zona pellucidae. This is the largest catalog of mature mouse oocyte proteins compiled to date. According to their pattern of expression, we screened 76 maternal proteins with high levels of mRNA expression both in oocytes and fertilized eggs. Many well known maternal effect proteins were included in this subset, including MATER and NPM2. In addition, our mouse oocyte proteome was compared with a recently published mouse embryonic stem cell (ESC) proteome and 371 overlapping proteins were identified. CONCLUSION: This proteomics analysis will be a valuable resource to aid in the characterization of important maternal proteins involved in oogenesis, fertilization, early embryonic development and in revealing their mechanisms of action. PMID- 19646287 TI - The Queensland experience of participation in a national drug use evaluation project, Community-Acquired Pneumonia Towards Improving Outcomes Nationally (CAPTION). AB - BACKGROUND: Multicentre drug use evaluations are described in the literature infrequently and usually publish only the results. The purpose of this paper is to describe the experience of Queensland hospitals participating in the Community Acquired Pneumonia Towards Improving Outcomes Nationally (CAPTION) project, specifically evaluating the implementation of this project, detailing benefits and drawbacks of involvement in a national drug use evaluation program. METHODS: Emergency departments from nine hospitals in Queensland, Australia, participated in CAPTION, a national quality improvement project, conducted in 37 Australian hospitals. CAPTION was aimed at optimising prescribing in the management of Community-Acquired Pneumonia according to the recommendations of the Australian Therapeutic Guidelines: Antibiotic 12th edition. The project involved data collection, and evaluation, feedback of results and a suite of targeted educational interventions including audit and feedback, group presentations and academic detailing.A baseline audit and two drug use evaluation cycles were conducted during the 2-year project. The implementation of the project was evaluated using feedback forms after each phase of the project (audit or intervention). At completion a group meeting with the hospital coordinators identified positive and negative elements of the project. RESULTS: Evaluation by hospitals of their participation in CAPTION demonstrated both benefits and drawbacks. The benefits were grouped into the impact on the hospital dynamic such as; improved interdisciplinary working relationships (e.g. between pharmacist and doctor), recognition of the educational/academic role of the pharmacist, creation of ED Pharmacist positions and enhanced involvement with the National Prescribing Service, and personal benefits. Personal benefits included academic detailing training for participants, improved communication skills and opportunities to present at conferences. The principal drawback of participation was the extra burden on already busy staff members. CONCLUSION: A national multicentre drug use evaluation project such as CAPTION allows hospitals which would otherwise not undertake such projects the opportunity to participate. The Queensland arm of CAPTION demonstrated benefits to both the individual participants and their hospitals, highlighting the additional value of participating in a multicentre project of this type. PMID- 19646288 TI - Pulmonary tuberculosis among women with cough attending clinics for family planning and maternal and child health in Dar Es Salaam, Tanzania. AB - BACKGROUND: Tuberculosis (TB) case detection in women has remained low in developing world. This study was conducted to determine the proportion of smear positive TB among women with cough regardless of the duration attending family Planning (FP) and Maternal and child health (MCH) clinics in Dar es Salaam. METHODS: We conducted a cross sectional study in all three municipal hospitals of Dar es Salaam, between October 2007 and June 2008. All women with cough attending FP and MCH clinics were screened for TB by smear microscopy. Pearson chi-square was used to compare group difference for categorical variables. Risk factors for smear positive were estimated by logistics regression with 95% confidence intervals (CI) given for odds ratios indicating statistically significant relationship if the CI did not include one. RESULTS: We enrolled a total of 749 TB suspects. Five hundred and twenty nine patients (70.6%) were from MCH clinics. Mean (SD) age was 27.6 (5.2) years. A total of 616 (82.2%) patients were coughing for less than two weeks as compared to 133 (17.8%), who coughed for two or more weeks. Among 616 TB suspects, 14 (2.3%) were smear positive TB patients, and of the 133 who had coughed for two or more weeks, 13 (9.8%) were smear positive TB patients. Risk factors associated with smear positive results were having attended more than one visit to any facility prior to diagnosis (OR = 6.8; 95%CI 2.57-18.0) and having HIV/AIDS (OR = 4.4; 95%CI 1.65-11.96). Long duration of cough was not a risk factor for being smear positive (OR = 1.6; 95%CI 0.59-4.49). CONCLUSION: The proportion of smear positive TB patients among women with cough attending MCH and FP was 3.8%. Visits to any health facility prior to Diagnosis and HIV infection were risk for having a smear positive TB. PMID- 19646289 TI - A theoretical model for analysing gender bias in medicine. AB - During the last decades research has reported unmotivated differences in the treatment of women and men in various areas of clinical and academic medicine. There is an ongoing discussion on how to avoid such gender bias. We developed a three-step-theoretical model to understand how gender bias in medicine can occur and be understood. In this paper we present the model and discuss its usefulness in the efforts to avoid gender bias. In the model gender bias is analysed in relation to assumptions concerning difference/sameness and equity/inequity between women and men. Our model illustrates that gender bias in medicine can arise from assuming sameness and/or equity between women and men when there are genuine differences to consider in biology and disease, as well as in life conditions and experiences. However, gender bias can also arise from assuming differences when there are none, when and if dichotomous stereotypes about women and men are understood as valid. This conceptual thinking can be useful for discussing and avoiding gender bias in clinical work, medical education, career opportunities and documents such as research programs and health care policies. Too meet the various forms of gender bias, different facts and measures are needed. Knowledge about biological differences between women and men will not reduce bias caused by gendered stereotypes or by unawareness of health problems and discrimination associated with gender inequity. Such bias reflects unawareness of gendered attitudes and will not change by facts only. We suggest consciousness-rising activities and continuous reflections on gender attitudes among students, teachers, researchers and decision-makers. PMID- 19646290 TI - Elongation Factor 1 alpha interacts with phospho-Akt in breast cancer cells and regulates their proliferation, survival and motility. AB - BACKGROUND: Akt/PKB is a serine/threonine kinase that has attracted much attention because of its central role in regulating cell proliferation, survival, motility and angiogenesis. Activation of Akt in breast cancer portends aggressive tumour behaviour, resistance to hormone-, chemo-, and radiotherapy-induced apoptosis and it is correlated with decreased overall survival. Recent studies have identified novel tumor-specific substrates of Akt that may provide new diagnostic and prognostic markers and serve as therapeutic targets. This study was undertaken to identify pAkt-interacting proteins and to assess their biological roles in breast cancer cells. RESULTS: We confirmed that one of the pAkt interacting proteins is the Elongation Factor EF1alpha. EF1alpha contains a putative Akt phosphorylation site, but is not phosphorylated by pAkt1 or pAkt2, suggesting that it may function as a modulator of pAkt activity. Indeed, downregulation of EF1alpha expression by siRNAs led to markedly decreased expression of pAkt1 and to less extent of pAkt2 and was associated with reduced proliferation, survival and invasion of HCC1937 cells. Proliferation and survival was further reduced by combining EF1alpha siRNAs with specific pAkt inhibitors whereas EF1alpha downregulation slightly attenuated the decreased invasion induced by Akt inhibitors. CONCLUSION: We show here that EF1alpha is a pAkt interacting protein which regulates pAkt levels. Since EF1alpha is often overexpressed in breast cancer, the consequences of EF1alpha increased levels for proliferation, survival and invasion will likely depend on the relative concentration of Akt1 and Akt2. PMID- 19646291 TI - Plant foods and the risk of cerebrovascular diseases: a potential protection of fruit consumption. AB - Studies on the association between plant foods and cerebrovascular diseases have given contradictory results suggesting the existence of some effect-modifying factors. The present study determines whether the consumption of plant foods (i.e. fruits and berries, vegetables, and cereals) predicts a decreased cerebrovascular disease incidence in a population with low fruit and vegetable and high wholegrain intake. This cohort study on 3932 men and women was based on data from the Finnish Mobile Clinic Health Examination Survey, conducted in 1968 72. The participants were 40-74 years of age and free of cardiovascular diseases at baseline. Data on the plant food consumption were derived from a 1-year dietary history interview. During a 24-year follow-up 625 cases of cerebrovascular diseases occurred, leading to either hospitalisation or death. An inverse association was found between fruit consumption and the incidence of cerebrovascular diseases, ischaemic stroke and intracerebral haemorrhage. The adjusted relative risks (RR) between the highest and lowest quartiles of intake of any cerebrovascular disease, ischaemic stroke and intracerebral haemorrhage were 0.75 (95 % CI 0.59, 0.94), 0.73 (95 % CI 0.54, 1.00) and 0.47 (95 % CI 0.24, 0.92), respectively. These associations were primarily due to the consumption of citrus fruits and occurred only in men. Total consumption of vegetables or cereals was not associated with the cerebrovascular disease incidence. The consumption of cruciferous vegetables, however, predicted a reduced risk of cerebrovascular diseases (RR 0.79; 95 % CI 0.63, 0.99), ischaemic stroke (RR 0.67; 95 % CI 0.49, 0.92) and intracerebral haemorrhage (RR 0.49; 95 % CI 0.25, 0.98). In conclusion, the consumption of fruits, especially citrus, and cruciferous vegetables may protect against cerebrovascular diseases. PMID- 19646292 TI - Dietary capsanthin, the main carotenoid in paprika (Capsicum annuum), alters plasma high-density lipoprotein-cholesterol levels and hepatic gene expression in rats. AB - The effects of dietary capsanthin, the main carotenoid in paprika (Capsicum annuum), on lipid metabolism were examined. Young male Wistar rats were fed diets containing paprika powder, paprika organic solvent extract, residue of paprika extract, and purified capsanthin. Administration of purified capsanthin for 2 weeks resulted in a significant increase in plasma HDL-cholesterol (P < 0.05) without detectable differences in plasma total cholesterol and TAG concentrations. A statistically significant correlation (r 0.567; P < 0.001) was found between dietary capsanthin concentrations and plasma HDL-cholesterol concentrations. Animals receiving diets containing two different capsanthin concentrations exhibited dose-dependent increases in plasma HDL-cholesterol (r 0.597; P < 0.005). While capsanthin was absent in the liver of animals fed the basal diet, it increased markedly in capsanthin-fed animals (P < 0.001). Quantitative analyses of hepatic mRNA levels revealed that capsanthin administration resulted in up-regulation of mRNA for apoA5 and lecithin cholesterol acyltransferase (LCAT), without significant differences in other mRNA levels related to HDL-cholesterol metabolism. These results suggest that capsanthin had an HDL-cholesterol-raising effect on plasma, and the potential to increase cholesterol efflux to HDL particles by increasing apoA5 levels and/or enhancement of LCAT activity. PMID- 19646293 TI - Marsupialisation and strap muscle transposition laryngoplasty for vocal cysts with vocal fold atrophy. AB - OBJECTIVES: Vocal cysts with fold atrophy often result in more severe glottal incompetence than vocal cysts along during phonation. Although total excision or marsupialisation are reliable treatments for vocal fold cysts, any post-operative vocal deficit with significant glottal gap will need further treatment. This study aimed to evaluate the efficacy of combined treatment consisting of marsupialisation of the cyst immediately followed by strap muscle transposition laryngoplasty. METHOD: Under direct laryngomicroscopy, microscissors were used to make a disc-shaped incision encircling the equator of the cyst. After marsupialisation of the cyst, a simultaneous medialisation laryngoplasty with strap muscle transposition was performed. RESULTS: Seven patients with vocal cysts and marked vocal fold atrophy were included in the study. After surgery, subjective improvement in voice quality was reported by all patients. Patients' glottal incompetence and vocal performance were markedly improved. CONCLUSION: Marsupialisation is a simple and effective surgical technique for vocal fold cysts. For cases of vocal cysts with marked vocal fold atrophy, marsupialisation followed by medialisation laryngoplasty with strap muscle transposition may be considered. PMID- 19646294 TI - An unusual presentation of inverted papilloma: case report and literature review. AB - OBJECTIVE: Inverted papilloma is a rare but locally aggressive tumour with the potential for malignant transformation. Intracranial extension or complications secondary to inverted papilloma are extremely rare. We report a case of inverted papilloma with a large frontal sinus mucocele eroding the frontal sinus, which presented with sudden neurological compromise. A literature review on intracranial extension of such tumours is also included. METHODS: A Medline search of articles, using the terms 'inverted papilloma', 'Ringertz tumour', 'intracranial extension' and 'complication'. Suitable references from the collected articles were also reviewed. Articles published in English were selected and reviewed. RESULTS: A total of 10 cases was identified. Intracranial spread was more commonly seen in recurrent cases, especially if the recurrence involved the cribriform plate, fovea ethmoidalis or orbits. Cases with extradural disease seemed to have a better prognosis than those with intradural spread. CONCLUSIONS: Intracranial involvement of inverted papilloma is extremely rare, and is usually seen in recurrent cases. This case report highlights an unusual but serious case of inverted papilloma presenting with acute neurological deterioration secondary to a large frontal sinus mucocele eroding the frontal sinus. A literature review on intracranial extension of inverted papilloma indicated that common sites of intracranial spread include the cribriform plate, fovea ethmoidalis and orbits. The prognosis for patients with such tumours depends on the type of dural involvement, with intradural extension carrying a poorer prognosis. PMID- 19646295 TI - Semicircular canal versus otolithic involvement in idiopathic sudden hearing loss. AB - OBJECTIVE: To evaluate the results of vestibular evoked myogenic potential testing in patients with idiopathic sudden hearing loss, and to correlate these results with the findings of caloric testing, the clinical appearance of vertigo and the influence of age. MATERIALS AND METHODS: Eighty-six patients with unilateral idiopathic sudden hearing loss and 35 healthy controls underwent a standard protocol of neurotological evaluation. Vestibular evoked myogenic potential responses were measured and compared with caloric responses. RESULTS: On the affected side, 30.2 per cent of patients showed abnormal vestibular evoked myogenic potential responses, while 52.3 per cent had abnormal caloric responses. A statistically significant relationship was found between the results of these two tests. A statistically significant relationship was also found between the type of vestibular lesion and the occurrence of vertigo. Advancing age correlated statistically with more extensive labyrinthic lesions. CONCLUSIONS: A combination of vestibular evoked myogenic potential and electronystagmography testing indicated the existence of vestibular involvement in many patients with idiopathic sudden hearing loss. Both tests are necessary in order to obtain a more thorough and in-depth knowledge of the pathophysiology of idiopathic sudden hearing loss. PMID- 19646296 TI - Spontaneous pneumomediastinum: benefits of contrast computed tomography imaging. AB - OBJECTIVE: We report a case of spontaneous pneumomediastinum presenting with chest and anterior neck pain. METHOD: The clinical findings, differential diagnosis and selection of radiological investigations are discussed. RESULTS: Spontaneous pneumomediastinum is an uncommon condition usually presenting in young patients. Presentation to the otolaryngology department occurs due to the presence of symptoms such as neck pain. Differential diagnoses must be considered and excluded, using the clinical features and the results of radiological investigation. Once the diagnosis is confirmed, conservative management is undertaken. CONCLUSION: Spontaneous pneumomediastinum is uncommon and the clinical features are variable. The recommended investigation is a computed tomography scan with orally administered, water soluble contrast to exclude important differential diagnoses and thus enable definitive diagnosis. PMID- 19646297 TI - Tuberculous cervical lymphadenitis in a patient with laryngeal carcinoma. AB - OBJECTIVE: We report an extremely rare presentation of concomitant tuberculous cervical lymphadenitis in a patient with carcinoma of the larynx. CASE REPORT: A 66-year-old man presented with a nine-month history of hoarseness. He was found to have an exophytic lesion over the posterior half of the right vocal fold. He also had a palpable right jugulodigastric node. Biopsy of the vocal fold lesion revealed invasive squamous cell carcinoma. Histological analysis of an excision biopsy specimen from the lymph node was highly suggestive of tuberculosis. On further assessment of the slides, one acid-fast bacillus was seen. The patient was treated with radiotherapy to the larynx and concomitant anti-tuberculosis chemotherapy. Five months following treatment, there was no sign of laryngeal cancer recurrence; however, the patient continued to have a productive cough and night sweats. CONCLUSION: To our knowledge, this is the first report of a laryngeal carcinoma with concurrent tuberculous cervical lymphadenitis. In the face of an unhelpful fine needle aspiration cytology examination, an assumption of metastatic neck disease could have been made. Subsequent surgical and/or oncological intervention would have been highly inappropriate, with potentially catastrophic effects. This case highlights the importance of proper diagnosis, and emphasises the fact that tuberculosis should always be borne in mind in the differential diagnosis. PMID- 19646298 TI - Septotomy: a useful approach to the anterior maxillary sinus. AB - In endonasal surgery, approaching the anterior maxillary wall via the ipsilateral nostril is difficult. It is necessary to have good visual and instrument control when removing lesions such as inverted papilloma. We describe an approach through a temporary septotomy which provides good access from the contralateral nostril. The contralateral mucoperichondrial incision is anterior and the ipsilateral one posterior. The cartilage is hinged superiorly. There is minimal chance of perforation. PMID- 19646299 TI - Treatment results for ethmoid sinus carcinoma. AB - OBJECTIVE: The aim of this study was to describe the results of treatment in patients with ethmoid sinus carcinoma. MATERIALS AND METHOD: We performed a retrospective study of 34 patients with carcinoma of the ethmoid sinus, and collected the following data: age, sex, employment, tobacco and alcohol consumption, tumour-node-metastasis stage, treatment, and survival. RESULTS: The mean patient age was 64 years. Seventy-six per cent of patients were men and 24 per cent women. Squamous cell carcinoma was the most frequent histological tumour type (44 per cent). Eleven patients were classified as T(2), six as T(3), six as T(4a) and 11 as T(4b). Two patients (6 per cent) had nodal metastasis at the time of diagnosis. The anterior skull base was involved in 17 patients (50 per cent) and the anterior orbital contents were affected in seven patients (21 per cent). The five-year actuarial observed survival rate for all patients was 44 per cent. CONCLUSIONS: Combined treatment with surgery and post-operative radiotherapy permitted good local control in patients with ethmoid sinus carcinoma. We do not recommend prophylactic neck treatment for ethmoid sinus carcinoma. PMID- 19646300 TI - Intracranial hypertension secondary to sigmoid sinus compression by group A streptococcal epidural abscess. AB - OBJECTIVE: We present an extremely rare case of severe intracranial hypertension secondary to sigmoid sinus compression by a group A streptococcal epidural abscess. METHOD: Case report and review of the world literature. RESULTS: A five year-old boy was treated for acute otitis media and group A streptococcal bacteraemia, but subsequently developed severe intracranial hypertension. Computed tomography revealed that, although the sigmoid sinuses were not thrombosed, the patient had a dominant right sigmoid sinus that was almost completely compressed by a small epidural abscess. After surgical decompression of the epidural abscess, with aggressive debridement of the granulation tissue from the sigmoid sinus wall, the patient awoke from general anaesthesia with complete resolution of his symptoms and signs of intracranial hypertension. He suffered no sequelae over the subsequent six months' follow up. CONCLUSION: This is the first reported case of intracranial hypertension due to an epidural abscess causing sigmoid sinus compression without thrombosis. This case illustrates the fact that, even in the absence of thrombosis of the sigmoid sinus, a small epidural abscess may require urgent surgical treatment. PMID- 19646301 TI - Congenital cholesteatoma of the infratemporal fossa. AB - OBJECTIVE: We report an extremely rare case of congenital cholesteatoma of the infratemporal fossa. METHOD: The clinical, radiological and intra-operative findings of the patient are presented. RESULTS: A five-year-old girl presented to our hospital with symptoms in the left ear consistent with middle-ear effusion. A congenital cholesteatoma was not suspected until an enlarging mass in the anteroinferior quadrant of the tympanic membrane was observed. Radiological studies revealed that the mass was located largely in the infratemporal fossa, with limited extension into the tympanic cavity. The patient underwent surgical treatment, which confirmed the clinical and radiological findings. CONCLUSION: This patient's clinical, radiological and intra-operative findings strongly suggested the infratemporal fossa as the site of origin of her congenital cholesteatoma. PMID- 19646302 TI - Polypoid intranasal mass caused by Rosai-Dorfman disease: a diagnostic pitfall. AB - BACKGROUND: Rosai-Dorfman disease is a rare, idiopathic, histiocytic proliferative disorder with a distinctive microscopic appearance, which was formerly thought to be a disease process limited to lymph nodes. However, extranodal involvement has been documented in less than half of the reported patients, but rarely without associated lymphadenopathy. CASE REPORT: We report the case of a 43-year-old Senegalese woman who presented with a polypoid, intranasal mass caused by Rosai-Dorfman disease. A diagnosis of a granulomatous process, including rhinoscleroma, was initially discussed. The correct diagnosis was made histologically by demonstrating aggregates of histiocytes with large amounts of cytoplasm, emperipolesis and protein S100 antigen expression. Despite using ancillary methods (molecular biology and electron microscopy), we failed to demonstrate any associated pathogen. CONCLUSION: Diagnosis of Rosai-Dorfman disease can be very difficult, in particular in adults from Africa with pure, isolated, intranasal localisation, in whom clinical and radiological features may mimic other infectious or neoplastic disorders. The diagnosis is made based on the histological presence of large histiocytes with lymphophagocytosis. Moreover, immunohistochemical analysis of these histiocytes using anti-protein S100 antibody shows strong positivity. PMID- 19646303 TI - Leishmania major H-line attenuated under pressure of gentamicin, induces a Th1 response which protects susceptible BALB/c mice against infection with virulent L. major. AB - An attenuated line of Leishmania major (L. major H-line) has been established by culturing promastigotes in vitro under gentamicin pressure. A modification of the previously described method for the generation of attenuated L. major is described, giving rise to attenuated parasites after 8 rather than 12 subpassages. No lesions developed in BALB/c mice infected with L. major H-line, whereas L. major wild-type (WT) induced a Th2 like response with progressive lesions. Analysis of splenocyte IFN-gamma and IL-4 production following stimulation with promastigotes shows that the L. major H-line preferentially induces Th1-like responses and possibly down-regulates Th2 responses in BALB/c mice. L. major H-line parasites remained localized in the skin and draining lymph node, whereas L. major WT parasites disseminated into the visceral organs of BALB/c mice. Mice infected with L. major H-line acquired some resistance against L. major WT. These results show that the attenuated cell line of L. major is not only avirulent but that it may also modulate the host immune response. PMID- 19646304 TI - Schistosoma mansoni cercariae experience influx of macromolecules during skin penetration. AB - We have observed that when cercariae penetrate the skin of mice, there is influx into their tissues of Lucifer Yellow and certain labelled molecules of up to 20 kDa molecular weight. This observation was made using a variety of fluorescent membrane-impermeant compounds injected into the skin before the application of cercariae. This unexpected phenomenon was investigated further by transforming cercariae in vitro in the presence of the membrane-impermeant compounds and examining the distribution by microscopy. In schistosomula derived from this procedure, the nephridiopore and surface membrane were labelled while the pre- and post-acetabular glands were not labelled. The region associated with the oesophagus within the pharyngeal muscle clearly contained the fluorescent molecules, as did the region adjacent to the excretory tubules and the germinal mass. We used cercariae stained with carmine to aid identification of regions labelled with Lucifer Yellow. Although the mechanism of this influx is unclear, the observation is significant. From it, we can suggest an hypothesis that, during skin penetration, exposure of internal tissues of the parasite to external macromolecules represents a novel host-parasite interface. PMID- 19646305 TI - The malaria merozoite, forty years on. AB - The invasive blood stage of malaria parasites, merozoites, are complex entities specialized for the capture and entry of red blood cells. Their potential for vaccination and other anti-malaria strategies have attracted much research attention over the last 40 years, and there is now a considerable body of data relating to their biology. In this article some of the major advances over this period and remaining challenges are reviewed. PMID- 19646306 TI - Parasite communities of a fish assemblage from the intertidal rocky zone of central Chile: similarity and host specificity between temporal and resident fish. AB - The different species of a fish assemblage can, to some extent, be similar in terms of their parasite communities, which can be associated with certain ecological host traits. This study compared the parasite community descriptors between temporal and resident fish species composing an intertidal assemblage from central Chile. Host specificity and similarity indices of parasite communities among the fish species were also considered. A total of 1097 fish representing 14 species were collected during spring and summer of 2 consecutive years. A total spectrum of 40 parasite species was found, of which copepods and trematodes were the commonest. Congeneric fish species had the highest similarities in their parasite communities. Based on a cluster analysis, using only some fish species, no group was distinguished using abundance or prevalence of parasites, because 50% of parasite species had high host specificity and only few of them were shared among fish species. Adult parasites showed high host specificity and were found mainly in resident intertidal fish, whereas the temporal fish had parasites with different degrees of specificity. Consequently, resident intertidal fish were characterized by their own parasite species, meaning that their transmissions might be restricted to the intertidal zone. PMID- 19646307 TI - Rapid diagnostic multiplex PCR (RD-PCR) to discriminate Schistosoma haematobium and S. bovis. AB - Schistosoma haematobium and S. bovis are widespread schistosome species causing human and cattle schistosomiasis, respectively, in Africa. The sympatric occurrence of these two species and their ability to infect the same Bulinus intermediate snail hosts necessitates precise methods of identification of the larval stages. A rapid diagnostic 'mulitplex' one-step polymerase chain reaction protocol (RD-PCR) was developed using cytochrome oxidase subunit 1 (COX1) mitochondrial DNA (mtDNA) to discriminate between S. haematobium and S. bovis. A single forward primer and two species-specific reverse primers were used to produce a polymerase chain reaction (PCR) fragment of 306 bp and 543 bp for S. bovis and S. haematobium, respectively. Serial dilutions were carried out on various lifecycle stages and species combinations to test the sensitivity and specificity of the primers. This RD-PCR proved highly sensitive, detecting a single larval stage and as little as 0.78 ng of genomic DNA (gDNA) from an adult schistosome, providing a cost-effective, rapid and robust molecular tool for high throughput screening of S. haematobium and S. bovis populations. In areas where human and cattle schistosomiasis overlap and are transmitted in close proximity, this mitochondrial assay will be a valuable identification tool for epidemiological studies, especially when used in conjunction with other nuclear diagnostic markers. PMID- 19646308 TI - Staphylococcus aureus is the most common identified cause of cellulitis: a systematic review. AB - We utilized Medline to perform a systematic review of the literature to quantify the aetiology of cellulitis with intact skin. Of 808 patients with cellulitis, 127-129 (15.7-16.0%) patients had positive needle aspiration and/or punch biopsy cultures from intact skin. Of the patients with positive cultures, 65 (50.4 51.2%) had cultures positive for Staphylococcus aureus, 35 (27.1-27.6%) for group A streptococcus, and 35-37 (27.1-29.1%) for other pathogens. The most common aetiology of cellulitis with intact skin, when it can be determined, is S. aureus, outnumbering group A streptococcus by a ratio of nearly 2:1. Given the increasing incidence of community-associated methicillin-resistant S. aureus infections, our findings may have critical therapeutic implications. PMID- 19646309 TI - Extramammary Paget's disease of the vulva. PMID- 19646311 TI - Vaginal breech delivery guideline: the time has come. PMID- 19646314 TI - Diffusion MRI brain findings in neonates exposed to chorioamnionitis: a case series. AB - OBJECTIVE: The primary objective of this study was to determine the feasibility of using diffusion-weighted magnetic resonance imaging (DWMRI) to assess white matter changes in high-risk neonates. Secondary objectives were to determine if exposure to chorioamnionitis (clinical or histopathologic) is associated with DWMRI findings in the neonatal brain, and to calculate the sample size required for a more definitive prospective cohort study. METHODS: Seventeen women with PPROM (preterm premature rupture of the membranes) who delivered 18 infants not requiring ventilatory support were recruited to participate in this case series. When stable, infants underwent DWMRI scanning. All placentas were examined for evidence of histopathologic chorioamnionitis (HCA). RESULTS: There was histopathologic evidence of chorioamnionitis in seven of the 18 placentas examined; three of these patients had clinical chorioamnionitis. Diffusion MRI revealed changes in both the diffusion-weighted imaging and the apparent diffusion coefficient in three of the seven infants confirmed to have HCA (43%), while only one of the 11 infants with normal placentas (9%) showed similar findings. Routine head ultrasound examination demonstrated abnormal cortical findings that would normally prompt further investigation in only one of these infants. CONCLUSION: Exposure to HCA may be associated with abnormal DWMRI findings on imaging of the neonatal brain within 96 hours of delivery. Further study is required to delineate the association of chorioamnionitis and white matter changes with long-term neurodevelopmental sequelae. PMID- 19646313 TI - Pregnancy outcomes in diabetes subtypes: how do they compare? A province-based study of Ontario, 2005-2006. AB - OBJECTIVE: To ascertain differences in pregnancy outcomes between women with diabetes subtypes (type 1 [DM1], type 2 [DM2], women with gestational [GDM])] and non-diabetic women within a large Canadian population. METHODS: We performed a retrospective multi-cohort analysis of all obstetrical deliveries that occurred in the province of Ontario between April 1, 2005, and March 31, 2006. Data were extracted from the Ontario Niday Perinatal Database. RESULTS: Increased rates of major negative maternal and perinatal outcomes (i.e. preterm delivery, Caesarean section, pregnancy-induced hypertension/preeclampsia) occurred in women with DM1. Both DM1 and GDM subtypes were associated with the greatest risk of macrosomia, shoulder dystocia, and congenital anomalies. DM2 did not demonstrate an association with an increased risk of congenital malformations and stillbirth. CONCLUSION: Diabetes in pregnancy, irrespective of subtype, predisposes women to poorer outcomes than those of the general obstetric population. However, this large population analysis is consistent with previous studies in showing that the adversity remains greatest for women with type 1 diabetes. PMID- 19646315 TI - Educational intervention for obstetrical nurses: introducing intravenous fentanyl to the labour floor. AB - OBJECTIVE: To determine the efficacy of an educational intervention in changing nurses' satisfaction and comfort with and their knowledge and use of a newly introduced analgesic agent, fentanyl, to manage pain during labour. METHODS: A written survey was completed by 19 labour and delivery nurses before and after the educational intervention in a small Northern Canadian city. RESULTS: Prior to the educational intervention, respondents rated their knowledge of and comfort with use of morphine and meperidine as significantly greater than their knowledge of and comfort with use of fentanyl (P<0.001 for all comparisons). Following the educational intervention, their knowledge and comfort with use of fentanyl increased to the same level as their knowledge and comfort with use of morphine and meperidine. Knowledge of and comfort with use of morphine and meperidine did not change after the educational intervention, but with use of fentanyl there was a significant increase in both knowledge (P<0.001) and comfort (P<0.001). Use of fentanyl subsequently increased significantly (P=0.016) and the nurses identified fewer barriers to its use. Satisfaction with (and self-reported use of) fentanyl also increased (P=0.001). CONCLUSION: Participation in education regarding fentanyl increased nurses' knowledge of and comfort and satisfaction with this agent. It also contributed to an increase in the use of this agent, which has been documented to be safer than other narcotics for both mother and baby. PMID- 19646316 TI - Pfannenstiel incision closure: a review of current skin closure techniques. AB - The goal of any skin closure technique is to produce appropriate skin approximation and adequate healing while minimizing pain, wound complications, cost, and scarring; the technique should be quick, cost-effective, and simple, while maximizing wound cosmesis and patient satisfaction. Although many studies have shown the superiority of staples for speed of closure, it is unclear if staples give a superior cosmetic result or reduce pain. Several randomized controlled trials have found that sutures are superior for cosmesis and that they decrease postoperative pain and are more cost-effective. There remains a paucity of data on wound infections and complications associated with closure technique. This review summarizes studies to date evaluating outcomes associated with wound closure using staples and sutures in repairing abdominal incisions and, in particular, assesses outcomes in the obstetric population with a Pfannenstiel incision. PMID- 19646317 TI - Changing practice from laparoscopic supracervical hysterectomy to total hysterectomy. AB - OBJECTIVE: To compare morbidity and mortality related to laparoscopic supracervical hysterectomy (LASH) and laparoscopic total hysterectomy (LTH). METHODS: We reviewed the medical records of 227 patients who underwent laparoscopic hysterectomy for benign gynaecological diseases between January 2004 and March 2008. Before January 2006, we performed mainly LASH (n: 122), and from January 2006 we performed LTH (n: 105). We reviewed and compared operating times, requirement for narcotics, duration of hospital stay, and complications of the two procedures. RESULTS: The mean age of the patients in the LASH group was 45.7+/-0.6 years, and in the LTH group was 45.9+/-0.7 years. Patients in each group were comparable in mean body mass index and preoperative hemoglobin concentration. There were no differences in the duration of hospital stay or mean postoperative hemoglobin concentration. Patients in the LASH group had a shorter mean operating time than the LTH group (111.0+/-2.9 vs. 136+/-3.6 minutes; 95% CI 16-33, P<0.001), but the patients in the LASH group required a greater mean dose of narcotic than those in the LTH group (28.0+/-2.9 mg of morphine or morphine equivalent vs. 37.5+/-3.4 mg; 95% CI 1.5-10.5, P=0.02). There was no difference between the two groups in the incidence of major and minor complications. However, five patients in the LASH group required a repeat operation, but none of the LTH group did. CONCLUSION: Laparoscopic total hysterectomy is associated with a longer operating time than laparoscopic supracervical hysterectomy, but with less need for postoperative narcotics. PMID- 19646318 TI - Accuracy of bladder scanning in the assessment of postvoid residual volume. AB - OBJECTIVE: To compare the accuracy of the 3D portable ultrasound with catheterization in the assessment of postvoid residual (PVR) urine volume among women in the urogynaecology clinic. METHODS: A prospective study was performed, assessing 101 women. After the patient voided four ultrasound (US) assessments were carried out using the BladderScan BVI 3000; the patient was then catheterized. The reproducibility of the US measurements and the difference between the two methods were assessed using Bland and Altman plots. The strength of the relationship was measured by a simple Pearson correlation coefficient. RESULTS: The results showed that 3D scanner measurements were highly reproducible and were also found to correlate significantly with catheterized volume (r=0.79, 95% CI 0.70-0.85, P<0.001). The mean difference between the two methods was 12.9 mL (95% CI 5.5-20.2 mL, P<0.001). CONCLUSION: In determining PVR volumes, the portable ultrasound BladderScan BVI 3000 is an accurate alternative to bladder catheterization. PMID- 19646319 TI - Umbilical cord hernia mimicking a cord teratoma. AB - BACKGROUND: Most umbilical cord masses detected by sonography are angiomyxomas, hematomas, or teratomas. Cord teratomas arise from totipotent stem cells and contain tissue from the three germ-cell layers. Tumour components are foreign to surrounding tissue and may have a polymorphic presentation. CASE: We report a case of a suspected umbilical cord teratoma, identified by sonographic and magnetic resonance imaging, which in fact camouflaged an umbilical cord hernia. The natural history of an omphalocele and umbilical cord hernia dictates the presence of such anterior abdominal wall defects by approximately 12 weeks' gestation, once the gut returns from the peritoneal space within the umbilical stalk to the peritoneal cavity. Adipose tissue is not described as a classic finding in an omphalocele or umbilical cord hernia. CONCLUSION: Our case of umbilical cord hernia is the first described as strictly distal to, and not contained within, the abdominal wall cord insertion site, and to contain fat, thereby mimicking a cord teratoma. PMID- 19646320 TI - Malignant chest wall endometriosis: a case report and literature review. AB - BACKGROUND: Endometriosis usually affects women in their reproductive years. Most commonly, the pelvic organs are involved. Involvement of the chest wall after hysterectomy is rare. The incidence of malignant transformation is less than 1% for ovarian endometriosis, but is unknown for extraovarian endometriosis. CASE: A 47-year-old woman who had undergone hysterectomy and bilateral salpingo oophorectomy for endometriosis presented four years after surgery with a well differentiated endometrioid adenocarcinoma arising in the background of endometriosis in the right chest wall. The tumour was resected, and the patient received six courses of adjuvant chemotherapy. CONCLUSION: Women with endometriosis-associated cancer require individualized management options, depending upon the histopathology and stage of the cancer. PMID- 19646321 TI - Probiotic safety in pregnancy: a systematic review and meta-analysis of randomized controlled trials of Lactobacillus, Bifidobacterium, and Saccharomyces spp. AB - Our objective in this study was to review systematically the evidence for safety of Lactobacillus, Bifidobacterium and Saccharomyces spp. during pregnancy and to conduct a meta-analysis of randomized controlled trials (RCTs). Eleven databases were searched from inception to September 2007 for RCTs of probiotic use during pregnancy. Two independent reviewers searched databases. Random-effects models combined data. Eleven studies on Lactobacillus and/or Bifidobacterium examined 1505 patients for four outcomes with no data heterogeneity; no miscarriage data were reported. Five studies reported Caesarean section outcomes (OR 0.88; 95% CI 0.65 to 1.19). Six studies reported birth weight (weighted difference 45 g; 95% CI -181 to 271). Three studies reported gestational age (weighted difference 0.4 weeks; 95%CI -0.4 to 1.2). No malformations were reported in the probiotic group. No RCTs were available for Saccharomyces during pregnancy. Lactobacillus and Bifidobacterium had no effect on the incidence of Caesarean section, birth weight, or gestational age. The safety of Saccharomyces during pregnancy is unknown. PMID- 19646322 TI - Breech birth can be safe, but is it worth the effort? PMID- 19646324 TI - Vaginal delivery of breech presentation. AB - OBJECTIVES: To review the physiology of breech birth; to discern the risks and benefits of a trial of labour versus planned Caesarean section; and to recommend to obstetricians, family physicians, midwives, obstetrical nurses, anaesthesiologists, pediatricians, and other health care providers selection criteria, intrapartum management parameters, and delivery techniques for a trial of vaginal breech birth. OPTIONS: Trial of labour in an appropriate setting or delivery by pre-emptive Caesarean section for women with a singleton breech fetus at term. OUTCOMES: Reduced perinatal mortality, short-term neonatal morbidity, long-term infant morbidity, and short- and long-term maternal morbidity and mortality. EVIDENCE: Medline was searched for randomized trials, prospective cohort studies, and selected retrospective cohort studies comparing planned Caesarean section with a planned trial of labour; selected epidemiological studies comparing delivery by Caesarean section with vaginal breech delivery; and studies comparing long-term outcomes in breech infants born vaginally or by Caesarean section. Additional articles were identified through bibliography tracing up to June 1, 2008. VALUES: The evidence collected was reviewed by the Maternal Fetal Medicine Committee of the Society of Obstetricians and Gynaecologists of Canada (SOGC) and quantified using the criteria and classifications of the Canadian Task Force on Preventive Health Care. VALIDATION: This guideline was compared with the 2006 American College of Obstetrician's Committee Opinion on the mode of term singleton breech delivery and with the 2006 Royal College of Obstetrician and Gynaecologists Green Top Guideline: The Management of Breech Presentation. The document was reviewed by Canadian and International clinicians with particular expertise in breech vaginal delivery. SPONSORS: The Society of Obstetricians and Gynaecologists of Canada. SUMMARY STATEMENTS: 1. Vaginal breech birth can be associated with a higher risk of perinatal mortality and short-term neonatal morbidity than elective Caesarean section. (I) 2. Careful case selection and labour management in a modern obstetrical setting may achieve a level of safety similar to elective Caesarean section. (II-1) 3. Planned vaginal delivery is reasonable in selected women with a term singleton breech fetus. (I) 4. With careful case selection and labour management, perinatal mortality occurs in approximately 2 per 1000 births and serious short-term neonatal morbidity in approximately 2% of breech infants. Many recent retrospective and prospective reports of vaginal breech delivery that follow specific protocols have noted excellent neonatal outcomes. (II-1) 5. Long term neurological infant outcomes do not differ by planned mode of delivery even in the presence of serious short-term neonatal morbidity. (I) RECOMMENDATIONS: LABOUR SELECTION CRITERIA: 1. For a woman with suspected breech presentation, pre or early labour ultrasound should be performed to assess type of breech presentation, fetal growth and estimated weight, and attitude of fetal head. If ultrasound is not available, Caesarean section is recommended. (II-1A) 2. Contraindications to labour include a. Cord presentation (II-3A) b. Fetal growth restriction or macrosomia (I-A) c. Any presentation other than a frank or complete breech with a flexed or neutral head attitude (III-B) d. Clinically inadequate maternal pelvis (III-B) e. Fetal anomaly incompatible with vaginal delivery (III-B) 3. Vaginal breech delivery can be offered when the estimated fetal weight is between 2500 g and 4000 g. (II-2B) LABOUR MANAGEMENT: 4. Clinical pelvic examination should be performed to rule out pathological pelvic contraction. Radiologic pelvimetry is not necessary for a safe trial of labour; good progress in labour is the best indicator of adequate fetal-pelvic proportions. (III-B) 5. Continuous electronic fetal heart monitoring is preferable in the first stage and mandatory in the second stage of labour. (I-A) When membranes rupture, immediate vaginal examination is recommended to rule out prolapsed cord. (III-B) 6. In the absence of adequate progress in labour, Caesarean section is advised. (II-1A) 7. Induction of labour is not recommended for breech presentation. (II-3B) Oxytocin augmentation is acceptable in the presence of uterine dystocia. (II-1A) 8. A passive second stage without active pushing may last up to 90 minutes, allowing the breech to descend well into the pelvis. Once active pushing commences, if delivery is not imminent after 60 minutes, Caesarean section is recommended. (I-A) 9. The active second stage of labour should take place in or near an operating room with equipment and personnel available to perform a timely Caesarean section if necessary. (III-A) 10. A health care professional skilled in neonatal resuscitation should be in attendance at the time of delivery. (III-A) DELIVERY TECHNIQUE: 11. The health care provider for a planned vaginal breech delivery needs to possess the requisite skills and experience. (II-1A) 12. An experienced obstetrician gynaecologist comfortable in the performance of vaginal breech delivery should be present at the delivery to supervise other health care providers, including a trainee. (I-A) 13. The requirements for emergency Caesarean section, including availability of the hospital operating room team and the approximate 30-minute timeline to commence a laparotomy, must be in accordance with the recommendations of the SOGC Policy Statement, "Attendance at Labour and Delivery" (CPG No. 89; update in press, 2009). (III-A) 14. The health care provider should have rehearsed a plan of action and should be prepared to act promptly in the rare circumstance of a trapped after-coming head or irreducible nuchal arms: symphysiotomy or emergency abdominal rescue can be life saving. (III-B) 15. Total breech extraction is inappropriate for term singleton breech delivery. (II-2A) 16. Effective maternal pushing efforts are essential to safe delivery and should be encouraged. (II-1A) 17. At the time of delivery of the after-coming head, an assistant should be present to apply suprapubic pressure to favour flexion and engagement of the fetal head. (II-3B) 18. Spontaneous or assisted breech delivery is acceptable. Fetal traction should be avoided, and fetal manipulation must be applied only after spontaneous delivery to the level of the umbilicus. (III-A) 19. Nuchal arms may be reduced by the Lovset or Bickenbach manoeuvres. (III-B) 20. The fetal head may deliver spontaneously, with the assistance of suprapubic pressure, by Mauriceau-Smellie-Veit manoeuvre, or with the assistance of Piper forceps. (III-B) SETTING AND CONSENT: 21. In the absence of a contraindication to vaginal delivery, a woman with a breech presentation should be informed of the risks and benefits of a trial of labour and elective Caesarean section, and informed consent should be obtained. A woman's choice of delivery mode should be respected. (III-A) 22. The consent discussion and chosen plan should be well documented and communicated to labour-room staff. (III-B) 23. Hospitals offering a trial of labour should have a written protocol for eligibility and intrapartum management. (III-B) 24. Women with a contraindication to a trial of labour should be advised to have a Caesarean section. Women choosing to labour despite this recommendation have a right to do so and should not be abandoned. They should be provided the best possible in-hospital care. (III-A) 25. The Society of Obstetricians and Gynaecologists of Canada (SOGC), in collaboration with the Association of Professors of Obstetrics and Gynaecology (APOG), The College of Family Physicians of Canada (CFPC), and The Canadian Association of Midwives (CAM) should revise the training requirements at the undergraduate and postgraduate levels. SOGC will continue to promote training of current health care providers through the MOREOB, ALARM (Advances in Labour and Risk Management), and other courses. (III-A) 26. Theoretical and hands-on breech birth training simulation should be part of basic obstetrical skills training programs such as ALARM, ALSO (Advanced Life Support Training in Obstetrics), and MOREOB to prepare health care providers for unexpected vaginal breech births. (III-B). PMID- 19646326 TI - Maintaining the system with tokenism: bolstering individual mobility beliefs and identification with a discriminatory organization. AB - Two experiments examined the effects of gender-based token hiring practices in organizational settings. In Expt 1, women were exposed to organizational hiring practices that were open, token, or closed. Token practices served to perpetuate inequality by maintaining individual mobility beliefs and organizational identification. In Expt 2, both men and women imagined working for a corporation that planned to implement open, token, or closed hiring practices. Although women reported experiencing negative emotions in the closed and token conditions compared to the open condition, token practices maintained positive perceptions of the organization and individual mobility beliefs compared to the closed condition. Men endorsed more individual mobility beliefs as well as positive emotions in the token and closed conditions compared to the open condition. Token practices distort perceptions of fairness in both women and men. For women, token practices make group boundaries seem more negotiable than they actually are, while for men token practices legitimize their group's dominance. PMID- 19646327 TI - Close women, distant men: line bisection reveals sex-dimorphic patterns of visuomotor performance in near and far space. AB - The mid-points of a series of lines which were positioned both within hand-reach (near space) and beyond hand-reach (far space) were estimated by 24 women and 24 men. When using a laser pointer to perform estimations, women were more accurate in the near condition than the far, whereas men were more accurate in the far condition than the near. When using a stick pointer for the far condition, women were more accurate than when using the laser, whereas men were more accurate using the laser pointer than the stick for the far condition. There was no difference between near and far accuracy scores for either sex using the stick. These results suggest that use of a tool which provides proprioceptive feedback causes the brain to remap far-space stimuli as if situated in near space. Possible origins and neural bases for these differences are considered. Finally, the study found evidence for pseudoneglect, but no evidence for pseudoneglect shift. PMID- 19646328 TI - Mimicry in social interaction: benefits for mimickers, mimickees, and their interaction. AB - Mimicry has benefits for people in social interactions. However, evidence regarding the consequences of mimicry is incomplete. First, research on mimicry has particularly focused on effects of being mimicked. Secondly, on the side of the mimicker evidence is correlational or lacks real interaction data. The present study investigated effects for mimickers and mimickees in face-to-face interaction. Feelings towards the immediate interaction partner and the interaction in which mimicry takes place were measured after an interaction between two participants in which mimicry did or did not occur. Results revealed that mimickers and mimickees became more affectively attuned to each other due to bidirectional influences of mimicry. Additionally, both mimickers and mimickees reported more feelings of having bonded with each other and rated the interaction as smoother. PMID- 19646329 TI - An interest in fame: confirming the measurement and empirical conceptualization of fame interest. AB - The following paper introduces and develops the conceptualization of Fame Interest. Study 1 (N=1,978), through the use of factor analysis techniques, introduces the Fame Interest Scale which comprises six dimensions of Fame Interest (intensity, vulnerability, celebrity life-style, drive, perceived suitability, and altruistic) with evidence for the reliability and validity of the scale. Study 2 (N=376) examined the relationship between an interest in fame and measures of the five-factor model of personality, narcissism, self-esteem, curiosity, attachment style and perceived family, and peer and media influence. From this second study four findings emerge; (1) Fame Interest typified by a perceived suitability and intensity for a celebrity life-style was associated with perceived family, peer and media influence, (2) Fame Interest that arises from a vulnerability is a reflection of neuroticism, low self-esteem, and problematic attachments, (3) Fame Interest for altruistic reasons is associated with agreeableness, and (4) Fame Interest that reflects an overall drive is associated with conscientiousness. PMID- 19646330 TI - Classifying health-related behaviours: exploring similarities and differences amongst behaviours. AB - OBJECTIVES: The classification of health behaviours may provide a useful framework for understanding their characteristics and therefore the ways in which they are similar and different. However, to date, little research has attempted to identify these characteristics and explore the dimensions along which behaviours differ. This paper uses an inductive approach to explore this issue. DESIGN AND METHODS: In Study 1, 25 repertory grid interviews and 3 focus groups encompassing lay public and health professionals identified 25 ways of describing health behaviours. These were refined into 11 key characteristics. In Study 2, 180 members of the general public rated 20 health behaviours on each of these characteristics. RESULTS: Principal components analysis indicated behaviours were perceived along three key dimensions: 'easy immediate pay-offs' versus 'effortful long-term pay-offs'; 'private unproblematic' versus 'public and problematic'; and 'important routines' versus 'unimportant one-offs'. Risk behaviours were clearly differentiated being perceived as 'easy immediate pay-offs' and 'public problematic'. In contrast with other approach behaviours such as diet or self examination, physical activity behaviours were perceived as 'effortful long-term pay-offs'. CONCLUSIONS: This research provides an useful starting point in the development of a framework that allows us to better understand differences and similarities between health behaviours. These dimensions may be important to consider when researchers set out to predict or change behaviour. PMID- 19646332 TI - Illness representations in women with fibromyalgia. AB - OBJECTIVE: In the US population, the prevalence of fibromyalgia is about 3.4% in women. For those who are affected, fibromyalgia is associated with significant limitations relating to quality of life, activity, and participation. Furthermore, fibromyalgia leads to serious socio-economic costs. The objective of the present paper is to describe the cognitive illness representations of women with fibromyalgia and to analyse their relationship to rehabilitation outcomes. METHODS: The outcome was measured using the SF-36 and fibromyalgia impact questionnaire. The illness perceptions were assessed using the Illness Perception Questionnaire - revised. The prediction of outcome was done using hierarchical multiple regression analyses. RESULTS: N=245 patients are included in the sample. The patients attribute a multitude of symptoms to fibromyalgia and name numerous triggering factors. Illness representations are correlated with the illness impact at the beginning of rehabilitation and predict the outcome after the end of rehabilitation. CONCLUSION: The fact that illness representations turn out to be predictors of outcome, even when the baseline health status is statistically controlled, highlights the relevance of the illness representations of patients with fibromyalgia. Therefore, effective and efficient methods should be developed for integrating patient's illness beliefs into the management of the illness as early as possible. PMID- 19646331 TI - Ecological momentary interventions: incorporating mobile technology into psychosocial and health behaviour treatments. AB - PURPOSE: Psychosocial and health behaviour treatments and therapies can be extended beyond traditional research or clinical settings by using mobile technology to deliver interventions to individuals as they go about their daily lives. These ecological momentary interventions (EMIs) are treatments that are provided to people during their everyday lives (i.e. in real time) and in natural settings (i.e. real world). The goal of the present review is to synthesize and critique mobile technology-based EMI aimed at improving health behaviours and psychological and physical symptoms. METHODS: Twenty-seven interventions using palmtop computers or mobile phones to deliver ambulatory treatment for smoking cessation, weight loss, anxiety, diabetes management, eating disorders, alcohol use, and healthy eating and physical activity were identified. RESULTS: There is evidence that EMI can be successfully delivered, are accepted by patients, and are efficacious for treating a variety of health behaviours and physical and psychological symptoms. Limitations of the existing literature were identified and recommendations and considerations for research design, sample characteristics, measurement, statistical analyses, and clinical implementation are discussed. CONCLUSIONS: Mobile technology-based EMI can be effectively implemented as interventions for a variety of health behaviours and psychological and physical symptoms. Future research should integrate the assessment and intervention capabilities of mobile technology to create dynamically and individually tailored EMI that are ecologically sensitive. PMID- 19646333 TI - Personal and situational predictors of test anxiety of students in post compulsory education. AB - BACKGROUND: Recent models of evaluation anxiety emphasize the importance of personal knowledge and self-regulatory processes in the development of test anxiety, but do not theorize a route for situational influences. AIM: To investigate the relationship between test anxiety and personal knowledge beliefs (achievement goals and perceived academic competence), parental pressure/support, and teachers' achievement goals. SAMPLE: One-hundred and seventy five students at a sixth-form college following pre-degree courses in Psychology and Sociology. METHOD: Self-report data were collected for test anxiety, personal achievement goals, academic self-concept, perceived test competence, teachers' achievement goals, and parental pressure/support. Relationships were examined through correlational and regression analyses. RESULTS: The relationship between test anxiety and personal knowledge beliefs differed for the various components of test anxiety. A mastery-avoidance goal was related to worry and tension, and a performance-approach goal to bodily symptoms. Perceived academic competence was related to worry and tension. Parental pressure was associated with stronger worry and test-irrelevant thinking components directly, and with a stronger bodily symptoms component indirectly through a performance-approach goal. Teachers' performance-avoidance goals were related to worry, tension, and bodily symptoms indirectly through personal performance-avoidance goals, and in the case of bodily symptoms additionally through a performance-approach goal. CONCLUSION: Findings provide partial support for the self-regulatory model of test anxiety suggesting that additional routes are required to account for the role of parental pressure and teachers' performance-avoidance goals and a re-examination of the relationship between test anxiety and achievement goals. PMID- 19646334 TI - An index-based short-form of the WISC-IV with accompanying analysis of the reliability and abnormality of differences. AB - OBJECTIVES: To develop an Index-based, seven subtest, short-form of the Wechsler intelligence scale for children fourth edition (WISC-IV) that offers the same comprehensive range of analytic methods available for the full-length version. DESIGN AND METHODS: Psychometric. RESULTS: The short-form Indexes had high reliability and criterion validity. Scores are expressed as Index scores and as percentiles. Methods are provided that allow setting of confidence limits on scores, and analysis of the reliability and abnormality of Index score differences. The use of the short-form is illustrated with a case example. A computer programme (that automates scoring and implements all the analytical methods) accompanies this paper and can be downloaded from the following web address: http://www.abdn.ac.uk/~psy086/dept/sf_wisc4.htm. CONCLUSIONS: The short form will be useful when pressure of time or client fatigue precludes use of a full-length WISC-IV. The accompanying computer programme scores and analyses an individual's performance on the short-form instantaneously and minimizes the chance of clerical error. PMID- 19646335 TI - Long-term outcome and post-treatment effects of psychoanalytic psychotherapy with young adults. AB - OBJECTIVES: The short- and long-term effects of open-ended, long-term psychoanalytic psychotherapy for young adults were investigated. Possible changes during the year and a half follow-up, as well as predictors of change, were explored. DESIGN: Patients aged 18-25 years who accepted the offered psychoanalytic individual or group psychotherapy were included. Patients filled out questionnaires and were interviewed at intake, termination, and follow-up. Alliance data were collected after the second session of psychotherapy proper. METHODS: The primary outcome measures were the Symptom Checklist-90 and the Inventory of Interpersonal Problems. The Helping Alliance Questionnaire-II was used to measure alliance. Mixed model ANOVAs were used to analyse changeover time and prediction of change in relation to gender, treatment format, treatment duration, and in individual psychotherapy, therapist- and patient-rated alliance. RESULTS: All outcome measures changed significantly from intake to follow-up. None changed significantly during the follow-up period, but there was a tendency towards recurring symptoms and an improvement in one of the object relational measures during the follow-up. The latter was the only outcome measure that did not change significantly during treatment. Lower therapist-rated alliance was predictive of greater change in psychiatric symptoms for patients with high levels of symptoms at intake. CONCLUSIONS: The long-term effectiveness of psychoanalytic psychotherapy for young adults was supported. Low therapist-rated alliance implies that the therapists have identified problematic interactions, which might have mobilized their effort to solve the problems. Further research on cases reporting no gain or even deterioration is needed. PMID- 19646336 TI - Let's look at the elephant: metasynthesis of transference case studies for psychodynamic and cognitive psychotherapy integration. AB - OBJECTIVES: Although the movement towards psychotherapy integration is gaining momentum, theoretical polarization still prevails and prevents integration from maturing. This study strives for theoretical integration, shedding light on relations between two concepts from diametrically opposed therapies: the psychodynamic concept of transference and the cognitive concept of overgeneralization. DESIGN: A qualitative metasynthetic study. METHOD: The study maps core conflictual relationship themes transference components, codes other meaning units, and analyses relationship between categories. These procedures apply to published transference case descriptions. RESULTS: Of the 33 case studies, 30 (about 90%) were shown to include overgeneralization thinking distortion. In all these cases, such overgeneralization concerned a central theme in the same category as Luborsky's components of transference. The results show that overgeneralization thinking errors (cognitive therapy) are the current cognitive manifestation of the transference patterns (psychoanalytic therapy). This observation maps the complementary character of the concepts and thus takes an additional significant step forward towards the consolidation of a theoretical platform for integrative intervention. PMID- 19646337 TI - Primary angiitis of the central nervous system: reflections on 20 years of investigation. PMID- 19646339 TI - Effect of biopsy length on the rate of positive temporal artery biopsies. AB - OBJECTIVE: To investigate the relationship between temporal artery biopsy (TAB) length and the diagnostic sensitivity for giant cell arteritis (GCA). METHODS: TAB pathology reports were reviewed for histological findings and formalin-fixed TAB lengths. The patient's charts were reviewed for clinical data. TAB was considered positive if there was a mononuclear cell infiltrate in the vessel wall. Biopsy-negative GCA was diagnosed when patients fulfilled the American College of Rheumatology classification criteria, in addition to favorable rapid response to steroid therapy. Patients were divided into 3 groups according to the clinical and histological features: Biopsy-positive GCA, biopsy-negative GCA, and no GCA. RESULTS: 305 TAB reports of 173 individuals were reviewed. When only GCA patients TAB-positive and TAB-negative were considered, TAB in the biopsy positive patients was significantly longer than in biopsy-negative cases (p=0.008). The rate of positive biopsies was only 19% with TAB length of 5 mm or less, but increased to 71-79% with TAB lengths of 6-20 mm, and to 89% when TAB length was longer than 20 mm. Only 3% of positive biopsies were 5 mm or shorter, compared to 27% of TAB in biopsy-negative GCA cases (p<0.001). CONCLUSION: TAB with post-fixation length shorter than 5 mm carries an increased biopsy-negative rate therefore longer TAB length is required for accurate diagnosis. Increasing post-fixation TAB length beyond 20 mm may further increase the rate of positive biopsies, although data were insufficient in that regard. PMID- 19646340 TI - Interleukin-12 gene polymorphisim in patients with giant cell arteritis, polymyalgia rheumatica and elderly-onset rheumatoid arthritis. AB - OBJECTIVE: The cytokine profile suggests that giant cell arteritis (GCA) is a Th1 driven disease, in which local IFN-gamma plays a critical role in the development of a systemic arteritis. IL-12 is a potent inducer of IFN-gamma and is critically involved in biasing an immune response towards a Th1 pathway. The purpose of this study was to investigate whether there was an association between an IL-12 gene polymorphism (-1188 A/C 3UTR) and disease susceptibility for GCA and two other age-related inflammatory conditions, such as polymyalgia rheumatica (PMR) and elderly-onset rheumatoid arthritis (EORA). Furthermore, we attempted to correlate such polymorphism with in vitro IL-12 production. MATERIALS AND METHODS: We analyzed genotypes at -1188 in the 3UTR of the IL-12 promoter by PCR-RFLP in 68 GCA, 138 PMR, and 72 EORA patients as well as in 465 healthy controls (HC). IL 12p70 levels in culture supernatants after stimulation with PMA+Ionomycin was assessed by ELISA. RESULTS: All groups were in Hardy-Weinberg equilibrium. Allelic and gen-omic distribution was not significantly different among the study groups. None of the genetic variants was associated with disease severity. Although the differences were not statistically significant, HC genotypes were associated with distinct IL-12 p70 production. CONCLUSIONS: The IL-12 (-1188 A/C 3UTR) gene polymorphism is not associated with disease susceptibility or severity in three age-related chronic inflammatory syndromes. The production of IL-12 p70 is dependent on the genetic background in HC, although in patients such association may be biased by other unknown factors. PMID- 19646341 TI - Expression of CD57 on CD8+ T lymphocytes of patients with Wegener's granulomatosis and microscopic polyangiitis: evidence for continuous activation of CD8+ cells. AB - OBJECTIVES: To gain insight into the immune pathogenesis of Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA), the prevalence of circulating CD8+ T lymphocytes expressing CD57 as a marker for previous activation was analyzed. METHODS: Receptor expression of CD57 was measured in CD8+ T cells of patients with active disease (n=5) by cytofluorometry and compared with expression in patients in remission (n=80) and in age-matched healthy donors (n=34). The results were compared to clinical parameters including severity and duration of the disease. RESULTS: CD8+CD57+ were detected in patients with WG and MPA and in healthy donors as well and increased considerably with age. Compared to age-matched healthy donors, the prevalence of CD8+CD57+ was increased in the younger patients (up to 40 y). In most patients a high percentage of CD8+CD57+ coincided with severe disease and multiple organ involvement, while low CD8+CD57+ percentage was seen in patients with limited disease or in patients in complete remission. In patients with smoldering disease, the percentage of CD8+CD57+ increased with time. High numbers of CD8+CD57+ correlated with low CD4:CD8 ratio. CONCLUSIONS: In patients with WG and MPA a population of CD8+CD57+ expand, identifying terminally differentiated CD8+ cells. The prevalence of CD57+ cells was related to the course of disease. So far, the function of CD57 on CD8+ cells is not understood. However, these cells might produce certain cytokines, which play a role in the pathogenesis of AAV. The data support the hypothesis that CD8+ T cells are activated in the context of primary vasculitides. PMID- 19646342 TI - Polymyalgia rheumatica can recur years after discontinuation of corticosteroid therapy. AB - OBJECTIVE: To describe disease recurrence in polymyalgia rheumatica. METHODS: I present 12 patients with recurring PMR from a single clinical practice with long term clinical follow-up (mean 14.3 years). RESULTS: Despite a disease-free interval off corticosteroids of 2 years or longer, these patients experienced 1 overt recurrence (or more) of PMR. CONCLUSION: The course of PMR is not uniformly monophasic, and patient and physician should remain alert to the possibility of recurring disease. PMID- 19646343 TI - Two types of myeloperoxidase-antineutrophil cytoplasmic autoantibodies with a high affinity and a low affinity in small vessel vasculitis. AB - OBJECTIVE: Myeloperoxidase (MPO) -anti-neutrophil cytoplasmic autoantibodies (ANCAs) are detected at a high rate in microscopic polyangiitis and renal-limited vasculitis. MPO-ANCA titers are not always reflected in the disease activity. We studied the titer and affinity of MPO-ANCA in sera from patients in relation to vasculitis activity. METHODS: Blood samples were collected from 27 newly diagnosed or relapsed patients with MPO-ANCA-associated vasculitides. The MPO ANCA titer was determined by a direct enzyme-linked immunosorbent assay (ELISA) using homogeneously purified human MPO of leukocytes. The MPO-ANCA affinity was expressed as IC50 that was determined by a competitive inhibition method using the ELISA. RESULTS: The MPO-ANCA affinity of 27 sera from 27 patients could be classified into a high-affinity type (14 sera) and a low-affinity type (13 sera). The mean values for IC50 in the two types were 0.15+/-0.06 microg/ml and 0.54+/ 0.15 microg/ml, and the difference was statistically significant (p<0.0000000684). Between the two groups of patients divided by the affinity, there were differences in the Birmingham Vasculitis Activity Score (BVAS): and in C-reactive protein (CRP): (p<0.00093 and p<0.00129, respectively). However, the difference in titer was not statistically significant (p<0.0265). The affinity remained steady from the disease onset to remission or relapse. CONCLUSIONS: The affinity of MPO-ANCA from patients with MPO-ANCA-associated vasculitides were largely distinguished into a high and a low affinity, irrespective of the level of MPO-ANCA titers, and may be helpful for assessment of vasculitis activity affecting mainly the kidney and the lung. PMID- 19646344 TI - Takayasu arteritis: epidemiological, clinical, and immunogenetic features in Greece. AB - OBJECTIVE: Takayasu arteritis (TA) is an uncommon disease with clinical heterogeneity across different ethnic groups. We aimed to evaluate the epidemiological, clinical, and immuno-genetic features of TA in Greece. METHODS: Demographic, clinical, laboratory, angiographic, and therapeutic data of 42 patients from 4 large referral centers were retrieved. Serology and Human Lymphocyte Antigen (HLA) typing was performed in 22 patients. RESULTS: We studied 37 women and 5 men with a median age of 31 years at disease onset. Median delay in diagnosis was 24 months and median follow-up was 47 months (range 0-178). Constitutional or musculoskeletal symptoms were present in 86%, especially early in the disease course. Vascular findings were universal with reduced or absent pulse being the most common manifestation (98%). Hypertension was frequent (78%). Extensive disease prevailed and stenotic lesions were more common than aneurysms (95% vs. 40%). Erythrocyte sedimentation rate and C-reactive protein showed modest correlation with disease activity. HLA-B52 was expressed by 37% of the patients vs. 2.4% of the controls (p<0.001). Glucocorticoids and cytotoxic agents were used in most patients with remission rates of 83%. A total of 42 surgical procedures were performed with success rates of 87%. CONCLUSION: TA in Greece clinically and epidemiologically resembles the pattern of disease in Japan and the Western hemisphere. There is considerable delay in diagnosis, which may partially reflect failure to recognize a rare disease. New surrogate markers are needed to assess disease activity. Glucocorticoids are the cornerstone of treatment and cytotoxic drugs are frequently used as steroid sparing agents. PMID- 19646345 TI - Toll-like receptor 4 (TLR4) gene polymorphisms in giant cell arteritis. AB - OBJECTIVE: To investigate potential associations between toll-like receptor 4 (TLR4) gene polymorphisms and susceptibility to, and clinical features of giant cell arteritis (GCA). METHODS: A total of 155 patients with biopsy-proven GCA who were residents of Reggio Emilia, Italy, and 210 population-based controls from the same geographical area were genotyped for two coding single nucleotide polymorphisms of TLR4 (Asp299Gly and Thr399Ile) by molecular methods. The patients were subgrouped according to the presence or absence of polymyalgia rheumatica and severe ischemic complications (visual loss and/or cerebrovascular accidents). RESULTS: The distribution of allele and genotype frequencies did not differ significantly between GCA patients and healthy controls. Carriers of the 299 G allele (G/A+ G/G) [odds ratio (OR) 1.78, 95% confidence intervals (CI) 0.90 3.50)] were more frequent among GCA patients than among the controls, but the difference was not statistically significant. No significant associations were found when GCA patients with and without PMR or with and without severe ischemic complications were compared. CONCLUSION: Our data suggest that the TLR4 gene polymorphisms are not associated with susceptibility to, and clinical expression of, GCA in Italian patients. PMID- 19646348 TI - Takayasu's arteritis in Turkey - clinical and angiographic features of 248 patients. AB - OBJECTIVE: Takayasu's arteritis (TA) is a chronic, inflammatory vasculitis affecting the aorta and its major branches. Although it is more prevalent in Far East Asia, the distribution of the disease is worldwide with different vascular involvement patterns and clinical manifestations. The objective of this study was to evaluate the demographic, clinical, angiographic and prognostic features of TA patients in Turkey. METHODS: Clinical and angiographic findings of 248 TA patients (228 female, 27 male) followed at 15 Rheumatology Centers were prospectively evaluated according to a predefined protocol. RESULTS: The mean age was 40.1 years (30.2 years at the clinical onset). Clinical manifestations included constitutional symptoms in 66%, absent or diminished pulses in 88%, bruits in 77%, extremity pain in 69%, claudication in 48%, hypertension in 43% and cerebrovascular accidents (CVA) in 18% of the patients. Renal artery stenosis, aortic regurgitation and pulmonary hypertension were present in 26%, 33% and 12%, respectively. According to the new angiographic classification, type V (50.8%) and Type I (32%) were the most frequent types of involvement. Corticosteroids were the main treatment in 93% of the patients alone (9%) or in combination with immunosuppressive agents (84%). Most frequently preferred immunosuppressive agents were methotrexate (63%), azathioprine (22%) and cyclophosphamide (13%). Remission was observed at least once in 94% of the patients and sustained remission in 71% during follow-up. CONCLUSION: The demographical, clinical and angiographic findings of TA patients in our series were similar to those reported from Japan, Brazil and Colombia. Combination therapies with immunosuppressive agents were the preferred choice of treatment in Turkey. PMID- 19646347 TI - Learning and reliability of colour Doppler ultrasound in giant cell arteritis. AB - OBJECTIVE: To evaluate a standardized training program and a reliability exercise in colour Doppler ultrasound (CDUS) for giant cell arteritis (GCA). METHODS: Two workshops were conducted in 2007 and 2008 to train rheumatologists in CDUS for GCA ultrasound diagnosis. Twenty-nine and forty-three participants without previous experience in GCA ultrasound were admitted in 2007 and 2008, respectively. First, some theoretical knowledge about GCA ultrasound signs was provided; second, a reader evaluation session of temporal artery video recording examinations of 27 and 30 patients were projected in the 2007 meeting and the 2008 workshop, respectively (50% were cases and 50% were controls). Twenty-four cases were common to both reader sessions. A mean of six videos were shown of each patient. Each video had to be assessed as normal or pathologic. Finally, hands-on scanning training was performed. To assess the efficacy of the workshop: 1) a structured satisfaction questionnaire was graded (1-5 Likert scale), and 2) the reliability, specificity, and percentage of correctly classified cases by each participant were calculated. RESULTS: The kappa coefficient of inter-reader agreement for the 29 and 43 participants was excellent (Kappa: 0.846) in 2007 and (Kappa: 0.848) in 2008. The intra-reader kappa result was also excellent (Kappa: 0.950). The satisfaction, sensitivity, specificity, and percentage of correctly classified patients and controls were very high. CONCLUSION: The proposed learning method seemed to be effective and well accepted by the target audience. The inter-reader reliability of GCA ultrasound was excellent. These encouraging results support the need for planned standardized training programs. PMID- 19646349 TI - Clinical analysis of nervous system involvement in ANCA-associated systemic vasculitides. AB - OBJECTIVE: To assess the clinical features of nervous system (NS) involvement in patients with ANCA-associated vasculitides (AAV), including microscopic polyangiitis (MPA), Wegener's granulomatosis (WG), and Churg-Strauss syndrome (CSS). METHODS: One hundred and seventy-nine patients admitted to Peking Union Medical College Hospital from 1995 to 2008, including 93 cases of MPA, 61 cases of WG, and 25 cases of CSS, were enrolled in this study. Medical charts including demographic data, clinical features, laboratory findings, treatments and outcomes were systematically reviewed. RESULTS: NS involvements were observed in 36.6% of MPA, 50.8% of WG, and 76.0% of CSS patients. Peripheral neuropathy predominated in each type of AAV. In CSS and MPA, the majority was mononeuritis multiplex and distal symmetrical polyneuropathy, whereas, differently, 64.5% of WG patients with NS involvement had cranial neuropathy. Central nervous system (CNS) involvement accounted for 21.1%, 29.4%, and 32.3% of neuropathy respectively in CSS, MPA and WG patients, including arachnoid hemorrhage, cerebrovascular neuro pathy, meningitis, and diffuse brain damage. 157 (87.7%) AAV patients responded to treatment with high dose of prednisone plus immunosuppressants. Thirteen (14.0%) MPA and four (6.6%) WG patients died. The leading causes of death were diffuse alveolar hemorrhage (DAH) (6, 35.3%) and infection (6, 35.3%). No patient died directly of neuropathy. CONCLUSION: NS involvement was common in AAVs and the characteristic of NS involvement was different among MPA, WG and CSS patients. DAH and infection instead of NS damage remained the leading causes of death in AAVs. PMID- 19646350 TI - Impact of cardiac magnetic resonance imaging for assessment of Churg-Strauss syndrome: a cross-sectional study in 20 patients. AB - OBJECTIVE: To examine the diagnostic contributions of cardiac magnetic resonance imaging (CMRI) with delayed-enhancement (DE) in patients with Churg-Strauss syndrome (CSS). METHODS: We consecutively recruited 14 men and 6 women (mean age: 50+/-14 years) with CSS (mean disease duration: 4.5+/-3.6 years) and investigated them independently of the presence/absence of cardiac manifestations. Cardiac manifestations included heart failure in 6 patients, angina pectoris in 1, isolated ECG abnormality in 1, and isolated echocardiography and ECG abnormalities in 1. T1-weighted sequences were recorded after gadolinium injection to study myocardial DE. RESULTS: CMRI abnormalities were found in 13/20 patients, including all 9 patients with myocardial manifestations, and 4 of the 11 asymptomatic patients. DE was centromyocardial in 6 patients, subepicardial in 4, and subendocardial in 3. Most enhanced lesions were in the anteroseptal or lateral walls. Patients with myocardial symptoms and DE had higher transmyocardial wall DE scores (mean: 9.4 vs. 3.7, respectively; p=0.01) and lower left ventricular ejection fractions (mean: 42% vs. 59%; p=0.001) than asymptomatic patients with DE. CONCLUSION: CMRI with DE enabled the detection of myocardial involvement in CSS patients with or without clinical symptoms. The clinical relevance of CMRI abnormalities in patients without clinical, echocardiographic and ECG signs of cardiac involvement remains unknown and needs to be evaluated in future studies. It seems premature to intensify treatment or to prescribe systematically steroids and cytotoxic agents based on the presence of isolated CMRI anomalies. PMID- 19646346 TI - Glycosylation of proteinase 3 (PR3) is not required for its reactivity with antineutrophil cytoplasmic antibodies (ANCA) in Wegener's granulomatosis. AB - OBJECTIVE: The glycosylation status of autoantigens appears to be crucial for the pathogenesis of some autoimmune diseases, since carbohydrates play a crucial role in the distinction of self from non-self. Proteinase 3 (PR3), the main target antigen for anti-neutrophil cytoplasmic antibodies (ANCA) in patients with Wegener's granulomatosis (WG), contains two Asn-linked glycosylation sites. The present study explores the influence of the glycosylation status of PR3 on the PR3 recognition by ANCA in a well characterized population of patients with WG. METHODS: Forty-four patients with WG (459 serum samples) who participated in a multicenter randomized trial, were tested by capture ELISA for ANCA against PR3 and deglycosylated recombinant variants of PR3. RESULTS: The patients were followed for a median of 27 months, and the median number of serum samples per patient was 10. At baseline, the correlation between the levels of ANCA against PR3 and against all the deglycosylated recombinant variants of PR3 were greater than 0.94 (?<0.001 for all the comparisons). Longitudinal analyses comparing the levels of ANCA against PR3 versus all the deglycosylated recombinant variants of PR3, using linear mixed models, showed no significant statistical differences (rho >or=0.90 in all cases). CONCLUSION: The glycosylation status of PR3 has no impact on its recognition by ANCA in WG. PMID- 19646351 TI - Colour-duplex ultrasonography of the temporal and ophthalmic arteries in the diagnosis and follow-up of giant cell arteritis. AB - OBJECTIVE: To evaluate the diagnostic value of colour-duplex ultrasonography (CDU) of the temporal and ophthalmic arteries in the diagnosis of giant cell arteritis (GCA) and its usefulness in the follow-up of the disease. Furthermore, to examine the relationship between CDU abnormalities in ophthalmic arteries and blindness. METHODS: This is a prospective study of all patients with clinical suspicion of GCA or polymyalgia rheumatica (PMR) seen consecutively at the Internal Medicine Department at Vall d'Hebron University Hospital, Spain, between March 2003 and July 2006. Patients were evaluated with regard to the sensitivity and specificity of the dark halo sign in the temporal artery for the diagnosis of GCA, as well as the sensitivity and specificity of the presence of stenosis in temporal and/or ophthalmic arteries. Additionally, the usefulness of the dark halo sign in the follow-up of GCA was addressed. RESULTS: Forty-seven patients (30 with GCA, 17 with PMR) and 13 controls were included in the study. The sensitivity and specificity for the diagnosis of biopsy-proven GCA were higher for the temporal halo (72% in both cases) than for temporal artery stenosis (41% and 89%, respectively), or for ophthalmic artery stenosis (58% and 89%, respectively). Disappearance of the halo was observed in 50% of patients six months after diagnosis, although all patients were in clinical remission, and laboratory parameters were within normal values. CONCLUSION: CDU of the temporal arteries may be a valid tool in the diagnosis of GCA. However, its role in the follow up of the disease deserves re-evaluation. CDU of the ophthalmic arteries is less useful for CGA diagnosis and no relationship with blindness is suspected. PMID- 19646353 TI - Wegener's granulomatosis occurring de novo during pregnancy. AB - Wegener's granulomatosis (WG) is rarely diagnosed during the reproductive years and uncommonly manifests for the first time during pregnancy. We report a case of de novo WG presenting at 30 weeks gestation with classical symptoms of WG (ENT, pulmonary). The diagnosis was confirmed by radiological, laboratory, and histological investigations. With a multidisciplinary approach, she had a successful vaginal delivery of a healthy baby. She was treated successfully by a combination of steroids, azathioprine and intravenous immunoglobulin in the active phase of disease for induction of remission and by azathioprine and steroids for maintenance of remission. The significant improvement in her symptoms allowed us to continue her pregnancy to 37 weeks when delivery was electively induced. Transplacental transmission of PR3-ANCA occurred but the neonate remained well. This case of de novo WG during pregnancy highlights the seriousness of this disease and the challenge in management of such patients. PMID- 19646352 TI - Pericardial tamponade in a patient with polymyalgia rheumatica. AB - We report a patient who developed pericarditis and pericardial tamponade coinciding with polymyalgia rheumatica onset. Our patient did not show any clinical sign of vasculitis; temporal artery biopsies were negative for giant cell arteritis. Pericardial biopsy in our case shows inflammatory perivascular lymphocytary infiltrates thus we believe pericardial effusion has an inflammatory immunologic origin. Cardiac manifestations are exceptional in polymyalgia rheumatica, though it should be considered in the differential diagnosis in patients with pericarditis over 50 years. The recognition of this uncommon manifestation is very important due to the good response to corticosteroid treatment. PMID- 19646354 TI - Familial aggregation in giant cell arteritis and polymyalgia rheumatica: a comprehensive literature review including 4 new families. AB - OBJECTIVE: To review personal and published observations of giant cell (temporal) arteritis (GCA) or polymyal-gia rheumatica (PMR) with familial or conjugal aggregation and emphasise on epidemiological, clinical and genetic features of such cases. METHODS: We pooled data obtained from all cases of GCA or PMR with familial aggregation recruited in the department since 1976 and those from reports of familial or conjugal GCA or PMR published in the French-English literature since 1970. RESULTS: During the study period, we diagnosed 460 patients (128 with isolated PMR, 227 with isolated GCA, 105 with PMR/CGA). No conjugal couples were observed in the whole series. No familial cases were identified among PMR patients, whereas the prevalence of familial GCA was 1 in 83 (1 in 250 to 500 expected by chance), as we identified 4 patients (brother brother, sister with history of affected sister, and daughter with priory affected mother). An additional pair of sisters with TA, recruited several months after diagnosis, is also presented. Pooling data from 85 patients (74 with GCA) including our patients, representing 32 families and 8 conjugal pairs, enabled us to draw the following observations: 1) partial or full agreement in the clinical picture (GCA, PMR, or GCA/PMR) was observed in 96% of the siblings pairs, suggesting a common pathogenic mechanism; 2) five kindred were described in whom at least three members were affected; 3) the lag between manifested diseases in familial or conjugal pairs averaged 5.7 years, with synchronous or close disease occurrence in only 26% of the pairs; 4) 18 of 32 assessed patients (56%) carried the DR4 antigen. CONCLUSION: Our survey on familial aggregation of GCA and PMR accumulated data pointing to a genetic predisposition. However, environmental contagious factors could have trigger synchronous disease onset in up to one fourth of the cases. PMID- 19646356 TI - New advances in the pathogenesis of ANCA-associated vasculitides. AB - Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) are a group of autoimmune disorders including Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), Churg-Strauss syndrome (CSS) and renal-limited vasculitis (RLV). This paper reviews updated information on the pathogenesis of AAV. Additional clinical evidence for a pathogenic role of ANCA comes from the observation that patients with severe acute renal failure treated with plasma exchange had a lower risk for progression to end-stage renal disease than patients who received intravenous methylprednisolone therapy, both in addition to standard treatment. Recent data also suggest that antibodies to complementary proteinase-3 (cPR3), probably cross-reacting with plasminogen, may induce PR3 ANCA. Furthermore, a new ANCA, directed against human lysosome membrane protein-2 (LAMP-2), concurrent with PR3-ANCA or MPO-ANCA, was described as a sensitive and specific marker for renal AAV. In vitro, ANCA can further activate primed neutrophils to release reactive oxygen species and lytic enzymes, and, in conjunction with neutrophils, damage and lyse endothelial cells. In vivo, transfer of splenocytes from myeloperoxidase-deficient mice immunized with mouse myeloperoxidase into wild-type mice resulted in pauci-immune systemic vasculitis. A similar experiment in PR3-deficient mice did not cause significant vasculitic lesions. In the anti-MPO induced vasculitis mouse model, a critical role of complement activation was suggested. The anti- LAMP-2 antibody can also induce pauci-immune necrotizing crescentic glomerulonephritis in rats. Rats developed both cross-reactive antibodies to LAMP-2 and crescentic glomerulonephritis when immunized with FimH, an adhesin from Gram-negative bacteria which has strong homology with human LAMP-2. Together, clinical, in vitro and in vivo data support a pathogenic role for ANCA in AAV, although this role is more evident for myeloperoxidase-ANCA than for PR3-ANCA. The role of anti- LAMP-2 requires further studies. PMID- 19646357 TI - How HCV has changed the approach to mixed cryoglobulinemia. AB - Mixed cryoglobulinemia is a systemic disease due to a small vessel immune-complex mediated vasculitis. The discovery of a viral origin of the disease has launched a great expectancy among researchers and the years after this finding have been characterized by the effort to reach viral eradication in the hope of obtaining disease remission. Moreover, the use of immunosuppressives has been discouraged for many years as they could favour viral replication, and HCV infection has represented a contraindication to the more recent biological drugs directed against cytokines. The trials with antiviral agents in this disorder, however, has not met the expectations, especially when challenged with some of the most severe complications of the disease; moreover, these medications were not devoid of unexpected side effects, such as the occurrence of peripheral neuropathies. Since lymphoproliferation is one of the features of the disease, this has focused the attention of investigators on the potential benefit of newly targeted therapies specifically directed against B-lymphocytes (such as rituximab). Preliminary results on the use of these medications are promising. Furthermore, the use of biological agents in small open trials in HCV positive arthritis patients has demonstrated an acceptable safety profile. All these empirical observations should probably induce the scientific community to reconsider the therapeutical approach to HCV-related mixed cryoglobulinemia. Indeed, the use of aggressive chemotherapy treatments in the era preceding HCV discovery has not been associated with significant liver toxicities and standard chemotherapy during HCV-related lymphoma carried out a unexpected low rate of severe liver damage. Future efforts should probably focus on the potential benefit of a multi step, combined anti-viral and cytotoxic therapy (both with standard regimens and new medications). PMID- 19646355 TI - Primary angiitis of the central nervous system. AB - Primary angiitis of the central nervous system (PACNS) was first identified half a century ago, but it remains a rare and challenging disease. However, important advances have been made in the field of PACNS, mainly through recently published retrospective analyses of large groups of PACNS patients, and the consideration of reversible cerebral vasoconstriction syndrome as a distinct entity. Clinical manifestations of PACNS are variable and non-specific. Even though neuroimaging can be suggestive of vasculitis, only a leptomeningeal biopsy can definitively confirm vasculitis. However, a brain sample is taken in less than half the patients and cannot further help to distinguish between PACNS and secondary vasculitis of the central nervous system. Hence, physicians should be aware of all alternative diagnoses and PACNS mimickers, which are now well-known. Whereas prognosis now appears to be much better than for the first reported cases, probably attributable to the use of corticosteroids and immunosuppressants, mainly cyclophosphamide, the optimal therapeutic regimen, potentially based on each patient's characteristics, and its duration remain to be determined. Only multicenter studies and prospective therapeutic trials will be able to clarify these issues on therapy and eventually provide some data on PACNS physiopathogenesis, which remains a poorly explored domain. PMID- 19646358 TI - Cutaneous vasculitis and their differential diagnoses. AB - Vasculitis is defined as an inflammatory cell infiltration and destruction of blood vessels identified upon histologic examination. Cutaneous manifestations are frequent during the course of many systemic vasculitis. Lesions are often not specific, the most frequent being palpable purpura. They may be the first and only manifestation of the disease or be a part of a systemic condition. Histology is mandatory to confirm the diagnosis of vasculitis to avoid a delayed and inappropriate diagnosis that could lead to improper management. Cutaneous histology gave some data that may help to classify the vasculitis without determining precisely its type. A histological examination of all other skin lesions is necessary. The result of the biopsy has to be correlated to DIF data, medical history, physical examination, laboratory and radiological findings leading to the correct diagnosis and effective treatment.In this review, we discuss the diagnosis of cutaneous vasculitis (CV) and the pitfalls related to the cutaneous pathology. We also describe the essential features of the major categories of skin vasculitis. PMID- 19646359 TI - Progressive multifocal leukoencephalopathy in a patient with undifferentiated systemic vasculitis and bilateral acute retinal necrosis. PMID- 19646360 TI - Early diagnosis of pediatric Takayasu arteritis (TA) not fullfiling the ACR criteria. PMID- 19646362 TI - The use of carotid ultrasonography in the assessment of subclinical atherosclerosis and the paradoxical effect of corticosteroids on atherosclerosis in patients with rheumatoid arthritis. PMID- 19646363 TI - Regulated upon activation normal T-cell expressed and secreted (RANTES) and epithelial cell-derived neutrophil-activating peptide (ENA-78) gene polymorphisms in patients with biopsy-proven erythema nodosum. PMID- 19646364 TI - Cogan's syndrome and development of ANCA-associated renal vasculitis after lengthy disease remission. PMID- 19646365 TI - Association between attention-deficit/hyperactivity disorder and sleep impairment in adulthood: evidence from a large controlled study. AB - OBJECTIVE: To examine whether sleep impairment is associated with attention deficit/hyperactivity disorder (ADHD) in adults. METHOD: In a study conducted from 1998 to 2003, we identified sleep characteristics in a community sample of 182 cases of DSM-IV ADHD or ADHD not otherwise specified and 117 non-ADHD controls aged 18 to 55 years. Attention-deficit/hyperactivity disorder status, current and lifetime psychiatric comorbidity, and pharmacologic treatment of ADHD were identified with the Structured Clinical Interview for DSM-IV and with modules from the Schedule for Affective Disorders and Schizophrenia for School Age Children-Epidemiologic Version. Sleep problems were characterized by self report. We separately accounted for the contribution of age at ADHD onset, ADHD pharmacotherapy, lifetime bipolar disorder, and the following lifetime and current comorbidities: depression, generalized anxiety, substance abuse, and multiple anxiety disorders. RESULTS: Adults with ADHD went to bed later than control subjects and had a wider range of bedtimes (mean +/- SD = 18 +/- 92 min vs 54 +/- 69 min before midnight; P < .001), were more likely to take over an hour to fall asleep (OR = 5.22, P = .001), and were more likely (P < .003) to experience difficulty going to bed, going to sleep, sleeping restfully, or waking in the morning. Adults with ADHD experienced daytime sleepiness more often (OR = 2.23, P = .003) and reported more sleep problems (mean +/- SD = 6.7 +/- 2.5 vs 4.3 +/- 2.2; P < .001) than controls. All sleep impairments were significantly associated with ADHD independent of contributions to sleep disruption from ADHD pharmacotherapy, comorbidities likely to contribute to sleep disturbance, and age at ADHD onset. CONCLUSION: Sleep disturbances that are not attributable to comorbid mental health conditions or ADHD pharmacotherapy are associated with ADHD in adulthood. Clinicians and researchers should consider the potential contribution of sleep disruption to the clinical presentation of adults with ADHD. PMID- 19646366 TI - Psychiatric diagnoses in patients previously overdiagnosed with bipolar disorder. AB - OBJECTIVE: In a previous article from the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, we reported that bipolar disorder is often overdiagnosed in psychiatric outpatients. An important question not examined in that article was what diagnoses were given to the patients who had been overdiagnosed with bipolar disorder. In the present report from the MIDAS project, we examined whether there was a particular diagnostic profile associated with bipolar disorder overdiagnosis. METHOD: Eighty-two psychiatric outpatients reported having been previously diagnosed with bipolar disorder that was not confirmed when they were interviewed with the Structured Clinical Interview for DSM-IV (SCID). Psychiatric diagnoses were compared in these 82 patients and in 528 patients who were not previously diagnosed with bipolar disorder. Patients were interviewed by a highly trained diagnostic rater who administered a modified version of the SCID for DSM-IV Axis I disorders and the Structured Interview for DSM-IV Personality for DSM-IV Axis II disorders. This study was conducted from May 2001 to March 2005. RESULTS: The most frequent lifetime diagnosis in the 82 patients previously diagnosed with bipolar disorder was major depressive disorder (82.9%, n = 68). The patients overdiagnosed with bipolar disorder were significantly more likely to be diagnosed with borderline personality disorder compared to patients who were not diagnosed with bipolar disorder (24.4% vs 6.1%; P < .001). A previous diagnosis of bipolar disorder was also associated with significantly higher lifetime rates of major depressive disorder (P < .01), posttraumatic stress disorder (P < .05), impulse control disorders (P < .05), and eating disorders (P < .05), although only the association with impulse control disorders remained significant after controlling for the presence of borderline personality disorder. CONCLUSIONS: Psychiatric outpatients overdiagnosed with bipolar disorder were characterized by more Axis I and Axis II diagnostic comorbidity in general, and borderline personality disorder in particular. PMID- 19646367 TI - Somatic versus cognitive symptoms of depression as predictors of all-cause mortality and health status in chronic heart failure. AB - OBJECTIVE: Depression is a predictor of adverse health outcomes in chronic heart failure (CHF), but it is not known whether specific symptoms drive this relationship. We examined the impact of somatic/affective, cognitive/affective, and total depressive symptoms on all-cause mortality and health status in CHF. METHOD: Consecutive CHF outpatients (n = 366) completed the Beck Depression Inventory. The primary endpoint was all-cause mortality; the secondary endpoint was disease-specific health status, as measured by the Minnesota Living with Heart Failure Questionnaire (n = 285) at inclusion and 1-year follow-up. The study was conducted between October 2003 and March 2007. RESULTS: There were 68 (18.6%) deaths (mean +/- SD follow-up, 37.2 +/- 10.6 months). Patients high on somatic/affective depressive symptoms had a greater incidence of mortality compared to patients low on somatic/affective depressive symptoms (31% vs 15%; hazard ratio [HR] = 2.3; 95% CI, 1.38-3.69; P = .001). There was no significant difference in the incidence of mortality between patients high versus low on cognitive/affective depressive symptoms (23% vs 18%; HR = 1.4; 95% CI, 0.80-2.40; P = .25), but there was a significant difference between patients high versus low on total depressive symptoms (24% vs 16%; HR = 1.6; 95% CI, 1.01-2.63; P < .05). After adjusting for demographic and clinical characteristics, we found that somatic/affective depressive symptoms predicted all-cause mortality (HR = 1.8; 95% CI, 1.03-3.07; P = .04), while cognitive/affective and total depressive symptoms did not. Both dimensions of depressive symptoms predicted disease specific health status at 1 year. CONCLUSIONS: Only somatic/affective depressive symptoms significantly predicted all-cause mortality in CHF. In the context of diagnosing and intervening, awareness of subtypes of depressive symptoms is important. PMID- 19646368 TI - Treatment provider preference of Australian office workers for common neurologic and musculoskeletal conditions. AB - OBJECTIVE: The purpose of this study was to survey the choice of treatment provider by selected Australian office workers for common conditions that are managed in chiropractic practice. METHODS: Office workers of a medium-sized legal company in Sydney, Australia, were surveyed. The participants (n = 125) were asked to complete a written questionnaire on their preferred treatment choices for common physical conditions, such as back pain, neck pain, and headache. RESULTS: A total of 81 people returned completed questionnaires. Forty-two people (52%) reported that they would attend a general medical practitioner first for back pain. In comparison, 24% of people reported that they would attend a physiotherapist first for back pain. Eleven people (13%) reported that they would attend a chiropractor first for back pain. Fifty-one percent (51%) of employees reported that their preferred treatment first choice for neck pain was a general practitioner. Chiropractic was rated as third (30%) most common choice for the treatment of neck pain (equal with physiotherapy). The preferred first choice (63% of employees) for headache treatment was a general practitioner. The second most common choice for treatment of headache was a naturopath (50%). Eighty-one percent of employees ranked a general practitioner as their preferred treatment first choice for migraine, and 39% of employees also ranked the general practitioner as the second most common treatment choice for migraine. CONCLUSIONS: In this sample of Australian workers, chiropractic was rated within the top 3 choices for several common neuromusculoskeletal conditions for which they may have chosen a chiropractor. Because of the small sample size and limited parameters of this study, no strong conclusions can be made until further data are collected. PMID- 19646370 TI - A nutritional program improved lipid profiles and weight in 28 chiropractic patients: a retrospective case series. AB - OBJECTIVE: This study retrospectively examined the effects of a 21-day nutritional intervention program, which included fruit and vegetable consumption, energy restriction, and nutritional supplements, on serum lipid measures in 28 chiropractic patients. METHODS: Medical records were reviewed for 28 chiropractic patients who had completed a commercially available 21-day nutritional intervention program between April 2005 and August 2007 and for whom complete serum lipid and weight measures immediately pre- and postintervention were available. The primary outcome was change in serum lipids, and change in body weight was a secondary outcome variable. RESULTS: Significant reductions in total, low-density lipoprotein, very low-density lipoprotein, and high-density lipoprotein cholesterol, and triglycerides were observed. Serum triglycerides decreased from 116.3 +/- 54.6 (mean +/- SD) to 88.6 +/- 40.5 mg/dL (P < .01). Total cholesterol decreased from 223.3 +/- 40.7 to 176.2 +/- 30.0 mg/dL (P < .0001). Low-density lipoprotein cholesterol decreased from 145.7 +/- 36.8 to 110.9 +/- 25.3 mg/dL (P < .0001). High-density lipoprotein cholesterol decreased from 54.3 +/- 14.6 to 47.6 +/- 10.5 mg/dL (P < .001). Weight for patients decreased from 191.2 +/- 38.8 to 182.2 +/- 36.3 lb (P < .0001). CONCLUSIONS: This retrospective case series supports the hypothesis that a nutritional purification intervention program emphasizing fruit and vegetable consumption, energy restriction, and nutritional supplements reduces serum lipids and weight. PMID- 19646369 TI - Sympathetic and parasympathetic responses to specific diversified adjustments to chiropractic vertebral subluxations of the cervical and thoracic spine. AB - OBJECTIVE: The aims of this study were to investigate the response of the autonomic nervous system based upon the area of the spine adjusted and to determine if a cervical adjustment elicits a parasympathetic response and if a thoracic adjustment elicits a sympathetic response. METHODS: Forty patients (25 55 years old) met inclusion criteria that consisted of normal blood pressure, no history of heart disease, and being asymptomatic. Patients were evaluated pre- and post-chiropractic adjustment for the following autonomic responses: blood pressure and pulse rate. Seven patients were measured for heart rate variability. The subjects received either a diversified cervical segment adjustment or a diversified thoracic segment adjustment. RESULTS: Diastolic pressure (indicating a sympathetic response) dropped significantly postadjustment among those receiving cervical adjustments, accompanied by a moderate clinical effect (0.50). Pulse pressure increased significantly among those receiving cervical adjustments, accompanied by a large effect size (0.82). Although the decrease in pulse pressure for those receiving thoracic adjustments was not statistically significant, the decrease was accompanied by a moderate effect size (0.66). CONCLUSION: It is preliminarily suggested that cervical adjustments may result in parasympathetic responses, whereas thoracic adjustments result in sympathetic responses. Furthermore, it appears that these responses may demonstrate the relationship of autonomic responses in association to the particular segment(s) adjusted. PMID- 19646371 TI - Separation anxiety disorder in a 13-year-old boy managed by the Neuro Emotional Technique as a biopsychosocial intervention. AB - OBJECTIVE: To describe a case of an adolescent with separation anxiety disorder (SAD) presenting to a chiropractor for treatment. CLINICAL FEATURES: The patient was a 13-year-old boy who had consulted with a clinical psychologist and had been diagnosed with SAD using the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria. The patient was unable to attend school camps or sleep at friends' homes because of anxiety. INTERVENTION/OUTCOME: The patient underwent 8 sessions with a chiropractor certified in the Neuro Emotional Technique (NET). Two days after his last NET treatment, he attended his first school camp without incident. He also slept away from home at a friend's home for the first time without incident. Six months postintervention, he returned to his clinical psychologist, where she independently reevaluated him stating that he no longer met the criteria for SAD according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. CONCLUSION: This single case report cannot provide a causal relationship between the clinical outcome and NET without further investigations. Neuro Emotional Technique is a unique therapy that does not take the place of psychotherapy; however, it may be used as an adjunct to it. It is possible that, with valid and reliable follow-up research, the biopsychosocial principles that NET addresses may be of value to children and adolescents with SAD. PMID- 19646372 TI - Should the chiropractic profession embrace the doctrine of informed consent? AB - This commentary provides a narrative review of the literature focusing on the use of a health care informed consent process in the United States. This article reviews the current positions of the World Medical Association, American Medical Association, American Chiropractic Association, Wisconsin and New Jersey State Courts, US Federal Government Office of Health Policy and Clinical Outcomes, and 1 college of chiropractic regarding the doctrine of informed consent. The authors recommend that the chiropractic profession embrace the doctrine of informed consent and promulgate it as a standard of care. The implementation of this doctrine by chiropractic physicians promotes and improves the safety of chiropractic interventions. PMID- 19646373 TI - Chiropractic outcomes managing radiculopathy in a hospital setting: a retrospective review of 162 patients. AB - OBJECTIVE: The objective of this study was to gather descriptive information concerning the clinical outcomes of patients with cervical and lumbar radiculopathy treated with a nonsurgical, chiropractic treatment protocol in combination with other interventions. METHODS: This is a retrospective review of 162 patients with a working diagnosis of radiculopathy who met the inclusion criteria (312 consecutive patients were screened to obtain the 162 cases). Data reviewed were collected initially, during, and at the end of active treatment. The treatment protocol included chiropractic manipulation, neuromobilization, and exercise stabilization. Pain intensity was measured using the numerical pain rating scale. RESULTS: Of the 162 cases reviewed, 85.5% had resolution of their primary subjective radicular complaints. The treatment trial was 9 (mean) treatment sessions. The number of days between the first treatment date and the first symptom improvement was 4.2 days (mean). The change in numeric pain scale between initial and final score was 4.2 (median). There were 10 unresolved cases referred for epidural steroid injection, 10 unresolved cases referred for further medication management, and 3 cases referred for and underwent surgery. CONCLUSION: The conservative management strategy we reviewed in our sample produced favorable outcomes for most of the patients with radiculopathy. The strategy appears to be safe. Randomized clinical trials are needed to separate treatment effectiveness from the natural history of radiculopathy. PMID- 19646375 TI - Effect of laser acupoint treatment on blood pressure and body weight-a pilot study. AB - OBJECTIVE: This study reports on the effects of laser acupuncture on blood pressure, body weight, and heart rate variability by stimulating acupuncture points and meridians on college students and faculty members. METHODS: Forty-five students and faculty members from a chiropractic college were recruited in the study. All subjects signed a written informed consent before their participation in the study. This study was a randomized controlled pilot study with subjects divided into control and experimental groups. The control group received a sham low-level laser therapy treatment with no power output to the laser during their "treatment." The experimental group was treated with an activated laser. The acupuncture points used in this study were LI 4 and LI 11 for body weight and blood pressure. The treatment groups received 16 J of laser energy output for a total treatment time of 8 minutes (4 minutes for each of the 2 points). RESULTS: After using the laser treatment for 90 days (at least 12 treatments per subject), both the systolic and diastolic blood pressures decreased significantly (P < .01). The mean systolic blood pressure was 129.6 +/- 14.7 mm Hg before the treatment and was reduced to 122.5 +/- 17.2 mm Hg (P < .001). The mean diastolic blood pressure was 85.6 +/- 8.0 mm Hg before treatment and was reduced to 77.2 +/ 8.7 mm Hg (P < .001). Subject's body weight was reduced in the active acupoint group, but the weight reduction did not reach a significant level. There were no significant changes in the heart rate variability. CONCLUSION: It was concluded that low-level laser treatment of acupoint resulted in lower blood pressure by stimulating the LI 11 and LI 4. No significant difference was observed in both the body weight and heart rate variability after the laser acupoint treatment. PMID- 19646374 TI - Colorado workers' compensation: medical vs chiropractic costs for the treatment of low back pain. AB - OBJECTIVE: Low back disorders (LBDs) are the most common complaint among workers; therefore, many questions arise about cost-effective treatment approaches. This investigation evaluated the differences in cost-related factors among a population of patients selecting chiropractic vs allopathic care for the treatment of nonspecific LBDs. The study hypothesis was that chiropractic care would be more cost-effective or equivalent to allopathic care for the noncomplicated LBDs. METHODS: Cases were extracted from an insurance company database of patients reporting work-related low back injuries who were treated with either chiropractic or allopathic approaches. Cases were matched using the International Classification of Diseases, Ninth Revision, codes 722 (intervertebral disk disorders), 724 (other and unspecified disorders of the back), and 847 (sprains and strains of other and unspecified parts). The data set included 76 chiropractic cases and 2386 medical cases. RESULTS: The total amount paid by the insurance company was 1.7 times higher for patients treated by doctors of chiropractic (DCs) compared with those treated by medical doctors (MDs), and the cost of clinical treatment was 3.3 times higher for the DCs than MDs. CONCLUSION: The cost for treatment by DCs was greater than that of MDs for similarly classified conditions affecting the low back. The amount paid by the insurance company was primarily related to the number of services given by each provider. PMID- 19646376 TI - Radiographic disk height increase after a trial of multimodal spine rehabilitation and vibration traction: a retrospective case series. AB - OBJECTIVE: Although spinal decompression therapy has been touted as an effective treatment of disk pathologies, there is little existing research that specifically uses disk parameters as an outcome measure after a course of spinal decompression therapy. Our study presents multidimensional outcomes after a structured protocol of multimodal chiropractic rehabilitation and uses a radiographic parameter of disk disease as an indication of the effects of a vibration traction decompression-type table. CLINICAL FEATURES: Patients selected for this retrospective cohort reported a medical history of lumbar herniated or bulging disk verified by previous magnetic resonance imaging/computed tomography, history of paresthesia in one or both lower extremities, pain level reported as a minimum of 8/10, and/or history of sciatica or other radicular pain finding. INTERVENTION AND OUTCOME: A total of 6 patients' outcomes are reported in this study. All patients received a multimodal spinal rehabilitation treatment with vibration traction therapy. Positive and statistically significant outcomes were obtained in radiographic disk height, functional rating index, numeric pain rating, spirometry, and patient height. All patients achieved improved outcomes after treatment. CONCLUSION: The multidimensional outcomes reported here were achieved after a structured protocol of multimodal chiropractic rehabilitation. It is unknown which, if any, of these procedures were responsible for the observed improvements. PMID- 19646377 TI - Chiropractic management of a 47-year-old firefighter with lumbar disk extrusion. AB - OBJECTIVE: This case report describes the effect of exercise-based chiropractic treatment on chronic and intractable low back pain complicated by lumbar disk extrusion. CLINICAL FEATURES: A 47-year-old male firefighter experienced chronic, unresponsive low back pain. Pre- and posttreatment outcome analysis was performed on numeric (0-10) pain scale, functional rating index, and the low back pain Oswestry data. Secondary outcome assessments included a 1-rep maximum leg press, balancing times, push-ups and sit-ups the patient performed in 60 seconds, and radiographic analysis. INTERVENTION AND OUTCOME: The patient was treated with Pettibon manipulative and rehabilitative techniques. At 4 weeks, spinal decompression therapy was incorporated. After 12 weeks of treatment, the patient's self-reported numeric pain scale had reduced from 6 to 1. There was also overall improvement in muscular strength, balance times, self-rated functional status, low back Oswestry scores, and lumbar lordosis using pre- and posttreatment radiographic information. CONCLUSION: Comprehensive, exercise-based chiropractic management may contribute to an improvement of physical fitness and to restoration of function, and may be a protective factor for low back injury. This case suggests promising interventions with otherwise intractable low back pain using a multimodal chiropractic approach that includes isometric strengthening, neuromuscular reeducation, and lumbar spinal decompression therapy. PMID- 19646378 TI - Traumatic hand fracture in a patient with osteogenesis imperfecta. AB - OBJECTIVE: This article presents a case of osteogenesis imperfecta and reviews the clinical and radiographic features of this condition. CLINICAL FEATURES: A 27 year-old woman presented with pain in her left hand after a fall while dancing. Plain films revealed multiple fractures in the digits of her left hand. INTERVENTION AND OUTCOME: The patient was referred to an orthopedic specialist for treatment. CONCLUSION: Osteogenesis imperfecta is a heritable disorder of bone, which predisposes patients to fractures after trivial trauma, as was demonstrated in this case. PMID- 19646379 TI - Psychometric properties and clinical usefulness of the Oswestry Disability Index. AB - OBJECTIVE: Outcome measures with good reliability, validity, responsiveness, and low burden of administration are clinically useful. The Oswestry Disability Index (ODI) is one of the most commonly used outcome measures for individuals with low back pain. Psychometric properties of the ODI will determine the questionnaire's suitability as a useful clinical tool. METHODS: A literature search of relevant databases on psychometric evaluation of the ODI was performed. The search was done using the key words disability evaluation, and low back pain, and questionnaires, and reproducibility of results, and the term Oswestry. Inclusion criterion was direct reference regarding psychometric property, interpretability, and burden being included in the abstract. RESULTS: Eight articles met the inclusion criterion. The ODI shows good construct validity; internal consistency is rated as acceptable; test-retest reliability and responsiveness have been shown to be high; and burden of administration is low. CONCLUSIONS: The ODI is a valid, reliable, and responsive condition-specific assessment tool that is suited for use in clinical practice. It is easy to administer and score, objectifies clients' complaints, and monitors effects of therapy. PMID- 19646380 TI - Changes in back pain, sleep quality, and perceived stress after introduction of new bedding systems. AB - OBJECTIVE: This study compared sleep quality and stress-related symptoms between older beds (>/=5 years) and new bedding systems. METHODS: A convenience sample of healthy subjects (women = 30; men = 29) with minor musculoskeletal sleep-related pain and compromised sleep, but with no clinical history of disturbed sleep, participated in the study. Subjects recorded back discomfort and sleep quality upon waking for 28 consecutive days in their own beds (baseline) and for 28 consecutive days (post) on a new bedding system using visual analog scales. Following baseline measures, participant's beds were replaced by new, medium-firm beds, and they again rated their sleep quality and back discomfort. Stress was assessed by a modified stress questionnaire. RESULTS: Repeated-measures analysis of variance was used to treat sleep quality and efficiency and factored responses of the stress items. Results indicated that the subjects' personal bedding systems average 9.5 years old and were moderately priced. Significant (P < .01) improvements were found between pre- and posttest mean values in sleep quality and efficiency. Continued improvement was noted for each of the 4-week data gathering period. Stress measures yielded similar positive changes between pre- and posttest mean values. CONCLUSION: Based on these data, it was concluded that, in this population, new bedding systems increased sleep quality and reduced back discomfort, factors that may be related to abatement of stress-related symptoms. PMID- 19646381 TI - Effects of electrical stimulation of acupuncture points on blood pressure. AB - OBJECTIVE: Arterial hypertension is considered a major contributor to coronary arterial disease. The purpose of the study was to investigate the effects of Hans electrical stimulation of acupuncture points on blood pressure. METHODS: Subjects with normal and elevated blood pressure were recruited and randomly assigned into control and experimental groups. Only the experimental subjects received active Hans electrical stimulation on 2 acupuncture points for 30 minutes each session, twice a week for 5 weeks. RESULTS: Twenty-seven subjects (17 male) were recruited and completed the study. The average age of the subjects was 25 +/- 5 years. The youngest subject was 20 years old and the oldest was 36 years old. After using the Hans electrical stimulation on acupuncture points for 5 weeks, the systolic blood pressure decreased significantly in the experimental group with active treatment. The mean systolic blood pressure was 117.8 +/- 4.2 mm Hg before the treatment and was reduced to 110.8 +/- 5.5 mm Hg (P < .05) in the third week and to 110.1 +/- 5.8 mm Hg in the fifth week (P < .05). The mean diastolic blood pressure was 78.1 +/- 5.0 mm Hg before treatment and was reduced to 77.4 +/- 4.3 mm Hg (P > .05) in the third week and to 74.8 +/- 4.3 mm Hg (P > .05) in the fifth week, but both did not reach statistically significant levels. The systolic and diastolic blood pressures in the control group did not show statistically significant changes. The mean systolic blood pressure was 115.6 +/- 13.3 mm Hg before the treatment and was reduced to 113.0 +/- 12.6 mm Hg (P > 0.05) in the third week and to 112.2 +/- 10.3 mm Hg in the fifth week (P > .05). The mean diastolic blood pressure was 76.4 +/- 7.9 mm Hg before treatment and was reduced to 76.5 +/- 6.9 mm Hg (P > .05) in the third week and to 73.9 +/- 5.4 mm Hg (P > .05) in the fifth week. CONCLUSION: It was concluded that Hans electrical stimulation of acupuncture points reduced systolic blood pressure but not the diastolic blood pressure in the current subject population with normal and elevated blood pressure. PMID- 19646383 TI - Is physical activity contraindicated for individuals with scoliosis? A systematic literature review. AB - OBJECTIVE: The purpose of this study was to perform a systematic review of the literature and other authoritative sources for recommendations regarding the appropriateness of physical and sporting activity for those with scoliosis. METHODS: The literature was systematically searched in PubMed, the Cumulative Index to Nursing and Allied Health Literature, the Index to Chiropractic Literature, and the National Guidelines Clearinghouse from the earliest date of each database through July 2008. All languages and research designs were included. Web sites of respected organizations were searched for position/white papers on scoliosis and physical activity. Included articles were rated using the Oxford Centre for Evidence-Based Medicine criteria, and recommendations for physical activity were made using the Oxford Centre's criteria for grades of recommendation. RESULTS: Of 42 articles retrieved, 11 met the inclusion criteria. The Internet review of 18 organizations yielded no previous guidelines or position papers for physical activity and scoliosis. Recommendations were made from 3 level 3b studies and 8 level 5 studies; they include the following: (1) brace-treated and surgically treated scoliosis patients have demonstrated that they can physically participate in physical activities at the same level as nonsurgical patients (grade C recommendation); (2) nonsurgically treated patients are encouraged to participate in sports and physical activity and (3) scoliosis is not a contraindication to participation in most sports (grade D recommendation); (4) brace-treated scoliosis patients are encouraged to exercise with their brace on; however, exercise may also be done outside of the brace (grade D recommendation); and (5) physical activity may be commenced after surgery for scoliosis; however, no high-quality evidence exists that guides the timing of return to physical activity (grade D recommendation). A potential association between elite-level competition in specific sports at an early age and an increased prevalence of scoliosis has been reported (grade C recommendation). CONCLUSION: This article offers evidence-based guidance to health care providers and to patients with scoliosis when making decisions to participate in physical and sporting activities. PMID- 19646384 TI - A proposed protocol for hand and table sanitizing in chiropractic clinics and education institutions. AB - OBJECTIVE: By nature, chiropractic is a hands-on profession using manipulation applied to the joints with direct skin-to-skin contacts. Chiropractic tables are designed with a face piece to accommodate the prone patient's head in a neutral position and hand rests to allow for relaxed shoulders and upper spine so treatment is facilitated. The purpose of this article is to present a proposed guideline for hand and treatment table surface sanitizing for the chiropractic profession that is evidence-based and can easily be adopted by teaching institutions and doctors in the field. METHODS: A review of the chiropractic literature demonstrated that pathogenic microbes are present on treatment tables in teaching clinics at multiple facilities, yet no standardized protocols exist in the United States regarding table sanitizing and hand hygiene in chiropractic clinics or education institutions. This article reviews the scientific literature on the subject by using several search engines, databases, and specific reviews of documents pertaining to the topic including existing general guidelines. RESULTS: The literature has several existing guidelines that the authors used to develop a proposed protocol for hand and table sanitizing specific to the chiropractic profession. Recommendations were developed and are presented on hand hygiene and table sanitizing procedures that could lower the risk of infection for both clinical personnel and patients in chiropractic facilities. CONCLUSION: This article offers a protocol for hand and table sanitizing in chiropractic clinics and education institutions. The chiropractic profession should consider adoption of these or similar measures and disseminate them to teaching clinics, institutions, and private practitioners. PMID- 19646385 TI - Building a team of champion chiropractors. PMID- 19646382 TI - High-dose folic acid supplementation effects on endothelial function and blood pressure in hypertensive patients: a meta-analysis of randomized controlled clinical trials. AB - OBJECTIVE: Folic acid supplementation has been shown to be an effective agent for improving endothelial function, a prognostic factor for cardiovascular disease; but its effects on systolic and diastolic blood pressure in hypertensive individuals has been met with mixed results. Therefore, the purpose of this study was to provide a comprehensive meta-analysis of randomized controlled trials to investigate the effect of high-dose folic acid supplementation on blood pressure and endothelial function in hypertensive patients. METHODS: Twelve randomized controlled trials published between 1970 and December 2007 were identified using Medline and a manual search. All 12 studies used hypertensive subjects who were supplemented with at least 5000 mug/d of folic acid for between 2 and 16 weeks. Three separate meta-analyses were carried out using a random-effects model, and the overall effect sizes were calculated for changes in systolic and diastolic blood pressures and for changes in endothelial function as measured through the percentage of change in flow-mediated dilation. RESULTS: The pooled estimate of effect of folic acid supplementation on systolic and diastolic blood pressure was -2.03 mm Hg (95% confidence interval [CI], -3.63 to -0.43; P = .04) and 0.01 mm Hg (95% CI, -1.12 to 1.13; not significant), respectively. The pooled estimate of effect of folic acid supplementation on change in flow-mediated dilation was 1.61% (95% CI, 1.27 to 1.96; P = .000). CONCLUSION: Based upon the studies used in this meta-analysis, supplementation with at least 5000 mug/d of folic acid, for a minimum of 6 weeks, can lower systolic blood pressure slightly; but the real clinical benefit is achieved through improved endothelial function. PMID- 19646386 TI - The effects of smoking on intersegmental motion in the upper thoracic spine. PMID- 19646387 TI - A pilot study to determine the effects of a supine sacroiliac orthopedic blocking procedure on cervical spine extensor isometric strength. AB - OBJECTIVE: The purpose of this study was to determine if an orthopedic pelvic blocking procedure affects cervical spine extensor isometric strength. METHODS: Twenty-two participants were sequentially assigned into treatment and control groups. Treatment consisted of a 2-minute procedure using orthopedic blocks (padded wedges with a 45 degrees incline) that were placed bilaterally under the ilia as determined by leg length assessment. Isometric strength measurements took place in 2 sessions with a day of rest between. The treatment group received therapy at the second session immediate to postisometric measures. RESULTS: Outcome measures were the pre- and posttreatment measurements of cervical isometric extension strength in pounds. The t tests showed no statistically significant difference between groups in isometric extension strength before treatment. One-way analysis of variance demonstrated a significant difference between groups after treatment (F(1,21) = 7.174, P = .014). The treatment group demonstrated an average increase of 6.35 (8.18) lb in extensor strength. CONCLUSIONS: The current study showed a statistically significant change in cervical isometric extensor strength after sacroiliac joint blocking. PMID- 19646388 TI - An exploratory mixed-method study to determine factors that may affect satisfaction levels of athletes receiving chiropractic care in a nonclinic setting. AB - OBJECTIVES: The objectives of this study were to determine factors that may affect satisfaction levels of participants in a nonclinic (sport) setting through participant observation and participation. Factors associated with general satisfaction (observed) were determined along with a participant demographic profile, participant knowledge about chiropractic, and satisfaction with treatment received from a chiropractic student. Thereafter, the relationships between the demographic factors, participant knowledge, and participant general satisfaction were determined. Lastly, factors affecting satisfaction levels were compared between the participants and the observers. METHODS: An exploratory mixed-method observational study that compared results reported by 30 participants and 2 observers, regarding the treatment process, by completion of a self-administered questionnaire. Statistical significance was set at P less than or equal to .05. RESULTS: Of the 30 participants, 83.3% were South African, 90% were white, and 63.3% were male, with a mean age of 35.6 years, who reported they were very satisfied with chiropractic care (P = .229). The only factor to produce a significant difference between participants and observers was communication (P = .082 with Spearman = .332). CONCLUSION: In this study, communication had the greatest impact; therefore, it is suggested that positive verbal and nonverbal communication be emphasized in the training of future chiropractic professionals. PMID- 19646389 TI - Asymmetry in atlas bone specimens: a pilot study using radiographic analysis. AB - OBJECTIVE: Vertebral asymmetries can present a challenge to analysis of the anatomical and biomechanical misalignment component of chiropractic vertebral subluxation. The objective of this study was to determine the extent of asymmetry among 10 natural bone atlas specimens using radiographic analysis. METHODS: Ten natural atlas bone specimens' images were recorded using a digital radiographic system, and evaluations were made by 2 independent examiners using the system's software. Mean differences, standard deviations, and agreements were evaluated in regard to bilateral differences. RESULTS: The mean bilateral difference for both examiners was 0.96 mm, with a standard deviation of +/-0.67 mm. There were no statistically significant differences between the mean values for left and right measurements. DISCUSSION: The mean of 0.96 +/- 0.67 mm indicates that measurements up to 1.63 mm (1 SD) or 2.30 mm (2 SDs) are clearly within a reference range of variation for this sample. This information could be used to assist the clinician measuring lateral misalignment of the atlas in determining the amount of expected normal asymmetry for the individual patient before concluding that lateral misalignment of the atlas is present. CONCLUSIONS: These 10 specimens showed an average difference of 0.95 mm +/- 1 SD (0.67 mm) or 2 SDs (1.34 mm) between the left and right sides of the atlas vertebrae. Differences found on radiographs may be due to asymmetry and not actual misalignment. On the average, for these 10 vertebra specimens, a lateral disposition of 1.62 mm on either side should be allowed when arriving at a conclusion for lateral displacement of the atlas. PMID- 19646390 TI - Chiropractic treatment of lumbar spinal stenosis: a review of the literature. AB - OBJECTIVE: The objective of this article was to review the literature on the use of chiropractic for the treatment of lumbar spinal stenosis. METHODS: A literature search was conducted on 4 electronic databases (Medline, Index to Chiropractic Literature, Cumulative Index to Nursing and Allied Health Literature, and Allied and Complementary Medicine Database) for clinical research pertaining to chiropractic treatment of lumbar spinal stenosis. Retrieved articles were hand searched for relevant references. Inclusion criteria consisted of any clinical study design (including case reports) using chiropractic care on patients with lumbar spinal stenosis published in English in the past 25 years. RESULTS: Six articles on a total of 70 patients met the inclusion criteria for the review. These articles included 4 case studies, a case series, and an observational cohort study. Treatments included spinal manipulation and, most often, flexion-distraction manipulation. Numerous other interventions including exercise, activity of daily living modifications, and various passive care modalities were selectively used in the included studies. CONCLUSIONS: There is a paucity of evidence available with respect to chiropractic treatment of spinal stenosis. The limited evidence that is available points toward chiropractic care being potentially beneficial in the treatment of patients with lumbar spinal stenosis, but further clinical investigations are necessary. PMID- 19646391 TI - Upper gastrointestinal hemorrhage after nonresponsive thoracic spine pain: a case report. AB - OBJECTIVE: This case study reports the findings of an upper gastrointestinal hemorrhage in a patient with thoracic spine pain reporting to a chiropractic clinic. The purpose of this article is to highlight the importance of identifying a patient's medication history as well as reviewing the signs and symptoms of gastrointestinal bleeding from a nonvariceal lesion. CLINICAL FEATURES: A 61-year old woman presented with worsening middle thoracic spine pain of 3 months' duration along with recent abdominal pain. Medications, physical therapy, and spinal manipulation did not provide considerable improvement. The patient was taking ibuprofen daily to cope with her back pain. INTERVENTION AND OUTCOME: The initial physical examination demonstrated mild increased tissue tension in the thoracic paraspinal muscles with mild restriction of thoracic spine range of motion secondary to the patient's pain. There was pain on palpation of the T4-5 and T7-8 spinal segments. The physical examination findings did not correlate to the patient's pain presentation, and she was referred back to her primary care physician. Two days after the initial examination, the patient experienced an upper gastrointestinal hemorrhage and underwent emergency surgery. It was determined postoperatively that she had a medication-induced duodenal ulcer that subsequently ruptured. CONCLUSION: An upper gastrointestinal bleed should be considered in the differential diagnosis of a patient with a history of prolonged aspirin or nonsteroidal anti-inflammatory drug use with nonspecific abdominal symptoms. PMID- 19646392 TI - Should the chiropractic profession embrace the doctrine of informed consent? Lehman et al. Journal of Chiropractic Medicine 2008;7:107-114. PMID- 19646393 TI - Should the chiropractic profession embrace the doctrine of informed consent? PMID- 19646394 TI - Surface area congruence of atlas superior articulating facets and occipital condyles. PMID- 19646395 TI - Reply. PMID- 19646396 TI - CK20/CK7 protein expression in colorectal cancer: a marker for progression of colorectal cancer. PMID- 19646400 TI - Struck dysphagic. PMID- 19646399 TI - Phosphorylation and truncation sites of bovine lens connexin 46 and connexin 50. AB - Connexins 46 and 50 combine to form the gap junctions in ocular lens fiber cells. These proteins are known to be modified with fiber cell age; however, limited work has been done to characterize specific lens connexin modifications. In this report, bovine lens membrane proteins were isolated, digested by multiple enzymes, and analyzed by HPLC-tandem mass spectrometry. Automated database searching revealed the locations of both phosphorylation and truncation sites. The results confirmed the full sequence of connexin 46 and 99% of the connexin 50 sequence. Eighteen phosphorylation sites on connexin 50 and nine phosphorylation sites on connexin 46 were identified, all on serine or threonine residues. All but three phosphorylation sites on connexin 50 were located the cytoplasmic C terminus. All of the truncation sites of connexin 50 were localized in the cytoplasmic C-terminus (region 280-304). Truncation sites in connexin 46 were found in four different regions including: the N-terminus (residue G2), the cytoplasmic loop (residues 121-124), the cytoplasmic C-terminus (residues 251 285), and the distal C-terminus (residues 344-395). In an analysis of dissected lenses some truncation sites were specific to nucleus samples and others were detected in both nucleus and cortex samples. PMID- 19646401 TI - Atypical esophagitis. PMID- 19646402 TI - Unusual colon polyps. PMID- 19646403 TI - Young female with pancreatic mass. PMID- 19646404 TI - Can too much acid sour your pancreas? PMID- 19646406 TI - Codon stabilization analysis of the "248" temperature sensitive mutation for increased phenotypic stability of respiratory syncytial virus vaccine candidates. AB - Human respiratory syncytial virus (RSV) is the most important viral agent of serious pediatric respiratory tract illness worldwide. Presently, the most promising vaccine candidate is a live, attenuated, cDNA-derived virus, RSV rA2cp248/404/1030DeltaSH, whose attenuation phenotype is based in large part on a series of point mutations including a glutamine to leucine (Q to L) substitution at amino acid residue 831 of the polymerase protein L, a mutation originally called "248". This mutation specifies both a temperature sensitive (ts) and attenuation phenotype. Reversion of this mutation from leucine back to glutamine was detected in some samples in clinical phase 1 trials. To identify the most genetically stable "attenuating" codon at this position to be included in a more stable RSV vaccine, we sought to create and evaluate recombinant RSVs representing all 20 possible amino acid assignments at this position, as well as small insertions and deletions. The recoverable viruses constituted a panel representing 18 different amino acid assignments, and were evaluated for temperature sensitivity in vitro and attenuation in mice. The original leucine mutation was found to be the most attenuating, followed only by phenylalanine. The paucity of highly attenuating assignments limited the possibility of increasing genetic stability. Indeed, it was not possible to find a leucine or phenylalanine codon requiring more than a single nucleotide change to yield a "non-attenuating" codon, as is necessary for the stabilization strategy. Nonetheless, serial passage of the six possible leucine codons in vitro at increasing temperatures revealed differences, with slower reversion to non attenuated phenotypes for a subset of codons. Thus, it should be possible to modestly increase the phenotypic stability of the rA2cp248/404/1030DeltaSH vaccine virus by codon modification at the locus of the 248 mutation. In addition to characterizing the phenotypes associated with a particular locus in the RSV L protein, this manuscript provides insight into the problem of the instability of point mutations and the limitations of strategies to stabilize them. PMID- 19646407 TI - Expression of tak1 and tram induces synergistic pro-inflammatory signalling and adjuvants DNA vaccines. AB - Improving vaccine immunogenicity remains a major challenge in the fight against developing country diseases like malaria and AIDS. We describe a novel strategy to identify new DNA vaccine adjuvants. We have screened components of the Toll like receptor signalling pathways for their ability to activate pro-inflammatory target genes in transient transfection assays and assessed in vivo adjuvant activity by expressing the activators from the DNA backbone of vaccines. We find that a robust increase in the immune response necessitates co-expression of two activators. Accordingly, the combination of tak1 and tram elicits synergistic reporter activation in transient transfection assays. In a mouse model this combination, but not the individual molecules, induced approximately twofold increases in CD8+ T-cell immune responses. These results indicate that optimal immunogenicity may require activation of distinct innate immune signalling pathways. Thus this strategy offers a novel route to the discovery of a new generation of adjuvants. PMID- 19646408 TI - In silico prediction and ex vivo evaluation of potential T-cell epitopes in glycoproteins 4 and 5 and nucleocapsid protein of genotype-I (European) of porcine reproductive and respiratory syndrome virus. AB - T-cell epitopes of porcine reproductive and respiratory syndrome virus (PRRSV) glycoproteins 4 (GP4), 5 (GP5) and nucleocapsid (N) were predicted using bioinformatics and later tested by IFN-gamma ELISPOT in pigs immunized with either a modified live vaccine (MLV) or DNA (open reading frames 4, 5 or 7). For MLV-vaccinated pigs, immunodominant epitopes were found in N but T-epitopes were also found in GP4 and GP5. For DNA-immunized pigs, some peptides were differently recognized. Using a large set of PRRSV sequences it was shown that N contains a conserved epitope and that for GP5, the genotype-I counterparts of previously reported epitopes of genotype-II strains were also immunogenic. PMID- 19646410 TI - Divergent regulation of adipose tissue metabolism by calorie restriction and inhibition of growth hormone signaling. AB - Calorie restriction (CR) and a reduced growth hormone (GH) signal affect insulin sensitivity and lifespan in mammals in a similar manner. We investigated the effects of CR and moderate inhibition of GH on glucose-stimulated activation of insulin signaling and the expression of genes related to fat metabolism in white adipose tissue (WAT) in rats. We used 10-month-old male, wild-type (W) Wistar rats, fed ad libitum (AL) or a 30% CR diet from 6weeks of age, and transgenic (Tg) rats with moderately suppressed GH signaling. Rats were killed 15min after an intraperitoneal injection of glucose or saline. In control W-AL rats, the levels of serum insulin, phosphorylated (p) insulin receptor (pY-IR), p-Akt, and the expression of glucose transporter (Glut) 4 in the membrane fraction were greater in the glucose-injected group than in the saline-injected group, indicating significant activation of insulin signaling in response to glucose loading. In the W-CR and Tg-AL rats, the serum insulin and pY-IR levels were lower than those in the W-AL rats. The Akt-Glut pathway was up-regulated even after saline-injection. Expression levels of adipogenic and lipogenic genes including PPARgamma, adiponectin, and its receptors, were higher in the W-CR rats than in the W-AL and Tg-AL rats. The present findings indicate adipose tissue metabolic profiles specific to CR. PMID- 19646409 TI - Immune response of horses to vaccination with the recombinant Hc domain of botulinum neurotoxin types C and D. AB - Botulinum neurotoxins, predominantly serotypes C and D, cause equine botulism through forage poisoning. The C-terminal part of the heavy chain of botulinum neurotoxin types C and D (HcBoNT/C and D) was expressed in Escherichia coli and evaluated as a recombinant mono- and bivalent vaccine in twelve horses in comparison to a commercially available toxoid vaccine. A three-dose subcutaneous immunization of adult horses elicited robust serum antibody response in an ELISA using the immunogen as a capture antigen. Immune sera showed dose-dependent high potency in neutralizing specifically the active BoNT/C and D in the mouse protection assay. The aluminium hydroxide based mono- and bivalent recombinant HcBoNT/C and D vaccines were characterized by good compatibility and the ability to elicit protective antibody titers similar or superior to the commercially available toxoid vaccine. PMID- 19646411 TI - Identification of the lipid mediator prostaglandin E2 in tissue immune cells of humans infected with the filaria Onchocerca volvulus. AB - Prostaglandins generated by multiple tissue and immune cells exhibit regulatory effects on the vascular and immune systems. Prostaglandin E(2) (PGE(2)), in particular, affects innate as well as adaptive immune mechanisms. We identified PGE(2) in host immune cells adjacent to Onchocerca volvulus in subcutaneous onchocercomas and the affected skin. Using immunohistology, PGE(2) was predominantly detected in infiltrating macrophages but also in plasma cells. Consecutive sections revealed concomitant presence of PGE(2) and transforming growth factor-beta (TGF-beta), representing a second immunoregulative mediator in macrophages and plasma cells. TGF-beta was preferentially observed in the infiltrating macrophages in patients with a generalized hyporeactive onchocerciasis and less in patients with the hyperreactive form. The presence of PGE(2) and TGF-beta in adjoining host cells infiltrating in the onchocercoma and dermis may indicate containment of inflammatory responses that could favour survival of the filarial parasite. PMID- 19646412 TI - Chagas disease in Spain, the United States and other non-endemic countries. AB - Due to recent trends in migration, there are millions of people from Chagas disease-endemic countries now living in North America, Europe, Australia and Japan, including thousands of people with Trypanosoma cruzi infection. Most infected individuals are not aware of their status. Congenital, transfusion- and/or transplant-associated transmission has been documented in the United States, Spain, Canada and Switzerland; most instances likely go undetected. High priorities include the implementation of appropriate screening, evaluation and clinical management, and better assessment of the true burden associated with this disease. PMID- 19646413 TI - Simultaneous assay of isotopic enrichment and concentration of guanidinoacetate and creatine by gas chromatography-mass spectrometry. AB - A gas chromatography-mass spectrometry (GC-MS) method for the simultaneous measurement of isotopic enrichment and concentration of guanidinoacetate (GAA) and creatine in plasma sample for kinetic studies is reported. The method, based on preparation of the bis(trifluoromethyl)pyrimidine methyl ester derivatives of GAA and creatine, is robust and sensitive. The lowest measurable m(1) and m(3) enrichment for GAA and creatine, respectively, was 0.3%. The calibration curves for measurements of concentration were linear over ranges of 0.5 to 250microM GAA and 2 to 500microM for creatine. The method was reliable for inter- and intraassay precision, accuracy, and linearity. The technique was applied in a healthy adult to determine the in vivo fractional synthesis rate of creatine using primed-constant rate infusion of [1-(13)C]glycine. It was found that isotopic enrichment of GAA reached a plateau by 30min of infusion of [1 (13)C]glycine, indicating either a small pool size or a rapid turnover rate (or both) of GAA. In contrast, the tracer appearance in creatine was slow (slope=0.00097), suggesting a large pool size and a slow rate of synthesis of creatine. This method can be used to estimate the rate of synthesis of creatine in vivo in human and animal studies. PMID- 19646414 TI - An enzyme-coupled continuous spectrophotometric assay for magnesium protoporphyrin IX methyltransferases. AB - The second committed step in chlorophyll biosynthesis is the transfer of a methyl group from S-adenosyl-L-methionine (SAM) to magnesium protoporphyrin IX (MgP) forming MgP monomethylester (MgPME). This reaction is catalyzed by the enzyme MgP methyltransferase (ChlM). Previous investigation of this enzyme has involved the use of time-consuming techniques requiring separation of products from substrates. More recent methyltransferase studies use coupling enzymes to monitor changes in absorption/fluorescence for the measurement of activity. However, due to the spectral properties of porphyrins, many of these assays are unsuitable for analysis of the catalytic properties of ChlM. Here we report the successful development of a coupled, continuous spectrophotometric assay to measure the activity of ChlM. The product of the methyltransferase reaction, S-adenosyl-l homocysteine (SAH), is converted into adenine and then hypoxanthine by the recombinant coupling enzymes SAH nucleosidase and adenine deaminase, respectively. The appearance of hypoxanthine results in a decrease in absorbance at 265nm. The utility of this assay was shown by the characterization of ChlM from the cyanobacterium Synechocystis sp. PCC 6803. Kinetic parameters obtained support data acquired using the discontinuous HPLC-based assay and provide further evidence for the stimulation of ChlM by the H subunit of magnesium chelatase (ChlH). PMID- 19646415 TI - NF-kappab facilitates oridonin-induced apoptosis and autophagy in HT1080 cells through a p53-mediated pathway. AB - In this study, we investigated the molecular mechanisms involving in oridonin induced apoptosis and autophagy. We found that apoptosis and autophagy were simultaneously induced by oridonin time-dependently in HT1080 cells, and inhibition of autophagy by 3MA decreased oridonin-induced apoptosis, indicating that they act in synergy to mediate cell death. In addition, treatment with oridonin caused an increase in NF-kappaB and p53 activities in a time-dependent manner. Inhibition of NF-kappaB or p53 activation by its specific inhibitor PDTC or pifithrin-alpha respectively, significantly reduced both oridonin-induced apoptosis and autophagy accompanied by the decrease in Beclin 1 and LC3 levels. Further experiments confirmed that oridonin-induced p53 activation was reduced by the NF-kappaB inhibitor whereas the activation of NF-kappaB was not affected by p53 inhibition. Taken together, these results demonstrate that NF-kappaB promotes oridonin-induced apoptotic and autophagic cell death through regulating p53 activation in HT1080 cells. PMID- 19646416 TI - Enhancement of BK(Ca) channel activity induced by hydrogen peroxide: involvement of lipid phosphatase activity of PTEN. AB - Large-conductance calcium and voltage-dependent potassium (BK(Ca)) channel is an important determinant of vascular tone. It is activated by hydrogen peroxide (H(2)O(2)) which occurs in various physiological and pathological processes. However, the regulation mechanism is not fully understood. In the present study, the mSlo in the presence or absence of hbeta1 were cotransfected with the PTEN(wt), PTEN(C124S), PTEN(G129E) in HEK 293 cells. Typical BK(Ca) channel currents could be recorded in cell-attached configurations. We found that PTEN(wt) reduced the H(2)O(2)-induced BK(Ca) channel activation during the initial 10 min treatment. In contrast, coexpression with catalytically inactive PTEN(C124S)/PTEN(G129E) mutants that lack lipid phosphatase activity produced no regulation on the H(2)O(2)-induced BK(Ca) channel activation. These results demonstrated that PTEN regulated the H(2)O(2)-induced BK(Ca) channel activation through phosphatidylinositol 3-phosphatse. However, the inhibitory effect of PTEN on the H(2)O(2)-induced BK(Ca) channel activation was attenuated when cells were treated with H(2)O(2) at concentrations higher than 100 microM or at 100 microM for long-term treatment. In addition, the p-AKT expression level in PTEN(wt) overexpressing cells was lower than that in control cells, and the increase of cytoplasmic free calcium concentration ([Ca(2+)](i)) induced by H(2)O(2) was also inhibited. These findings may elucidate a new mechanism for H(2)O(2)-induced BK(Ca) channel activation and provide some evidences for the role of PTEN on vasodilation induced by H(2)O(2). PMID- 19646417 TI - Mixed modes in opening of KcsA potassium channel from a targeted molecular dynamics simulation. AB - Potassium channels conduct K(+) flow selectively across the membrane through a central pore. During a process called gating, the potassium channels undergo a conformational change that opens or closes the ion-conducting pore. The potassium channel KcsA has been structurally determined in its closed state. However, the dynamic mechanism of the gating transition of the KcsA channel is still being investigated. Here, a targeted molecular dynamics simulation up to 150ns is performed to investigate the detailed opening process of the KcsA channel with an open Kv1.2 structure serving as the target. The channel arrived at a self determined quasi-stable state within 60ns. The rigid-body and hinge-bending modes are observed mixed together in the remaining 90ns long quasi-stable state. The mixed-mode movement seems come from the competition between the helix rigidity and the biased-applied gating force. PMID- 19646418 TI - Nicotine can skew the characterization of the macrophage type-1 (MPhi1) phenotype differentiated with granulocyte-macrophage colony-stimulating factor to the MPhi2 phenotype. AB - Macrophages (MPhis) exhibit functional heterogeneity and plasticity in the local microenvironment. Recently, it was reported that MPhis can be divided into proinflammatory MPhis (MPhi1) and anti-inflammatory MPhis (MPhi2) based on their polarized functional properties. Here, we report that nicotine, the major ingredient of cigarette smoke, can modulate the characteristics of MPhi1. Granulocyte-macrophage colony-stimulating factor-driven MPhi1 with nicotine (Ni MPhi1) showed the phenotypic characteristics of MPhi2. Like MPhi2, Ni-MPhi1 exhibited antigen-uptake activities. Ni-MPhi1 suppressed IL-12, but maintained IL 10 and produced high amounts of MCP-1 upon lipopolysaccharide stimulation compared with MPhi1. Moreover, we observed strong proliferative responses of T cells to lipopolysaccharide-stimulated MPhi1, whereas Ni-MPhi1 reduced T cell proliferation and inhibited IFN-gamma production by T cells. These results suggest that nicotine can change the functional characteristics of MPhi and skew the MPhi1 phenotype to MPhi2. We propose that nicotine is a potent regulator that modulates immune responses in microenvironments. PMID- 19646419 TI - NIK is involved in constitutive activation of the alternative NF-kappaB pathway and proliferation of pancreatic cancer cells. AB - Pancreatic cancer has one of the poorest prognoses among human neoplasms. Constitutive activation of NF-kappaB is frequently observed in pancreatic cancer cells and is involved in their malignancy. However, little is known about the molecular mechanism of this constitutive NF-kappaB activation. Here, we show that the alternative pathway is constitutively activated and NF-kappaB-inducing kinase (NIK), a mediator of the alternative pathway, is significantly expressed in pancreatic cancer cells. siRNA-mediated silencing of NIK expression followed by subcellular fractionation revealed that NIK is constitutively involved in the processing of p100 and nuclear transport of p52 and RelB in pancreatic cancer cells. In addition, NIK silencing significantly suppressed proliferation of pancreatic cancer cells. These results clearly indicate that NIK is involved in the constitutive activation of the alternative pathway and controls cell proliferation in pancreatic cancer cells. Therefore, NIK might be a novel target for the treatment of pancreatic cancer. PMID- 19646420 TI - PTP inhibitor IV protects JNK kinase activity by inhibiting dual-specificity phosphatase 14 (DUSP14). AB - Protein phosphorylation plays critical roles in the regulation of protein activity and cell signaling. The level of protein phosphorylation is controlled by protein kinases and protein tyrosine phosphatases (PTPs). Disturbance of the equilibrium between protein kinase and PTP activities results in abnormal protein phosphorylation, which has been linked to the etiology of several diseases, including cancer. In this study, we screened protein tyrosine phosphatases (PTPs) by in vitro phosphatase assays to identify PTPs that are inhibited by bis (4 trifluoromethyl-sulfonamidophenyl, TFMS)-1,4-diisopropylbenzene (PTP inhibitor IV). PTP inhibitor IV inhibited DUSP14 phosphatase activity. Kinetic studies with PTP inhibitor IV and DUSP14 revealed a competitive inhibition, suggesting that PTP inhibitor IV binds to the catalytic site of DUSP14. PTP inhibitor IV effectively and specifically inhibited DUSP14-mediated dephosphorylation of JNK, a member of the mitogen-activated protein kinase (MAPK) family. PMID- 19646421 TI - Resistin differentially modulates neuropeptide gene expression and AMP-activated protein kinase activity in N-1 hypothalamic neurons. AB - Intraventricular resistin is known to reduce food intake, modify hypothalamic gene expression (e.g. NPY, POMC) and influence the activity of novel metabolic enzymes (e.g. 5'AMP-activated protein kinase; AMPK) in the rodent brain. Previously we demonstrated that the hypothalamus, and the N-1 hypothalamic neuronal cell line, also expressed several adipokines, including resistin and adiponectin (ADPN). These data suggested that they might also impact brain function and metabolism. We used the N-1 hypothalamic neuronal cell line to examine NPY, AgRP, POMC, and ADPN expression following acute resistin treatment (45 min; 100 ng/mL and 1000 ng/mL). The total and phosphorylated levels of AMPKalpha and acetyl-CoA carboxylase (ACC) were subsequently assessed using Western blot analysis. Parallel investigations were also conducted following a) resistin overexpression, or b) after the RNAi-mediated attenuation of resistin mRNA in N-1 neurons. Resistin overexpression lowered POMC (-35%, p<0.01), ADPN ( 23%, p<0.05) and NPY (-36%, p<0.05) mRNA as evaluated using realtime RT-PCR, although AgRP remained unchanged, and significant increases in pAMPKalpha and pACC were detected (+47% and +34% respectively, p<0.001). In contrast recombinant resistin only significantly increased the level of pAMPKalpha (+31%; p<0.05), but failed to significantly modify gene expression, in N-1 neurons. Conversely the RNAi-mediated silencing of resistin expression increased AgRP (+37%, p<0.05), POMC (+66%, p<0.0001), ADPN (+87%, p<0.0001), whereas NPY was reduced (-22%, p<0.01) along with pAMPKalpha and pACC (-43% and -35% respectively, p<0.001). In summary, these in vitro data suggest that endogenous resistin might be capable of fine-tuning the expression and enzymatic activity of various hypothalamic targets previously implicated in the delicate homeostatic control of food intake. As such, resistin may be part of an autocrine/paracrine loop, which may in turn contribute to some of the reported effects of resistin on energy metabolism. PMID- 19646423 TI - Alpha-synuclein knockdown attenuates MPP+ induced mitochondrial dysfunction of SH SY5Y cells. AB - Alpha-synuclein is one of the main constituents of Lewy bodies and plays an important role in the pathology of Parkinson's disease. Mutation or overexpression of alpha-synuclein causes Parkinson's disease, and downregulation of alpha-synuclein resists MPP(+)-induced cell death, but the mechanism remains elusive. In this study, we attempted to explore the effect of alpha-synuclein knockdown on mitochondrial function in MPP(+)-treated SH-SY5Y cells. We reconstructed the short hairpin RNA expression vector, pGenesil-2, specially targeting alpha-synuclein mRNA, and it was stably transfected into SH-SY5Y cells. Cell viability, nuclear morphology, and mitochondrial membrane potential were then detected, and the expression of alpha-synuclein, cytochrome c, Bcl-2 and Bax were analyzed by Western blotting. The results showed that after exposure to 500 microM MPP(+) for 24 h, about 41.0+/-1.5% control cells showed low mitochondrial membrane potential. However, the percentage was 13.6+/-1.2% in MPP(+) treated alpha-synuclein knockdown cells. MPP(+) induced cytochrome c release significantly, which was about 3.1-fold compared with that of control. However, in alpha-synuclein knockdown cells, the release of cytochrome c was blocked, which was about 1.4-fold compared with that of control. The Bcl-2/Bax ratio of SH SY5Y cells reduced to 35.5+/-3.8% after MPP(+) treatment, and this ratio was 85.2+/-3.0% in MPP(+) treated alpha-synuclein knockdown cells. These data suggest that knockdown of alpha- synuclein might be an effective means in rescuing MPP(+) induced mitochondrial dysfunction of SH-SY5Y cells. PMID- 19646422 TI - Saccade trajectories evoked by sequential and colliding stimulation of the monkey superior colliculus. AB - Using microstimulation we employed an explicit experimental control of activity in the superior colliculus at two sites within the motor map. We compared saccade metrics and dynamics evoked at each site independently with those caused by sequential presentation and collisions of the two stimulation trains. Essentially, we forced controlled spatio-temporal patterns of activity into the saccade control circuit with various timing relationships from known sites within the collicular motor map, thus revealing the spatio-temporal transformation from superior colliculus to eye movement dynamics under experimentally controlled conditions. We extend prior findings about decreasing time intervals between sequential presentations of stimulations to include mid-flight combinations and dynamic modifications of trajectory. We explore how asynchronous collisions between two movements systematically engage a normalization mechanism of movement metrics, and demonstrate how dynamic patterns of activity across the SC motor map can create mid-flight curvature of movement through the post-collicular dynamics of a displacement controller. The explicit control addresses feasibility for systems control models and provides benchmark data for experimental verification of model mechanisms. PMID- 19646424 TI - Regulation of alcohol-seeking by orexin (hypocretin) neurons. AB - Orexins (hypocretins) are found primarily within a restricted portion of neurons within the hypothalamus, but provide innervation across the neuraxis. Orexin A (hypocretin 1) has been implicated in drug and food reward. Not surprisingly therefore, interest has come to bear on whether orexins are implicated in aspects of alcohol consumption and/or seeking. This mini-review provides a concise, but timely, discussion on this issue. The evidence to date would suggest a role for orexins in alcohol use, and integration of orexin-containing neurons in reward seeking circuitry. There are however still many unanswered questions, some of which are canvassed herein. PMID- 19646425 TI - cGMP promotes neurite outgrowth and growth cone turning and improves axon regeneration on spinal cord tissue in combination with cAMP. AB - Cyclic adenosine monophosphate (cAMP) has been intensively studied in recent years in order to elucidate its contribution in intracellular signalling mechanisms that regulate axon growth and guidance, and also to test if its activation can promote axon regeneration after injury. Cyclic guanosine monophosphate (cGMP), however, has been given considerably less attention even though it too mediates intracellular signalling cascades activated by extracellular guidance cues. cGMP can promote neurite outgrowth in neuronal cell lines but its role in promoting growth and regeneration of primary neurons is not well established. Here, we have examined the effects of elevating cGMP activity on axon growth, guidance and regeneration in vitro. We have found that, like cAMP elevation, activation of cGMP increases rat dorsal root ganglion (DRG) neurite outgrowth on a polylysine substrate and that asymmetric cGMP elevation promotes attractive growth cone turning. When grown in an in vitro model of axon regeneration activation of cGMP alone was not sufficient to promote adult neurite outgrowth. However, when combined with cAMP elevation substantial regeneration of adult neurites is achieved, superior to that achieved with either cAMP or cGMP alone. Regeneration is enhanced still further with simultaneous application of a Nogo receptor blocking peptide, suggesting this combinatorial strategy could achieve far greater axon regeneration in vivo than targeting individual cell signalling mechanisms. PMID- 19646427 TI - Another potential marker linking gender and cardiac mortality: PAPP-A--a new marker in risk stratification for women presenting with chest pain. PMID- 19646426 TI - Bone marrow-derived cells are the major source of MMP-9 contributing to blood brain barrier dysfunction and infarct formation after ischemic stroke in mice. AB - Matrix metalloproteinase (MMP)-9 has been shown to contribute to blood-brain barrier (BBB) disruption, infarct formation, and hemorrhagic transformation after ischemic stroke. The cellular source of MMP-9 detectable in the ischemic brain remains controversial since extracellular molecules in the brain may be derived from blood. We here demonstrate that bone marrow-derived cells are the major source of MMP-9 in the ischemic brain. We made bone marrow chimeric mice with MMP 9 null and wild-type as donor and recipient. After 90 min of transient focal cerebral ischemia, MMP-9 null mice receiving wild-type bone marrow showed comparable outcomes to wild-type in brain MMP-9 levels and BBB disruption (endogenous albumin extravasation) at 1 h post-reperfusion and infarct size at 24 h post-reperfusion. In contrast, wild-type animals replaced with MMP-9 null bone marrow showed barely detectable levels of MMP-9 in the ischemic brain, with attenuations in BBB disruption and infarct size. MMP-9 null mice receiving wild type bone marrow showed enhanced Evans blue extravasation as early as 1 h post reperfusion compared to wild-type mice replaced with MMP-9 null bone marrow. These findings suggest that MMP-9 released from bone marrow-derived cells influences the progression of BBB disruption in the ischemic brain. PMID- 19646428 TI - Heparin interference in the cerebrospinal fluid protein assay measured with a pyrogallol red-molybdate complex. AB - BACKGROUND: Increased cerebrospinal fluid (CSF) total protein is a useful indicator of meningeal or central nervous system disease. Occasionally the primary care physicians added heparin to CSF samples to avoid clotting. The aim of this study is to investigate the interference of heparin on CSF total protein measurement. METHODS: CSF specimens were collected from 230 in-patients with various diseases and analyzed by the Vitros 950 PROT slide and the Toshiba TBA 120FR assay. After adding 0, 0.0625, 0.25, 0.5, 0.75, 1, 2 and 4 IU/ml of heparin that was diluted in 20 microl of normal saline to 180 microl of CSF aliquots, CSF total protein concentrations were determined again by the 2 assay systems in the absence or presence of protamine. RESULTS: At low (<40 mg/dl) and mildly increased (40-or<100 mg/dl) CSF total protein, the measured protein concentrations significantly decreased up to 91% when 4 IU/ml of heparin was added to the samples before being analyzed by the Toshiba TBA-120FR assay. At moderately increased (100-or<200 mg/dl) and high (>or=200 mg/dl) CSF total protein, 62% and 27% decreases were found, respectively. Only 1-8% decline was found when 4 IU/ml of heparin was added to the samples before being analyzed by the Vitros 950 PROT assay. Addition of protamine partially reversed the interference of heparin. CONCLUSIONS: The interference of heparin in the CSF total protein assay is dependent on the reaction principle, especially when the CSF total protein level is normal to mildly elevated. PMID- 19646429 TI - Elevated concentrations of oxidized lipoprotein(a) are associated with the presence and severity of acute coronary syndromes. AB - OBJECTIVE: To investigate possible mechanisms and association of increased oxidized Lp(a) [ox-Lp(a)] levels with presence and extent of acute coronary syndromes (ACS). METHODS: Ox-Lp(a) levels were studied in 96 patients with ACS, 89 patients with stable coronary artery disease (CAD), and 100 control subjects. RESULTS: Compared to control, ox-Lp(a) levels increased in stable CAD patients (P<0.001), and especially in ACS (P<0.001) (ACS, 16.29+/-13.80 microg/ml; stable CAD, 10.04+/-10.32 microg/ml; control, 7.10+/-9.16 microg/ml). The ratio of ox Lp(a) to Lp(a) was higher in the ACS than those in the stable CAD (P<0.05) and control (P<0.001). Ox-Lp(a) levels were found associated with a graded increase in extent of angiographically documented CAD in the ACS (R=0.275, P=0.007), while not in the stable CAD (R=0.090, P=0.402). Multiple linear regression analysis found ox-Lp(a) (beta=0.271, P=0.019), age (beta=0.244, P=0.038) and TG (beta=0.213, P=0.070) accounted for 11.1% of the variation in the extent of angiographically documented CAD in ACS patients; Lp(a) (beta=0.415, P=0.000) and extent of CAD (beta=0.193, P=0.071) accounted for 21.5% of that in ox-Lp(a) levels. CONCLUSION: Elevated ox-Lp(a) levels are associated with presence and severity of ACS, and may be useful for identification of patients with ACS. PMID- 19646430 TI - Differential expression profiling of microRNAs and their potential involvement in renal cell carcinoma pathogenesis. AB - OBJECTIVE: We seek to identify the differentially expressed miRNAs in the clear cell subtype (ccRCC) of kidney cancer. DESIGN AND METHODS: We performed a miRNA microarray analysis to compare the miRNA expression levels between ccRCC tissues and their normal counterpart. The top dysregulated miRNAs were validated by quantitative RT-PCR analysis. Bioinformatics analysis was also performed. RESULTS: A total of 33 dysregulated miRNAs were identified in ccRCC, including 21 upregulated miRNAs and many of these miRNAs have been reported to be dysregulated in other malignancies and have a potential role in cancer pathogenesis. The miRNAs showed a significant correlation with reported chromosomal aberration sites. We also utilized target prediction algorithms to identify gene targets. Preliminary analyses showed these targets can be directly involved in RCC pathogenesis. CONCLUSION: We identified miRNAs that are dysregulated in ccRCC and bioinformatics analysis suggests that these miRNAs may be involved in cancer pathogenesis and have the potential to be biomarkers. PMID- 19646431 TI - Enhancing prostate cancer cryotherapy using tumour necrosis factor related apoptosis-inducing ligand (TRAIL) sensitisation in an in vitro cryotherapy model. AB - Cryotherapy is a minimally invasive treatment for prostate cancer. Complete ablation of cancer tissue some times fails and results in disease recurrence. In this study we investigate the effect of TRAIL as a sensitising agent to enhance the effects of cryotherapy on prostate cancer cells. Prostate cancer cells were cooled using Endocare cryo-system to mimic temperatures achieved during clinical cryotherapy. The effects of TRAIL, cryotherapy or combination of both treatment on DU-145 and PC-3 were evaluated. Viability and mode of cell death was assessed following treatment. Cryotherapy did not result in complete cell death at temperature -40 degrees C. Cells died by both necrosis and apoptosis. Cells which survived freeze-thaw cycle became more sensitive to a second freezing injury. TRAIL resulted in minimal cell death. Concomitant treatment of the tumour cells with TRAIL and cryotherapy resulted in complete loss of viability at -10 and -20 degrees C. Cell death was mainly due to marked increase in necrosis. Our finding demonstrates that combined treatment of TRAIL and cryotherapy represent a novel approach to increase the sensitivity to cryotherapy. This combined approach may be feasible for locally advanced prostate cancer. PMID- 19646432 TI - Osmotic tolerance limits and membrane permeability characteristics of stallion spermatozoa treated with cholesterol. AB - Stallion spermatozoa exhibit osmotic damage during the cryopreservation process. Recent studies have shown that the addition of cholesterol to spermatozoal membranes increases the cryosurvival of bull, ram and stallion spermatozoa, but the exact mechanism by which added cholesterol improves cryosurvival is not understood. The objectives of this study were to determine if adding cholesterol to stallion sperm membranes alters the osmotic tolerance limits and membrane permeability characteristics of the spermatozoa. In experiment one, stallion spermatozoa were treated with cholesterol-loaded cyclodextrin (CLC), subjected to anisotonic solutions and spermatozoal motility analyzed. The spermatozoa were then returned to isotonic conditions and the percentages of motile spermatozoa again determined. CLC treatment increased the osmotic tolerance limit of stallion spermatozoa in anisotonic solutions and when returned to isotonic conditions. The second and third experiments utilized an electronic particle counter to determine the plasma membrane characteristics of stallion spermatozoa. In experiment two, stallion spermatozoa were determined to behave as linear osmometers. In experiment three, spermatozoa were treated with CLC, incubated with different cryoprotectants (glycerol, ethylene glycol or dimethyl formamide) and their volume excursions measured during cryoprotectant removal at 5 degrees and 22 degrees C. Stallion spermatozoa were less permeable to the cryoprotectants at 5 degrees C than 22 degrees C. Glycerol was the least permeable cryoprotectant in control cells. The addition of CLC's to spermatozoa increased the permeability of stallion spermatozoa to the cryoprotectants. Therefore, adding cholesterol to spermatozoal membranes reduces the amount of osmotic stress endured by stallion spermatozoa during cryopreservation. PMID- 19646434 TI - Non-invasive diagnosis of early pulmonary disease in PECAM-deficient mice using infrared pulse oximetry. AB - Pulse oximetry is a common tool for detecting reduced pulmonary function in human interstitial lung diseases. It has not previously been used in a mouse model of interstitial lung disease. Further, platelet endothelial cell adhesion molecule deficient mice rarely show symptoms until disease is advanced. Using blood oxygen saturation, different stages of disease could be identified in a non-invasive manner. These stages could be correlated to pathology. Collagen deposition, using Picrosirius Red, did correlate with blood oxygen saturation. These studies are the first to show the use of an infrared pulse oximetry system to analyze the progression of a fibrotic interstitial lung disease in a mouse model of the human diseases. Further, these studies show that an early alveolar damage/enlargement event precedes the fibrosis in this mouse model, a stage that represents the best targets for disease analysis and prevention. This stage does not have extensive collagen deposition. Most importantly, targeting this earliest stage of disease for therapeutic intervention may lead to novel treatment for human disease. PMID- 19646433 TI - Drosophila cortex and neuropile glia influence secondary axon tract growth, pathfinding, and fasciculation in the developing larval brain. AB - Glial cells play important roles in the developing brain during axon fasciculation, growth cone guidance, and neuron survival. In the Drosophila brain, three main classes of glia have been identified including surface, cortex, and neuropile glia. While surface glia ensheaths the brain and is involved in the formation of the blood-brain-barrier and the control of neuroblast proliferation, the range of functions for cortex and neuropile glia is less well understood. In this study, we use the nirvana2-GAL4 driver to visualize the association of cortex and neuropile glia with axon tracts formed by different brain lineages and selectively eliminate these glial populations via induced apoptosis. The larval central brain consists of approximately 100 lineages. Each lineage forms a cohesive axon bundle, the secondary axon tract (SAT). While entering and traversing the brain neuropile, SATs interact in a characteristic way with glial cells. Some SATs are completely invested with glial processes; others show no particular association with glia, and most fall somewhere in between these extremes. Our results demonstrate that the elimination of glia results in abnormalities in SAT fasciculation and trajectory. The most prevalent phenotype is truncation or misguidance of axon tracts, or abnormal fasciculation of tracts that normally form separate pathways. Importantly, the degree of glial association with a given lineage is positively correlated with the severity of the phenotype resulting from glial ablation. Previous studies have focused on the embryonic nerve cord or adult-specific compartments to establish the role of glia. Our study provides, for the first time, an analysis of glial function in the brain during axon formation and growth in larval development. PMID- 19646435 TI - Effects of inhibition of neuronal nitric oxide synthase on basal retinal blood flow regulation. AB - Nitric oxide (NO) has been observed to regulate blood flow under basal and stimulated conditions in the retina. Recent evidence suggests that NO produced by neuronal nitric oxide synthase (nNOS) may regulate blood flow in addition to that produced by endothelial nitric oxide synthase (eNOS). The objective of the current study was to investigate the contribution of NO produced by nNOS in the regulation of basal retinal blood flow. A non-specific NOS inhibitor N (G)-nitro l-arginine methyl ester (l-NAME) and the specific nNOS inhibitors 1-(2 trifluoromethylphenyl) imidazole (TRIM) and (4S)-N-(4-amino-5 [aminoethyl] aminopentyl)-N-nitroguanidine (AAAN) were injected into the vitreous (intravitreal) of Long-Evans rats. Vessel diameters, velocities and volumetric blood flow rates (VBF) in the retinal circulation were determined prior to and in 30-min intervals for 4-4.5h after injection. In addition, the basal amount of nNOS in the rat retina was quantified using a specific enzyme linked immunoassay (ELISA). Treatment with l-NAME and TRIM significantly decreased diameters and VBF. Compared with saline, treatment with l-NAME and TRIM produced a significant (p<0.001) decrease of approximately 12-17% in vessel diameters. Treatment with AAAN significantly decreased vessel diameters and venous VBF. Compared with saline AAAN produced a significant decrease of approximately 7% in arterial (p<0.001) and 5% in venous (p=0.011) diameters, respectively. The amount of nNOS in the rat retina was 0.17+/- 0.0147 pmol mg(-1) of dry retina. The results suggest that though inhibition of nNOS decreases basal diameters, constant VBF is maintained in the retinal circulation. PMID- 19646436 TI - A spatio-temporal analysis of motoneuron survival, axonal regeneration and neurotrophic factor expression after lumbar ventral root avulsion and implantation. AB - Reimplantation of avulsed rat lumbar spinal ventral roots results in poor recovery of function of the denervated hind limb muscles. In contrast, reimplantation of cervical or sacral ventral roots is a successful repair strategy that results in a significant degree of regeneration. A possible explanation for this difference could be that following lumbar root avulsion, axons have to travel longer distances towards their target muscles, resulting in prolonged denervation of the distal nerve and a diminished capacity to support regeneration. Here we present a detailed spatio-temporal analysis of motoneuron survival, axonal regeneration and neurotrophic factor expression following unilateral avulsion and implantation of lumbar ventral roots L3, L4, and L5. Reimplantation prolongs the survival of motoneurons up to one month post-lesion. The first regenerating motor axons entered the reimplanted ventral roots during the first week and large numbers of fibers gradually enter the lumbar plexus between 2 and 4 weeks, indicating that axons enter the reimplanted roots and plexus over an extended period of time. However, motor axon counts show that relatively few axons reach the distal sciatic nerve in the 16 week post-lesion period. The observed initial increase and subsequent decline in expression of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor correlate with the apparent spatio-temporal decline in the regenerative capacity of motor axons, indicating that the distal nerve is losing its capacity to support regenerating motor axons following prolonged denervation. These findings have important implications for future strategies to promote long-distance regeneration through distal, chronically denervated peripheral nerves. PMID- 19646437 TI - In-vivo imaging with small animal FDG-PET: a tool to unlock the secrets of epileptogenesis? PMID- 19646438 TI - Endogenous BDNF regulates induction of intrinsic neuronal growth programs in injured sensory neurons. AB - Identification of the molecule(s) that globally induce a robust regenerative state in sensory neurons following peripheral nerve injury remains elusive. A potential candidate is brain-derived neurotrophic factor (BDNF), the sole neurotrophin upregulated in sensory neurons after peripheral nerve injury. Here we tested the hypothesis that BDNF plays a critical role in the regenerative response of mature rat sensory neurons following peripheral nerve lesion. Neutralization of endogenous BDNF was performed by infusing BDNF antibodies intrathecally via a mini-osmotic pump for 3 days at the level of the fifth lumbar dorsal root ganglion, immediately following unilateral spinal nerve injury. This resulted in decreased expression of the injury/regeneration-associated genes growth-associated protein-43 and Talpha1 tubulin in the injured sensory neurons as compared to injury plus control IgG infused or injury alone animals. Similar results were observed following inhibition of BDNF expression by intrathecal delivery of small interfering RNAs (siRNA) targeting BDNF starting 3 days prior to injury. The reduced injury/regeneration-associated gene expression correlated with a significantly reduced intrinsic capacity of these neurons to extend neurites when assayed in vitro. In contrast, delayed infusion of BDNF antibody for 3 days beginning 1 week post-lesion had no discernible influence on the elevated expression of these regeneration-associated markers. These results support an important role for endogenous BDNF in induction of the cell body response in injured sensory neurons and their intrinsic ability to extend neurites, but BDNF does not appear to be necessary for maintaining the response once it is induced. PMID- 19646439 TI - Babesia bovis: a comprehensive phylogenetic analysis of plastid-encoded genes supports green algal origin of apicoplasts. AB - Apicomplexan parasites commonly contain a unique, non-photosynthetic plastid-like organelle termed the apicoplast. Previous analyses of other plastid-containing organisms suggest that apicoplasts were derived from a red algal ancestor. In this report, we present an extensive phylogenetic study of apicoplast origins using multiple previously reported apicoplast sequences as well as several sequences recently reported. Phylogenetic analysis of amino acid sequences was used to determine the evolutionary origin of the organelle. A total of nine plastid genes from 37 species were incorporated in our study. The data strongly support a green algal origin for apicoplasts and Euglenozoan plastids. Further, the nearest green algae lineage to the Apicomplexans is the parasite Helicosporidium, suggesting that apicoplasts may have originated by lateral transfer from green algal parasite lineages. The results also substantiate earlier findings that plastids found in Heterokonts such as Odontella and Thalassiosira were derived from a separate secondary endosymbiotic event likely originating from a red algal lineage. PMID- 19646440 TI - Genotyping, physiological features and proteolytic activities of a potentially pathogenic Acanthamoeba sp. isolated from tap water in Brazil. AB - Acanthamoeba spp., known to cause keratitis and granulomatous encephalitis in humans, are frequently isolated from a variety of water sources. Here we report for the first time the characterization of an Acanthamoeba sp. (ACC01) isolated from tap water in Brazil. This organism is currently being maintained in an axenic growth medium. Phylogenetic analysis based on SSU rRNA gene sequences positioned the new isolate in genotype T4, closest to the keratitis-causing isolate, A. polyphaga ATCC 30461 ( approximately 99% similarity). Acanthamoeba ACC01 and A. polyphaga 30461 both grew at 37 degrees C and were osmotically resistant, multiplying in hyperosmolar medium. Both isolates secreted comparable amounts of proteolytic enzymes, including serine peptidases that were optimally active at a near neutral/alkaline pH and resolved identically in gelatin gels. Incubation of gels at pH 4.0 with 2mM DTT also indicated the secretion of similar cysteine peptidases. Altogether, the results point to the pathogenic potential of Acanthamoeba ACC01. PMID- 19646441 TI - Entamoeba invadens: cloning and molecular characterization of chitinases. AB - Entamoeba histolytica, the causative agent of amebiasis infects through its cyst form and this transmission may be blocked using encystation specific protein as drug target. In this study, we have characterized the enzyme chitinase which express specifically during encystation. The reptilian parasite Entamoeba invadens, used as a model for encystation study contain three chitinases. We report the molecular cloning, over-expression and biochemical characterization of all three E. invadens chitinase. Cloned chitinases were over-expressed in bacterial system and purified by affinity chromatography. Their enzymatic profiles and substrate cleaving patterns were characterized. All of them showed binding affinity towards insoluble chitin though two of them lack the chitin binding domain. All the chitinases cleaved and released dimmers from the insoluble substrate and act as an exochitinase. Homology modeling was also done to understand the substrate binding and cleavage pattern. PMID- 19646442 TI - Binding of divalent cations is essential for the activity of the organellar peptidasome in Arabidopsis thaliana, AtPreP. AB - The dual-targeted mitochondrial and chloroplastic zinc metallooligopeptidase from Arabidopsis, AtPreP, functions as a peptidasome that degrades targeting peptides and other small unstructured peptides. In addition to Zn located in the catalytic site, AtPreP also contains two Mg-binding sites. We have investigated the role of Mg-binding using AtPreP variants, in which one or both sites were rendered unable to bind Mg(2+). Our results show that metal binding besides that of the active site is crucial for AtPreP proteolysis, particularly the inner site appears essential for normal proteolytic function. This is also supported by its evolutionary conservation among all plant species of PreP. PMID- 19646444 TI - Characterization of a corticotropin-releasing factor (CRF)/diuretic hormone-like peptide from tunicates: insight into the origins of the vertebrate CRF family. AB - The corticotropin-releasing factor (CRF) superfamily of peptides includes the four paralogous vertebrate peptide lineages of CRF, urotensin 1/urocortin/sauvagine, urocortin 2 and urocortin 3, as well as the diuretic hormones (DH) and peptides of the arthropods. However, there are considerable sequence differences between the group of vertebrate peptides and those of the arthropods, notably insects. Because of the likely incidence of the formation of paralogous forms within the insects and the great variation in primary structures among these peptides, establishing the structure of the ancestral vertebrate version has not been possible. We screened the genomes of the tunicates, Ciona intestinalis and Ciona savignii, in silico, using the various conserved motifs of both the vertebrate CRF paralogues and the insect diuretic hormone sequences to identify the structure of the Ciona CRF/DH-like peptide genes. A single peptide gene was found in both genomes that possessed motifs reflective of both groups of peptides. These structures suggest a single CRF-like peptide was inherited by vertebrates and possibly chordates. Moreover, the conserved structure of the CRF peptide may have become constrained once it became associated with the regulation of the hypothalamus-pituitary-adrenal/interrenal axis. PMID- 19646443 TI - Lanreotide reduces the volume of polycystic liver: a randomized, double-blind, placebo-controlled trial. AB - BACKGROUND & AIMS: Therapy for polycystic liver is invasive, expensive, and has disappointing long-term results. Treatment with somatostatin analogues slowed kidney growth in patients with polycystic kidney disease (PKD) and reduced liver and kidney volume in a PKD rodent model. We evaluated the effects of lanreotide, a somatostatin analogue, in patients with polycystic liver because of autosomal dominant (AD) PKD or autosomal-dominant polycystic liver disease (PCLD). METHODS: We performed a randomized, double-blind, placebo-controlled trial in 2 tertiary referral centers. Patients with polycystic liver (n = 54) were randomly assigned to groups given lanreotide (120 mg) or placebo, administered every 28 days for 24 weeks. The primary end point was the difference in total liver volume, measured by computerized tomography at weeks 0 and 24. Analyses were performed on an intention-to-treat basis. RESULTS: Baseline characteristics were comparable for both groups, except that more patients with ADPKD were assigned to the placebo group (P = .03). The mean liver volume decreased 2.9%, from 4606 mL (95% confidence interval (CI): 547-8665) to 4471 mL (95% CI: 542-8401 mL), in patients given lanreotide. In the placebo group, the mean liver volume increased 1.6%, from 4689 mL (95% CI: 613-8765 mL) to 4895 mL (95% CI: 739-9053 mL) (P < .01). Post hoc stratification for patients with ADPKD or PCLD revealed similar changes in liver volume, with statistically significant differences in patients given lanreotide (P < .01 for both diseases). CONCLUSIONS: In patients with polycystic liver, 6 months of treatment with lanreotide reduces liver volume. PMID- 19646446 TI - LPLRFamide causes anorexigenic effects in broiler chicks and Bobwhite quail. AB - Although LPLRFamide was the first member of the RFamide family to be isolated from a vertebrate species, its effects on hunger and satiety-related processes are poorly documented. Thus, we intracerebroventricularly administered LPLRFamide (3.0-15.0 nmol) to both Cobb-500 (a broiler type of Gallus gallus) and Bobwhite quail (Colinus virginianus) chicks and measured their food intake. The threshold of anorexigenic response was 7.0 nmol in Cobb-500 chicks and the effect had diminished by 30 min post-injection. In Bobwhite quail all doses of LPLRFamide tested caused anorexia that remained throughout the 60 min observation period. A comprehensive behavior analysis was conducted and Cobb-500 chicks had increased food pecks early in the observation period and spent a greater amount of time in deep rest. Although food pecks were increased pecking efficiency was decreased. In Bobwhite quail, feeding pecks and the number of jumps were reduced after LPLRFamide treatment. We judged that these behaviors in both species were likely not competitive with ingestion and thus did not secondarily contribute to anorexia. These results demonstrate that LPLRFamide is associated with satiety related processes in Cobb-500 chicks and Bobwhite quail, while threshold of responses are different. PMID- 19646445 TI - Maternal gestational androgen levels in female marmosets (Callithrix geoffroyi) vary across trimesters but do not vary with the sex ratio of litters. AB - Maternal hormones can dramatically modify offspring phenotypes via organizational actions on morphological and behavioral development. In placental mammals, there is the possibility that some portion of hormones in maternal circulation may be derived from fetal origin. We tested the possibility that maternal androgens in pregnant female marmosets reflected, in part, contributions from male fetuses by comparing levels of urinary androgens across pregnancy in females carrying varying numbers of male offspring. We monitored urinary androgen excretion in 18 pregnancies from five female white-faced marmosets (Callithrix geoffroyi). Androgen levels rose significantly in the first trimester of pregnancy, reached a peak in the middle of the second trimester, and then declined gradually until parturition. At no point in pregnancy were levels of urinary androgens higher in females carrying litters that had 50% or more males than in females carrying litters that were less than 50% male. Levels of maternal androgens were not associated with litter size, the number of males in the litter, or with the proportion of the litter that was male. The high levels of androgen in pregnant females are therefore likely of strictly maternal origin, and any modification of fetal growth and development can be considered a 'maternal effect'. PMID- 19646447 TI - Changes in retinoic acid receptor status, 5'-deiodinase activity and neuroendocrine response to voluntary wheel running. AB - Little information is available on the involvement of retinoic acid in processes related to physical activity. The aim of this study was to test the hypotheses that long-term voluntary wheel running (1) modifies RARs concentration as well as the expression of RAR subtypes and (2) alters Iiodothyronine deiodinase (5'-DI) activity in rat liver. To evaluate relevant mechanisms, hepatic gene expression of specific nuclear receptor coregulators and stress hormone levels in plasma have also been measured. Sprague-Dawley rats were housed either in standard cages or in cages with access to running wheel attached for 3 weeks. RAR maximal binding capacity in the liver was found to be significantly lower while gene expression of RAR beta increased in rats exposed to voluntary running compared to that in sedentary controls. Gene expression of RAR alpha, RXR alpha and RXR beta was found to be unaffected. Voluntary running led to a significant decrease of 5' DI activity in the liver. No significant changes in the gene expression of specific nuclear receptor coregulators in the liver were observed. Significant elevation of aldosterone while no changes in ACTH and corticosterone concentrations were observed in rats exposed to wheel running compared to those in controls. In conclusion, this study provided first evidence on the reduction of liver RAR concentrations and 5'-DI activity in response to long-term voluntary wheel running. Neuroendocrine mechanisms involved in these changes may include adrenal mineralo- and glucocorticoids. PMID- 19646448 TI - Hormonal and testing conditions for the induction of conditioned place preference by paced mating. AB - The ability to control or pace the sexual interaction has important physiological and behavioral consequences for the female rat. Paced mating favors reproduction and induces a positive affective state as revealed by conditioned place preference (CPP). In the present experiment we evaluated: 1) If paced mating induces CPP in naturally cycling females; 2) If females developed a positive affective state if they paced the sexual interaction through a 1- or a 3-hole pacing chamber; 3) If females that mate with the same male without pacing the sexual interaction develop CPP. In the first experiment intact females were divided in 4 different groups; 2 paced the sexual interaction until receiving 1 or 3 ejaculations; the other 2 groups mated, without pacing the sexual interaction, until receiving 1 or 3 ejaculations. Only the group that paced the sexual interaction until receiving 3 ejaculations developed a positive affective state. In experiments 2 and 3 hormonally treated ovariectomized females were used. In experiment 2 females were allowed to pace the sexual interaction through a 1- or a 3-hole pacing chamber: A clear positive affective state was induced in both testing conditions. Finally, in experiment 3 females did not develop CPP for non-paced sex despite the fact that they mated with the same male in the conditioning sessions. These results demonstrate that the pattern of vaginocervical stimulation that the females received by engaging in approach and avoidance behaviors to pace the sexual interaction can induce a positive affective state in naturally cycling females. They also confirm the existence of a threshold of vaginocervical stimulation for paced mating to induce CPP in female rats. PMID- 19646449 TI - Structure and cleavage specificity of the chymotrypsin-like serine protease (3CLSP/nsp4) of Porcine Reproductive and Respiratory Syndrome Virus (PRRSV). AB - Biogenesis and replication of the porcine reproductive and respiratory syndrome virus (PRRSV) include the crucial step of replicative polyprotein processing by self-encoded proteases. Whole genome bioinformatics analysis suggests that nonstructural protein 4 (nsp4) is a 3C-like serine protease (3CLSP), responsible for most of the nonstructural protein processing. The gene encoding this protease was cloned and expressed in Escherichia coli in order to confirm this prediction. The purified protein was crystallized, and the structure was solved at 1.9 A resolution. In addition, the crystal structure of the Ser118Ala mutant was determined at 2.0 A resolution. The monomeric enzyme folds into three domains, similar to that of the homologous protease of equine arteritis virus, which, like PRRSV, is a member of the family Arteriviridae in the order of Nidovirales. The active site of the PRRSV 3CLSP is located between domains I and II and harbors a canonical catalytic triad comprising Ser118, His39, and Asp64. The structure also shows an atypical oxyanion hole and a partially collapsed S1 specificity pocket. The proteolytic activity of the purified protein was assessed in vitro. Three sites joining nonstructural protein domains in the PRRSV replicative polyprotein are confirmed to be processed by the enzyme. Two of them, the nsp3/nsp4 and nsp11/nsp12 junctions, are shown to be cleaved in trans, while cis cleavage is demonstrated for the nsp4/nsp5 linker. Thus, we provide structural evidence as well as enzymatic proof of the nsp4 protein being a functional 3CLSP. We also show that the enzyme has a strong preference for glutamic acid at the P1 position of the substrate. PMID- 19646450 TI - Sampling bottlenecks in de novo protein structure prediction. AB - The primary obstacle to de novo protein structure prediction is conformational sampling: the native state generally has lower free energy than nonnative structures but is exceedingly difficult to locate. Structure predictions with atomic level accuracy have been made for small proteins using the Rosetta structure prediction method, but for larger and more complex proteins, the native state is virtually never sampled, and it has been unclear how much of an increase in computing power would be required to successfully predict the structures of such proteins. In this paper, we develop an approach to determining how much computer power is required to accurately predict the structure of a protein, based on a reformulation of the conformational search problem as a combinatorial sampling problem in a discrete feature space. We find that conformational sampling for many proteins is limited by critical "linchpin" features, often the backbone torsion angles of individual residues, which are sampled very rarely in unbiased trajectories and, when constrained, dramatically increase the sampling of the native state. These critical features frequently occur in less regular and likely strained regions of proteins that contribute to protein function. In a number of proteins, the linchpin features are in regions found experimentally to form late in folding, suggesting a correspondence between folding in silico and in reality. PMID- 19646451 TI - Matching biochemical reaction kinetics to the timescales of life: structural determinants that influence the autodephosphorylation rate of response regulator proteins. AB - In two-component regulatory systems, covalent phosphorylation typically activates the response regulator signaling protein, and hydrolysis of the phosphoryl group reestablishes the inactive state. Despite highly conserved three-dimensional structures and active-site features, the rates of catalytic autodephosphorylation for different response regulators vary by a factor of almost 10(6). Previous studies identified two variable active-site residues, corresponding to Escherichia coli CheY residues 59 and 89, that modulate response regulator autodephosphorylation rates about 100-fold. Here, a set of five CheY mutants, which match other "model" response regulators (ArcA, CusR, DctD, FixJ, PhoB, or Spo0F) at variable active-site positions corresponding to CheY residues 14, 59, and 89, were characterized functionally and structurally in an attempt to identify mechanisms that modulate autodephosphorylation rate. As expected, the autodephosphorylation rates of the CheY mutants were reduced 6- to 40-fold relative to wild-type CheY, but all still autodephosphorylated 12- to 80-fold faster than their respective model response regulators. Comparison of X-ray crystal structures of the five CheY mutants (complexed with the phosphoryl group analogue BeF(3)(-)) to wild-type CheY or corresponding model response regulator structures gave strong evidence for steric obstruction of the phosphoryl group from the attacking water molecule as one mechanism to enhance phosphoryl group stability. Structural data also suggested that impeding the change of a response regulator from the active to the inactive conformation might retard the autodephosphorylation reaction if the two processes are coupled, and that the residue at position '58' may contribute to rate modulation. A given combination of amino acids at positions '14', '59', and '89' adopted similar conformations regardless of protein context (CheY or model response regulator), suggesting that knowledge of residue identity may be sufficient to predict autodephosphorylation rate, and hence the kinetics of the signaling response, in the response regulator family of proteins. PMID- 19646452 TI - Generalized lattice graphs for 2D-visualization of biological information. AB - Several graph representations have been introduced for different data in theoretical biology. For instance, complex networks based on Graph theory are used to represent the structure and/or dynamics of different large biological systems such as protein-protein interaction networks. In addition, Randic, Liao, Nandy, Basak, and many others developed some special types of graph-based representations. This special type of graph includes geometrical constrains to node positioning in space and adopts final geometrical shapes that resemble lattice-like patterns. Lattice networks have been used to visually depict DNA and protein sequences but they are very flexible. However, despite the proved efficacy of new lattice-like graph/networks to represent diverse systems, most works focus on only one specific type of biological data. This work proposes a generalized type of lattice and illustrates how to use it in order to represent and compare biological data from different sources. We exemplify the following cases: protein sequence; mass spectra (MS) of protein peptide mass fingerprints (PMF); molecular dynamic trajectory (MDTs) from structural studies; mRNA microarray data; single nucleotide polymorphisms (SNPs); 1D or 2D-Electrophoresis study of protein polymorphisms and protein-research patent and/or copyright information. We used data available from public sources for some examples but for other, we used experimental results reported herein for the first time. This work may break new ground for the application of Graph theory in theoretical biology and other areas of biomedical sciences. PMID- 19646453 TI - Mutation-selection equilibrium in games with mixed strategies. AB - We develop a new method for studying stochastic evolutionary game dynamics of mixed strategies. We consider the general situation: there are n pure strategies whose interactions are described by an nxn payoff matrix. Players can use mixed strategies, which are given by the vector (p(1),...,p(n)). Each entry specifies the probability to use the corresponding pure strategy. The sum over all entries is one. Therefore, a mixed strategy is a point in the simplex S(n). We study evolutionary dynamics in a well-mixed population of finite size. Individuals reproduce proportional to payoff. We consider the case of weak selection, which means the payoff from the game is only a small contribution to overall fitness. Reproduction can be subject to mutation; a mutant adopts a randomly chosen mixed strategy. We calculate the average abundance of every mixed strategy in the stationary distribution of the mutation-selection process. We find the crucial conditions that specify if a strategy is favored or opposed by selection. One condition holds for low mutation rate, another for high mutation rate. The result for any mutation rate is a linear combination of those two. As a specific example we study the Hawk-Dove game. We prove general statements about the relationship between games with pure and with mixed strategies. PMID- 19646454 TI - A Segmental Semi Markov Model for protein secondary structure prediction. AB - Hidden Markov Models (HMMs) are practical tools which provide probabilistic base for protein secondary structure prediction. In these models, usually, only the information of the left hand side of an amino acid is considered. Accordingly, these models seem to be inefficient with respect to long range correlations. In this work we discuss a Segmental Semi Markov Model (SSMM) in which the information of both sides of amino acids are considered. It is assumed and seemed reasonable that the information on both sides of an amino acid can provide a suitable tool for measuring dependencies. We consider these dependencies by dividing them into shorter dependencies. Each of these dependency models can be applied for estimating the probability of segments in structural classes. Several conditional probabilities concerning dependency of an amino acid to the residues appeared on its both sides are considered. Based on these conditional probabilities a weighted model is obtained to calculate the probability of each segment in a structure. This results in 2.27% increase in prediction accuracy in comparison with the ordinary Segmental Semi Markov Models, SSMMs. We also compare the performance of our model with that of the Segmental Semi Markov Model introduced by Schmidler et al. [C.S. Schmidler, J.S. Liu, D.L. Brutlag, Bayesian segmentation of protein secondary structure, J. Comp. Biol. 7(1/2) (2000) 233 248]. The calculations show that the overall prediction accuracy of our model is higher than the SSMM introduced by Schmidler. PMID- 19646455 TI - Correlation analysis between mtDNA 4977-bp deletion and ageing. AB - Mitochondrial DNA 4977-bp deletion (common deletion) has been associated with ageing human tissues and a few studies have demonstrated their presence in breast cancer patients too; however, no previous publication evaluated both topics in the same samples group. First, when analyzing 95 breast cancer patients, we found a higher percentage of cases carrying the deletion in non-tumoral tissue 73.68% (70/95) than in the tumoral counterparts 45.26% (43/95), showing that the 4977-bp deletion is a phenomenon which commonly appear first in the non-tumoral breast tissue rather than tumoral tissue. Secondly, we analyzed and compared the ageing related distribution of the common deletion rates, in a control group of 199 samples (ages ranging from 10 to 80 years), with those found in cancer patients. Significant correlation was observed in control cases, between individual age ranges and rates of deletion (chi2: 23.21 and p<0.01). In contrast, non-tumoral breast tissue did not show a pattern of correlation, chi2: 0.042 and p: 0.837. However, interestingly, we found that the risk of having deleted mtDNAs was higher for non-tumoral breast samples than for the control group samples, OR: 2.32 [1.22-4.42, 95% CI]; this could be reflecting that other mechanisms are involved in mitochondrial genome deletion increased rate detected in breast cancer cases, than the normal ageing process. PMID- 19646456 TI - Early methylphenidate exposure enhances morphine antinociception and tolerance in adult rats. AB - Methylphenidate (MPH) is often used to reduce the symptoms of Attention Deficit/Hyperactivity Disorder. Early MPH treatment in rats has been shown to enhance adult morphine-induced antinociception. Although this enhanced antinociception could improve pain treatment, it could also lead to enhanced tolerance to morphine. This hypothesis was tested by examining the effects of MPH administration during the pre-weanling period on morphine-induced antinociception and tolerance in adulthood. Male and female Sprague-Dawley rats received daily IP injections of saline or MPH (2 or 5 mg/kg) for 10 consecutive days beginning on post-natal day (PD) 11. At 60 days of age, morphine (0, 1.8, 3.2, 5.6, 10.0, and 18 mg/kg) antinociception was assessed. Beginning one day later, rats received two daily injections of either saline or morphine (5 mg/kg) for two consecutive days to induce tolerance. On PD 63 cumulative doses of morphine were administered as before to assess the development of tolerance. Rats pretreated with MPH showed enhanced acute morphine antinociception compared to saline pretreated controls. In addition, tolerance to morphine was greater in rats pretreated with MPH early in life. The magnitude of this decrease in morphine potency was dependent on the dose of MPH, such that animals that received 5 mg/kg of MPH from PD 11 to 20 showed the greatest tolerance. These findings demonstrate that MPH exposure during the pre-weanling period has long-lasting effects that include enhanced morphine antinociception and tolerance. PMID- 19646457 TI - Calcium-sensing receptor: a high-affinity presynaptic target for aminoglycoside induced weakness. AB - Administration of aminoglycoside antibiotics can precipitate sudden, profound bouts of weakness that have been attributed to block of presynaptic voltage activated calcium channels (VACCs) and failure of neuromuscular transmission. This serious adverse drug reaction is more likely in neuromuscular diseases such as myasthenia gravis. The relatively low affinity of VACC for aminoglycosides prompted us to explore alternative mechanisms. We hypothesized that the presynaptic Ca(2+)-sensing receptor (CaSR) may contribute to aminoglycoside induced weakness due to its role in modulating synaptic transmission and its sensitivity to aminoglycosides in heterologous expression systems. We have previously shown that presynaptic CaSR controls a non-selective cation channel (NSCC) that regulates nerve terminal excitability and transmitter release. Using direct, electrophysiological recording, we report that neuronal VACCs are inhibited by neomycin (IC(50) 830 +/- 110 microM) at a much lower affinity than CaSR-modulated NSCC currents recorded from acutely isolated presynaptic terminals (synaptosomes; IC(50) 20 +/- 1 microM). Thus, at clinically relevant concentrations, aminoglycoside-induced weakness is likely precipitated by enhanced CaSR activation and subsequent decrease in terminal excitability rather than through direct inhibition of VACCs themselves. PMID- 19646458 TI - Revisiting 23-iodospirostanes. New facts and full characterization. AB - In addition to a previous report, the reaction of tigogenin acetate with ICl in refluxing CHCl(3) produced the hitherto unknown 23R-iodotigogenin acetate, bearing an axial iodine atom at C-23 and its already reported 23S-epimer. The same treatment of sarsasapogenin acetate led to a single diasteromer characterized as 23S-iodosarsasapogenin acetate. A full characterization of the obtained compound including (1)H, (13)C NMR, MS and X-ray diffraction is provided. PMID- 19646459 TI - Synthesis and antitumor activity of new D-seco and D-homo androstane derivatives. AB - Starting from 3beta-hydroxy-17-oxo-16,17-secoandrost-5-ene-16-nitrile (1), the new 16,17-secoandrostane derivatives 4-9 were synthesized. On the other hand, 3beta-hydroxy-17-oxa-D-homoandrost-5-ene-16-one (10) yielded the new d-homo derivatives 12, 13 and 15. In vitro antiproliferative activity of selected compounds against three tumor cell lines (human breast adenocarcinoma ER+, MCF-7, human breast adenocarcinoma ER-, MDA-MB-231, prostate cancer AR-, PC-3, and normal fetal lung fibroblasts, MRC-5) was evaluated. Compounds 3 and 12 showed strong antiproliferative activity against PC-3 cells, the IC(50) values being 2 microM and 0.55 microM, respectively. Compounds 6 (10 microM) and 14 (9 microM) showed moderate activity against MDA-MB-231 cells. The synthesized compounds 1-3, 5-8, 10 and 12-15 were not toxic to normal fetal lung fibroblasts cells, MRC-5. PMID- 19646460 TI - Lithocholate--a promising non-calcaemic calcitriol surrogate for promoting human osteoblast maturation upon biomaterials. AB - BACKGROUND AND AIMS: Calcitriol, an active vitamin D metabolite, has a limited application in bone repair because of its undesirable hypercalcaemic action. However it has emerged that lithocholic acid (LCA) is a non-calcaemic vitamin D receptor ligand but whether this steroid can support osteoblast maturation has not been reported. Using the human osteoblast cell line, MG63, we explored the potential of LCA and LCA derivatives to secure osteoblast maturation. RESULTS: The co-stimulation of cells with LCA, LCA acetate or LCA acetate methyl ester (0.5-5 microM) and lysophosphatidic acid (LPA, 20 microM) resulted in clear, synergistic increases in MG63 maturation that was both time and dose dependent. Cells grown upon both titanium and hydroxyapatite, two widely used implant materials, responded well to co-treatment with LCA acetate (5 microM) and LPA (20 microM) as demonstrated by stark, synergistic increases in ALP activity. Evidence of activator protein-1 (AP-1) stimulation by LCA acetate (30 microM) was demonstrated using an AP-1 luciferase reporter assay. Synergistic increases in ALP activity, and therefore osteoblast maturation, were observed for MG63 cells co-stimulated with LCA acetate (5 microM) and either epidermal growth factor (10 ng/ml) or transforming growth factor-beta (10 ng/ml). Ligands acting on either the farnesoid X receptor or pregnane X receptor could not substitute for the action of LCA acetate on MG63 maturation. CONCLUSIONS: Lithocholate is able to act as a calcitriol surrogate in generating mature osteoblasts. Given that LCA is non-calcaemic it is likely to find an application in bone repair/regeneration by aiding matrix calcification at implant sites. PMID- 19646461 TI - Effects of a high-salt diet on adipocyte glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase 1 in salt-sensitive hypertensive rats. AB - High-salt diets decrease insulin sensitivity in salt-sensitive hypertensive rats, and glucocorticoids promote adipocyte growth and may have pathophysiological roles in the metabolic syndrome. The aim of this study was to clarify the relationship between high-salt diet and the adipocyte glucocorticoid hormones in salt-sensitive hypertensive rats. Six-week-old Dahl salt-sensitive (DS) hypertensive rats and salt-resistant (DR) rats were fed a high-salt diet or a normal-salt diet for 4 weeks. Fasting blood glucose (FBG), serum adiponectin, plasma insulin, and corticosterone in plasma and in visceral adipose tissues, 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) activities in adipose tissues and glucose uptake in isolated muscle were measured. Animals underwent an oral glucose tolerance test (OGTT). The expression of mRNA for glucocorticoid receptor (GR), 11beta-HSD1 and tumor necrosis factor-alpha (TNF-alpha) in adipose tissues were measured using a real-time PCR. A high-salt diet did not influence FBG; however, decreased 2-deoxy glucose uptake and plasma insulin during OGTT in DS rats. The high-salt diet increased significantly adipose tissue corticosterone concentration and 11beta-HSD1 activities, gene expression for GR, 11beta-HSD1 and TNF-alpha in adipose tissues in DS rats compared with DR rats (p<0.05). The high salt diet did not influence plasma corticosterone and serum adiponectin concentration in DS and DR rats. These results suggest that changes in GR and 11beta-HSD1 in adipose tissue may contribute to insulin sensitivity in salt sensitive hypertensive rats. PMID- 19646463 TI - Nrf2 protects against airway disorders. AB - Nuclear factor-erythroid 2 related factor 2 (Nrf2) is a ubiquitous master transcription factor that regulates antioxidant response elements (AREs)-mediated expression of antioxidant enzyme and cytoprotective proteins. In the unstressed condition, Kelch-like ECH-associated protein 1 (Keap1) suppresses cellular Nrf2 in cytoplasm and drives its proteasomal degradation. Nrf2 can be activated by diverse stimuli including oxidants, pro-oxidants, antioxidants, and chemopreventive agents. Nrf2 induces cellular rescue pathways against oxidative injury, abnormal inflammatory and immune responses, apoptosis, and carcinogenesis. Application of Nrf2 germ-line mutant mice has identified an extensive range of protective roles for Nrf2 in experimental models of human disorders in the liver, gastrointestinal tract, airway, kidney, brain, circulation, and immune or nerve system. In the lung, lack of Nrf2 exacerbated toxicity caused by multiple oxidative insults including supplemental respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke, allergen, virus, bacterial endotoxin and other inflammatory agents (e.g., carrageenin), environmental pollution (e.g., particles), and a fibrotic agent bleomycin. Microarray analyses and bioinformatic studies elucidated functional AREs and Nrf2 directed genes that are critical components of signaling mechanisms in pulmonary protection by Nrf2. Association of loss of function with promoter polymorphisms in NRF2 or somatic and epigenetic mutations in KEAP1 and NRF2 has been found in cohorts of patients with acute lung injury/acute respiratory distress syndrome or lung cancer, which further supports the role for NRF2 in these lung diseases. In the current review, we address the role of Nrf2 in airways based on emerging evidence from experimental oxidative disease models and human studies. PMID- 19646465 TI - The state of U.S. freshwater harmful algal blooms assessments, policy and legislation. AB - The incidence of harmful algal blooms (HABs) is increasing in the United States and worldwide. HAB toxins cause a substantial but unquantified amount of human and animal morbidity and mortality from exposures in recreational, commercial, drinking-source and potable waters. HAB biomass and toxins threaten the sustainability of aquatic ecosystems. U.S. Congressional legislation mandated the establishment of a National Research Plan for Coastal Harmful Algal Blooms, but no similar plan exists for freshwater HABs (FHABs). Eutrophication and FHABs are conservatively estimated to cost the U.S. economy 2.2-4.6 billion dollars annually. A National Research Plan for Freshwater Harmful Algal Blooms is needed to develop U.S. policy and regulations or guidelines to confront FHAB risks. This report reviews the state of FHAB occurrence, risk and risk management assessments in the U.S. Research is identified that must be accomplished to characterize occurrence and risks, and develop cost effective strategies for preventing, suppressing and mitigating FHABs. U.S. Congressional legislation is needed to mandate a National Research Plan for FHABs, establish a timeline for developing policy and fund competitive research-grant programs. The research results will provide a sound scientific basis for making policy determinations and implementing risk management strategies. Successfully confronting FHAB risks will strengthen the U.S. economy, protect human and animal health and help ensure the sustainability of our Nation's freshwater bodies. PMID- 19646464 TI - Subcellular distribution of okadaic acid in the digestive gland of Mytilus galloprovincialis: first evidences of lipoprotein binding to okadaic acid. AB - The subcellular distribution of okadaic acid, the main diarrhetic shellfish poisoning (DSP) toxin, in the cells of the digestive gland of the mussel Mytilus galloprovincialis was studied. By means of differential centrifugation, ultrafiltration and extraction with methanol, it was found that most okadaic acid was stored in the cytosol. Notwithstanding only a small proportion of the total toxin was found to be in free form, being most of it bound to a soluble cellular compound with a molecular mass which ranged from 30 to 300 kDa. A series of fractionations of samples digested with a protease, a lipase, and amylase suggested that the component to which okadaic acid is bound is a high density lipoprotein. A new fractionation after digestion with a protein lipase additionally supports the previous conclusion. PMID- 19646462 TI - Vanadium induces dopaminergic neurotoxicity via protein kinase Cdelta dependent oxidative signaling mechanisms: relevance to etiopathogenesis of Parkinson's disease. AB - Environmental exposure to neurotoxic metals through various sources including exposure to welding fumes has been linked to an increased incidence of Parkinson's disease (PD). Welding fumes contain many different metals including vanadium typically present as particulates containing vanadium pentoxide (V2O5). However, possible neurotoxic effects of this metal oxide on dopaminergic neuronal cells are not well studied. In the present study, we characterized vanadium induced oxidative stress-dependent cellular events in cell culture models of PD. V2O5 was neurotoxic to dopaminergic neuronal cells including primary nigral dopaminergic neurons and the EC50 was determined to be 37 microM in N27 dopaminergic neuronal cell model. The neurotoxic effect was accompanied by a time dependent uptake of vanadium and upregulation of metal transporter proteins Tf and DMT1 in N27 cells. Additionally, vanadium resulted in a threefold increase in reactive oxygen species generation, followed by release of mitochondrial cytochrome c into cytoplasm and subsequent activation of caspase-9 (>fourfold) and caspase-3 (>ninefold). Interestingly, vanadium exposure induced proteolytic cleavage of native protein kinase Cdelta (PKCdelta, 72-74 kDa) to yield a 41 kDa catalytically active fragment resulting in a persistent increase in PKCdelta kinase activity. Co-treatment with pan-caspase inhibitor Z-VAD-FMK significantly blocked vanadium-induced PKCdelta proteolytic activation, indicating that caspases mediate PKCdelta cleavage. Also, co-treatment with Z-VAD-FMK almost completely inhibited V2O5-induced DNA fragmentation. Furthermore, PKCdelta knockdown using siRNA protected N27 cells from V2O5-induced apoptotic cell death. Collectively, these results demonstrate that vanadium can exert neurotoxic effects in dopaminergic neuronal cells via caspase-3-dependent PKCdelta cleavage, suggesting that metal exposure may promote nigral dopaminergic degeneration. PMID- 19646467 TI - Assessment of cyanobacteria toxins in freshwater fish: a case study of Murchison Bay (Lake Victoria) and Lake Mburo, Uganda. AB - There is little information on the distribution of microcystins (MCs) in Oreochromis niloticus (ON) and Lates niloticus (LN) obtained from L. Mburo and Murchison Bay of L. Victoria. These fishes are harvested and sold both for local human consumption and for export. The presence of MC-RR, MC-LR and MC-YR in different organs (gut, muscle and liver) was determined using Liquid Chromatography coupled with a Mass Spectrometry Detector (LC/MS/MS). The total MCs in ON gut, muscle and liver were 1312.08, 208.65 and 73.10 ng g(-1) from L. Mburo and 1479.24, 9.65 and 48.07 ng g(-1) from Murchison Bay, respectively, while for LN from Murchison Bay they were 27.78, 1.86 and 3.74 ng g(-1). Generally, in both lakes, MC-RR was the most dominant followed by MC-YR and MC LR, respectively. Gut showed a high MC content, followed by liver and muscle, in that order. The presence of MCs in muscle indicated possible fish contamination, which implied that it was possible to transfer the toxins to humans who are at the end of the food chain. This poses a risk to them since the MCs are heat stable. The local authorities should warn the public of the risk of possible poisoning by eating the contaminated fish. PMID- 19646466 TI - Contribution of metalloproteases, serine proteases and phospholipases A2 to the inflammatory reaction induced by Bothrops jararaca crude venom in mice. AB - Various toxins isolated from Bothrops snake venoms induce inflammatory reactions and have been claimed to contribute to the severity of local symptoms present in this envenomation. Notwithstanding, the relative participation of serine proteases, metalloproteases and phospholipases A(2) in the inflammatory reaction produced by crude Bothrops venoms is poorly understood. Herein, crude Bothrops jararaca venom was treated with phenylmethanesulfonyl fluoride (PMSF), 1,10 phenanthroline (oPhe), or p-bromophenacyl-bromide (p-BPB) to inhibit those classes of enzymes, respectively, and inflammatory parameters were evaluated and compared to those induced by the control crude venom. The intensity of edema and hyperalgesia/allodynia was remarkably reduced in animals administered with oPhe treated venom. Leukocyte-endothelium interactions (LEI), such as adhesion and migration of leukocytes, were also modified at 2h and 24h. Edema and LEI parameters induced by p-BPB-treated venom were similar to those observed with the control venom, but hyperalgesia/allodynia was significantly lower. Inflammatory parameters induced by PMSF-treated venom were similar to those induced by the crude venom, except for a mild reduction in edema intensity. Our results indicate that metalloproteases have a pivotal role in the inflammatory reactions induced by B. jararaca venom, and phospholipases A(2) and serine proteases have a minor role. PMID- 19646468 TI - Analysis of Caribbean ciguatoxin-1 effects on frog myelinated axons and the neuromuscular junction. AB - Caribbean ciguatoxin-1 (C-CTX-1) induced, after about 1h exposure, muscle membrane depolarisation and repetitive post-synaptic action potentials (APs) in frog neuromuscular preparations. This depolarising effect was also observed in a Ca(2+)-free medium with a strong enhancement of spontaneous quantal transmitter release, compared with control conditions. The ciguatoxin-induced increase in release could be accelerated when Ca(2+) was present in the extracellular medium. C-CTX-1 also enhanced nerve-evoked quantal acetylcholine (ACh) release. At normal neuromuscular junctions loaded with the fluorescent dye FM1-43, C-CTX-1 induced swelling of nerve terminals, an effect that was reversed by hyperosmotic d mannitol. In myelinated axons, C-CTX-1 increased nodal membrane excitability, inducing spontaneous and repetitive APs. Also, the toxin enlarged the repolarising phase of APs in control and tetraethylammonium-treated axons. Overall, our data suggest that C-CTX-1 affects nerve excitability and neurotransmitter release at nerve terminals. We conclude that C-CTX-1-induced up regulation of Na(+) channels and the inhibition of K(+) channels, at low nanomolar concentrations, produce a variety of functional dysfunctions that are in part responsible for the human muscle skeletal symptoms observed in ciguatera. All these dysfunctions seem to result from the subtle balance between ionic currents, intracellular Na(+) and Ca(2+) concentrations, and engaged second messengers. PMID- 19646469 TI - Marine toxic cyanobacteria: diversity, environmental responses and hazards. AB - Toxic cyanobacterial blooms have been a primary concern predominantly in the plankton of freshwater bodies. Recently, however, the toxicity of benthic cyanobacteria is increasingly attracting attention of the scientific community and environmental agencies. The occurrence of toxic strains in benthic cyanobacteria is intimately linked to our understanding of the diversity and ecological responses of these organisms under field conditions. To that effect, we are engaged in combined morphotypic and genotypic characterization (polyphasic) of benthic natural populations of cyanobacteria in tropical lagoons and coral reefs, with the objective to provide a reliable reference for further comparative work. The methods of identification based on phenotypic properties and those based on molecular tools for genotypic identification are correlated. The approach is based on identifying the occurrences of cyanobacterial benthic blooms, tested for purity and analyzed by application of molecular tools. The questions addressed include the distinction between marine and freshwater taxa, between populations in geographically separate regions as well as between their potential vs. expressed toxicity. PMID- 19646470 TI - "Pushing" physical activity, and justice. AB - OBJECTIVE: There has been an increasing realization of the need for environmental interventions to increase physical activity levels in the population. Although promising, the impact of these strategies in reducing obesity-related disparities will be limited by the presence of inequities in the distribution of activity related resources in the community. Advocacy efforts are critically needed to ensure that all communities benefit from environmental strategies being implemented. METHOD AND RESULTS: This paper describes two activist community based organizations in Southern California, The City Project and Latino Health Access, and their successful efforts to mandate equitable access to public resources critical for reducing obesity-related disparities. CONCLUSION: Principles for equitable development of public land are also presented as well as lessons learned that can inform future advocacy efforts. PMID- 19646471 TI - Influence of body weight on the relationships of alcohol drinking with blood pressure and serum lipids in women. AB - OBJECTIVE: To determine whether body weight influences the associations of habitual alcohol drinking with blood pressure and serum lipids in women. METHODS: The subjects were 16,805 healthy women at ages of 35-54 years, and data were collected at work places of the subjects in Yamagata Prefecture in Japan from April 1999 to March 2000. The subjects were divided into three tertile groups of body weight and were further divided into three subgroups by average ethanol intake [non-, light (<15 g per day), and heavy (> or =15 g per day) drinkers]. RESULTS: In the first and second tertile groups of body weight, mean systolic and diastolic blood pressure and prevalence of high systolic or diastolic blood pressure were significantly higher in heavy drinkers than in non-drinkers, while these differences were not observed in the third tertile group of body weight. On the other hand, in all tertile groups of body weight, mean serum HDL and LDL cholesterol levels were higher and lower, respectively, in light and heavy drinkers than in non-drinkers, and prevalence of low HDL cholesterol or high LDL cholesterol was significantly lower in heavy drinkers than in non-drinkers. CONCLUSIONS: The results suggest that body weight influences the association of alcohol drinking with blood pressure but not the associations of alcohol drinking with serum HDL and LDL cholesterol. PMID- 19646472 TI - Expression of immune-related genes in the digestive organ of shrimp, Penaeus monodon, after an oral infection by Vibrio harveyi. AB - In all previous studies, to study shrimp immune response, bacteria were directly injected into the shrimp body and as a consequence the initial step of a natural interaction was omitted. In this study we have instead used an immersion technique, which is a more natural way of establishing an infection, to study immune responses in black tiger shrimp (Penaeus monodon). Normally, Vibrio harveyi (Vh) is highly pathogenic to post-larval shrimp, but not to juveniles which usually resist an infection. In post-larvae, Vh causes a massive destruction of the digestive system, especially in the hepatopancreas and in the anterior gut. We have therefore investigated changes in transcription levels of fifteen immune-related genes and morphological changes in juvenile shrimp following an immersion of shrimp in Vh suspension. We found that a pathogenic bacterium, Vh, has the capacity to induce a local expression of some immune related genes in shrimp after such a bacterial immersion. Our results show that in the juvenile gut small changes in expression of the antimicrobial peptide (AMP) genes such as antilipopolysaccharide factor isoform 3, crustin and penaeidin were observed. However some other genes were more strongly induced in their expression compared to the AMP genes. C-type lectin, Tachylectin 5a1 and mucin-like peritrophic membrane were increased in their expression and the C-type lectin was affected most in its expression. Several other examined genes did not change their expression levels. By performing histology studies it was found that Vh infection induced a strong perturbation of the midgut epithelium in some regions. As a consequence, the epithelial cells and basement membrane of the infected site were completely damaged and necrotic and massive hemocyte infiltration occurred underneath the affected tissue to combat the infection. PMID- 19646474 TI - Validation of a novel method to interrupt sleep in the mouse. AB - Interrupted sleep, fragmented sleep or restricted sleep is a corollary of many psychiatric, neurological and respiratory disorders and also results from disruptive environments such as that of the intensive care unit (ICU). Recent rodent studies have revealed that sleep interruption (SI) can have more significant consequences for cognitive and neurophysiological variables than were expected and may even be equivalent to those of total sleep deprivation. Results from this research are therefore being increasingly recognized for their implications, which may include delayed recovery from critical illness in the ICU. Here we describe in detail a method for interrupting sleep in a murine model, which we had previously adopted to show an increase in mortality after septic insult. Interrupting sleep for 30s every 2 min over 48 h significantly decreased rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. The technique, which is based on using a standard laboratory orbital shaker to oscillate the cage containing the mouse, can easily be adapted to use different parameters for SI. During recovery, mice exhibited a rebound in REM sleep time and an increase in the depth of NREM sleep as measured by delta (1-4 Hz) power in the electroencephalogram. The changes in sleep both during and after SI showed some differences from those previously observed in the rat using the same SI parameters. In conclusion, the mouse may provide a useful alternative model for studying the effects of SI. PMID- 19646475 TI - A new tool for assessing human movement: the Kinematic Assessment Tool. AB - The study of human behaviour ultimately requires the documentation of human movement. In some instances movements can be recorded through a simple button press on a computer input device. In other situations responses can be captured through questionnaire surveys. Nevertheless, there is a need within many neuroscience settings to capture how complex movements unfold over time (human kinematics). Current methods of measuring human kinematics range from accurate but multifarious laboratory configurations to portable but simplistic and time consuming paper and pen methods. We describe a new system for recording the end point of human movement that has the power of laboratory measures but the advantages of pen-and-paper tests: the Kinematic Assessment Tool. KAT provides a highly portable system capable of measuring human movement in configurable visual spatial tasks. The usefulness of the system is shown in a study where 12 participants undertook a tracing and copying task using their preferred and non preferred hand. The results show that it is possible to capture behaviour within complex tasks and quantify performance using objective measures automatically generated by the KAT system. The utility of these measures was indexed by our ability to distinguish the performance of the preferred and non-preferred hand using a single variable. PMID- 19646476 TI - Spatio-temporal analysis of monofractal and multifractal properties of the human sleep EEG. AB - Fractality is a common property in nature. It can also be observed in time series representing dynamics of complex processes. Therefore fractal analysis could be a useful tool to describe the dynamics of brain electrical activities in physiological and pathological conditions. In this study, we carried out a spatio temporal analysis of monofractal and multifractal properties of whole-night sleep EEG recordings. We estimated the Hurst exponent (H) and the range of fractal spectra (dD) in 10 healthy subjects. We found higher H values during NREM4 compared to NREM2 and REM in all electrodes. Measure dD showed an opposite trend. Differences of H and dD between NREM2 and REM reached significancy at circumscribed regions only. Our results contribute to a deeper understanding of the fractal nature of brain electrical activities and may have implications for automatic classification of sleep stages. PMID- 19646473 TI - Incorporating genetics and genomics in risk assessment for inhaled manganese: from data to policy. AB - Manganese is an essential nutrient, and a healthy human with good liver and kidney function can easily excrete excess dietary manganese. Inhaled manganese is a greater concern, because it bypasses the body's normal homeostatic mechanisms and can accumulate in the brain. Prolonged exposure to high manganese concentrations (>1mg/m(3)) in air leads to a Parkinsonian syndrome known as "manganism." Of greatest concern are recent studies which indicate that neurological and neurobehavioral deficits can occur when workers are exposed to much lower levels (<0.2mg/m(3)) of inhaled manganese in welding fumes. Consequently, researchers at NIOSH are conducting a risk assessment for inhaled manganese. Novel components of this risk assessment include an attempt to quantify the range of inter-individual differences using data generated by the Human Genome Project and experimental work to identify genetically based biomarkers of exposure, disease and susceptibility. The difficulties involved in moving from epidemiological and in vivo data to health-based quantitative risk assessment and ultimately enforceable government standards are discussed. PMID- 19646477 TI - Multiplex detection of Solenopsis invicta viruses -1, -2, and -3. AB - Multiplex reverse transcription and polymerase chain reaction (PCR) methods were developed to detect Solenopsis invicta viruses -1, -2, and -3 simultaneously in their host, the red imported fire ant, S. invicta. cDNA synthesis was conducted in a single reaction containing an oligonucleotide primer specific for each virus. Multiplex PCR was subsequently conducted with oligonucleotide primer pairs specific for each virus. The method was specific and sensitive, capable of detecting as few as 500 copies of the viral genomes consistently. Specificity was verified by PCR and amplicon sequencing. The method was evaluated against field collected samples of ant workers from colonies in Argentina (n=135 ant colonies) and the United States (n=172 ant colonies). The prevalence of each virus in fire ant colonies varied considerably from site to site. A number of colonies exhibited multiple virus infections. However, the multiple SINV infection rate was lower than for single infections. Comparison of viral infection prevalence between S. invicta colonies in Argentina and the U.S. showed no statistical differences, regardless of infection category. This method is anticipated to facilitate epidemiological and related studies concerning the S. invicta viruses in fire ants. PMID- 19646478 TI - Expression of H5N1 influenza virus hemagglutinin protein fused with protein transduction domain in an alphavirus replicon system. AB - Alphavirus replicons, in which structural protein genes are replaced by heterologous genes, express high levels of the heterologous proteins. On the basis of the potencies of replicons to self-replicate and express foreign proteins and the remarkable intercellular transport property of VP22, a novel alphavirus Semliki Forest virus (SFV) replicon system of VP22 fused with a model antigen, hemagglutinin (HA), of the human-avian H5N1 influenza virus, was explored in this study. Further, replicon particles expressing HA, VP22, and enhanced green fluorescent protein (EGFP) individually were used as controls. By flow cytometry based on the analysis of transfection efficiency, SFV-EGFP replicon particle titer was 1.13 x 10(7)transducing units (TU)/ml. The titers of SFV-HA, SFV-VP22 and SFV-VP22-HA replicon particles, which were titrated by using SFV-EGFP replicon particles, were 1.42 x 10(7), 3.23 x 10(7), and 1.01 x 10(7)TU/ml, respectively. HA and VP22-HA expression was observed in SFV-HA- and SFV-VP22-HA-transfected BHK-21 cells, respectively. Immunofluorescence staining revealed that the fluorescence intensity in the SFV-VP22-HA-transfected BHK-21 cells was more than that in the SFV-HA-transfected BHK-21 cells. Both SFV-VP22-HA and SFV-HA replicon particles presented a promising approach for developing vaccines against human-avian influenza. VP22-HA fusion protein with similar trafficking properties may also enhance vaccine potency. PMID- 19646479 TI - A three-plasmid system for construction of armed oncolytic adenovirus. AB - There is growing interest in the use of oncolytic virus as a tool in cancer gene therapy. However, construction of oncolytic adenovirus (Ad) is not an easy task due to lack of convenient, robust methods. A three-plasmid system was introduced for construction of armed oncolytic Ad. Besides the pShuttle-CMV and pAdEasy-1, a third plasmid (pTE-ME1), harboring the E1 region of Ad5, was generated and included in this system. In pTE-ME1, the promoter of E1A was deleted and replaced with a multiple-cloning site (MCS). A therapeutic gene and tissue-specific promoter (TSP) could be inserted routinely into the MCS of pShuttle-CMV and pTE ME1, respectively. The modified E1 region could then be excised from pTE-ME1 and integrated into the therapeutic gene-containing pShuttle-CMV to form the final shuttle plasmid. This shuttle plasmid was recombined with pAdEasy-1 in Escherichia coli strain BJ5183 to generate Ad plasmid. Finally, the oncolytic Ad could be rescued in Ad plasmid-transfected packaging cells. The GFP gene and the promoter of telomerase reverse transcriptase (TERTp) were chosen as the transgene and TSP, respectively, to test this system. Two oncolytic Ads, Ad-GFP-TPE and Ad GFP-D19K, were generated successfully. Their oncolytic and replicating abilities were investigated in TERT-positive tumor cells. The results suggest that the three-plasmid system was practicable and could be used to construct other transcriptionally regulated oncolytic Ads carrying a therapeutic gene. PMID- 19646480 TI - Real time PCR TaqMan assays for detection of polyomaviruses KIV and WUV in clinical samples. AB - Recently, polyomaviruses KI and WU were identified in the airways of patients with acute respiratory symptoms. The epidemiology and pathogenesis of these two viruses are not fully understood, and the development of molecular assays, such as Real Time PCR, was useful for examining their biology and role in different clinical syndromes. The evaluation of different target regions for the amplification of polyomaviruses KI and WU, comparing published primer/probe sets and sets designed in the laboratory is described and was used for testing 175 clinical specimens (84 stools and 91 tonsils). The results showed that the laboratory designs were more sensitive for the detection of polyomaviruses KI and WU DNA in clinical samples. The choice of the primer/probe set, and primarily of the region for amplification, may be relevant for understanding the pathogenic role of viruses such as polyomaviruses KI and WU. PMID- 19646481 TI - Expression of Peste des petits ruminants virus nucleocapsid protein in prokaryotic system and its potential use as a diagnostic antigen or immunogen. AB - In this study, both partial and full-length nucleocapsid (N) gene of Peste des petits ruminants virus (PPRV) were cloned into pET33b vector and expressed in Escherichia coli (BL21) with the objective of replacing live PPRV antigen with recombinant protein in ELISA. The expressed proteins were characterized by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blot by using a PPRV N protein specific monoclonal antibody. The expressed histidine-tagged fusion proteins were purified using affinity Ni-NTA column and were assessed for their conformation in terms of reactivity by ELISA. The immunogenicity of recombinant proteins was also assessed in rabbits and anti-N antibody response against PPRV was observed in all the immunized rabbits, when tested by competitive and indirect ELISAs. In sandwich ELISA, a mean OD(492 nm) of 1.4 and 0.90 was obtained for crude lysate having expressed the N protein and the PPRV antigen, respectively. Further, the N protein was tested as a coating antigen in competitive ELISA instead of PPRV antigen for serological diagnosis of PPR infection. This indicates the diagnostic potential of the PPRV recombinant N proteins, which are safe and better alternatives to live PPRV antigen in ELISA for clinical or sero-surveillance of PPR in enzootic or non-enzootic countries. PMID- 19646482 TI - A novel method for concentrating hepatitis A virus and caliciviruses from bottled water. AB - Human enteric viruses are detected frequently in various types of environmental water samples, such as irrigation water, wastewater, recreational water, ground or subsurface water and even drinking water, constituting a primary source of gastroenteritis or hepatitis outbreaks. Only a few, but still infective number of viral particles are normally present in water samples, therefore an efficient virus concentration procedure is essential prior to molecular detection of the viral nucleic acid. In this study, a novel chromatographic technology, Convective Interaction Media (CIM) monolithic supports, were optimized and applied to the concentration of hepatitis A virus (HAV) and feline calicivirus (FCV), a surrogate of norovirus (NoV), from water samples. Two-step real-time RT-qPCR was used for quantitation of the virus concentration in the chromatographic fractions. Positively charged CIM QA (quaternary amine) monolithic columns were used for binding of HAV and FCV present in previously inoculated 1.5 l bottled water samples. Column bound viruses were eluted from the monolith using 1M NaCl to a final volume of 15 ml. Elution volume was concentrated further by ultracentrifugation. When the CIM/ultracentrifugation method was compared with another concentration method employing positively charged membranes and ultrafiltration, the recovery of HAV was improved by approximately 20%. PMID- 19646483 TI - Real-time reverse transcription loop-mediated isothermal amplification for rapid detection of yellow head virus in shrimp. AB - A real-time reverse transcription loop-mediated isothermal amplification (real time RT-LAMP) method was applied for detecting the replicase polyprotein-encoding gene of yellow head virus (YHV) in shrimp, Penaeus monodon. It is a novel, gene specific assay that amplifies nucleic acid with high specificity, sensitivity and rapidity under isothermal conditions using a set of six specially designed primers that recognize eight distinct sequences of the target gene. This method works with even low copies of DNA and is based on magnesium pyrophosphate turbidity detection by an inexpensive photometer for quantitative analysis. A user-friendly protocol was developed with optimal conditions standardized at 63 degrees C for 60 min. With this protocol, the assay sensitivity was 10 times higher than the widely used YHV nested RT-PCR system. Cross-reactivity analysis using other shrimp virus DNA/cDNA and YHV-negative shrimp demonstrated high specificity of the assay. The real-time RT-LAMP method was performed also for an internal control gene, EF-1alpha, to compare with the expressions of the YHV gene in different organs of infected shrimp, and the resulting standard curves showed high correlation coefficient values. These results suggest that this assay is applicable widely as a new quantitative detection method in the pursuit of YHV free shrimp culture. PMID- 19646485 TI - Inhibition of rabies virus replication by multiple artificial microRNAs. AB - The RNA interference (RNAi) technology has been recognized as a promising antiviral therapy for a few years. One of the potential limitations for applying this technology against wild type rabies virus is its high rate of genetic variation. Recently, an RNAi vector system that incorporated modified dsRNA within microRNA structure [or artificial miRNAs(amiRNAs)] has been described. This allowed expression of multiple amiRNAs of single or multiple targets from a single construct. In this study, we evaluated a benefit of using amiRNA vector against different rabies strains. We found that applying single targeting amiRNA against challenged rabies virus standard (CVS) rabies nucleocapsid (N) mRNA resulted in more than 90% reduction of viral genome in Neuro2A cells up to 72 h after infection. Multiple amiRNAs aiming at single or multiple NmRNA target(s) yielded comparable inhibitory results as with a single amiRNA against perfectly matched target. Although the level of each mature miRNA generated from multiple amiRNA construct was slightly reduced as assessed by stem-loop RT and real-time PCR techniques, its effectiveness remained unchanged even when an ineffective or scrambled amiRNA was also included in the transcript. Against highly pathogenic wild type virus, single amiRNA construct activity was reduced when mismatching with target sequence occurred at critical site whereas multiple targeting amiRNA construct remained highly effective. Our results suggest the benefit of using multiple targeting amiRNAs when confronting with wild type rabies virus, the sequence of which is not completely known. PMID- 19646484 TI - Simultaneous detection and identification of four sugarcane viruses by one-step RT-PCR. AB - Sugarcane mosaic disease (SMD) caused by the Sugarcane mosaic virus (SCMV), Sorghum mosaic virus (SrMV) and Sugarcane streak mosaic virus (SCSMV) and sugarcane yellow leaf disease (SYLD) caused by the Sugarcane yellow leaf virus (SCYLV) are the two most prevalent and economically important viral diseases of sugarcane. In this study, a one-step quadruplex reverse transcription (RT)-PCR method that employed virus-specific primers was developed for the simultaneous detection and differentiation of SCMV, SrMV, SCSMV and SCYLV. Several sets of primers for each target virus were evaluated for their sensitivity and specificity by simplex and quadruplex RT-PCR. The optimum primer combinations and concentrations, RT temperature and time, and PCR annealing temperature and extension time were determined for the quadruplex RT-PCR. The assay was then validated using sugarcane samples affected with SMD and/or SYLD collected from sugarcane breeding fields and farmers' fields in southern China. PMID- 19646486 TI - A novel combined vaccine candidate containing epitopes of HCV NS3, core and E1 proteins induces multi-specific immune responses in BALB/c mice. AB - Hepatitis C virus (HCV) has emerged as the major pathogen of liver disease worldwide. The mechanisms of HCV infection and interaction with a host are poorly understood. What exactly is required for efficient control of HCV infection is largely unknown. Standard treatment combining interferon-alpha (IFN-alpha) and ribavirine is effective in about 50% of the treated patients, however associated with significant toxicity and cost. Therefore, the development of new drugs or vaccines is urgently needed. An efficient vaccine against HCV infection requires induction of broad cellular and humoral immune responses against several viral proteins. We have engineered the combined vaccine candidate mT+mE1, an inclusion of multiple epitopes from HCV NS3, core (C) and E1 proteins. mT contains multiple conserved CD4(+) and CD8(+) T cell epitopes from HCV NS3 and C proteins. mE1 is based on eight dominant neutralizing epitopes of E1 protein from six HCV genotypes. In current study, we showed that immunization with mT+mE1 induced high titers of IgG, IgG1 and IgG2a antibodies to mE1, and high level of NS3- or C specific CTLs. Furthermore, mT+mE1 elicited a Th1-biased immune response with secretion of high amounts of IFN-gamma, compared with mT alone. Prophylactic as well as therapeutic administration of mT+mE1 in BALB/c mice led to protecting mice against SP2/0 tumor cells expressing HCV NS3 protein. These results suggested that mT+mE1 elicited strong humoral immune responses and multiple specific cellular immune responses. The vaccine candidate is now being tested in pre-clinical trials. PMID- 19646488 TI - Neonatal ventral hippocampal lesions disrupt set-shifting ability in adult rats. AB - Set-shifting in a T-maze task was assessed in rats with a neonatal ventral hippocampal lesion (NVHL), a proposed animal model of schizophrenia. NVHL animals tested as adults were impaired in shifting to a new rule; an increase in perseverative errors suggested that this impairment stemmed from an inability to suppress the previously learned strategy. The NVHL animals' performance is reminiscent of humans with prefrontal damage and patients with schizophrenia. PMID- 19646487 TI - Behavioral phenotyping of neuropeptide S receptor knockout mice. AB - Central administration of neuropeptide S (NPS) in rodents induces arousal and prolonged wakefulness as well as anxiolytic-like effects. NPS has also been implicated in modulation of cognitive functions and energy homeostasis. Here we present a comprehensive phenotypical analysis of mice carrying a targeted mutation in the NPS receptor (NPSR) gene. NPSR knockout mice were found to exhibit reduced exploratory activity when challenged with a novel environment, which might indicate attenuated arousal. We also observed attenuated late peak wheel running activity in NPSR knockout mice, representing reduced activity during the subjective evening. These mice also displayed increased anxiety-like behaviors when compared to their wildtype littermates, although analysis of anxiety behaviors was limited by genetic background influences. Unexpectedly, NPSR knockout mice showed enhanced motor performance skills. No phenotypical differences were detected in the forced-swim test, startle habituation and pre pulse inhibition paradigms. Together, these data indicate that the endogenous NPS system might be involved in setting or maintaining behavioral arousal thresholds and that the NPS system might have other yet undiscovered physiological functions. PMID- 19646489 TI - Exploitation of the diverse insertion sequence element content of dairy Lactobacillus helveticus starters as a rapid method to identify different strains. AB - The species Lactobacillus helveticus is a commonly used thermophilic starter and/or adjunct culture for Swiss and Cheddar cheese manufacture. Its use is normally associated with flavour improvement which is known to be associated with culture traits such as rapid autolysis and high proteolytic activity. The genome of the commercial strain, DPC4571, was recently sequenced and found to have an abundance of IS sequences in terms of both abundance (213 intact) and diversity (21 types). Given this unique diversity for a lactic acid bacterium, we investigated whether PCR-based IS fingerprinting could be used as a discriminatory tool to distinguish between different strains of Lb. helveticus. A set of ten primers targeting five of the most numerous groups (ISL1201, ISLhe65, ISLhe2, ISLhe15 and ISL2) of IS elements was designed. Multiplex-PCR with all primers resulted in 1-12 discreet amplicons for each strain tested. The resultant fingerprints (in the 0.5 kb-3 kb range) were found to be strain specific and reproducible. This approach thus provides a valuable method to distinguish between Lb. helveticus strains while giving some indication of the relative abundance of IS sequences in each strain. PMID- 19646490 TI - Cardiac responses predict decisions: an investigation of the relation between orienting response and decisions in the ultimatum game. AB - Emotion-based behaviors in humans cannot be fully explained by economic rationality. Particularly, in the ultimatum game, which incorporates conflict between self-interest and fairness, negative emotions evoked by an unfair offer seem to promote an economically irrational decision. In accordance with this suggestion, the previous studies have reported that physiological arousal is associated with rejecting unfair offers. In the present study, we investigated electrocardiogram and electrodermal activities in individuals which received fair, advantageously unfair, and disadvantageously unfair offers to specify the relations of the orienting and the defensive responses with these offers and with the decisions to accept and reject them. The results indicated that when an offer that would be rejected was presented, heart rate initially decelerated more than when an offer that would be accepted was presented. Additionally, there was a linear relationship between the deceleration and unfairness of offers. On the other hand, such different patterns were not seen in late cardiac acceleration or electrodermal response. The results suggest that because of perception of disadvantage and unpleasantness in a social context, the orienting response is evoked when an offer will be rejected. In addition, these results are discussed regarding the effect of the autonomic activity in decision-making. PMID- 19646491 TI - The vase-face illusion seen by the brain: an event-related brain potentials study. AB - In the present study, we provided a cue (face or vase) beforehand to make subjects attend the target stimuli in the vase-face ambiguous figure, and compared the spatiotemporal cortical activation patterns underlying face (face face) or vase (vase-vase) processing to the ambiguous figure using high-density (64-channel) event-related brain potential (ERP) recordings. Scalp ERP analysis found that the anterior N100, P160, N320 and posterior P100 and N160 were elicited by the face-face and vase-vase responses. The results of the ANOVAs showed that the anterior N100 and N320 elicited by the vase-vase response were more negative than the face-face response. The anterior N100 might reflect deployment of attention (conscious effort) to identify the target stimuli (face or vase) in early processing of the ambiguous figure, and the N320 might be the reversal negativity (RN) and was involved in involuntary perceptual reversals (from face to vase or reverse). Moreover, the mean amplitude (a late positive component: LPC) between 350 and 450 ms of the face-face response was larger than the vase-vase response on positive orientation over the front-central scalp regions. This result might support the view that the LPC reflect post-perceptual processing and indicated that the perceptual reversal of the vase-face illusion is influenced by top-down control. PMID- 19646492 TI - Prevention of ischemia/reperfusion injury by hepatic targeting of nitric oxide in mice. AB - Macromolecular nitric oxide (NO) donors possessing the ability to target a specific type of liver cells were developed for delivering NO to the liver. Six NO molecules were covalently bound to mannosylated (Man) or galactosylated (Gal) bovine serum albumin (BSA) through an S-nitrosothiol linkage to obtain Man-poly SNO-BSA and Gal-poly SNO-BSA, respectively. The carrier parts of Man-poly SNO-BSA and Gal-poly SNO-BSA predominantly accumulated in the liver after intravenous injection in mice. In an ischemia/reperfusion injury mouse model, in which hepatic injury was induced by occluding the portal vein for 15 min followed by a 6 h reperfusion, the elevation of plasma alanine aminotransferase and aspartate aminotransferase levels was significantly inhibited by a bolus intravenous injection of Man-poly SNO-BSA or Gal-poly SNO-BSA, just before the start of reperfusion. In marked contrast, S-nitroso-N-acetyl penicillamine and NO conjugated BSA, two classical S-nitrosothiols, had no statistically significant effects on the serum levels of the markers. The released NO in mouse liver was detected by electron spin resonance spectrometry only in the liver of mice receiving Man-poly SNO-BSA or Gal-poly-SNO-BSA. These findings indicate that Man poly SNO-BSA and Gal-poly SNO-BSA are promising compounds for preventing hepatic ischemia/reperfusion injury by delivering pharmacologically active NO to the liver. PMID- 19646493 TI - Electrospun materials as potential platforms for bone tissue engineering. AB - Nanofibrous materials produced by electrospinning processes have attracted considerable interest in tissue regeneration, including bone reconstruction. A range of novel materials and processing tools have been developed to mimic the native bone extracellular matrix for potential applications as tissue engineering scaffolds and ultimately to restore degenerated functions of the bone. Degradable polymers, bioactive inorganics and their nanocomposites/hybrids nanofibers with suitable mechanical properties and bone bioactivity for osteoblasts and progenitor/stem cells have been produced. The surface functionalization with apatite minerals and proteins/peptides as well as drug encapsulation within the nanofibers is a promising strategy for achieving therapeutic functions with nanofibrous materials. Recent attempts to endow a 3D scaffolding technique to the electrospinning regime have shown some promise for engineering 3D tissue constructs. With the improvement in knowledge and techniques of bone-targeted nanofibrous matrices, bone tissue engineering is expected to be realized in the near future. PMID- 19646495 TI - Experimentally induced chocolate craving leads to an attentional bias in increased distraction but not in speeded detection. AB - In the present study, the causal influence of chocolate craving on attentional bias for chocolate-related information was examined by experimentally inducing chocolate craving in a sample of high trait chocolate cravers vs. low trait chocolate cravers. A sample of 35 high trait chocoholics and 33 low trait chocolate cravers were randomly assigned to either the exposure condition in which craving was manipulated or the non-exposure condition. To measure attentional bias, a pictorial version of the visual search paradigm [Smeets, E., Roefs, A., van Furth, E., & Jansen, A. (2008). Attentional bias for body and food in eating disorders: increased distraction, speeded detection, or both? Behaviour Research and Therapy, 46, 229-238] was used, assessing two components: distraction and detection. It was found that experimentally induced chocolate craving led to increased distraction by chocolate pictures in the high trait chocolate cravers, in comparison to the low trait chocolate cravers. Moreover, this measure of distraction correlated strongly with self-reported craving, but only in the chocoholics and in the exposure condition. In the non-exposure condition, high trait chocolate cravers showed speeded detection of chocolate pictures relative to non-chocoholics, but this component did not correlate with self-reported craving. It is concluded that experimentally induced craving for chocolate causes a bias in, specifically the increased distraction component of attention in high trait chocolate cravers. PMID- 19646494 TI - Food for thought. What you eat depends on your sex and eating companions. AB - In a naturalistic study, we investigated the influence of gender, group size and gender composition of groups of eaters on food selected for lunch and dinner (converted to total calories per meal) of 469 individuals (198 groups) in three large university cafeterias. In dyads, women observed eating with a male companion chose foods of significantly lower caloric value than those observed eating with another woman. Overall, group size was not a significant predictor of calories, but women's calories were negatively predicted by numbers of men in the group, while the numbers of women in the group had a marginally significant positive impact on calorie estimates. Men's calorie totals were not affected by total numbers of men or women. This study supports previous investigations, but is unique in making naturalistic observations. PMID- 19646496 TI - Electrophysiological effects of ghrelin on laterodorsal tegmental neurons in rats: an in vitro study. AB - Ghrelin, a gut and brain peptide, is a potent stimulant for growth hormone (GH) secretion and feeding. Recent studies further show a critical role of ghrelin in the regulation of sleep-wakefulness. Laterodorsal tegmental nucleus (LDT), that regulates waking and rapid eye movement (REM) sleep, expresses GH secretagogue receptors (GHS-Rs). Thus, the present study was carried out to examine electrophysiological effects of ghrelin on LDT neurons using rat brainstem slices, and to determine the ionic mechanism involved. Whole cell recording revealed that ghrelin depolarizes LDT neurons dose-dependently in normal artificial cerebrospinal fluid (ACSF). The depolarization persisted in tetrodotoxin-containing ACSF (TTX ACSF), and is partially blocked by the application of [D-Lys3]-GHRP-6, a selective antagonist for GHS-Rs. Membrane resistance during the ghrelin-induced depolarization increased by about 18% than that before the depolarization. In addition, the ghrelin-induced depolarization was drastically reduced in high-K+ TTX ACSF with a K+ concentration of 13.25 mM. Reversal potentials obtained from I-V curves before and during the depolarization were about -83 mV, close to the equilibrium potential of the K+ channel. Most of the LDT neurons recorded were characterized by an A-current or both the A-current and a low threshold Ca2+ spike, and they were predominantly cholinergic. These results indicate that ghrelin depolarizes LDT neurons postsynaptically and dose dependently via GHS-Rs, and that the ionic mechanisms underlying the ghrelin induced depolarization include a decrease of K+ conductance. The results also suggest that LDT neurons are implicated in the cellular processes through which ghrelin participates in the regulation of sleep-wakefulness. PMID- 19646497 TI - Bolus intravenous injection of obestatin does not change blood pressure level of spontaneously hypertensive rat. AB - Ghrelin, an endogenous ligand for the GH secretagogue receptor, has been shown to decrease arterial pressure. Obestatin, a sibling of ghrelin derived from preproghrelin, opposes several physiological actions of ghrelin. The aim of this study was to determine the effects of bolus intravenous injection of obestatin on blood pressure in spontaneously hypertensive rats. Three different dosages of obestatin (10, 50, and 100 microg/kg) and one dosage of ghrelin (10 microg/kg) were applied. The mean arterial pressure and heart period were continuously recorded for 30 min after injection of drugs. Baroreflex sensitivity was also investigated. In this study, we first demonstrated that intravenous injection of obestatin showed no significant effects on mean blood pressure (10 microg/kg: 113.8+/-2.0 mmHg vs. 114.4+/-1.6 mmHg; 50 microg/kg: 110+/-2.4 mmHg vs. 109+/-3.2 mmHg; 100 microg/kg: 115.9+/-1.5 mmHg vs. 115.8+/-2.4 mmHg; all P>0.05), heart period (10 microg/kg: 184.7+/-3.9 ms vs. 185.5+/-4.1ms; 50 microg/kg: 185.9+/-4.1 ms vs. 193.4+/-4.5 ms; 100 microg/kg: 137.7+/-4.5 ms vs. 143.9+/-5.6 ms; all P>0.05), or baroreflex sensitivity (10 microg/kg: 0.414+/-0.03 ms/mmHg vs. 0.442+/-0.02 ms/mmHg; 50 microg/kg: 0.453+/-0.04 ms/mmHg vs. 0.439+/-0.01 ms/mmHg; 100 microg/kg: 0.398+/-0.02 ms/mmHg vs. 0.401+/-0.01 ms/mmHg; all P>0.05), however, intravenous injection of ghrelin could decrease mean arterial pressure (115.9+/-1.5 mmHg vs. 108.6+/-3.6 mmHg, P<0.01) and increase heart period (132.4+/-2.8 ms vs. 152.6+/-7.4 ms, P<0.05), but did not change baroreflex sensitivity (0.36+/-0.009 ms/mmHg, P>0.05) in spontaneously hypertensive rats. PMID- 19646499 TI - VEGFR-3/Flt-4 mediates proliferation and chemotaxis in glial precursor cells. AB - Neuronal and vascular cells share common chemical signals. Vascular endothelial growth factor (VEGF)-C and -D and their receptor VEGFR-3/Flt-4 mediate lymphangiogenesis, but they occur also in the brain. Quantitative RT-PCR of mouse brain tissues and cultivated cells showed that the VEGFR-3 gene is highest transcribed in postnatal brain and in glial precursor cells whereas VEGF-C and -D are variably produced by different neuronal and glial cells. In neurospheres (neural stem cells) VEGFR-3 was induced by differentiation with platelet-derived growth factor (PDGF). In functional studies with an A2B5- and nestin-positive, O4 negative murine glial precursor cell line, VEGF-C and -D stimulated phosphorylation of the kinases Erk1/2; this signal transduction was inhibited by UO126. Both peptides induced the proliferation of glial precursor cells which could be inhibited by UO126. Furthermore, VEGF-D considerably enhanced their migration into an open space in a wound-healing assay. These results show that VEGF-C/-D together with its receptor VEGFR-3 provides an auto-/paracrine growth and chemotactic system for glial precursors in the developing brain. PMID- 19646500 TI - Drug-induced Pisa syndrome under quetiapine. PMID- 19646498 TI - Analysis of the therapeutic functions of novel melanocortin receptor agonists in MC3R- and MC4R-deficient C57BL/6J mice. AB - Melanocortin receptor agonists act in the brain to regulate food intake and body weight and, independently of these actions, affect insulin sensitivity. These experiments investigated the function of novel non-selective melanocortin receptor agonists (BIM-22493, BIM-22511) that cross the blood-brain barrier when administered peripherally. Treatment of diet induced obese C57BL/6J (B6) mice with melanocortin agonists administered peripherally improved obesity, hyperinsulinemia (approximately 50%) and fatty liver disease. Specificity of function was determined using B6 melanocortin-3 and melanocortin-4 receptor knockout mice (MC3RKO, MC4RKO). Chow fed MC4RKO but not MC3RKO used for these tests exhibited obesity, hyperinsulinemia and severe hepatosteatosis associated with increased expression of insulin-stimulated genes involved in lipogenesis. Reduced food intake associated with acute BIM-22493 treatment, and weight loss associated with 14 days of treatment with BIM-22511, required functional MC4R but not MC3R. However, while 14 days of treatment with BIM-22511 did not affect body weight and even increased cumulative food intake in MC4RKO, a significant reduction (approximately 50%) in fasting insulin was still observed. Despite lowering insulin, chronic treatment with BIM-22511 did not improve hepatosteatosis in MC4RKO, and did not affect hepatic lipogenic gene expression. Together, these results demonstrate that peripherally administered melanocortin receptor agonists regulate body weight, liver metabolism and glucose homeostasis through independent pathways. MC4R are necessary for melanocortin agonist-induced weight loss and improvements in liver metabolism, but are not required for improvements in hyperinsulinemia. Agonists with activity at MC4R improve glucose homeostasis at least partially by causing weight loss, however other melanocortin receptors may have potential for treating aberrations in glucose homeostasis associated with obesity. PMID- 19646501 TI - Chemical allergens--what are the issues? AB - Chemical allergy describes the adverse health effects that may result when exposure to a chemical elicits an immune response. Allergy develops in two phases. In the first phase, exposure of an inherently susceptible subject results in stimulation of an immune response or immunological priming. If the then sensitised subject is exposed on a subsequent occasion to the same chemical then an accelerated and more aggressive secondary immune response will be provoked resulting in inflammation and the signs and symptoms of a clinically discernible allergic reaction. The two forms of chemical allergy of greatest relevance for occupational toxicology are skin sensitisation resulting in allergic contact dermatitis, and sensitisation of the respiratory tract associated with occupational rhinitis and asthma. In this brief survey we identify what we believe currently represent the key issues and key challenges in these areas. PMID- 19646502 TI - Parasporin-2 requires GPI-anchored proteins for the efficient cytocidal action to human hepatoma cells. AB - Parasporin-2 (PS2) is a Bacillus thuringiensis inclusion protein that reacts intensively with human hepatoma cells. This antitumour toxin oligomerizes at the cell surface via binding to lipid rafts, leading to the cell lysis with typical blebs around peripheral cells. We find here that glycosylphosphatidylinositol (GPI)-anchored proteins are involved in the cytocidal actions. Depletion of the cellular cholesterol and loss of sphingolipid in lipid rafts slightly decreased cytolysis by PS2. Beyond those, the cells temporally resisted PS2 with reduction of the toxin binding after GPI-anchored proteins were cleaved off by phosphatidylinositol-specific phospholipase C. PS2 and aerolysin showed individual cytocidal specificity while aerolysin's receptor is GPI-anchored proteins. When we confirmed expression of GPI-anchored proteins on four cell lines, showing different cytotoxicity by PS2, GPI-anchored proteins were evenly expressed on the cells. Therefore, PS2 requires a kind of GPI-anchored proteins for the effective cytolysis. PMID- 19646503 TI - Effects of cardiopulmonary baroreceptor activation on pain may be moderated by risk for hypertension. AB - Cardiopulmonary baroreceptor stimulation may modulate pain, though the literature is much smaller than research showing that sinoaortic baroreceptor stimulation can buffer pain. To examine the possibility that risk for established high blood pressure may moderate the effects of cardiopulmonary baroreceptor stimulation on pain, 22 borderline hypertensive and 18 normotensive men participated in a laboratory experiment. Group differences in blood pressure were documented by 24 h ambulatory blood pressure recording. Ratings of the intensity of acute heat pain were influenced by both group membership and leg position. Passive elevation of the legs, a technique that stimulates cardiopulmonary baroreceptors, reduced ratings of heat pain though only among borderline hypertensives. Alteration of pain sensitivity may reflect the development of the hypertensive process. PMID- 19646504 TI - Fast multi-feature paradigm for recording several mismatch negativities (MMNs) to phonetic and acoustic changes in speech sounds. AB - In this study, we addressed whether a new fast multi-feature mismatch negativity (MMN) paradigm can be used for determining the central auditory discrimination accuracy for several acoustic and phonetic changes in speech sounds. We recorded the MMNs in the multi-feature paradigm to changes in syllable intensity, frequency, and vowel length, as well as for consonant and vowel change, and compared these MMNs to those obtained with the traditional oddball paradigm. In addition, we examined the reliability of the multi-feature paradigm by repeating the recordings with the same subjects 1-7 days after the first recordings. The MMNs recorded with the multi-feature paradigm were similar to those obtained with the oddball paradigm. Furthermore, only minor differences were observed in the MMN amplitudes across the two recording sessions. Thus, this new multi-feature paradigm with speech stimuli provides similar results as the oddball paradigm, and the MMNs recorded with the new paradigm were reproducible. PMID- 19646505 TI - Cellular uptake of steroid carrier proteins--mechanisms and implications. AB - Steroid hormones are believed to enter cells solely by free diffusion through the plasma membrane. However, recent studies suggest the existence of cellular uptake pathways for carrier-bound steroids. Similar to the clearance of cholesterol via lipoproteins, these pathways involve the recognition of carrier proteins by endocytic receptors on the surface of target cells, followed by internalization and cellular delivery of the bound sterols. Here, we discuss the emerging concept that steroid hormones can selectively enter steroidogenic tissues by receptor mediated endocytosis, and we discuss the implications of these uptake pathways for steroid hormone metabolism and action in vivo. PMID- 19646506 TI - The expression of ENa(+)C and ASIC2 proteins in Pacinian corpuscles is differently regulated by TrkB and its ligands BDNF and NT-4. AB - Pacinian corpuscles are innervated by large myelinated Aalpha-beta axons from the large- and intermediate-sized sensory neurons of dorsal root ganglia. These neurons express different members of the degenerin/epithelial Na(+) channel (DEG/ENa(+)C) superfamily of proteins with putative mechanosensory properties, whose expression is regulated by the TrkB-BDNF system. Thus, we hypothesized that BDNF and/or NT-4 signalling through activation of TrkB may regulate the expression of molecules supposed to be necessary for the mechanosensory function of Pacinian corpuscles. To test this hypothesis we analyzed the expression and distribution of ENa(+)C subunits and acid-sensing ion channel 2 (ASIC2) in Pacinian corpuscles from 25 days old mice deficient in TrkB, BDNF and NT-4. Pacinian corpuscles in these animals are normal in number, structure, and expression of several immunohistochemical markers. Using immunohistochemistry we observed that the beta-ENa(+)C and gamma-ENa(+)C subunits, but not the alpha ENa(+)C subunit, were expressed in wild-type animals, and they were always found in the central axon. ASIC2 immunoreactivity was found in both the central axon and the inner core cells. The absence of TrkB or BDNF abolished expression of beta-ENa(+)C and ASIC2, whereas expression of gamma-ENa(+)C did not change. Expression of beta-ENa(+)C and gamma-ENa(+)C subunits in NT-4 deficient mice was found in the axons but also in the inner core cells whereas levels of expression of ASIC2 were increased in these animals. This study suggests that expression in Pacianian corpuscles of some potential mechanosensory proteins is regulated by BDNF, NT-4 and TrkB. PMID- 19646507 TI - Enlargement of neuronal size in rat auditory cortex after prolonged sound exposure. AB - Prolonged sound exposure produces functional changes in the auditory neurons. It remains unclear whether such changes are detectable with morphometric measures like cell size. Here, after exposing juvenile rats (starting on week-4) to a monotone for 7 days, we measured the size of their cortical neurons. Neuronal profiles (nuclei and perikarya) in deep layers of the primary auditory cortex were digitized and measured on photomicrographs taken from 7 microm-thick histological sections stained with toluidine blue. To facilitate digitizing cell profiles, we used an image-analysis software that contains a confocal-like image merging function to sharpen the edges. After sound exposure, both nuclei and perikarya expanded by about 1/3 in volume compared with controls (p<0.0001, Student's t-test). Such changes were not found in the visual cortex. Results showed that prolonged sound exposure increased the size of auditory neurons. Such activity-driven cell enlargement can be used as a simple measure to find other plastic changes in the brain. PMID- 19646508 TI - Sex and regional differences in decrease of estrogen receptor alpha immunoreactive cells by estrogen in rat hypothalamus and midbrain. AB - Sensitivity of neurons to estrogen in down-regulation of estrogen receptor alpha (ERalpha) can be thought to make a sex difference in regulatory system of reproductive activities. In this study, to investigate the sex difference of expression of ERalpha in the hypothalamus and midbrain, the number of ERalpha immunoreactive (-ir) cells was counted in orchidectomized (OCX) and ovariectomized (OVX) rats with or without treatment with estrogen. A week after the gonadectomy, 5 rats in each female and male were injected with 1mg estradiol benzoate (EB). The remaining 5 rats in both sexes did not receive EB. The brain was fixed 24h after EB-injection and 50 microm-serial frozen sections were made. After immunohistochemical staining for ERalpha, the number of ERalpha-ir cells was counted in a 0.2-mm2 frame in the anteroventral periventricular nucleus (AVPvN), the ventrolateral part of the ventromedial hypothalamic nucleus (vlVMN), the arcuate nucleus (ARCN), and the lateral mesencephalic central gray (lMCG) in 2 or 3 sections. The total number of ERalpha-ir cells was changed to a density value (number per 1mm3). As the results, in EB-treated rats, the density of ERalpha-ir cells in all regions, except the male AVPvN and male lMCG, were lower than those in untreated rats of both sexes. In the vlVMN, the density of ERalpha ir cells in OVX rats was higher than in OCX rats. These results suggest that there are sex and regional differences in the mechanisms of down-regulation of ERalpha by estrogen in the rat brain. PMID- 19646509 TI - Inhibition of apoptosis signal-regulating kinase 1 reduces endoplasmic reticulum stress and nuclear huntingtin fragments in a mouse model of Huntington disease. AB - Huntington's disease (HD) is characterized clinically by chorea, psychiatric disturbances, and dementia, while it is characterized pathologically by neuronal inclusions as well as striatal and cortical neurodegeneration. The neurodegeneration arises from the loss of long projection neurons in the cortex and striatum. In this study, we investigated the role of apoptosis signal regulating kinase 1 (Ask1) in the pathogenesis of HD. We analyzed the expression of Ask1 and huntingtin (htt) within the striatum and cortex and also examined the interaction of Ask1 with htt fragments in HD (R6/2) mice. Additionally, we inhibited Ask1 and analyzed the resulting changes in brain-derived neurotrophic factor (BDNF) expression, motor function, and striatal atrophy. Ask1 activity was blocked using an Ask1 antibody raised against the C-terminus of the Ask1 protein. The anti-Ask1 antibody was infused into the striatum of the HD mice for four weeks using a micro-osmotic pump. The levels of Ask1 protein and endoplasmic reticulum (ER) stress were increased in HD mice. Binding of inactivated Ask1 to htt fragments was more prevalent in the cytosol than the nucleus of cortical neurons. Binding of inactivated Ask1 to htt fragments prevented translocation of the htt fragments into the nucleus, resulting in an improvement in motor dysfunction and atrophy. In the normal state, active Ask1 may help htt fragments enter the nucleus, while inactivated Ask1 hinders this translocation by binding to but not releasing fragmented htt into the nucleus. We propose that Ask1 may interact with htt fragments and subsequently induce ER stress. BDNF depletion may be prevented by targeting Ask1; this would decrease ER stress and possibly ameliorate behavioral or anatomical abnormalities that accompany HD. Therefore, regulating the amounts and activity of the Ask1 protein is a novel strategy for treatment of HD. PMID- 19646512 TI - The effect of breed, time spent with dam and late pregnancy induction of parturition on behavioural development in dairy calves. AB - Three experiments examined the impact of breed, time spent with dam (TWD), gender, and late pregnancy induction of parturition and caesarean on the behavioural and heart rate responses of dairy calves at 2 and 6 weeks of age to Open field, Novel object and Startle tests and a Learning task. In Experiment 1 with male Jersey, Friesian and Friesian x Angus calves, there were some significant breed effects on responses to the Open field and the Novel object tests; Jersey calves appeared more curious and less fearful than Friesian x Angus calves. In Experiment 2, in which male and female Friesian calves were removed from their dams either between 0 and 12h or 12 and 24h after birth, there were no significant effects of gender or TWD. In Experiment 3, which studied the effect of induction of parturition using a long-acting glucocorticoid combined with short-acting progesterone 10 days prior to due calving date, there were no significant effects of late pregnancy induction of parturition. Across all three experiments, age at testing was the main factor influencing the responses of the calves. However, a number of interactions suggest that gender, time spent with dam and late pregnancy induction of parturition modified some of the responses to the tests as the calves developed. PMID- 19646511 TI - The protective effects of Achyranthes bidentata polypeptides in an experimental model of mouse sciatic nerve crush injury. AB - We have separated the active polypeptides from aqueous extracts of Achyranthes bidentata Blume (ABPP), a commonly prescribed Chinese medicinal plant with a range of pharmaceutical properties. We investigated the effects of ABPP administration on peripheral nerve regeneration in a mouse sciatic nerve crush injury model. After nerve crush, the mice received daily tail vein injections of 1, 4, and 16 mg/kg of ABPP, 65 microg/kg of methylcobalamin, and vehicle saline, respectively, over a 21-day period. At 1, 3, 6, 9, 12, 15, 18 and 21 days after nerve crush, the animals were subjected to walking track analysis for evaluating the sciatic functional index (SFI) values. At day 21 the animals were anesthetized, and the compound muscle action potential and nerve conduction velocity were respectively recorded. After the animals were killed, the sciatic nerve was examined with immunohistochemistry and electron microscopy, and gastrocnemius muscle was analyzed with Masson trichome staining. The results indicated that treatment with ABPP at a dose range (1-16 mg/kg) promoted histological regeneration and functional recovery of the injured sciatic nerve and its target muscle, yielding a desired efficacy greater than that by vehicle treatment and close to that by methylcobalamin (65 microg/kg). These findings suggest that plant polypeptides, ABPP, may be a potential agent in ameliorating of neuropathy caused by sciatic nerve crush. PMID- 19646513 TI - Regulation of the mouse CTP: phosphoethanolamine cytidylyltransferase gene Pcyt2 during myogenesis. AB - The expression of the CTP: phosphoethanolamine cytidylyltransferase gene Pcyt2 is significantly up-regulated during C2C12 muscle cell differentiation, which was demonstrated by elevated Pcyt2 protein ( approximately 2.3-fold), mRNA ( approximately 2.6-fold) and promoter activity ( approximately 2-fold) in myotubes relative to myoblasts. Mutation and 5' deletion analyses of Pcyt2 promoter established the minimal core sequence and three main upstream regulatory regions. The core promoter (-111/+29 bp) strongly depends on the binding of cEBP to an inverse CCAAT-box located at position -82/-77 bp. Transcription factors Sp1 and Sp3 bind to regions A (-508/-378 bp) and C (-157/-111 bp), and muscle-specific differentiation factor MyoD targets the region C. Region B (-228/-157 bp) is weakly regulated by Sp factors and binds unknown protein complexes that acts as negative regulatory elements. Sp1 is less present in myotubes than in myoblasts and when over-expressed in myotubes significantly reduces promoter activity. These results demonstrate that elevated content of MyoD, reduced content of Sp1, and changed ratio of Sp1 to Sp3 all together contributed to a stimulated transcription of Pcyt2 gene during muscle cell differentiation. PMID- 19646510 TI - Cochlear nucleus neurons redistribute synaptic AMPA and glycine receptors in response to monaural conductive hearing loss. AB - Neurons restore their function in response to external or internal perturbations and maintain neuronal or network stability through a homeostatic scaling mechanism. Homeostatic responses at synapses along the auditory system would be important for adaptation to normal and abnormal fluctuations in the sensory environment. We investigated at the electron microscopic level and after postembedding immunogold labeling whether projection neurons in the cochlear nucleus responded to modifications of auditory nerve activity. After unilaterally reducing the level of auditory inputs by approximately 20 dB by monaural earplugging, auditory nerve synapses on bushy cells somata and basal dendrites of fusiform cells of the ventral and dorsal cochlear nucleus, respectively, upregulated GluR3 AMPA receptor subunit, while inhibitory synapses decreased the expression of GlyRalpha1 subunit. These changes in expression levels were fully reversible once the earplug was removed, indicating that activity affects the trafficking of receptors at synapses. Excitatory synapses on apical dendrites of fusiform cells (parallel fibers) with different synaptic AMPA receptor subunit composition, were not affected by sound attenuation, as the expression levels of AMPA receptor subunits were the same as in normal hearing littermates. GlyRalpha1 subunit expression at inhibitory synapses on apical dendrites of fusiform cells was also found unaffected. Furthermore, fusiform and bushy cells of the contralateral side to the earplugging upregulated the GluR3 subunit at auditory nerve synapses. These results show that cochlear nucleus neurons innervated by the auditory nerve, are able to respond to small changes in sound levels by redistributing specific AMPA and glycine receptor subunits. PMID- 19646514 TI - Perfluorononanoic acid induces apoptosis involving the Fas death receptor signaling pathway in rat testis. AB - Perfluorononanoic acid (PFNA, C9), a synthetic perfluorinated chemical containing nine carbons, accumulates and is biomagnified through food webs. This compound has been detected in the serum of humans and wildlife and has the potential for reproductive interference. Few studies, however, have reported the effects of PFNA exposure on male reproduction. To determine this, male rats were orally dosed for 1, 3 and 5mg/kgday PFNA or with vehicle for 14 days. In the present study, serum testosterone levels were decreased, while estradiol levels were increased dramatically in rats receiving 5mg PFNA/kgday. Spermatogenic cells from rats that received 5mg PFNA/kgday exhibited apoptotic features including crescent chromatin condensation and chromatin margination. Flow cytometric analysis and TUNEL assays revealed a dose-dependent increase of apoptotic cell numbers. In addition, expression of Fas and Bax mRNA levels were upregulated significantly, and Bcl-2 mRNA levels were downregulated markedly in the 3 and 5mg/kgday groups. A dose-dependent increase in levels of active caspase-8 and no significant changes of active caspase-9 were observed. Our results indicate that PFNA exposure can lead to cell apoptosis in rat testis, and this apoptosis was probably associated with the Fas death receptor-dependent apoptotic pathway. PMID- 19646516 TI - Ofloxacin targeting to lungs by way of microspheres. AB - The efficacy of drug candidates is frequently limited by their inability to reach the target site of action, especially when they are administered through conventional dosage forms or drug delivery systems. Targeted drug delivery systems have increased the amount of drug reaching the site and simultaneously decrease the amount being distributed to other parts of the body. Microspheres have emerged as a remedial measure to improve site-specific drug delivery to a considerable extent. As an application, lung-targeting albumin loaded ofloxacin microspheres (ALOME) were prepared by water in oil emulsion method. The appearance and size distribution were examined by scanning electron microscopy, and the aspects such as in vitro release characteristics, stability, drug loading, loading efficiency, pharmacokinetics and tissue distribution in albino mice were studied. The experimental results showed that the microspheres have an average particle size of 11.32 microm. The drug loading and loading efficiency were (66.95 and 94.8%) respectively. The in vitro release profile of the microspheres matched the Korsmeyer's Peppas release pattern, and the release after 1h was 42%, while for the original drug, ofloxacin, under the same conditions, 90.02% released in the first half an hour. After intravenous administration (15 min), the drug concentration of microspheres group in lung of albino mice was 432 microg g(-1) while that of controlled group was 1.32 microg g(-1) ALOME found to release the drug to a maximum extent in the target tissue, lung. Histopathological studies proved the tissue compatibility of ALOME to be safe. PMID- 19646515 TI - Efficiency of cell-penetrating peptides on the nasal and intestinal absorption of therapeutic peptides and proteins. AB - The purpose of our study was to investigate the potential of cell-penetrating peptides; penetratin as novel delivery vector, on the systemic absorption of therapeutic peptides and proteins across different mucosal administration sites. The absorption-enhancing feasibility of l- and d-penetratin (0.5mM) was used for glucagon-like peptide-1 (GLP-1), and exendin-4 as novel antidiabetic therapy, in addition to interferon-beta (IFN-beta) as protein biotherapeutic model from nasal and intestinal route of administration was evaluated as first time in rats. Nasal route is the most feasible for the delivery of therapeutic peptides coadministered with penetratin whereas the intestinal route appears to be more restricted. The absolute bioavailability (BA (%)) values depend on the physichochemical characters of drugs, stereoisomer character of penetratin, and site of administration. Penetratin significantly increased the nasal more than intestinal absorption of GLP-1 and exendin-4, as the BA for nasal and intestinal administration of GLP-1 was 15.9% and 5%, and for exendin-4 were 7.7% and 1.8%, respectively. Moreover, the BA of IFN-beta coadministered with penetratin was 11.1% and 0.17% for nasal and intestinal administration, respectively. From these findings, penetratin is a promising carrier for transmucosal delivery of therapeutic peptides and macromolecules as an alternative to conventional parenteral routes. PMID- 19646517 TI - Synthesis of composites of sodium oleate/Mg-Al-ascorbic acid-layered double hydroxides for drug delivery applications. AB - Mg-Al-ascorbic acid (ASA)-layered double hydroxides (ASA-LDHs) with Mg/Al=3 were synthesized by ion-exchange, coprecipitation and reconstruction methods. Composites with sodium oleate (SOA)/ASA-LDH were prepared by an ion-exchange method using various concentrations of SOA solutions. The (003) basal spacing of the ASA-LDHs changed from 0.76nm in the CO(3)-LDH to 0.78 and 0.86nm after intercalation of the ASA ions and these basal spacings are in good agreement with models based on the assumption as mono layers and double layers of ASA ions in the LDH interlayers, respectively. The amounts of ASA in the LDHs prepared by the reconstruction method were higher than those by the ion-exchange and coprecipitation methods. In the preparation of composites of SOA/ASA-LDH, an ion exchange method was more suitable than a reconstruction method to cause surface sorption of the SOA molecules with maintaining intercalated ASA ions in the LDH interlayers. The acid-resistant properties of the composites of SOA/ASA-LDH were found to be much higher than for the pure ASA-LDH and mixture of CO(3)-LDH and ASA. The surfaces of the LDH particles in the composites are, thus, mostly covered with sorbed SOA molecules and they are good candidates as drug delivery materials for intestines through the stomach. PMID- 19646518 TI - Self-assembled drug delivery systems. Part 4. In vitro/in vivo studies of the self-assemblies of cholesteryl-phosphonyl zidovudine. AB - An amphiphilic prodrug of anti-HIV nucleoside analogue, cholesteryl-phosphonyl zidovudine (CPNZ) was synthesized. An aqueous suspension containing CPNZ self assemblies was obtained through injecting the ethanol solution of CPNZ and cholesteryl succinyl poly(ethylene glycol) 1500 (20:1, mol/mol) into water under agitation. Hydrophobic interaction may be the driving force of molecular self assembly. The self-assemblies were nanoscale with approximately 100nm in size, and remained stable for a long time. Degradation of CPNZ self-assemblies was investigated in various environments including buffered solutions, plasma and rabbit tissue homogenates. CPNZ was degraded very slowly in neutral solutions but rapidly in various plasma with the half-lives (t(1/2)) of less than 20h. Tissue homogenates degraded CPNZ with varied rates depending on enzyme activity. CPNZ self-assemblies showed potent anti-HIV activity on MT4 cell model, the anti-HIV 50% effective concentration (EC(50)) of which was 1nM, only equal to 1/5 of AZT EC(50). CPNZ was rapidly eliminated from circulation and distributed into the mononuclear phagocyte system (MPS) including liver, spleen and lung after bolus intravenous administration of CPNZ self-assemblies followed slowly elimination. The possible products include AZT-5'-H-phosphonate, AZT and their derivatives. The MPS-targeted effect and high anti-HIV activity of CPNZ self-assemblies make them become a promising self-assembled drug delivery system (SADDS). PMID- 19646519 TI - Improved cellular uptake of chitosan-modified PLGA nanospheres by A549 cells. AB - The authors have previously developed poly(DL-lactic-co-glycolic acid) (PLGA) nanospheres (NSs) as a nanoparticulate drug carrier for pulmonary administration. The present study demonstrates that chitosan (CS)-modified PLGA NSs (CS-PLGA NSs) are preferentially taken up by human lung adenocarcinoma cells (A549). PLGA NSs prepared using a water-oil-water emulsion solvent evaporation method were surface modified by adsorption of CS. The physicochemical parameters of PLGA NS, including average size and surface charge, were measured to identify which parameter influenced cellular uptake of PLGA NS. Uptake was confirmed using fluorescence spectrophotometry and was visualized in A549 cells with confocal laser scanning microscopy (CLSM). The cytotoxicities of non- and CS-PLGA NS systems were compared in vitro by MTS assay. Cellular uptake of PLGA NS increased with decreasing diameter to the submicron level and with CS-mediated surface modification. Cellular uptake of PLGA NS was energy dependent, as shown by a reduction in uptake at lower incubation temperatures and in hypertonic growth medium used as an inhibitor of clathrin-coated pit endocytosis. CS-PLGA NSs were taken up by A549 cells in an energy-dependent manner, suggesting a clathrin mediated endocytic process. CS-PLGA NS demonstrated low cytotoxicity, similar to non-PLGA NS. PMID- 19646520 TI - Antidiarrhoeal and intestinal modulatory activities of Wei-Chang-An-Wan extract. AB - AIM OF THE STUDY: Wei-Chang-An-Wan (WCAW), a traditional pharmaceutical preparation, has been used for treating various gastrointestinal (GI) diseases for several decades, but it is still poorly understood how it works on those disorders. This study was to investigate the effects of WCAW extract on GI tract. MATERIALS AND METHODS: The activities of the methanol extract (ME) of WCAW on castor oil-induced diarrhoea, gastrointestinal transit (GIT) in mice, and contractions of isolated rabbit jejunum were investigated. We further assessed the safety of ME in vivo. Additionally, a HPLC fingerprint of ME was appraised to ensure its chemical consistency. RESULTS: Ten peaks were identified in the HPLC fingerprint of ME. At the doses of 400 and 800 mg/kg, ME significantly protected mice against castor oil-induced diarrhoea as well as the number of faeces and wet faeces. Interestingly, administration of ME significantly accelerated GIT in normal mice and reduced stimulated GIT induced by neostigmine. ME also dose dependently attenuated spontaneous contractions of the isolated rabbit jejunum, and those induced by acetylcholine (Ach) and neostigmine. Moreover, oral administration of ME up to 5 g/kg did not produce any toxic effects. Taken together, ME is able to inhibit diarrhoea, increase normal GIT, and decrease GIT induced by neostigmine, which indicate that ME might play a bidirectional role in GI tract. CONCLUSIONS: Our study provides a scientific basis for the clinical use of WCAW. PMID- 19646521 TI - Retinal astrocyte differentiation mediated by leukemia inhibitory factor in cooperation with bone morphogenetic protein 2. AB - Retinal astrocytes and their precursor cells migrate from the optic nerve. Interleukin 6 family cytokines, whose signal transduction requires gp130, promote astrocyte differentiation in the optic nerve, though the mechanism of astrocyte differentiation in the retina has not been clarified. We found that GFAP-positive astrocytes were significantly decreased in number but that a considerable number of astrocytes were still present in gp130-deficient mouse retina. These findings suggest that gp130-dependent signaling pathways play essential roles in retinal astrocyte differentiation and that retinal astrocyte differentiation can also be promoted by other signaling pathways. We found that leukemia inhibitory factor, bone morphogenetic proteins, and their receptors are expressed in P0 retina. In addition, leukemia inhibitory factor and bone morphogenetic protein 2 synergistically promote astrocyte differentiation of retinal precursor cells isolated from P0 mouse retina. These observations demonstrated that not only gp130-dependent signaling but also bone morphogenetic proteins play essential roles in retinal astrocyte differentiation. PMID- 19646522 TI - Structural analysis of 83-kb genomic DNA from Thellungiella halophila: sequence features and microcolinearity between salt cress and Arabidopsis thaliana. AB - Salt cress (Thellungiella halophila) has become a desirable plant model for molecular analysis of the mechanisms of salt tolerance. Analysis of its physiological action and expressed EST has resulted in better understanding. However, less is known about its genomic features. Here we determined a continuous sequence approximately 83 kb from a salt cress BAC clone, providing the first insight into the genomic feature for this species. The gene density is approximately one gene per 3.6 kb in this sequence. Many types of repetitive sequences are present in this salt cress sequence, including LTR retroelements, DNA transposons and a number of simple sequence repeats. Comparison of sequence similarity indicated that salt cress shares a close relationship with Arabidopsis. Extensive conservation and high-level microcolinearity were uncovered for both genomes. Our study also indicated that genomic DNA alternations (involving chromosome inversion, sequence loss and gene translocation) contributed to the genomic discrepancies between salt cress and Arabidopsis. PMID- 19646523 TI - An evaluation of the chick cardiomyocyte micromass system for identification of teratogens in a blind trial. AB - The chick micromass culture system has advantages over the validated rat system - ready availability and non-culling of the donor parent - but needs to give comparable results. This study confirmed comparability and the ability to extend the system to cover cardiac effects. It was also compared with the validated embryonic stem cell cardiomyocyte model. A teratogen and paired non-teratogen with known in vivo effects were used. Differential effects were measured via changes in cell protein content, cell viability (resazurin reduction and neutral red uptake), and cell contractility. Results showed that teratogens [L-ethionine, 5-fluorouracil and sulphisoxazole] could be distinguished from non-teratogens [DL methionine, 6-methyluracil and sulphanilamide respectively]. Dichloroacetone and dichloropropanol affected embryonic stem cells but not the micromass; dichloropropanol had a greater effect than dichloroacetone. This approach revealed differential effects on contractility independent of effects on activity/viability, whilst the total cell protein remained unchanged. We suggest that pre-validation of this system should be examined. PMID- 19646524 TI - Impact effects of puerarin on mouse embryonic development. AB - In this report, we examine the cytotoxic effects of puerarin, an isoflavone compound, on the blastocyst stage of mouse embryos and subsequent embryonic attachment and outgrowth in vitro and in vivo implantation by embryo transfer. Mouse blastocysts were incubated in medium with or without puerarin (2.5, 5 or 10 microM) for 24h. Cell proliferation and growth was investigated by dual differential staining, apoptosis was analyzed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), and implantation and post implantation development of embryos were measured by in vitro development analysis and in vivo embryo transfer, respectively. We found that blastocysts treated with 5 or 10 microM puerarin showed significant increases in apoptosis and significant decreases in total cell number. Interestingly, there was no significant difference of implantation success rate between puerarin-pretreated blastocysts and controls, but in vitro treatment with 5 or 10 microM puerarin was associated with increased resorption of post-implantation embryos and decreased fetal weight. Our results collectively indicate that in vitro exposure to puerarin induced apoptosis and after transfer to host mice retards early post implantation development. The extent to which puerarin may have teratogenic potential in early human development is not yet known. PMID- 19646525 TI - Male-enriched transcription of genes encoding ASPs and Kunitz-type protease inhibitors in Ancylostoma species. AB - Various transcripts coding for proteins considered to be central to parasite-host interactions were identified previously as male-enriched in the hookworm Ancylostoma braziliense. Among these genes were an ASP-5-like homologue and a Kunitz-type protease inhibitor. The present study extends this previous work to investigate similar molecules in other hookworms (Ancylostomatidae). Specifically, partial cDNA sequences encoding three different ASP molecules and two different Kunitz-type protease inhibitors were isolated, and the differential transcription between adult male and female worms was compared by conventional and quantitative reverse transcription (RT)-PCR for three species, A. braziliense, Ancylostoma caninum and Ancylostoma ceylanicum. In accordance with previous findings, male-enriched transcription was observed for all molecules explored. Based on this information, it is hypothesized that adult males are responsible for producing proteins essential to the survival of hookworms inside the host and for supporting developmental and reproductive processes in female worms. PMID- 19646526 TI - Protective role of cytosolic 2-cys peroxiredoxin in the TNF-alpha-induced apoptotic death of human cancer cells. AB - Cytosolic 2-cys peroxiredoxin (2-cysPrx) exhibiting thioredoxin-dependent hydroperoxide reductase activity has been demonstrated to be involved in a number of signaling processes, such as receptor tyrosine kinase and MAP kinase activation. However, its role in the cell death pathway has yet to be elucidated. Here we show that cytosolic 2-cysPrx suppresses the TNF-alpha-induced apoptosis of human cervical cancer cells in a caspase-8-dependent manner. The HeLa cervical cancer cells expressing a dominant negative mutant (DN) of a cytosolic 2-cysPrx manifested remarkable increase in intracellular reactive oxygen species level, which was counteracted by catalase administration, and apoptotic cell death induced by combined treatment of TNF-alpha and cycloheximide compared to the control (CT) cells. Similarly, the DN cells were also susceptible to apoptosis induced by the TNF-related apoptosis-inducing ligand. The apoptosis enhanced by DN expression was shown to be dependent on a typical FADD/caspase pathway. The DN cells undergoing apoptosis showed enhanced caspase-8 and -3 activations, as compared to the CT cells. In contrast, there was no difference observed in the sustained JNK activation between CT and DN cells. Thus, this study illustrates that intracellular reactive oxygen species regulated by cytosolic 2-cysPrx is involved in the TNF-alpha-induced apoptotic cell death via controlling caspase activation. PMID- 19646527 TI - Functional analysis of the Volvox carteri asymmetric division protein GlsA. AB - The Zuotin-family J protein chaperone GlsA is essential for the asymmetric divisions that establish germ and somatic cell initials during embryogenesis in the green alga Volvox carteri, but it is not known on what cellular process GlsA acts to carry out this function. Most GlsA protein is nuclear, and GlsA possesses two SANT domains, suggesting that GlsA may function as a transcriptional regulator. On the other hand, close homologs from yeast and mice are ribosome associated factors that regulate translation fidelity, implying GlsA might also regulate translation. Here we set out to gain additional evidence regarding the function of GlsA, specifically with respect to its possible involvement in transcription and translation. We found that like zuotin mutants, glsA mutants are ultrasensitive to both cold and to the ribosome-binding aminoglycoside antibiotic paromomycin, so some fraction of GlsA is likely to be ribosome associated. We also found that GlsA co-immunoprecipitates with histones and that this interaction is dependent on the presence of intact SANT domains. Through rescue experiments using transgenes that encode GlsA variants, we determined that the growth and asymmetric division defects of the glsA mutant are separable-a GlsA variant that rescued the growth defects did not completely rescue the asymmetric division phenotype. Considered in total, our results suggest that GlsA acts both at the level of translation and transcription, but the function that is essential for tolerance to paromomycin and cold is not sufficient for asymmetric cell division. PMID- 19646528 TI - Dendrimers: emerging polymers for drug-delivery systems. AB - Dendrimers are new class of polymeric materials. It is generally described as a macromolecule, which is characterized by its extensively branched 3D structure that provides a high degree of surface functionality and versatility. The unique properties associated with these dendrimers such as uniform size, high degree of branching, water solubility, multivalency, well-defined molecular weight and available internal cavities make them attractive for biological and drug-delivery applications. Commercialization of dendrimers is now forthcoming. The present review briefly describes about dendrimer synthesis strategies, types of dendrimers with different functionalities, properties which having crucial importance and their potential applications. PMID- 19646529 TI - High concentration of basidiolichens in a single family of agaricoid mushrooms (Basidiomycota: Agaricales: Hygrophoraceae). AB - The Agaricales is the largest and most diverse order of mushroom-forming Basidiomycota, with over 100 natural groups recognized in recent Fungal Tree of Life studies. Most agarics are either saprotrophic or ectomycorrhizal fungi, but the family Hygrophoraceae is in part characterized by a unique and remarkable diversity of lichenized forms. The most familiar of these is the chlorolichen genus Lichenomphalia, whose phylogenetic position in the Agaricales has been established. Recent limited evidence suggested that Hygrophoraceae also contains cyanolichens in the genus Dictyonema, which indicates a remarkable concentration and diversity of lichen-formers in a single family of agarics. To demonstrate the relationships of lichen-formers to other fungi in the family, we assembled ribosomal sequences from 52 species representing recognized groups within the Hygrophoraceae, among them new sequences representing Acantholichen and most species and forms of Dictyonema. The molecular data were evaluated using parsimony, likelihood, Bayesian, and distance analyses, including coding of ambiguous regions by means of INAASE and ARC, all of which indicate that Dictyonema and Acantholichen form a monophyletic clade derived from the primarily bryophilous genus Arrhenia and sister to the enigmatic Athelia pyriformis, a species unrelated to the Atheliales for which we are proposing a new genus name Eonema. The chlorolichen genus Lichenomphalia may be polyphyletic. Fungi in the Dictyonema-Acantholichen clade are typically tropical, entirely lichenized, and associate with cyanobacterial photobionts. Our data indicate a transition from agaricoid-omphalinoid basidiomes observed in Arrhenia to stereoid-corticioid forms in Dictyonema, and also support a previous suggestion of a connection between loss of clamp connections and lichenization. The diverse basidiome and thallus morphologies and nutritional ecologies of these fungi indicate a remarkable evolutionary flexibility that appears to have developed in part as a consequence of symbiosis. PMID- 19646530 TI - Feedback regulation of NEUROG2 activity by MTGR1 is required for progression of neurogenesis. AB - The sequential steps of neurogenesis are characterized by highly choreographed changes in transcription factor activity. In contrast to the well-studied mechanisms of transcription factor activation during neurogenesis, much less is understood regarding how such activity is terminated. We previously showed that MTGR1, a member of the MTG family of transcriptional repressors, is strongly induced by a proneural basic helix-loop-helix transcription factor, NEUROG2 in developing nervous system. In this study, we describe a novel feedback regulation of NEUROG2 activity by MTGR1. We show that MTGR1 physically interacts with NEUROG2 and represses transcriptional activity of NEUROG2. MTGR1 also prevents DNA binding of the NEUROG2/E47 complex. In addition, we provide evidence that proper termination of NEUROG2 activity by MTGR1 is necessary for normal progression of neurogenesis in the developing spinal cord. These results highlight the importance of feedback regulation of proneural gene activity in neurodevelopment. PMID- 19646531 TI - The dimer formed by the periplasmic domain of EpsL from the Type 2 Secretion System of Vibrio parahaemolyticus. AB - The Type 2 Secretion System (T2SS), occurring in many Gram-negative bacteria, is responsible for the transport of a diversity of proteins from the periplasm across the outer membrane into the extracellular space. In Vibrio cholerae, the T2SS secretes several unrelated proteins including the major virulence factor cholera toxin. The T2SS consists of three sub-assemblies, one of which is the Inner Membrane Complex which contains multiple copies of five proteins, including the bitopic membrane protein EpsL. Here, we report the 2.3A resolution crystal structure of the periplasmic domain of EpsL (peri-EpsL) from Vibrio parahaemolyticus, which is 56% identical in sequence to its homolog in V. cholerae. The domain adopts a circular permutation of the "common" ferredoxin fold with two contiguous sub-domains. Remarkably, this infrequently occurring permutation was for the first time observed in the periplasmic domain of EpsM (peri-EpsM), another T2SS protein which interacts with EpsL. These two domains are 18% identical in sequence which may indicate a common evolutionary origin. Both peri-EpsL and peri-EpsM form dimers, but the organization of the subunits in these dimers appears to be entirely different. We have previously shown that the cytoplasmic domain of EpsL is also dimeric and forms a heterotetramer with the first domain of the "secretion ATPase" EpsE. The latter enzyme is most likely hexameric. The possible consequences of the combination of the different symmetries of EpsE and EpsL for the architecture of the T2SS are discussed. PMID- 19646532 TI - Neurofeedback: A promising tool for the self-regulation of emotion networks. AB - Real-time functional magnetic resonance imaging (fMRI) affords the opportunity to explore the feasibility of self-regulation of functional brain networks through neurofeedback. We localised emotion networks individually in thirteen participants using fMRI and trained them to upregulate target areas, including the insula and amygdala. Participants achieved a high degree of control of these networks after a brief training period. We observed activation increases during periods of upregulation of emotion networks in the precuneus and medial prefrontal cortex and, with increasing training success, in the ventral striatum. These findings demonstrate the feasibility of fMRI-based neurofeedback of emotion networks and suggest a possible development into a therapeutic tool. PMID- 19646534 TI - A regularized discriminative framework for EEG analysis with application to brain computer interface. AB - We propose a framework for signal analysis of electroencephalography (EEG) that unifies tasks such as feature extraction, feature selection, feature combination, and classification, which are often independently tackled conventionally, under a regularized empirical risk minimization problem. The features are automatically learned, selected and combined through a convex optimization problem. Moreover we propose regularizers that induce novel types of sparsity providing a new technique for visualizing EEG of subjects during tasks from a discriminative point of view. The proposed framework is applied to two typical BCI problems, namely the P300 speller system and the prediction of self-paced finger tapping. In both datasets the proposed approach shows competitive performance against conventional methods, while at the same time the results are easier accessible to neurophysiological interpretation. Note that our novel approach is not only applicable to Brain imaging beyond EEG but also to general discriminative modeling of experimental paradigms beyond BCI. PMID- 19646533 TI - Sources of group differences in functional connectivity: an investigation applied to autism spectrum disorder. AB - An increasing number of fMRI studies are using the correlation of low-frequency fluctuations between brain regions, believed to reflect synchronized variations in neuronal activity, to infer "functional connectivity". In studies of autism spectrum disorder (ASD), decreases in this measure of connectivity have been found by focusing on the response to task modulation, by using only the rest periods, or by analyzing purely resting-state data. This difference in connectivity, however, could result from a number of different mechanisms- differences in noise, task-related fluctuations, task performance, or spontaneous neuronal activity. In this study, we investigate the difference in functional connectivity between adolescents with high-functioning ASD and typically developing control subjects by examining the residual fluctuations occurring on top of the fMRI response to an overt verbal fluency task. We find decreased correlations of these residuals (a decreased "connectivity") in ASD subjects. Furthermore, we find that this decrease was not due to task-related effects, block-to-block variations in task performance, or increased noise, and the difference was greatest when primarily rest periods are considered. These findings suggest that the estimate of disrupted functional connectivity in ASD is likely driven by differences in task-unrelated neuronal fluctuations. PMID- 19646535 TI - Bayesian spatiotemporal model of fMRI data. AB - This research describes a new Bayesian spatiotemporal model to analyse block design BOLD fMRI studies. In the temporal dimension, we parameterise the hemodynamic response function's (HRF) shape with a potential increase of signal and a subsequent exponential decay. In the spatial dimension, we use Gaussian Markov random fields (GMRF) priors on activation characteristics parameters (location and magnitude) that embody our prior knowledge that evoked responses are spatially contiguous and locally homogeneous. The result is a spatiotemporal model with a small number of parameters, all of them interpretable. Simulations from the model are performed in order to ascertain the performance of the sampling scheme and the ability of the posterior to estimate model parameters, as well as to check the model sensitivity to signal to noise ratio. Results are shown on synthetic data and on real data from a block-design fMRI experiment. PMID- 19646536 TI - Imagery of a moving object: the role of occipital cortex and human MT/V5+. AB - Visual imagery--similar to visual perception--activates feature-specific and category-specific visual areas. This is frequently observed in experiments where the instruction is to imagine stimuli that have been shown immediately before the imagery task. Hence, feature-specific activation could be related to the short term memory retrieval of previously presented sensory information. Here, we investigated mental imagery of stimuli that subjects had not seen before, eliminating the effects of short-term memory. We recorded brain activation using fMRI while subjects performed a behaviourally controlled guided imagery task in predefined retinotopic coordinates to optimize sensitivity in early visual areas. Whole brain analyses revealed activation in a parieto-frontal network and lateral occipital cortex. Region of interest (ROI) based analyses showed activation in left hMT/V5+. Granger causality mapping taking left hMT/V5+ as source revealed an imagery-specific directed influence from the left inferior parietal lobule (IPL). Interestingly, we observed a negative BOLD response in V1-3 during imagery, modulated by the retinotopic location of the imagined motion trace. Our results indicate that rule-based motion imagery can activate higher-order visual areas involved in motion perception, with a role for top-down directed influences originating in IPL. Lower-order visual areas (V1, V2 and V3) were down-regulated during this type of imagery, possibly reflecting inhibition to avoid visual input from interfering with the imagery construction. This suggests that the activation in early visual areas observed in previous studies might be related to short- or long-term memory retrieval of specific sensory experiences. PMID- 19646537 TI - Altered brain response without behavioral attention deficits in healthy siblings of schizophrenic patients: an event-related fMRI study. AB - Attention deficits are common in schizophrenics and sometimes reported in their healthy relatives. The aim of this study was to analyse the behavioural performance and the brain activation of healthy siblings of schizophrenic patients during a sustained-attention task. Eleven healthy siblings of schizophrenic patients and eleven matched controls performed a Continuous Performance Test (CPT), during 1.5 T fMRI. The stimuli were presented at three difficulty-levels, using different degrees of degradation (0, 25 and 40%). There were no significant differences in CPT performance (mean reaction time and percentage of errors) between the two groups. Performance worsened with increasing degradation in both groups. Differences were found when comparing the BOLD signal change in the medial frontal gyrus/dorsal anterior cingulate, right precentral gyrus, bilateral posterior cingulate and bilateral insula. The most evident between group differences were observed in the left insula/inferior frontal gyrus: siblings showed a larger activation during wrong responses and a reduced activation during correct responses in the degraded runs. In conclusion, healthy siblings of schizophrenic patients showed differences in brain function in several brain regions previously reported in schizophrenic subjects, in the absence of behavioral attention deficits. The differences were greater in the two more difficult levels of attention demand and might be expressions of altered and/or compensatory mechanisms in subjects at increased risk for schizophrenia. PMID- 19646538 TI - Core networks for visual-concrete and abstract thought content: a brain electric microstate analysis. AB - Commonality of activation of spontaneously forming and stimulus-induced mental representations is an often made but rarely tested assumption in neuroscience. In a conjunction analysis of two earlier studies, brain electric activity during visual-concrete and abstract thoughts was studied. The conditions were: in study 1, spontaneous stimulus-independent thinking (post-hoc, visual imagery or abstract thought were identified); in study 2, reading of single nouns ranking high or low on a visual imagery scale. In both studies, subjects' tasks were similar: when prompted, they had to recall the last thought (study 1) or the last word (study 2). In both studies, subjects had no instruction to classify or to visually imagine their thoughts, and accordingly were not aware of the studies' aim. Brain electric data were analyzed into functional topographic brain images (using LORETA) of the last microstate before the prompt (study 1) and of the word type discriminating event-related microstate after word onset (study 2). Conjunction analysis across the two studies yielded commonality of activation of core networks for abstract thought content in left anterior superior regions, and for visual-concrete thought content in right temporal-posterior inferior regions. The results suggest that two different core networks are automatedly activated when abstract or visual-concrete information, respectively, enters working memory, without a subject task or instruction about the two classes of information, and regardless of internal or external origin, and of input modality. These core machineries of working memory thus are invariant to source or modality of input when treating the two types of information. PMID- 19646540 TI - The polyphyletic genus Sebaea (Gentianaceae): a step forward in understanding the morphological and karyological evolution of the Exaceae. AB - Within the Gentianaceae-Exaceae, the most species-rich genus Sebaea has received very little attention in terms of phylogenetic or karyological investigations. As a result, the exact number of species remains vague and the relationships with the other members of the Exaceae poorly understood. In this paper, we provide the first comprehensive phylogeny of the Exaceae including most Sebaea species known so far based on four cpDNA sequence regions. In addition, morphological and karyological characters were mapped on the inferred phylogenetic trees to detect possible non-molecular synapomorphies. Our results reveal the paraphyly of Sebaea and highlight new generic relationships within the Exaceae. Sebaea pusilla (lineage S1--Lagenias) forms a highly supported and early diverging clade with Sebaeas.str. (clade S2 -Sebaea). A third clade of the former Sebaea s.l. (clade S3--Exochaenium) contains exclusively tropical African species, and is sister with a large clade containing all the remaining genera of Exaceae. Within the latter, the proposed sister relationships between the recently described Klackenbergia and Ornichia are highly supported. Optimization of several morphological characters onto the inferred phylogenetic trees reveals several synapomorphies for most highly supported clades. In particular, lineage S1 (Lagenias) is supported by medifixed anthers that are inserted at the base of the corolla tube and cubical seeds with polygonal testa cells; clade S2 (Sebaea) is supported by both the presence of secondary stigmas along the style and ridged seeds with rectangular testa cells arranged in row; clade S3 (Exochaenium) is supported by its particular gynoecium (stylar polymorphism and clavate, papillose stigma). Finally, karyological reconstructions suggest a basal number of x=7 for the Exaceae and several episodes of dysploidy leading to x=8 and 9. PMID- 19646541 TI - Flanking regions of monomorphic microsatellite loci provide a new source of data for plant species-level phylogenetics. AB - Well-resolved phylogenetic trees are essential for us to understand evolutionary processes at the level of species. The degree of species-level resolution in the plant phylogenetic literature is poor, however, largely due to the dearth of sufficiently variable molecular markers. Unlike the common genic approach to marker development, we generated DNA sequences of monomorphic nuclear microsatellite flanking regions in a phylogenetic study of Annona species (Annonaceae). The resulting data showed no evidence of paralogy or allelic diversity that would confound attempts to reconstruct the species tree. Microsatellite flanking regions are short, making them practical to use, yet have astounding proportions of variable characters. They have 3.5- to 10-fold higher substitution rates compared to two commonly used chloroplast markers, have no rate heterogeneity among nucleotide positions, evolve in a clock-like fashion, and show no evidence of saturation. These advantages are offset by the short length of the flanking regions, resulting in similar numbers of parsimony informative characters to the chloroplast markers. The neutral evolution and high variability of flanking regions, together with the wide availability of monomorphic microsatellite loci in angiosperms, are useful qualities for species level phylogenetics. The general methodology we present here facilitates to find phylogenetic markers in groups where microsatellites have been developed. PMID- 19646542 TI - Resistance of a recombinant Escherichia coli to dehydration. AB - Dehydration of microorganisms, rendering them anhydrobiotic, is often an efficient method for the short and long term conservation of different strain producers. However, some biotechnologically important recombinant bacterial strains are extremely sensitive to conventional treatment. We describe appropriate conditions during dehydration of the recombinant Escherichia coli strain HB 101 (GAPDH) that can result dry cells having a approximately 88% viability on rehydration. The methods entails air-drying after addition of 100 mM trehalose to the cultivation medium or distilled water (for short term incubation). PMID- 19646539 TI - Event-related functional MRI of cortical activity evoked by microsaccades, small visually-guided saccades, and eyeblinks in human visual cortex. AB - We used event-related functional magnetic resonance imaging (fMRI) to determine blood oxygen-level-dependent (BOLD) signal changes following microsaccades, visually-guided saccades, and eyeblinks in retinotopically mapped visual cortical areas V1-V3 and hMT+. A deconvolution analysis revealed a similar pattern of BOLD activation following a microsaccade, 0.16 degrees voluntary saccade, and 0.16 degrees displacement of the image under conditions of fixation. In all areas, an initial increase in BOLD signal peaking at approximately 4.5 s after the event was followed by a decline and decrease below baseline. This modulation appears most pronounced for microsaccades and small voluntary saccades in V1, diminishing in strength from V1 to V3. In contrast, 0.16 degrees real motion under conditions of fixation yields the same level of BOLD signal increase in V1 through V3. BOLD signal modulates parametrically with the size of voluntary saccades (0.16 degrees , 0.38 degrees , 0.82 degrees , 1.64 degrees , and 3.28 degrees ) in V1-V3, but not in hMT+. Eyeblinks generate larger modulation that peaks by 6.5 s, and dips below baseline by 10 s post-event, and also exhibits diminishing modulation from V1 to V3. Our results are consistent with the occurrence of transient neural excitation driven by changes in input to retinal ganglion cell receptive fields that are induced by microsaccades, visually-guided saccades, or small image shifts. The pattern of results in area hMT+ exhibits no significant modulation by microsaccades, relatively small modulation by eyeblinks, and substantial responses to saccades and background jumps, suggesting that spurious image motion signal arising from microsaccades and eyeblinks is relatively diminished by hMT+. PMID- 19646543 TI - Down-regulation of cough sensitivity after eucapnic dry air provocation in chronic idiopathic cough. AB - Down-regulation of cough sensitivity in humans is rarely discussed in terms other than pharmacological treatment of cough or hypersensitive cough reflex. Chronic cough and increased cough sensitivity could be due to a number of airway and other diseases. When such conditions are excluded, there still remains a group of patients with no evident medical explanation for persistent coughing; such patients are often described as having "chronic idiopathic cough". The aim of this study was to use a standardized eucapnic dry air provocation among patients with chronic idiopathic cough in order to study physiological parameters and measure their possible influence on capsaicin cough sensitivity. Fourteen female patients with chronic idiopathic cough and ten healthy controls underwent a capsaicin inhalation provocation on two occasions. In all patients, irritating environmental factors were known to induce cough and airway symptoms. One of the two capsaicin provocations was preceded by a eucapnic dry air provocation. Number of coughs, spirometry, respiratory rate, pulse rate, end-tidal CO(2), and oxygen saturation by pulse oximetry (PSaO(2)) were registered and compared. The patients showed increased capsaicin sensitivity compared with the control subjects. This sensitivity was decreased when the capsaicin test was preceded by a eucapnic dry air provocation. Before the dry air provocation and after the capsaicin provocations, end-tidal CO(2) was decreased among the patients in comparison with the controls. After dry air provocation, spirometry values remained unchanged. The results suggest that in patients with chronic idiopathic cough, physiological down-regulation of the cough sensitivity is possible with a eucapnic dry air provocation. PMID- 19646545 TI - Application of dynamic flux balance analysis to an industrial Escherichia coli fermentation. AB - We have developed a reactor-scale model of Escherichia coli metabolism and growth in a 1000 L process for the production of a recombinant therapeutic protein. The model consists of two distinct parts: (1) a dynamic, process specific portion that describes the time evolution of 37 process variables of relevance and (2) a flux balance based, 123-reaction metabolic model of E. coli metabolism. This model combines several previously reported modeling approaches including a growth rate-dependent biomass composition, maximum growth rate objective function, and dynamic flux balancing. In addition, we introduce concentration-dependent boundary conditions of transport fluxes, dynamic maintenance demands, and a state dependent cellular objective. This formulation was able to describe specific runs with high-fidelity over process conditions including rich media, simultaneous acetate and glucose consumption, glucose minimal media, and phosphate depleted media. Furthermore, the model accurately describes the effect of process perturbations--such as glucose overbatching and insufficient aeration--on growth, metabolism, and titer. PMID- 19646544 TI - Preserved pulmonary vasodilative properties of aerosolized brain natriuretic peptide. AB - INTRODUCTION: Inhalation of vasoactive substances is an effective treatment of pulmonary hypertension. The B-type natriuretic peptide (BNP) leads to relaxation of smooth muscle cells, caused by an increased formation of cyclic guanosine monophosphate (cGMP). The biologic activity of BNP using an inhalative approach has not been addressed. METHODS: In order to assess the vasorelaxing capacity of exogenous BNP in the isolated ventilated and buffer perfused rabbit lung model, a stable pulmonary vasoconstriction was established by either the application of endothelin-1 or the thromboxane A(2) mimetic U46619. This was followed by an intravascular or aerosol application of BNP. CGMP was measured in the recirculating buffer fluid using a radioimmunoassay technique. RESULTS: During a stable plateau of U46619 induced pulmonary vasoconstriction (mean pulmonary artery pressure, PAP 25.5+/-0.23 mmHg), the intravascular administration of BNP induced a rapid vasodilation (mean PAP 18.13+/-0.95 mmHg, p<0.001). This vasodilation was dose dependent and was paralleled by a 6-fold increase of cGMP. When BNP was aerosolized, pulmonary vasoconstriction was also significantly alleviated in the U46619 model (mean PAP 22+/-2.1 mmHg) and during endothelin-1 induced vasoconstriction (mean PAP 17.1+/-2.47 mmHg). Correspondingly, inhalation caused a significant augmentation of cGMP levels was. CONCLUSION: The vasodilative capability of BNP as an indicator of the biologic activity of this peptide is preserved during its aerosolization. Presumably these vascular actions are caused at least in part by an increased availability of cGMP. PMID- 19646546 TI - Calpain activates caspase-8 in neuron-like differentiated PC12 cells via the amyloid-beta-peptide and CD95 pathways. AB - The neurotoxic amyloid-beta-peptide (Abeta) is important in the pathogenesis of Alzheimer's disease (AD). Calpain (Ca(2+)-dependent protease) and caspase-8 (the initiating caspase for the extrinsic, receptor-mediated apoptosis pathway) have been implicated in AD/Abeta toxicity. We previously found that Abeta promoted degradation of calpastatin (the specific endogenous calpain inhibitor); calpastatin degradation was prevented by inhibitors of either calpain or caspase 8. The results implied a cross-talk between the two proteases and suggested that one protease was responsible for the activity of the other one. We now report on the previously unrecognized caspase-8 activation by calpain. In neuron-like differentiated PC12 cells, calpain promotes active caspase-8 formation from procaspase-8 via the Abeta and CD95 pathways, along with degradation of the procaspase-8 processing inhibitor caspase-8 (FLICE)-like inhibitory protein, short isoform (FLIP(S)). Inhibition of calpain (by pharmacological inhibitors and by overexpression of calpastatin) prevents the cleavage of procaspase-8 to mature, active caspase-8, and inhibits FLIP(S) degradation in the Abeta-treated and CD95-triggered cells. Increased cellular Ca(2+) per se results in calpain activation but does not lead to caspase-8 activation or FLIP(S) degradation. The results suggest that procaspase-8 and FLIP(S) association with cell membrane receptor complexes is required for calpain-induced caspase-8 activation. The results presented here add to the understanding of the roles of calpain, caspase 8, and CD95 pathway in AD/Abeta toxicity. Calpain-promoted activation of caspase 8 may have implications for other types of CD95-induced cell damage, and for nonapoptotic functions of caspase-8. Inhibition of calpain may be useful for modulating certain caspase-8-dependent processes. PMID- 19646547 TI - Vascular endothelial growth factor-A: a multifunctional molecular player in diabetic retinopathy. AB - Vascular endothelial growth factor-A (VEGF-A), first described as "vascular permeability factor", is a critical molecule in the pathogenesis of diabetic retinopathy at several levels. Previous studies have outlined the importance of VEGF-A in mediating vascular pathology in both experimental models and clinical diabetic retinopathy, which are characterized by retinal vascular leakage, preretinal neovascularisation and neuronal degeneration. Paradoxically, recent reports have emphasized the potential neurotrophic effects of VEGF-A on the quiescent vasculature, as well as its direct and indirect protective effects on retinal neurons. VEGF-A has also been identified as an important signalling regulator in the normal central nervous system. Consequently, anti-VEGF therapy for diabetic retinopathy has become a controversal issue. This review outlines recently developed concepts relating to the role of VEGF-A in the pathogenesis of diabetic retinopathy, with particular emphasis on its implications for clinical practice. PMID- 19646548 TI - Wnt signaling and hepatocarcinogenesis: the hepatoblastoma model. AB - The Wnt/beta-catenin pathway plays a key role in liver development, regeneration and tumorigenesis. Among human cancers tightly linked to abnormal Wnt/beta catenin signaling, hepatoblastoma (HB) presents with the highest rate (50-90%) of beta-catenin mutations. HB is the most common malignant tumor of the liver in childhood. This embryonic tumor differs from hepatocellular carcinoma by the absence of viral etiology and underlying liver disease, and by distinctive morphological patterns evoking hepatoblasts, the bipotent precursors of hepatocytes and cholangiocytes. Recent studies of the molecular pathogenesis of hepatoblastoma have led to identify two major tumor subclasses resembling early and late phases of prenatal liver development and presenting distinctive chromosomal alterations. It has been shown that the molecular signature of Wnt/beta-catenin signaling in hepatoblastoma is mainly imposed by liver context, but differs according to developmental stage. Finally, the differentiation stage of tumor cells strongly influences their invasive and metastatic properties, therefore affecting clinical behavior. PMID- 19646549 TI - Rhabdias rhampholeonis n. sp. and Rhabdias mariauxi n. sp. (Nematoda, Rhabdiasoidea), first lung worms from leaf chameleons: description, molecular evidence and notes on biology. AB - Rhabdias rhampholeonis n. sp. from Rhampholeon (Rh.) spectrum, Cameroon, and Rhabdias mariauxi n. sp. from Rieppeleon brevicaudatus, Tanzania, are the first lung worms from leaf chameleons. The new species are similar to the majority of species parasitic in chamaeleonids by having a long (>or=10 mm) and thick body (>or=500 microm), long oesophagus (>or=800 microm), wide buccal capsule (>or=40 microm) and low buccal ratio (<0.5). They most closely resemble Rhabdias chamaeleonis and Rhabdias cristati parasitic in Trioceros spp. from East Africa and Cameroon, respectively. Main distinctive characters are a buccal capsule composed of two segments and the head shape. The dorso-ventrally flattened buccal capsule of R. mariauxi n. sp. is unique in Rhabdias parasitising Chamaeleonidae. Sequences of the 12S rDNA and mitochondrial cytochrome c oxidase subunit 1 (coxI) genes were obtained and compared to those of Rhabdias okuensis, the only sequences published for chamaeleonid lung worms. The smallest nucleotide interspecific distances were found between R. mariauxi n. sp. and the former species of Trioceros from Cameroon. Hermaphroditism in females in the lungs, and R. mariauxi n. sp. free-living stages are like in other species from Chamaeleonidae, but the number of infective larvae produced per free-living female (one or two) was not fixed. PMID- 19646551 TI - Rule-based information extraction from patients' clinical data. AB - The paper describes a rule-based information extraction (IE) system developed for Polish medical texts. We present two applications designed to select data from medical documentation in Polish: mammography reports and hospital records of diabetic patients. First, we have designed a special ontology that subsequently had its concepts translated into two separate models, represented as typed feature structure (TFS) hierarchies, complying with the format required by the IE platform we adopted. Then, we used dedicated IE grammars to process documents and fill in templates provided by the models. In particular, in the grammars, we addressed such linguistic issues as: ambiguous keywords, negation, coordination or anaphoric expressions. Resolving some of these problems has been deferred to a post-processing phase where the extracted information is further grouped and structured into more complex templates. To this end, we defined special heuristic algorithms on the basis of sample data. The evaluation of the implemented procedures shows their usability for clinical data extraction tasks. For most of the evaluated templates, precision and recall well above 80% were obtained. PMID- 19646552 TI - Oral administration of dehydroepiandrosterone-sulfate (DHEAS) increases in vitro lymphocyte function and improves in vivo response of pigs to immunization against keyhole limpet hemocyanin (KLH) and ovalbumin. AB - The present study tested the hypothesis that the oral administration of DHEAS enhances the in vitro and the in vivo immune response of young pigs. Crossbred, female pigs (80 days of age; 49+/-2 kg) were separated into two treatment groups (n=4/treatment) receiving either 0mg/kg (control) or 1mg/kg DHEAS twice daily (DHEAS) for 5 weeks. On day 7 pigs were immunized against KLH and ovalbumin. Body weight increased weekly throughout the study but did not differ between treatment groups. While white blood cell counts increased in response to immunization but did not differ between treatments, the neutrophil:lymphocyte ratio was enhanced (P<0.05) in DHEAS-supplemented pigs. Concanavalin A (ConA) induced an in vitro dose-dependent increase (P<0.05) in lymphocyte proliferation, but treatment did not affect proliferation prior to immunization. However, lymphocytes isolated from DHEAS-supplemented pigs displayed a greater increase in proliferation following immunization relative to control pigs (P<0.05). Dexamethasone (DEX) attenuated ConA-induced lymphocyte proliferation, with DHEAS-supplemented pigs retaining a greater proliferative response relative to control pigs (P<0.05). Serum IgG concentrations and relative concentrations of antigen-specific IgG increased after immunization with maximum values attained at 21 and 28 days for control and DHEAS-supplemented pigs, respectively. The DHEAS-supplemented pigs had greater (P<0.05) concentrations of IgG and relative concentrations of antigen specific IgG compared to control pigs. Collectively these data suggest DHEAS supplementation increases the responsiveness of young pigs to antigenic challenge, and may be beneficial for improving their immune function. PMID- 19646550 TI - Fibrillar collagen type I stimulation of apolipoprotein B secretion in Caco-2 cells is mediated by beta1 integrin. AB - Caco-2 cells spontaneously differentiate into enterocyte-like cells and secrete apolipoprotein B (apoB) lipoproteins. We evaluated the effect of different extracellular matrix proteins on lipoprotein secretion by these cells. Caco-2 cells grown on human amnion connective tissue (HACT) secreted twice as much apoB as control cells on Transwells, but secreted similar amounts of apoA1. Cells cultured on fibrillar collagen type I secreted increased amounts of apoB similar to the cells cultured on HACT, but cells cultured on non-fibrillar collagen type I, type IV collagen or laminin-1 did not. The increased secretion was nullified by a function inhibiting anti-integrin beta1 monoclonal antibody. Therefore, interactions between type I collagen and beta1 integrins augment apoB secretion by Caco-2 cells. Cells on HACT formed a more uniform columnar epithelium with lipid droplets polarized to the basolateral membrane. We also studied the effect of extracellular matrix proteins on transepithelial resistance (TER) of differentiated Caco-2 cells. TER in cells cultured on HACT was similar to that on Transwells, but cells on laminin-1 and collagen IV exhibited higher TER. Thus, various extracellular matrix proteins regulate apoB secretion and TER differently. This new observation that extracellular matrix proteins can enhance apoB secretion in Caco-2 cells could be useful to explore the modulation of lipid transport by these proteins. PMID- 19646554 TI - Optimization of lipase-catalyzed biodiesel by isopropanolysis in a continuous packed-bed reactor using response surface methodology. AB - Isopropanolysis reactions were performed using triglycerides with immobilized lipase in a solvent-free environment. This study modeled the degree of isopropanolysis of soybean oil in a continuous packed-bed reactor when Novozym 435 was used as the biocatalyst. Response surface methodology (RSM) and three level-three-factor Box-Behnken design were employed to evaluate the effects of synthesis parameters, reaction temperature ( degrees C), flow rate (mL/min) and substrate molar ratio of isopropanol to soybean oil, on the percentage molar conversion of biodiesel by transesterification. The results show that flow rate and temperature have a significant effect on the percentage of molar conversion. On the basis of ridge max analysis, the optimum conditions for synthesis were as follows: flow rate 0.1 mL/min, temperature 51.5 degrees C and substrate molar ratio 1:4.14. The predicted value was 76.62+/-1.52% and actual experimental value was 75.62+/-0.81% molar conversion. Moreover, continuous enzymatic process for seven days did not show any appreciable decrease in the percent of molar conversion (75%). This work demonstrates the applicability of lipase catalysis to prepare isopropyl esters by transesterification in solvent-free system with a continuous packed-bed reactor for industrial production. PMID- 19646553 TI - Optimal production of a novel endo-acting beta-1,4-xylanase cloned from Saccharophagus degradans 2-40 into Escherichia coli BL21(DE3). AB - To date, gene xyn10C from Saccharophagus degradans 2-40 has only been identified to encode a potential xylanase. In the present study, xyn10C was cloned and overexpressed in Escherichia coli BL21(DE3). The protein produced by xyn10C, Xyn10C, was expressed in a soluble active form and found to be an endotype beta 1,4-xylanase that preferentially produces xylobiose from xylan. Recombinant cell fermentation revealed that induction of the gene at low temperatures fostered expression of the recombinant xylanase with high volumetric and specific activities. Additionally, low growth rates were favorable for producing soluble active xylanase via a reduction in the formation of inclusion bodies. Furthermore, the optimal concentration of isopropyl-beta-D-thiogalactopyranoside for induction was found to be 100 microm after two hours of precultivation at 37 degrees C. Finally, enzyme production conducted using a fermentor with a working volume of 1.5-l resulted in slightly higher specific activities of xylanase when compared with the generation of enzymes in flasks with a working volume of 100ml. PMID- 19646555 TI - Letter from the editors. PMID- 19646556 TI - SPECT/CT imaging in general orthopedic practice. AB - The availability of hybrid devices that combine the latest single-photon emission computed tomography (SPECT) imaging technology with multislice computed tomography (CT) scanning has allowed us to detect subtle, nonspecific abnormalities on bone scans and interpret them as specific focal areas of pathology. Abnormalities in the spine can be separated into those caused by pars fractures, facet joint arthritis, or osteophyte formation on vertebral bodies. Compression fractures can be distinguished from severe degenerative disease, both of which can cause intense activity across the spine on either planar or SPECT imaging. Localizing activity in patients who have had spinal fusion can provide tremendous insight into the causes of therapeutic failures. Infections of the spine now can be diagnosed with gallium SPECT/CT, despite the fact that gallium has long been abandoned because of its failure to detect spine infection on either planar or SPECT imaging. Small focal abnormalities in the feet and ankles can be localized well enough to make specific orthopedic diagnoses on the basis of their location. Moreover, when radiographic imaging provides equivocal or inadequate information, SPECT/CT can provide a road map for further diagnostic studies and has been invaluable in planning surgery. Our ability to localize activity within a bone or at an articular surface has allowed us to distinguish between fractures and joint disease. Increased activity associated with congenital anomalies, such as tarsal coalition and Bertolotti's syndrome have allowed us to understand the pathophysiology of these conditions, to confirm them as the cause of the patient's symptoms, and to provide information that is useful in determining appropriate clinical management. As our experience broadens, SPECT/CT will undoubtedly become an important tool in the evaluation and management of a wider variety of orthopedic patients. PMID- 19646557 TI - Hybrid imaging (SPECT/CT and PET/CT): improving therapeutic decisions. AB - The incremental diagnostic value of integrated positron emission tomography computed tomography (PET/CT) or single-photon emission computed tomography (SPECT)/CT images compared with PET or SPECT alone, or PET or SPECT correlated with a CT obtained at a different time includes the following: (1) improvement in lesion detection on both CT and PET or SPECT images, (2) improvement in the localization of foci of uptake resulting in better differentiation of physiological from pathologic uptake, (3) precise localization of the malignant foci, for example, in the skeleton vs soft tissue or liver vs adjacent bowel or node (4) characterization of serendipitous lesions, and (5) confirmation of small, subtle, or unusual lesions. The use of these techniques can occur at the time of initial diagnosis, in assessing the early response of disease to treatment, at the conclusion of treatment, and in continuing follow-up of patients. PET/CT and SPECT/CT fusion images affect the clinical management in a significant proportion of patients with a wide range of diseases by (1) guiding further procedures, (2) excluding the need of further procedures, (3) changing both inter- and intramodality therapy, including soon after treatment has been initiated, and (4) by providing prognostic information. PET/CT fusion images have the potential to provide important information to guide the biopsy of a mass to active regions of the tumor and to provide better maps than CT alone to modulate field and dose of radiation therapy. It is expected that the role of PET/CT and SPECT/CT in changing management will continue to evolve in the future and that these tools will be fundamental components of the truly "personalized medicine" we are striving to deliver. PMID- 19646558 TI - Hybrid SPECT/CT and PET/CT imaging: the next step in noninvasive cardiac imaging. AB - The past few years have witnessed impressive advances in the field of noninvasive cardiac imaging. For example, computed tomography (CT) coronary angiography has been adopted into daily clinical routine and, at least in some patient populations, is challenging the role of invasive angiography as the anatomic standard of reference. This is because the latter is associated with a nonnegligible periprocedural morbidity and mortality, which suggests confining its use to patients who will benefit from a revascularization procedure. Many factors that are beyond the quantification of anatomic narrowing and therefore cannot be fully appreciated with morphologic assessment will eventually determine whether or not a given lesion produces stress-induced ischemia. Myocardial perfusion imaging with single-photon emission computed tomography (SPECT) is among the most widely used and well-established noninvasive tools for the diagnosis of ischemic coronary disease. It allows assessment of the physiological relevance of coronary lesions and offers a high prognostic predictive value. Although positron emission tomography (PET) may achieve a higher accuracy than SPECT, its use has so far often been limited to large centers. Recent advances in image processing software and the advent of hybrid scanners have paved the way for fusion of image datasets from different modalities. An ideal, noninvasive technique for the diagnosis of coronary artery disease should provide complementary information on coronary anatomy as well as on pathophysiologic lesion severity. SPECT/CT and PET/CT hybrid imaging can provide such unique information, which not only improves diagnostic assessment and risk stratification but may also guide decision making with regard to revascularization in patients with coronary artery disease. PMID- 19646560 TI - Letter to the editor. PMID- 19646559 TI - Multimodality imaging: beyond PET/CT and SPECT/CT. AB - Multimodality imaging with positron emission tomography/computed tomography (PET/CT) and single-photon emission computed tomography (SPECT)/CT has become commonplace in clinical practice and in preclinical and basic biomedical research. Do other combinations of imaging modalities have a similar potential to impact medical science and clinical medicine? Presently, the combination of PET or SPECT with magnetic resonance imaging (MRI) is an area of active research, while other, perhaps less obvious combinations, including CT/MRI and PET/optical also are being studied. In addition to the integration of the instrumentation, there are parallel developments in synthesizing imaging agents that can be viewed by multiple imaging modalities. Is the fusion of PET and SPECT with CT the ultimate answer in multimodality imaging, or is it just the first example of a more general trend toward harnessing the complementary nature of the different modalities on integrated imaging platforms? PMID- 19646561 TI - Discussion: 'Add-back regimens in patients using a GnRH agonist for premenstrual dysphoric disorder' by Segebladh et al. AB - In the roundtable that follows, clinicians discuss a study published in this issue of the Journal in light of its methodology, relevance to practice, and implications for future research. Article discussed: Segebladh B, Borgstrom A, Nyberg S, et al. Evaluation of different add-back estradiol and progesterone treatments to gonadotropin-releasing hormone agonist treatment in patients with premenstrual dysphoric disorder. Am J Obstet Gynecol 2009;201:139.e1-8. PMID- 19646562 TI - HPV induced triple neoplasms: a case report. AB - The incidence of multiple primary cancers has greatly increased in the last decade. We report the first case of a woman who suffered from 3 distinct HPV induced neoplasms: cervical, vulvar, and head and neck carcinomas. PMID- 19646563 TI - Uterine artery Doppler flow studies in obstetric practice. AB - The advent of sonography has changed the practice of obstetrics by providing a window to the womb through which the anatomic structure of the fetus can be evaluated. The addition of Doppler flow studies of maternal and fetal vessels has provided a tool where the physiology of the maternal-fetal unit can be assessed. This information can provide the physician and the patient with vital information for a subsequent approach to the pregnancy. The use of fetal Doppler blood flow studies has become common in the evaluation and management of pregnancies complicated by conditions such as suspected fetal growth restriction and red blood cell isoimmunization to guide intrauterine therapy and delivery. The most commonly assessed Doppler flow studies of the fetus are the umbilical artery and middle cerebral artery (MCA). Doppler flow studies of the MCA are used in the assessment of the fetus at risk for anemia and growth-restricted fetus. Doppler flow studies of the umbilical artery can reflect abnormalities in "down-stream" or the fetal side of placental resistance, and the assessment of the maternal vasculature evaluates "up-stream" blood flow or the maternal side of placental resistance. The purpose of this review is to describe the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in low and high risk populations. PMID- 19646564 TI - Uterine fibroid embolization: a viable alternative to hysterectomy. AB - Benign uterine fibroids, or leiomyomas, are the most common tumors found in gynecologic practice. Symptomatic fibroids present with menorrhagia, pelvic pain, leukorrhea, pressure and bloating, increased abdominal girth, and severe dysmenorrhea. Traditional treatment has relied on surgery because long-term medical therapies have demonstrated only minimal response. Uterine fibroid embolization (UFE) using particulate emboli to occlude the uterine arteries, thereby disrupting the blood supply to fibroids and leading to devascularization and infarction, has been reported to be effective in alleviating fibroid-related symptoms. UFE is a safe, effective, and durable nonsurgical alternative to hysterectomy. PMID- 19646565 TI - Emergency contraceptive use as a marker of future risky sex, pregnancy, and sexually transmitted infection. AB - OBJECTIVE: The objective of the study was to examine whether emergency contraceptive use predicts future sex at risk for pregnancy, pregnancy, or sexually transmitted infection among young women. STUDY DESIGN: A secondary analysis of control group participants (n = 718) from a recent trial of advanced provision of emergency contraception was conducted. RESULTS: We found no association between use of emergency contraception and either pregnancy or infection. Recent use predicted decreased occurrence of subsequent sex at risk for pregnancy among women with a history of sexually transmitted infection (relative risk [RR], 0.39; 95% confidence interval [CI], 0.15-0.97), whereas ever having used predicted increased occurrence among women who either were highly effective method users (RR, 1.45; 95% CI, 1.05-2.01) or had no history of sexually transmitted infection (RR, 1.31; 95% CI, 1.04-1.65). CONCLUSION: Information about prior emergency contraceptive use was not a useful predictor of subsequent pregnancy, infection, or sex at risk for pregnancy among these young women. PMID- 19646566 TI - Late recognition of pregnancy as a predictor of adverse birth outcomes. AB - OBJECTIVE: We examined the relationship between the time of recognition of pregnancy and birth outcomes, such as premature births, low birthweight (LBW), admission to the neonatal intensive care unit (NICU), and infant mortality. STUDY DESIGN: A secondary analysis was performed using the Pregnancy Risk Assessment and Monitoring System (PRAMS) multistate data from 2000-2004. The sample consisted of 136,373 women who had a live childbirth. Analysis involved multiple logistic regression models, appropriately weighted for point and variance estimation to reflect the complex survey design of the PRAMS using STATA 9.2 (Stata Corp, College Station, TX). RESULTS: Approximately 27.6% recognized their pregnancy late (after 6 weeks of gestation). Late recognition was significantly associated with an increased odds of having premature births (odds ratio [OR], 1.09; 99% confidence interval [CI], 1.01-1.19), LBW (OR, 1.08; 99% CI, 1.01 1.15), and NICU admissions (OR, 1.12; 99% CI, 1.03-1.21). CONCLUSION: These results provide a rationale and an impetus for developing interventions that promote early recognition of pregnancy. PMID- 19646567 TI - First-trimester maternal serum screening and the risk for fetal distress during labor. AB - OBJECTIVE: The purpose of this study was to assess whether low pregnancy associated plasma protein-A (PAPP-A) levels in the first trimester are related to the risk of emergency cesarean section delivery (CS) for fetal distress during labor and fetal intrapartum acidemia. STUDY DESIGN: We prospectively studied patients who requested first-trimester biochemical screening for Down syndrome. RESULTS: Among the 1037 women who were enrolled, 152 women (14.7%) had a low first-trimester PAPP-A value, and 855 women (85.3%) had a normal first-trimester PAPP-A value. Excluding elective CS, 19 of 117 women (16.2%) with low PAPP-A values vs 59 of 749 women (7.9%) with normal PAPP-A values underwent CS for concerning fetal status during labor (P = .003; odds ratio, 2.27; 95% confidence interval, 1.30-3.97). This difference remained significant after correction for possible confounders (hypertension, preterm delivery, small for gestational age, labor induction). Among these 78 women, umbilical artery pH was significantly lower in fetuses from mothers with low vs normal PAPP-A values (pH = 7.19 [range, 6.95-7.39] vs pH = 7.26 [range, 7.02-7.39]; P = .022). CONCLUSION: Low PAPP-A levels at first-trimester screening are associated independently with higher rates of emergency CS for nonreassuring fetal status during labor and lower pH. PMID- 19646568 TI - Discontinuation of antihypertensive drug use during the first trimester of pregnancy and the risk of preeclampsia and eclampsia among women with chronic hypertension. AB - OBJECTIVE: The goal of this study was to investigate the association between the discontinuation of antihypertensive medication use during the first trimester of pregnancy and the risk of preeclampsia and eclampsia. STUDY DESIGN: We conducted a nested case-control approach within a cohort that was reconstructed from the linkage of 3 databases. To be included in the study, women had to match the following criteria: (1) between 15-45 years old on the first day of gestation, (2) covered by Quebec's Drug Insurance Plan for at least 12 months before and during pregnancy, (3) exposed to an antihypertensive drug on the first day of gestation, and (4) have had a delivery. Multivariate conditional logistic regression models were used to estimate the risk. RESULTS: Adjusting for confounders, the odds ratio was 0.66; 95% confidence interval, 0.27-1.56. CONCLUSION: Our finding does not support the presence of a statistically significant association between antihypertensive discontinuation during the first trimester of pregnancy and the risk of preeclampsia and eclampsia. PMID- 19646569 TI - Effect of dyssynergic defecation during pregnancy on third- and fourth-degree tear during a first vaginal delivery: a case-control study. AB - OBJECTIVE: Determine whether dyssynergic defecation is a risk factor for third- or fourth-degree tear during a first vaginal delivery. STUDY DESIGN: A retrospective case-control study was conducted on 549 primiparous women. The case group (n = 140) sustained an anal sphincter tear and the control group (n = 409) had a perineal laceration lower or equal to a second-degree tear. The Knowles Eccersley-Scott Symptom questionnaire identified women who had dyssynergic defecation. A logistic regression analysis was performed. RESULTS: Anal sphincter tear were 2.94 times higher for women reporting dyssynergic defecation (P = .002; 95% confidence interval [CI], 1.47-5.88). Odds ratios (ORs) were also significant for forceps (P < .001; OR, 6.90; 95% CI, 3.27-14.59), vacuum extraction (P = .009; OR, 2.36; 95% CI, 1.17-4.76), median episiotomy (P = .009; OR, 2.71; 95% CI, 1.54-4.78), and high infant weight (P < .001; OR, 2.25 for each 500 g increase; 95% CI, 1.69-2.99). CONCLUSION: Dyssynergic defecation seems to increase anal sphincter tear, but prospective studies are needed to confirm the association. PMID- 19646570 TI - Systematic antigenic profiling of hematopoietic antigens on ovarian carcinoma cells identifies membrane proteins for targeted therapy development. AB - OBJECTIVE: We studied ovarian cancers for the expression of membrane markers of hematopoietic origin. STUDY DESIGN: We used flow cytometry to systematically characterize the expression of more than 30 hematologic antigens on ovarian carcinoma cell lines and to assess their stability under estrogen exposure. The expression of the antigens was validated by a bioinformatics survey and immunohistochemical staining of ovarian cancer specimens. RESULTS: Several antigens were expressed by the majority of the cells, such as CD15, CD71, and CD138, whereas others were found on small and distinct cellular subpopulations. The expression patterns of the different markers were unaffected by estrogen exposure, indicating their stability. CONCLUSION: The antigens described in our work may serve as potential targets for new and existing targeted drugs. PMID- 19646571 TI - Understanding barriers to cervical cancer screening among Hispanic women. AB - OBJECTIVE: We investigated issues affecting Papanicolaou smear screening access, health services utilization, acculturation, social networking, and media venues most conducive to acquiring health information among Hispanics. STUDY DESIGN: Self-identified Hispanics were surveyed. Participants were stratified based on age, time living in the United States, and Papanicolaou screening frequency. RESULTS: Of 318 participants, Hispanics aged 30 years or older and living in the United States less than 5 years prefer speaking Spanish. Women with 5 or more lifetime Papanicolaou smears were 1.610 times more likely to have lived in the United States 5 or more years, 1.706 times more likely to speak a second language, and 1.712 times less likely to need a translator during their health care encounter. CONCLUSION: Age and years living in the United States may be independent risk factors for participation in Papanicolaou screening programs. Social difficulties inherent to acculturation inform health behavior and translate to health disparity among Hispanics. Our results may help design federally funded and community-level programs. PMID- 19646572 TI - Hyaluronan in vaginal secretions: association with recurrent vulvovaginal candidiasis. AB - OBJECTIVE: We evaluated whether vaginal concentrations of hyaluronan were altered in women with recurrent vulvovaginal candidiasis (RVVC). STUDY DESIGN: Lavage samples from 17 women with acute RVVC, 27 women who were receiving a maintenance antifungal regimen, and 24 control women were tested for hyaluronan and interleukin (IL)-6, IL-12, and IL-23 by enzyme-linked immunosorbent assay. RESULTS: Median vaginal hyaluronan concentrations were 33.8 ng/mL (range, 21.6 66.3 ng/mL) in women with acute RVVC, 15.0 ng/mL (range, 11.2-50.6 ng/mL) in women who were receiving maintenance therapy, and 4.2 ng/mL (range, 3.6-12.0 ng/mL) in control subjects (P or =20 micromol/h/g Hb. The mean value did not differ from the mean of the normal Dutch population, which was 31.6 (SD=5.0) mumol/h/g Hb. CONCLUSION: GALT deficiency is not an explanation for Mullerian aplasia, at least in the Dutch population. PMID- 19646669 TI - Contraceptive withdrawal in adolescents: a complex picture of usage. AB - STUDY OBJECTIVE: Contraceptive withdrawal, or coitus interruptus, is a widespread method in adolescents, but factors affecting usage have not been longitudinally investigated. Study objectives were to examine usage numbers of withdrawal among a group of sexually active adolescent females and to investigate the influence of personal, partner, and family factors on usage patterns. DESIGN/SETTING/PARTICIPANTS: Subjects (N=387; 14 to 17 years at enrollment; 92% African American) were recruited from primary care adolescent health clinics in areas with high rates of pregnancy and sexually transmitted infection. As part of a larger longitudinal study, subjects contributed face-to-face quarterly and annual questionnaires assessing contraceptive behavior, recent sexual behaviors, as well as partner- and family-based attitudes/beliefs. INTERVENTIONS, MAIN OUTCOME MEASURES: The outcome variable was: withdrawal use during the previous 12 weeks (no/yes); predictor variables included 19 individual, family and partner variables. All models additionally controlled for any current hormonal use (no/yes; any method), current condom use (no/yes) and past withdrawal use (past 30 days; no/yes). Logistic regression, with GEE estimation to adjust for repeated within-subject observations, was performed in SUDAAN, 9.0. RESULTS: Subjects supplied 1632 quarterly interviews; withdrawal was mentioned in about 25% of the interviews (392/1632). Controlling for primary contraceptive method, withdrawal was mentioned in 13.2% (51/307) of interviews with hormonal methods, in 32.4% (255/787) of the interviews with condoms and in 4.7% (78/1632) of interviews with no method. Current hormonal use was associated with a decreased likelihood of also using withdrawal (OR=0.34), whereas past withdrawal use increased the likelihood of current withdrawal by about 4-fold (OR=4.18). Condom use was not associated with withdrawal use. Current withdrawal use was more likely with a more diverse sexual repertoire (OR=1.65), more sexual partners in the past 3 months (OR=1.46), higher sexual control (OR=1.15), lower perceived STI risk (OR=0.46), higher sexual self-efficacy (OR=1.24), lower sexual coercion (OR=0.56) higher condom negativity (OR=1.16), living with a boyfriend (OR=2.17) and lower family sexual health support (OR=0.88). CONCLUSION: Contraceptive withdrawal in adolescents should not be considered 'rare.' Careful clinical consideration of usage within the context of other contraceptive behaviors, sexual behaviors/attitudes, and relationship issues could better inform effective contraceptive counseling efforts. PMID- 19646670 TI - Obstetrician-gynecologists and the HPV vaccine: practice patterns, beliefs, and knowledge. AB - STUDY OBJECTIVE: Human papillomavirus (HPV), the most common sexually transmitted infection in the United States, can be contracted by young girls shortly after sexual debut. Human papillomavirus can lead to cervical and anogenital cancers and genital warts. A vaccine has been developed to protect against precancerous lesions. We examined obstetrician-gynecologists' practices, opinions, and knowledge regarding this vaccine. DESIGN: A 37-item questionnaire was sent out by the American College of Obstetricians and Gynecologists (ACOG) to its fellows and junior fellows between May and November of 2007. PARTICIPANTS: Surveys went to 3896 fellows and junior fellows of ACOG. Of these surveys, 771 were Collaborative Ambulatory Research Network (CARN) members who have volunteered to receive several surveys per year. The remaining 3125 questionnaires were sent to all fellows and junior fellows in ACOG's District V (Ohio, Kentucky, Indiana, Michigan and Ontario, Canada). Response rates were 51.0% and 30.7% for CARN and District V, respectively. RESULTS: Of those who administer vaccines, most offer the HPV vaccine. Most know this vaccine protects against 4 HPV types. Fewer knew the percentages of cervical cancers and genital warts prevented. Over 20% knew all 3 answers. Only a minority answered all incorrectly. Approximately 15% view HPV vaccine as safe in pregnancy. Many agree cost is a reason for patient refusal and a deterrent from mandating the vaccine. CONCLUSION: Obstetrician gynecologists are knowledgeable of the HPV vaccine and are incorporating it into practice. Financial concerns may limit widespread immunization. PMID- 19646671 TI - Success of treatment modalities for labial fusion: a retrospective evaluation of topical and surgical treatments. AB - STUDY OBJECTIVE: Standard treatment for girls with labial fusion has included topical estrogen cream, manual separation, or surgery. Side effects may limit the use of topical estrogen. Betamethasone has recently shown efficacy at separating labial fusion. Local irritation and inflammation may be an initiator of labial fusion. No adverse effects of betamethasone treatment have been documented. Long term side effects are unknown. This study compares therapies for conservative management of labial fusion for efficacy and focuses on the response rate, time to separation, recurrence, and side effects of treatment. DESIGN: A retrospective chart review. PARTICIPANTS: One hundred fifty-one prepubertal girls, mean age 3 years (range 0.25-8.75 years) diagnosed with labial fusion. MAIN OUTCOME MEASURES: To investigate the incidence of related symptoms, length of topical estrogen or betamethasone treatment, side effects, rate of successful separation, rates of recurrence, percentage requiring surgery, and postoperative outcomes in patients with labial adhesion who underwent treatment. RESULTS: Of 151 patients with labial adhesion, 11 (7.3%) presented with urinary frequency, 30 (19.9%) with urinary tract infections, 13 (8.6%) with vaginitis, and 19 (12.6%) with post-void dripping. When compared to patients treated with betamethasone (1.3 months), patients treated primarily with premarin took nearly twice as long (2.2 months) for resolution of their adhesions. Rates of recurrence were lower for patients receiving betamethasone therapy. Side effects for estrogen therapy included breast budding and vaginal bleeding, and for betamethasone, local irritation was reported. Some patients went on to surgery and experienced recurrence after surgery. CONCLUSION: Initial comparison of topical estrogen and betamethasone treatment of labial fusion suggests that betamethasone may separate fusion quicker with less recurrence and fewer side effects than topical estrogen therapy. PMID- 19646672 TI - Pap smear knowledge among young women following the introduction of the HPV vaccine. AB - STUDY OBJECTIVE: Investigate sexually active young women's knowledge of the term Pap smear since development of the HPV vaccine. DESIGN: Cross-sectional study conducted January-May 2007. SETTING: University health services clinic at a university in southern United States. PARTICIPANTS: Sexually active women, age 18 24, presenting for a Pap smear or STD testing (N=145). MAIN OUTCOME MEASURES: Pap smear knowledge was assessed by participants' written definition of the term Pap smear and by multiple choice responses indicating Pap smear as a test for cervical cancer/ HPV and not a pelvic exam, STD test, or pregnancy test. RESULTS: 9.7% provided accurate definitions; 12.4% checked appropriate Pap smear synonyms. 68.5% incorrectly responded that Pap smear was the same as "pelvic exam"; 42.5% indicated "STD test"; 11.7% indicated "pregnancy test." Indicators of HPV risk (age of sexual debut, previous abnormal Pap smear, previous STD diagnosis) were not associated with knowledge. Never using condoms, increasing age, and lower depression scores predicted accurate Pap smear definition rating (R2=0.08). Never using condoms, Caucasian race, and decreased lifetime number of sex partners predicted accurate identification of Pap smear synonyms (R2=0.15). RESULTS: Few participants understood the meaning of the term Pap smear; there does not appear to be improvement in women's knowledge after development of the HPV vaccine. Poor Pap smear knowledge may affect young women's understanding of their overall sexual health. PMID- 19646673 TI - The effect of combined surgical-medical intervention on the progression of endometriosis in an adolescent and young adult population. AB - STUDY OBJECTIVE: To evaluate the effect of combined surgical-medical treatment on endometriosis progression in adolescents as measured by disease stage. DESIGN: Retrospective chart review. SETTING: Two academic medical centers. PARTICIPANTS: Sequential cases of young women identified on chart review with chronic pelvic pain unresponsive to dysmenorrheal treatment who underwent initial laparoscopy for diagnosis and surgical destruction of endometriosis. All patients were then treated with standard continuous medical therapy. Patients with exacerbation of pain on anti-endometriosis medical therapy who elected a subsequent laparoscopic procedure were eligible for this study. INTERVENTION: Retrospective chart review MAIN OUTCOME MEASURES: Endometriosis stage and adhesions at subsequent laparoscopy as compared to the initial surgical procedure. RESULTS: 90 patients met inclusion criteria. Eligible patients were 12 to 24 years of age at the time of the initial laparoscopy. The median endometriosis stage at first and second laparoscopy was I. No stage change was observed in 70% of patients, 19% improved by one stage, 1% improved by two stages, and 10% worsened by one stage. Regardless of initial stage, a trend toward disease progression was not observed. There was a significant likelihood for stage improvement at second laparoscopy, with those initially diagnosed as stage II or III most likely to exhibit improvement. CONCLUSIONS: Based on the concept that endometriosis can be progressive, these data suggest that combined surgical-medical management retards disease progression in adolescents and young adults. PMID- 19646674 TI - Early polycystic ovary syndrome as a possible etiology of unexplained premenarcheal ovarian torsion. AB - STUDY OBJECTIVE: To study evidence of polycystic ovary syndrome (PCOS) in premenarcheal adolescents with unexplained ovarian torsion. DESIGN: Retrospective observational case series. SETTING: Tertiary university clinical center PARTICIPANTS: Six premenarcheal adolescents and six adults with acute ovarian torsion INTERVENTION: A chart review. MAIN OUTCOME MEASURES: Contralateral ovarian size, operative findings, ovarian pathology, hormone testing RESULTS: Five of the six premenarcheal cases had no pathologic explanation for their ovarian torsion. In four of the cases, size measurements of the contralateral ovary were noted to be larger than the criterion of their respective age group. Three of the four cases had either an ovarian volume (28.5 cm(3)) or an area (16.0 cm(2) and 57.6 cm(2)) that was above the size criterion for a polycystic ovary (volume >10 cm(3) or area>5.5 cm(2)). Pathology of a wedge biopsy of one of the contralateral ovaries suggested evidence of polycystic ovary. Finally, hormone testing available in three of the cases revealed elevated testosterone levels in two. Among the adults, half of the cases had a pathologic explanation for ovarian torsion. One out of the five cases had a contralateral ovary that was significantly enlarged and this was noted in a woman with a diagnosis of PCOS. The remaining two cases had extensive necrosis of the torsed ovary and no other diagnosis was made. CONCLUSION: We propose that premenarcheal girls presenting with ovarian torsion, without obvious ovarian pathology, be screened for ultrasound and biochemical evidence of PCOS. In those with evidence of PCOS, treatment with oral contraceptives should be considered taking into account the age and pubertal development, to decrease ovarian volume. PMID- 19646675 TI - A counterchange mechanism for the perception of motion. AB - A computational model for the perception of counterchange-specified motion is examined in detail and compared with various versions of the Reichardt motion detection model [Reichardt, W. (1961). Autocorrelation, a principle for the evaluation of sensory information by the central nervous system. In W. A. Rosenblith (Ed.), Sensory communication (pp. 303-317). New York: Wiley]. The counterchange model is composed of a pair of temporally biphasic subunits at two retinal locations, one detecting decreases and the other increases in input activation. Motion is signaled when both subunits are simultaneously excited, as determined by the multiplicative combination of their transient responses. In contrast with the Reichardt detector, which effectively tracks motion energy and accounts solely for results obtained with standard apparent motion stimuli (a surface is visible at one location, then at another), the counterchange model also accounts for the generalized apparent motion perceived between pairs of simultaneously visible surfaces. This indicates that standard apparent motion can be perceived via the same non-sequential, non-motion-energy mechanism as generalized apparent motion. There is no need for either an explicit delay mechanism to account for optimal motion perception at non-zero inter-stimulus intervals, or for inhibitory interaction between subunits to account for the absence of motion in the detector's null direction (Barlow, H. B., & Levick, W. R., 1965). Both are emergent properties that result from the inhibitory states of the counterchange detector's biphasic subunits. In addition to apparent motion, the counterchange principle potentially accounts for the perception of motion for drifting gratings, the short range motion perceived for random-dot cinematograms, and the motion perceived for continuously moving objects. PMID- 19646677 TI - CMIP and ATP2C2 modulate phonological short-term memory in language impairment. AB - Specific language impairment (SLI) is a common developmental disorder characterized by difficulties in language acquisition despite otherwise normal development and in the absence of any obvious explanatory factors. We performed a high-density screen of SLI1, a region of chromosome 16q that shows highly significant and consistent linkage to nonword repetition, a measure of phonological short-term memory that is commonly impaired in SLI. Using two independent language-impaired samples, one family-based (211 families) and another selected from a population cohort on the basis of extreme language measures (490 cases), we detected association to two genes in the SLI1 region: that encoding c-maf-inducing protein (CMIP, minP = 5.5 x 10(-7) at rs6564903) and that encoding calcium-transporting ATPase, type2C, member2 (ATP2C2, minP = 2.0 x 10(-5) at rs11860694). Regression modeling indicated that each of these loci exerts an independent effect upon nonword repetition ability. Despite the consistent findings in language-impaired samples, investigation in a large unselected cohort (n = 3612) did not detect association. We therefore propose that variants in CMIP and ATP2C2 act to modulate phonological short-term memory primarily in the context of language impairment. As such, this investigation supports the hypothesis that some causes of language impairment are distinct from factors that influence normal language variation. This work therefore implicates CMIP and ATP2C2 in the etiology of SLI and provides molecular evidence for the importance of phonological short-term memory in language acquisition. PMID- 19646676 TI - Skewed X chromosome inactivation and trisomic spontaneous abortion: no association. AB - Several studies suggest that highly skewed X chromosome inactivation (HSXI) is associated with recurrent spontaneous abortion. We hypothesized that this association reflects an increased rate of trisomic conceptions due to anomalies on the X chromosome that lead both to HSXI and to a diminished oocyte pool. We compared the distribution of X chromosome inactivation (XCI) skewing percentages (range: 50%-100%) among women with spontaneous abortions in four karyotype groups trisomy (n = 154), chromosomally normal male (n = 43), chromosomally normal female (n = 38), nontrisomic chromosomally abnormal (n = 61)-to the distribution for age-matched controls with chromosomally normal births (n = 388). In secondary analyses, we subdivided the nontrisomic chromosomally abnormal group, divided trisomies by chromosome, and classified women by reproductive history. Our data support neither an association of HSXI with all trisomies nor an association of HSXI with chromosomally normal male spontaneous abortions. We also find no association between HSXI and recurrent abortion (n = 45). PMID- 19646678 TI - Spinal muscular atrophy with pontocerebellar hypoplasia is caused by a mutation in the VRK1 gene. AB - The spinal muscular atrophies (SMAs) are a genetically and clinically heterogeneous group of disorders characterized by degeneration and loss of anterior horn cells in the spinal cord, leading to muscle weakness and atrophy. Spinal muscular atrophy with pontocerebellar hypoplasia (SMA-PCH, also known as pontocerebellar hypoplasia type 1 [PCH1]) is one of the rare infantile SMA variants that include additional clinical manifestations, and its genetic basis is unknown. We used a homozygosity mapping and positional cloning approach in a consanguineous family of Ashkenazi Jewish origin and identified a nonsense mutation in the vaccinia-related kinase 1 gene (VRK1) as a cause of SMA-PCH. VRK1, one of three members of the mammalian VRK family, is a serine/threonine kinase that phosphorylates p53 and CREB and is essential for nuclear envelope formation. Its identification as a gene involved in SMA-PCH implies new roles for the VRK proteins in neuronal development and maintenance and suggests the VRK genes as candidates for related phenotypes. PMID- 19646679 TI - Molecular basis of DFNB73: mutations of BSND can cause nonsyndromic deafness or Bartter syndrome. AB - BSND encodes barttin, an accessory subunit of renal and inner ear chloride channels. To date, all mutations of BSND have been shown to cause Bartter syndrome type IV, characterized by significant renal abnormalities and deafness. We identified a BSND mutation (p.I12T) in four kindreds segregating nonsyndromic deafness linked to a 4.04-cM interval on chromosome 1p32.3. The functional consequences of p.I12T differ from BSND mutations that cause renal failure and deafness in Bartter syndrome type IV. p.I12T leaves chloride channel function unaffected and only interferes with chaperone function of barttin in intracellular trafficking. This study provides functional data implicating a hypomorphic allele of BSND as a cause of apparent nonsyndromic deafness. We demonstrate that BSND mutations with different functional consequences are the basis for either syndromic or nonsyndromic deafness. PMID- 19646681 TI - [Chylous fistula as a complication of thyroidectomy without lymphadenectomy]. PMID- 19646682 TI - [Fibrosarcoma simulating a benign mediastinal cystic lesion]. PMID- 19646680 TI - CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity in vivo. AB - Previous work has shown ICOS can function independently of CD28, but whether either molecule can compensate for the other in vivo is not known. Since ICOS is a potent inducer of Th2 cytokines and linked to allergy and elevated serum IgE in humans, we hypothesized that augmenting ICOS costimulation in murine allergic airway disease may overcome CD28 deficiency. While ICOS was expressed on T cells from CD28(-/-) mice, Th2-mediated airway inflammation was not induced in CD28(-/ ) mice by increased ICOS costimulation. Further, we determined if augmenting CD28 costimulation could compensate for ICOS deficiency. ICOS(-/-) mice had a defect in airway eosinophilia that was not overcome by augmenting CD28 costimulation. CD28 costimulation also did not fully compensate for ICOS for antibody responses, germinal center formation or the development of follicular B helper T cells. CD28 and ICOS play complementary non-overlapping roles in the development of Th2 immunity in vivo. PMID- 19646683 TI - [<> adrenalectomy secondary to lung cancer]. PMID- 19646684 TI - [Expected body mass index after bariatric surgery]. AB - INTRODUCTION: The body mass index (BMI) is the most practical method to measure and compare obesity between individuals. The Percentage of Excess BMI Loss (PEBMIL) is used to present results in operated patients and is based on the premise that a BMI-25 is the final aim, on being the upper limit in normal subjects. It is possible to achieve a BMI-25 in morbid obese (MO) patients with initial low BMIs (<50) but it is rare in overweight (OW) patients with a BMI>50. Expected BMI (EBMI) would be that which should be reached by all subjects depending on their initial BMI. OBJECTIVE: The objective of this study is to search for, using statistical methods, a formula based on clinical evidence that can identify the EBMI depending on the initial BMI. PATIENTS AND METHOD: We analysed the initial and final BMI in a group of 135 MO patients, operated on using the duodenal switch procedure and with a follow up of over 3 years. A linear regression method has been used to obtain a formula that could calculate the EBMI of each patient operated on. RESULTS: We obtained an algorithm in which EBMI=Initial BMIx0.33+14. If we apply the individualised EBMI instead of the BMI 25, the median PEBMIL was 99.48 (range: 76.75-110.46). CONCLUSION: This result suggests that the application of an individual EBMI is a more reliable estimate of the success or failure of bariatric operations. PMID- 19646685 TI - [Literary Meetings: the legacy of illustrated surgery]. AB - The Literary Meetings are a group of manuscripts which minuted regular meetings of the surgeons of the Royal College of Surgery (Real Colegio de Cirugia) of Barcelona during the "age of enlightment". Around 200 documents- or "minutes" (to which they had to add their respective criticisms or notes) are preserved. The earliest dates from 1765 and the last one is from 1835. The series of documents have time gaps which coincide with politically conflictive periods, which no doubt had an effect on the normal functioning of the College. In these meetings papers were presented on clinical questions and on the most flourishing basic sciences of the period, which was mainly chemistry. The documents, which have recently been completely transcribed and edited, represent an historic landmark in the exchange of experiences and continuous education of the Catalan surgeons. PMID- 19646687 TI - Feature extraction and dimensionality reduction for mass spectrometry data. AB - Mass spectrometry is being used to generate protein profiles from human serum, and proteomic data obtained from mass spectrometry have attracted great interest for the detection of early stage cancer. However, high dimensional mass spectrometry data cause considerable challenges. In this paper we propose a feature extraction algorithm based on wavelet analysis for high dimensional mass spectrometry data. A set of wavelet detail coefficients at different scale is used to detect the transient changes of mass spectrometry data. The experiments are performed on 2 datasets. A highly competitive accuracy, compared with the best performance of other kinds of classification models, is achieved. Experimental results show that the wavelet detail coefficients are efficient way to characterize features of high dimensional mass spectra and reduce the dimensionality of high dimensional mass spectra. PMID- 19646686 TI - [Major hepatectomies are safe in patients with cholangiocarcinoma and jaundice]. AB - BACKGROUND: Surgical resection is the only possibility of long term survival in patients with Klatskin tumours. However, surgical resection is a challenging problem and hepatic resection is often necessary. OBJECTIVE: The aim of our study was to assess the need for biliary drainage, resection rate and outcome of hilar cholangiocarcinoma in a single tertiary referral centre. PATIENTS AND METHODS: From 2005 to 2008, 26 patients with Klatskin tumours were identified and assessed prospectively with multidetector CT and MR cholangiography in special cases. Seven patients (27%) were deemed to be unresectable in pre-operative staging. A total of 19 surgical procedures were performed, 8 left hepatectomies, 5 right hepatectomies and 6 resections exclusively of the biliary tree. RESULTS: Resection rate was 73%, transfusion rate 53% and preoperative biliary drainage was performed only in 7 cases (37%). Major complications occurred in 11 (58%), including two post-operative deaths (10%). There were no differences in the epidemiological data, when we separately analysed the outcomes of the 9 patients with bilirubin<15 mg/dL and the 10 patients with bilirubin>15 mg/dL. Biliary drainage was required in 6 (67%) patients in the group with low bilirubin levels vs. 1(10%) in the other group (P=0.02). The mean bilirubin level in the jaundiced group was 22.1+/-3.9 vs. 4.7+/-4.3 (P<0.001) in the other group. There were no differences in the postoperative outcome between both groups. CONCLUSION: Resection and survival rates have increased recently but still carries the risk of significant morbidity and mortality. Major hepatectomies in selected patients without percutaneous biliary drainage are safe. PMID- 19646688 TI - Factors influencing intestinal cadmium uptake in pregnant Bangladeshi women--a prospective cohort study. AB - Experimental studies indicate that zinc (Zn) and calcium (Ca) status, in addition to iron (Fe) status, affect gastrointestinal absorption of cadmium (Cd), an environmental pollutant that is toxic to kidneys, bone and endocrine systems. The aim of this study was to evaluate how various nutritional factors influence the uptake of Cd in women, particularly during pregnancy. The study was carried out in a rural area of Bangladesh, where malnutrition is prevalent and exposure to Cd via food appears elevated. The uptake of Cd was evaluated by associations between erythrocyte Cd concentrations (Ery-Cd), a marker of ongoing Cd exposure, and concentrations of nutritional markers. Blood samples, collected in early pregnancy and 6 months postpartum, were analyzed by inductively coupled plasma mass spectrometry (ICPMS). Ery-Cd varied considerably (range: 0.31-5.4microg/kg) with a median of 1.1microg/kg (approximately 0.5microg/L in whole blood) in early pregnancy. Ery-Cd was associated with erythrocyte manganese (Ery-Mn; positively), plasma ferritin (p-Ft; negatively), and erythrocyte Ca (Ery-Ca; negatively) in decreasing order, indicating common transporters for Cd, Fe and Mn. There was no evidence of Cd uptake via Zn transporters, but the association between Ery-Cd and p-Ft seemed to be dependent on adequate Zn status. On average, Ery-Cd increased significantly by 0.2microg/kg from early pregnancy to 6 months postpartum, apparently due to up-regulated divalent metal transporter 1 (DMT1). In conclusion, intestinal uptake of Cd appears to be influenced either directly or indirectly by several micronutrients, in particular Fe, Mn and Zn. The negative association with Ca may suggest that Cd inhibits the transport of Ca to blood. PMID- 19646689 TI - Smooth endoplasmic reticulum aggregations in all retrieved oocytes causing recurrent multiple anomalies: case report. AB - OBJECTIVE: To document the relationship between smooth endoplasmic reticulum (SER) aggregations and recurrent fetal anomalies. DESIGN: Case report. SETTING: Private IVF center. PATIENT(S): A 28-year-old woman with an 11-year history of primary infertility. INTERVENTION(S): Three consecutive cycles of intracytoplasmic sperm injection (ICSI) in the same patient. MAIN OUTCOME MEASURE(S): Clinical pregnancy, live birth, fetal anomaly. RESULT(S): In three consecutive ICSI cycles, a total of 59 MII oocytes were retreived in the same patient, all displaying SER aggregations. The fertilization rate per cycle was 80%, 50%, and 42%, respectively. A total of 12 embryos were transferred in three ICSI cycles, of which 11 were grade 1 embryos. Two of the three cycles ended up with clinical ongoing pregnancies but with multiple fetal anomalies. CONCLUSION(S): This is the first case reported with SER aggregations in all retrieved oocytes in three consecutive ICSI cycles. The repetetive multiple fetal anomalies possibly related to oocyte dysmorphism are of concern. PMID- 19646690 TI - Analysis of spindle characteristics and embryo quality in mice stimulated with letrozole using Polscope imaging. AB - OBJECTIVE: To explore the effect of letrozole as an ovulation inducing agent on oocyte and embryo quality in mice model. DESIGN: Prospective study. SETTING: Institute of Reproductive Medicine, Kolkata, India. ANIMAL(S): Sixty-nine sexually mature female Swiss Albino mice 6-7 weeks old. INTERVENTION(S): Metaphase II (MII) oocytes from two groups of mice, one group injected with letrozole and the other with rFSH. MAIN OUTCOME MEASURE(S): Number of MII oocytes, number of oocytes with meiotic spindle (MS), different angles of MS relative to the polar body (PB), spindle characteristics, and fertilization outcome. RESULT(S): The MS was present in 84% and 71.2% of the oocytes in the letrozole and rFSH group, respectively. In the letrozole group, 73% of the oocytes had a 0 degrees spindle position compared with 35.7% in the rFSH group. With letrozole, 19% of the oocytes had 0 degrees > MS < 90 degrees and 8% had MS >90 degrees , compared with 46.1% oocytes with 0 degrees > MS < 90 degrees and 18.2% with MS >90 degrees with rFSH. Mean spindle area retardance, spindle dimensions, and 4-8-cell embryo formation rate were significantly higher with letrozole compared with rFSH. Two-cell and blastocyst formation rates were similar in both groups. CONCLUSION(S): Robust birefringent spindles were obtained in mice on superovulation with letrozole. Letrozole does not appear to increase the risk of spindle assembly and preimplantation developmental arrest in mouse oocytes. PMID- 19646691 TI - Femoral non-union models in the mouse. PMID- 19646692 TI - Nodular vulvar herpes in an HIV-positive woman. PMID- 19646693 TI - A prospective evaluation of the Transtheoretical Model of Change applied to exercise in young people. AB - OBJECTIVES: To investigate the utility of the Transtheoretical Model of Change in predicting exercise in young people. DESIGN: A prospective study: assessments were done at baseline and follow-up 6 months later. METHOD: Using stratified random sampling 1055 Chinese high school pupils living in Hong Kong, 533 of who were followed up at 6 months, completed measures of stage of change (SCQ), self efficacy (SEQ), perceptions of the pros and cons of exercising (DBQ) and processes of change (PCQ). Data were analysed using one-way ANOVA, repeated measures ANOVA and independent sample t tests. RESULTS: The utility of the TTM to predict exercise in this population is not strong; increases in self-efficacy and decisional balance discriminated between those remaining active at baseline and follow-up, but not in changing from an inactive (e.g., Precontemplation or Contemplation) to an active state (e.g., Maintenance) as one would anticipate given the staging algorithm of the TTM. CONCLUSION: The TTM is a modest predictor of future stage of change for exercise in young Chinese people. Where there is evidence that TTM variables may shape movement over time, self-efficacy, pros and behavioural processes of change appear to be the strongest predictors. PMID- 19646694 TI - The Hyperemesis Impact of Symptoms Questionnaire: development and validation of a clinical tool. AB - BACKGROUND: The Hyperemesis Impact of Symptoms Questionnaire is a clinical tool designed to assess holistically the impact of the physical and psychosocial symptoms of hyperemesis gravidarum (HG) on individuals. Its purpose is to aid planning and implementation of tailored care for women with HG. To our knowledge no similar tool exists. OBJECTIVE: To assess the validity and reliability of the HIS questionnaire. DESIGN: As no similar tool exists, we compared the HIS with three tools that reflect its key areas: physical impact (Pregnancy Unique Quantification of Emesis--PUQE score and markers of severity of HG), psychological impact (Hospital Anxiety and Depression Score--HADS) and social impact (SF12 quality of life score). SETTING: A large regional referral, women and children's hospital in the North West of England. PARTICIPANTS: The HIS was evaluated on 50 women admitted to hospital with HG and 50 women recruited from ante-natal clinic without severe nausea and vomiting of pregnancy and with an uncomplicated pregnancy. RESULTS: Good criterion validity was demonstrated by strong significant correlations with all three scores (PUQE, r=0.75, p<0.001, HADS, depression r=0.76, p<0.001, and SF12, mental component r=-0.65, p<0.001). The HIS showed good internal consistency, Cronbach alpha 0.87, split half 0.80. CONCLUSIONS: There is evidence for the validity and reliability of the HIS to assess the impact of the physical and psychosocial symptoms of HG. Further research is currently underway to establish the clinical utility of the HIS questionnaire in the care of women hospitalised with HG. PMID- 19646695 TI - The quest for conceptual consistency: Commentary on Rytterstrom et al. (2009). PMID- 19646696 TI - The conjoint detrimental effect of chronic periodontal disease and systemic inflammation on asymmetric dimethyl-arginine in untreated hypertensive subjects. AB - OBJECTIVE: To investigate the relationship between periodontal disease indexes (PDI) and endothelial dysfunction by means of asymmetric dimethyl-arginine (ADMA) in conditions of both increased and decreased systemic inflammation in the setting of hypertension. METHODS: We studied 108 - aged 52+/-9 years - untreated hypertensive subjects (24 h systolic/diastolic blood pressure [BP] 131+/-11/83+/ 9 mmHg) with diverse severity of periodontal disease (i.e. mean clinical loss of attachment, maximum probe depth and gingival index). Subjects underwent office and ambulatory BP measurements, echocardiography, periodontal examination; while from fasting venous blood samples we assessed metabolic profile, and we measured ADMA and high sensitivity C reactive protein (hsCRP) levels. RESULTS: With respect to the median of hsCRP and ADMA (1.79 mg/l and 0.81 micromol/l, respectively) the study population was divided in four groups: low-ADMA/low-hsCRP (n=30), low-ADMA/high-hsCRP (n=27), high-ADMA/low-hsCRP (n=21) and high-ADMA/high hsCRP (n=30). High-ADMA/high-hsCRP group resulted significantly older compared with both low-ADMA/low-hsCRP and high-ADMA/high-hsCRP groups, while high compared with low-ADMA groups demonstrated increased low-density lipoprotein cholesterol. PDIs were increased in those with high compared with those with low-hsCRP, while the addition of high-ADMA contributed significantly to that comparison. After adjustment for confounders, high-ADMA/high-hsCRP was significantly associated--by means of adjusted z-scores--with mean clinical loss of attachment, maximum probe depth and gingival index by 10.33, 8.84 and 2.74 times more often with respect to the low-ADMA/low-hsCRP pattern. CONCLUSION: PDI are associated in a dose dependent manner with ADMA in untreated hypertensives and increased systemic inflammation further contributes to that phenomenon. PMID- 19646697 TI - Modelling pulse wave propagation in the rabbit systemic circulation to assess the effects of altered nitric oxide synthesis. AB - Pulse wave propagation in the mature rabbit systemic circulation was simulated using the one-dimensional equations of blood flow in compliant vessels. A corrosion cast of the rabbit circulation was manufactured to obtain arterial lengths and diameters. Pulse wave speeds and inflow and outflow boundary conditions were derived from in vivo data. Numerical results captured the main features of in vivo pressure and velocity pulse waveforms in the aorta, brachiocephalic artery and central ear artery. This model was used to elucidate haemodynamic mechanisms underlying changes in peripheral pulse waveforms observed in vivo after administering drugs that alter nitric oxide synthesis in the endothelial cells lining blood vessels. According to our model, these changes can be explained by single or combined alterations of blood viscosity, peripheral resistance and compliance, and the elasticity of conduit arteries. PMID- 19646698 TI - Validity of architectural properties of the hamstring muscles: correlation of ultrasound findings with cadaveric dissection. AB - The purpose of this study was to compare the architectural parameters of the long head of biceps femoris (BFlh) and semitendinosus (ST) muscles by comparing measurements from ultrasound (US) with those obtained from direct dissection. The BFlh and ST architectures were examined bilaterally in 6 legs from 3 male cadavers. The fascicle length, pennation angle, muscle thickness and muscle and tendon length were obtained from direct measurement and US scans along each muscle. Intraclass correlation coefficients between the two methods ranged from 0.905 to 0.913 for the BFlh variables and from 0.774 to 0.974 for the ST parameters. Compared with the direct measurements, the US method showed a mean typical error of 0.09-0.14 cm for muscle thickness, 1.01-1.31 degrees for the pennation angle, 0.92-1.71 cm for fascicle length and muscle-tendon length measurements. The US method is a valid alternative tool for assessing basic architectural parameters of ST and BFlh components of the hamstring muscles. PMID- 19646699 TI - Automated tracking of muscle fascicle orientation in B-mode ultrasound images. AB - B-mode ultrasound can be used to non-invasively image muscle fascicles during both static and dynamic contractions. Digitizing these muscle fascicles can be a timely and subjective process, and usually studies have used the images to determine the linear fascicle lengths. However, fascicle orientations can vary along each fascicle (curvature) and between fascicles. The purpose of this study was to develop and test two methods for automatically tracking fascicle orientation. Images were initially filtered using a multiscale vessel enhancement (a technique used to enhance tube-like structures), and then fascicle orientations quantified using either the Radon transform or wavelet analysis. Tests on synthetic images showed that these methods could identify fascicular orientation with errors of less than 0.06 degrees . Manual digitization of muscle fascicles during a dynamic contraction resulted in a standard deviation of angle estimates of 1.41 degrees across ten researchers. The Radon transform predicted fascicle orientations that were not significantly different from the manually digitized values, whilst the wavelet analysis resulted in angles that were 1.35 degrees less, and reasons for these differences are discussed. The Radon transform can be used to identify the dominant fascicular orientation within an image, and thus used to estimate muscle fascicle lengths. The wavelet analysis additionally provides information on the local fascicle orientations and can be used to quantify fascicle curvatures and regional differences with fascicle orientation across an image. PMID- 19646700 TI - Use of a statistical model of the whole femur in a large scale, multi-model study of femoral neck fracture risk. AB - Interpatient variability is often overlooked in orthopaedic computational studies due to the substantial challenges involved in sourcing and generating large numbers of bone models. A statistical model of the whole femur incorporating both geometric and material property variation was developed as a potential solution to this problem. The statistical model was constructed using principal component analysis, applied to 21 individual computer tomography scans. To test the ability of the statistical model to generate realistic, unique, finite element (FE) femur models it was used as a source of 1000 femurs to drive a study on femoral neck fracture risk. The study simulated the impact of an oblique fall to the side, a scenario known to account for a large proportion of hip fractures in the elderly and have a lower fracture load than alternative loading approaches. FE model generation, application of subject specific loading and boundary conditions, FE processing and post processing of the solutions were completed automatically. The generated models were within the bounds of the training data used to create the statistical model with a high mesh quality, able to be used directly by the FE solver without remeshing. The results indicated that 28 of the 1000 femurs were at highest risk of fracture. Closer analysis revealed the percentage of cortical bone in the proximal femur to be a crucial differentiator between the failed and non-failed groups. The likely fracture location was indicated to be intertrochantic. Comparison to previous computational, clinical and experimental work revealed support for these findings. PMID- 19646701 TI - Obesity does not increase external mechanical work per kilogram body mass during walking. AB - Walking is the most common type of physical activity prescribed for the treatment of obesity. The net metabolic rate during level walking (W/kg) is approximately 10% greater in obese vs. normal weight adults. External mechanical work (W(ext)) is one of the primary determinants of the metabolic cost of walking, but the effects of obesity on W(ext) have not been clearly established. The purpose of this study was to compare W(ext) between obese and normal weight adults across a range of walking speeds. We hypothesized that W(ext) (J/step) would be greater in obese adults but W(ext) normalized to body mass would be similar in obese and normal weight adults. We collected right leg three-dimensional ground reaction forces (GRF) while twenty adults (10 obese, BMI=35.6 kg/m(2) and 10 normal weight, BMI=22.1 kg/m(2)) walked on a level, dual-belt force measuring treadmill at six speeds (0.50-1.75 m/s). We used the individual limb method (ILM) to calculate external work done on the center of mass. Absolute W(ext) (J/step) was greater in obese vs. normal weight adults at each walking speed, but relative W(ext) (J/step/kg) was similar between the groups. Step frequencies were not different. These results suggest that W(ext) is not responsible for the greater metabolic cost of walking (W/kg) in moderately obese adults. PMID- 19646702 TI - Finite element model development of a child pelvis with optimization-based material identification. AB - A finite element (FE) model of a 10-years-old child pelvis was developed and validated against experimental data from lateral impacts of pediatric pelves. The pelvic bone geometry was reconstructed from a set of computed tomography images, and a hexahedral mesh was generated using a new octree-based hexahedral meshing technique. Lateral impacts to the greater trochanter and iliac wing of the seated pelvis were simulated. Sensitivity analysis was conducted to identify material parameters that substantially affected the model response. An optimization-based material identification method was developed to obtain the most favorable material property set by minimizing differences in biomechanical responses between experimental and simulation results. This study represents a pilot effort in the development and validation of age-dependent musculoskeletal FE models for children, which may ultimately serve to evaluate injury mechanisms and means of protection for the pediatric population. PMID- 19646703 TI - Relationship between ultrasonic parameters and apparent trabecular bone elastic modulus: a numerical approach. AB - The physical principles underlying quantitative ultrasound (QUS) measurements in trabecular bone are not fully understood. The translation of QUS results into bone strength remains elusive. However, ultrasound being mechanical waves, it is likely to assess apparent bone elasticity. The aim of this study is to derive the sensitivity of QUS parameters to variations of apparent bone elasticity, a surrogate for strength. The geometry of 34 human trabecular bone samples cut in the great trochanter was reconstructed using 3-D synchrotron micro-computed tomography. Finite-difference time-domain simulations coupled to 3-D micro structural models were performed in the three perpendicular directions for each sample and each direction. A voxel-based micro-finite element linear analysis was employed to compute the apparent Young's modulus (E) of each sample for each direction. For the antero-posterior direction, the predictive power of speed of sound and normalized broadband ultrasonic attenuation to assess E was equal to 0.9 and 0.87, respectively, which is better than what is obtained using bone density alone or coupled with micro-architectural parameters and of the same order of what can be achieved with the fabric tensor approach. When the direction of testing is parallel to the main trabecular orientation, the predictive power of QUS parameters decreases and the fabric tensor approach always gives the best results. This decrease can be explained by the presence of two longitudinal wave modes. Our results, which were obtained using two distinct simulation tools applied on the same set of samples, highlight the potential of QUS techniques to assess bone strength. PMID- 19646704 TI - The influence of concentric and eccentric loading on the finger pulley system. AB - In this study we investigated the influence of the loading condition (concentric vs. eccentric loading) on the pulley system of the finger. For this purpose 39 cadaver finger (14 hands, 10 donors) were fixed into an isokinetic loading device. The forces in the flexor tendons and at the fingertip were recorded. In the concentric loading condition A2 and A4 ruptures as well as alternative events such as fracture of a phalanx or avulsion of the flexor tendons were almost equally distributed, whereas the A2 pulley rupture was the most common event (59%) in the eccentric loading condition and alternative events were rare (23.5%). The forces in the deep flexor tendon, the fingertip and in the pulleys were significantly lower in the eccentric loading condition. As the ruptures occurred at lower loads in the eccentric than in the concentric loading condition it can be concluded that friction may be an advantage for climbers, supporting the holding force of their flexor muscles but may also increase the susceptibility to injury. PMID- 19646705 TI - Age-related mechanical work expenditure during normal walking: the Baltimore Longitudinal Study of Aging. AB - The aim of this cross-sectional study was to delineate age-associated kinematic and kinetic gait patterns of normal walking, and to test the hypothesis that older adults exhibit gait patterns that reduce generative mechanical work expenditures (MWEs). We studied 52 adult Baltimore Longitudinal Study of Aging participants (means age 72+/-9, from 60 to 92 years) who could walk 4m unaided. Three-dimensional kinematic and kinetic parameters assessed during rotation defined gait periods were used to estimate MWEs for the rotation of lower extremities about the medial-lateral (ML) and anterior-posterior (AP) axes of proximal joints, which represent MWEs in the AP and ML sides, respectively. Relationships between gait parameters and age were examined using regression analysis with adjustments for walking speed, sex, height, and weight. Older age was associated with slower self-selected walking speed (p<0.001), shorter stride length (p<0.001), and greater propensity of landing flat-footed (p=0.003). With older age, hip generative MWE for thigh rotation was lower about the AP axis (hip abduction and adduction) during stance (p=0.010) and higher about the ML axis (hip extension and flexion) during late stance (p<0.001). Knee absorptive MWE for shank rotation about the AP axis (knee abduction and adduction) during early stance was also lower with older age (p<0.003). These age-related gait patterns may represent a compensatory effort to maintain balance and may also reflect mobility limitations. PMID- 19646706 TI - Separation of diisopropylnaphthalene isomers. AB - The separation of diisopropylnaphthalenes was reinvestigated. The application of GCxGC appears to be a clear and necessary improvement over the use of single column techniques, with a polar (CP-Wax-52) column as reference technique, and a non-polar (CP-Sil-8) column as an alternative. Both qualitative and quantitative separations of DIPN isomers showed to be superior on GCxGC. The composition of both a DIPN mixture resulting from a typical experiment with a zeolite catalyst and a commercial one could be quantitatively determined in this way. PMID- 19646707 TI - Development of an ionic liquid based dispersive liquid-liquid microextraction method for the analysis of polycyclic aromatic hydrocarbons in water samples. AB - A simple, rapid and efficient method, ionic liquid based dispersive liquid-liquid microextraction (IL-DLLME), has been developed for the first time for the determination of 18 polycyclic aromatic hydrocarbons (PAHs) in water samples. The chemical affinity between the ionic liquid (1-octyl-3-methylimidazolium hexafluorophosphate) and the analytes permits the extraction of the PAHs from the sample matrix also allowing their preconcentration. Thus, this technique combines extraction and concentration of the analytes into one step and avoids using toxic chlorinated solvents. The factors affecting the extraction efficiency, such as the type and volume of ionic liquid, type and volume of disperser solvent, extraction time, dispersion stage, centrifuging time and ionic strength, were optimised. Analysis of extracts was performed by high performance liquid chromatography (HPLC) coupled with fluorescence detection (Flu). The optimised method exhibited a good precision level with relative standard deviation values between 1.2% and 5.7%. Quantification limits obtained for all of these considered compounds (between 0.1 and 7 ng L(-1)) were well below the limits recommended in the EU. The extraction yields for the different compounds obtained by IL-DLLME, ranged from 90.3% to 103.8%. Furthermore, high enrichment factors (301-346) were also achieved. The extraction efficiency of the optimised method is compared with that achieved by liquid-liquid extraction. Finally, the proposed method was successfully applied to the analysis of PAHs in real water samples (tap, bottled, fountain, well, river, rainwater, treated and raw wastewater). PMID- 19646708 TI - Selective retention of explosives and related compounds on gas-chromatographic capillary columns coated with lanthanide(III) beta-diketonate polymers. AB - The purpose of this research was to investigate coating capillary columns with lanthanide(III) beta-diketonate polymers to provide gas-chromatographic columns with selectivity toward explosives and related compounds. Capillary columns were statically coated with a mixture of a lanthanide(III) beta-diketonate polymer, which utilized p-di(4,4,5,5,6,6,6-heptafluoro-1,3-hexanedionyl)benzene (dihed) as a ligand, and SE-30. A novel coating technique was developed that used a methanol containing azeotrope to provide solubility for both polymers while maintaining a low boiling point compatible with static coating. As based on temperature programmed retention indices, the experimental columns displayed selective retention of nitroaromatic, nitroalkane, and nitrate ester test probes relative to an appropriate SE-30 control column. Selective retention was more pronounced for strongest Lewis base analyte contained in the test mixture (i.e., cyclohexanone). Relative analyte retention on the La(dihed), Tb(dihed), and Eu(dihed) columns are discussed relative to Lewis acidity and solubility of the polymer in the azeotropic coating solution. PMID- 19646710 TI - Ultrasensitive detection of indoleamines by combination of nanoparticle-based extraction with capillary electrophoresis/laser-induced native fluorescence. AB - For the first time, citrate-capped gold nanoparticles (citrate-AuNPs) have been used for the selective extraction of indoleamines--5-hydroxytryptophan (5-HTP), tryptophan (Trp), tryptamine (TA), 5-hydroxytryptamine (5-HT), and 5 hydroxyindoleacetic acid (5-HIAA)--prior to their analysis by capillary electrophoresis/laser-induced native fluorescence (CE/LINF). The extinction spectra obtained for the citrate-AuNPs in the presence of indoleamines revealed that 5-HTP, 5-HT, and 5-HIAA were extracted mainly because of van der Waals interactions between the indole ring and the citrate-AuNPs (hydrophobic surface), while 5-HT and TA were extracted by electrostatic attractions between the amine group of the indoleamines and the citrate ligands adsorbed on the AuNP surface. The extracted indoleamines could be liberated from the AuNP surface by the addition of high concentrations of 2-mercaptoethanol (2-ME), which binds strongly to the AuNPs. The sensitivity of this method to indoleamines could be significantly enhanced by increasing the AuNP concentration, incubation time, and sample volume. Under optimal extraction and separation conditions, the combination of NP-based extraction and CE-LINF provided 48-, 4077-, 985-, 920-, and 4030-fold improvements in the limits of detection (signal-to-noise ratio of 3) for 5-HTP, Trp, TA, 5-HT, and 5-HIAA as compared to the analysis of five indoleamines by CE-LINF. In addition, this proposed method was successfully used for the determination of TA and 5-HT in urine. PMID- 19646709 TI - Relation of structure to performance characteristics of monolithic and perfusive stationary phases. AB - Commercially available polymer-based monolithic and perfusive stationary phases were evaluated for their applicability in chromatography of biologics. Information on bed geometry, including that from electron microscopy (EM), was used to interpret and predict accessible volumes, binding capacities, and pressure drops. For preparative purification of biologics up to at least 7 nm in diameter, monoliths and perfusive resins are inferior to conventional stationary phases due to their low binding capacities (20-30 g/L for BSA). For larger biologics, up to several hundred nanometers in diameter, calculations from EM images predict a potential increase in binding capacity to nearly 100 g/L. The accessible volume for adenovirus calculated from the EM images matched the experimental value. While the pores of perfusive resins are essentially inaccessible to adenovirus under binding conditions, under non-adsorbing conditions the accessible intrabead porosity is almost as large as the interbead porosity. Modeling of breakthrough curves showed that the experimentally observed slow approach to full saturation can be explained by the distribution of pore sizes. PMID- 19646711 TI - Synthesis and characterization of AgBr nanocomposites by templated amphiphilic comb polymer. AB - A novel amphiphilic graft copolymer, poly(vinylidene fluoride-co chlorotrifluoroethylene)-g-poly(4-vinyl pyridine) (P(VDF-co-CTFE)-g-P4VP) at 65:35 wt.%, respectively, was synthesized via atom transfer radical polymerization (ATRP), as confirmed by nuclear magnetic resonance (1H NMR) and transmission electron microscopy (TEM). Silver bromide (AgBr) nanoparticles were in situ generated within the self-assembled P(VDF-co-CTFE)-g-P4VP graft copolymer. TEM, UV-visible spectroscopy and X-ray diffraction (XRD) analyses support the successful formation of P(VDF-co-CTFE)-g-P4VP nanocomposites consisting of stabilized AgBr nanoparticles mostly 20-40 nm in size, which is presumably due to the capping action of the coordinating pyridine groups of the graft copolymer. The wavenumber of pyridine nitrogen in FT-IR spectra and the glass transition temperature (Tg) of the graft polymer measured by DSC shifted upon the formation of AgBr nanoparticles, indicating specific interactions between the nanoparticles and the graft copolymer matrix. PMID- 19646712 TI - Structural characterization of hierarchically porous alumina aerogel and xerogel monoliths. AB - Detailed nanostructures have been investigated for hierarchically porous alumina aerogels and xerogels prepared from ionic precursors via sol-gel reaction. Starting from AlCl3.-6H2O and poly(ethylene oxide) (PEO) dissolved in a H2O/EtOH mixed solvent, monolithic wet gels were synthesized using propylene oxide (PO) as a gelation initiator. Hierarchically porous alumina xerogels and aerogels were obtained after evaporative drying and supercritical drying, respectively. Macroporous structures are formed as a result of phase separation, while interstices between the secondary particles in the micrometer-sized gel skeletons work as mesoporous structures. Alumina xerogels exhibit considerable shrinkage during the evaporative drying process, resulting in relatively small mesopores (from 5.4 to 6.2 nm) regardless of the starting composition. For shrinkage-free alumina aerogels, on the other hand, the median mesopore size changes from 13.9 to 33.1 nm depending on the starting composition; the increases in PEO content and H2O/EtOH volume ratio both contribute to producing smaller mesopores. Small angle X-ray scattering (SAXS) analysis reveals that variation of median mesopore size can be ascribed to the change in agglomeration state of primary particles. As PEO content and H2O/EtOH ratio increase, secondary particles become small, which results in relatively small mesopores. The results indicate that the agglomeration state of alumina primary particles is influenced by the presence of weakly interacting phase separation inducers such as PEO. PMID- 19646714 TI - [Differences in the prognosis of patients in an intensive care unit by duration of mechanical ventilation]. PMID- 19646713 TI - Lack of modulating effects of the COMT Val(158)Met polymorphism on the association of serious life events (SLE) and impulsivity in patients with Borderline Personality Disorder. PMID- 19646715 TI - [Role of low molecular weight heparins in prophylaxis of thromboembolic events on oncological patients with indwelling central venous catheter]. AB - BACKGROUND AND OBJECTIVE: Our study was designed to assess the incidence of thrombosis in the upper limbs and of pulmonary embolism in oncological patients with indwelling central venous catheters, and to evaluate, also, the potential role of LMWH to prevent these events. PATIENTS AND METHODS: Oncological patients undergoing placement of a central venous acccess (port-a-cath type) were treated with or without bemiparin in a non-randomized fashion. Assessment included clinical and radiological follow-up. A phlebography on the first day and ecodoppler on days 1th, 45th and 90th were performed. Patients received or not prophylactic bemiparin (3500UI/day) in a non-randomized way. The incidence of thrombosis in both groups was assessed as well as its relation with some risk factors. RESULTS: One hundred and forty eight patients were eligible; 19 thrombotic events were found. The incidence of symptomatic upper extremity thrombosis was 5.41%, asymptomatic thrombosis in 2.03% ; there was one case of pulmonary embolism ( 0,68%); catheter failure occurred in 2.70%; incidence of lower extremities deep venous thrombosis was 2.03%. There was a higher percentage of events in the group of patients treated with bemiparin than in the not treated individuals (9.4%), although the difference did not reach statistical significance (p=0.27). The only risk factors reaching statistical significance were the prothrombin time, high blood pressure and overweight. CONCLUSIONS: Central venous catheters are very useful in oncology. The procedure was related with a low percentage of thrombotic complications. Sodic bemiparin does not reduce the thrombotic risk in these patients. PMID- 19646716 TI - [Patients' functional status and caregiver distress at the palliative care unit]. PMID- 19646717 TI - [Illicit drugs and driving]. PMID- 19646718 TI - [Primary hypothyroidism: Considerations for a rational use of levothyroxine therapy]. PMID- 19646719 TI - [Mortality in internal medicine departments]. AB - Mortality is an important indicator of clinical activity. The aim of this paper is to analyze the mortality in Internal Medicine (IM) departments in our country taking into account the characteristics of the patients seen at our hospitals. MATERIAL AND METHODS: Patients attended at the IM Departments of Spanish hospitals during 2006 were analyzed through the CMBD (minimum basic set of data; in Spanish: <>) which collects administrative and clinical data of all patients admitted to the public and private hospital of our state. Global and specific mortality by DRG were established and compared with the national standard published by the Spanish Health and Consume Ministry for that same year. RESULTS: In general hospitals of the National Health Service for the year 2006, 3,589,718 patients were discharged, 522,268 (14.5%) of them from IM departments. Of this last group, 46.6% were female, with a mean age of 70.4 years (SD 11.6) and a mean weight of 1.72 (SD 1.39). Global mortality was 9.5% compared to a national standard of 4.1%. Comparing by DRG, mortality was in general higher in IM. CONCLUSIONS: Global mortality as well as specific mortality by DRG is higher than the general mortality. This could be explained by the characteristics of the population admitted in IM: older, seriously ill, with more co-morbidities, admitted trough the emergency department and consuming more resources than the general population. PMID- 19646720 TI - [Inadequate information in the medication orders of hospital inpatients]. PMID- 19646721 TI - Molecular and biochemical evolution of maize terpene synthase 10, an enzyme of indirect defense. AB - Maize plants attacked by lepidopteran larvae emit a volatile mixture that consists mostly of the sesquiterpene olefins, (E)-alpha-bergamotene and (E)-beta farnesene. These volatiles are produced by the herbivore-induced terpene synthase TPS10 and attract natural enemies to the damaged plants. A survey of volatiles in maize lines and species of teosinte showed that the TPS10 products (E)-alpha bergamotene and (E)-beta-farnesene are consistently induced by herbivory, indicating that release of TPS10 volatiles is a defense trait conserved among maize and its wild relatives. Sequence comparison of TPS10 from maize and its apparent orthologs from four teosinte species demonstrated stabilizing selection on this defense trait. The teosinte volatiles and the enzymatic activity of the apparent TPS10 orthologs were not completely uniform but varied in the ratio of (E)-alpha-bergamotene to (E)-beta-farnesene products formed. We identified a single amino acid in the active center which determines the ratio of (E)-alpha bergamotene to (E)-beta-farnesene and has changed during the evolution of maize and teosinte species. Feeding experiments with the substrate (Z,E)-farnesyl diphosphate revealed that this amino acid controls the rate of isomerization of the (E,E)-farnesyl carbocation intermediate to the (Z,E)-configuration. PMID- 19646722 TI - Associations of diet behaviours and intention to eat healthily with tobacco use among motor freight workers. PMID- 19646723 TI - Small safe steps to prevention. PMID- 19646724 TI - A pilot study to assess workplace tuberculosis control activities in four districts in KwaZulu-Natal, South Africa. PMID- 19646725 TI - [Intraventricular cavernoma in the foramen of Monro: particularities due to its atypical location]. AB - Although cavernomas are relatively common vascular malformations in the central nervous system, they are rarely located in the ventricles and are even more rarely located in the region of the foramen of Monro. This atypical location results in a series of differential clinical and radiological characteristics that can make the diagnosis of these lesions extremely difficult and lead to inefficacious procedures like radiotherapy or a neuroendoscopic surgical approach or even to procedures that endanger the patient like stereotactic biopsy. We present a case of intraventricular cavernoma in the region of the foramen of Monro with the aim of illustrating the difficulties involved in the diagnosis of this rare lesion. PMID- 19646726 TI - [Intraventricular fibrous tumor: a case report]. AB - Solitary fibrous tumor was first reported in the pleura; however, it has since been reported in many other locations. Solitary fibrous tumors of the central nervous system are uncommon and the intraventricular location is exceptional. To our knowledge, only eight cases of intraventricular solitary fibrous tumor have been reported. We describe a case of intraventricular solitary fibrous tumor.The imaging characteristics of intraventricular solitary fibrous tumors are nonspecific; the differential diagnosis should include other tumors that can affect the ventricular system such as meningioma, high grade glioma, metastasis, subependymoma, choroid plexus papilloma, ependymoma, subependymal giant cell astrocytoma, and neurocytoma. At histological study, immunohistochemical techniques allow solitary fibrous tumor to be differentiated from fibrous meningioma and hemangiopericytoma. PMID- 19646727 TI - [Bizarre parosteal osteochondromatous proliferation or Nora's lesion]. AB - Bizarre parosteal osteochondromatous proliferation (BPOP) is a very rare benign lesion on face bones. The first line treatment is surgical exeresis. The frequency of recurrence after exeresis may suggest a malignancy. PMID- 19646729 TI - Bovine adenovirus serotype 3 utilizes sialic acid as a cellular receptor for virus entry. AB - Bovine adenovirus serotype 3 (BAd3) and porcine adenovirus serotype 3 (PAd3) entry into the host cells is independent of Coxsackievirus adenovirus receptor and integrins. The role of sialic acid in BAd3 and PAd3 entry was investigated. Removal of sialic acid by neuraminidase, or blocking sialic acid by wheat germ agglutinin lectin significantly inhibited BAd3, but not PAd3, transduction of Madin-Darby bovine kidney cells. Maackia amurensis agglutinin or Sambucus nigra (elder) agglutinin treatment efficiently blocked BAd3 transduction suggesting that BAd3 utilized alpha(2,3)-linked and alpha(2,6)-linked sialic acid as a cell receptor. BAd3 transduction of MDBK cells was sensitive to sodium periodate, bromelain, or trypsin treatment indicating that the receptor sialoconjugate was a glycoprotein rather than a ganglioside. To determine sialic acid-containing cell membrane proteins that bind to BAd3, virus overlay protein binding assay (VOPBA) was performed and showed that sialylated cell membrane proteins in size of approximately 97 and 34 kDa bind to BAd3. The results suggest that sialic acid serves as a primary receptor for BAd3. PMID- 19646730 TI - Quantitative evaluation of enterococci and Bacteroidales released by adults and toddlers in marine water. AB - Traditionally, the use of enterococci has been recommended as the fecal indicator bacteria of choice for testing marine recreational water quality, and prior studies have shown that bathers shed large numbers of enterococci into the water. The current study expands upon prior research by evaluating shedding from both toddlers and adults, and by the expansion of measurements to include enterococci shedding via three different methods (membrane filter (MF), chromogenic substrate (CS), and quantitative polymerase chain reaction (qPCR)) and shedding of alternative fecal indicator bacteria (Bacteroidales human markers UCD and HF8 via qPCR). Two sets of experiments were conducted. The first experiment consisted of two groups of 10 adults who bathed together in a large pool. The second study consisted of 14 toddlers who bathed individually in a small pool which allowed for sand recovery. Sand recovery was used to estimate the amount of sand transported on the bodies of toddlers and to estimate the number of fecal indicator bacteria released from this sand. The numbers of estimated enterococci shed per adult ranged from 1.8 x 10(4) to 2.8 x 10(6) CFU, from 1.9 x 10(3) to 4.5 x 10(6) MPN, and from 3.8 x 10(5) to 5.5 x 10(6) GEU based on the MF, CS, and qPCR methods, respectively. The estimated numbers of Bacteroidales human markers ranged from 1.8 x 10(4) to 1.3 x 10(6) for UCD, and ranged from the below detection limit to 1.6 x 10(5) for HF8. The estimated amount of sand transported per toddler (n=14) into the water column after sand exposure was 8+/-6g on average. When normalizing the numbers of enterococci shed from toddlers via sand by the 3.9 body surface area ratio, the differences between toddlers and adults were insignificant. Contributions of sands to the total enterococci (MF) shed per toddler was 3.7+/-4.4% on average. Although shedding via beach sand may contribute a small fraction of the microbial load during initial bathing, it may have a significant role if bathers go to water repetitively after sand exposure. PMID- 19646731 TI - Impacts of climate change on phosphorus loading from a grassland catchment: implications for future management. AB - Dynamic modelling was used to quantify the impact of projected climate change, and potential changes in population and land use, on phosphorus (P) export from a sub-catchment in SW Ireland using the Generalised Watershed Loading Functions (GWLF) model. Overall the results indicated that the increase in annual total phosphorus loads attributable to climate change was greater than that from either population or land use change, and therefore that future climate variability will pose an increasingly significant threat to the successful long-term implementation of catchment management initiatives. The seasonal pattern in projected P export mirrored changes in streamflow, with higher rates between January and April and lower rates in summer. The potential reduction in export in summer was, however, negated when increases in population were included in simulations. A change in the slurry spreading period from that stipulated in national regulations to the months between April and September could potentially mitigate against future increases in dissolved P export in spring. The results indicate that projected changes in climate should be included when undertaking modelling exercises in support of decision making for catchment management plans. PMID- 19646728 TI - TLR3 and TLR4 are innate antiviral immune receptors in human microglia: role of IRF3 in modulating antiviral and inflammatory response in the CNS. AB - In the CNS, microglia are the primary targets of HIV infection. In this study, we investigated the effect of activation of the innate antiviral receptors TLR3 and TLR4 on HIV infection of primary human microglia, as well as microglial cell signaling and gene expression. Ligands for both TLR3 and TLR4 potently inhibited HIV replication in microglia through a pathway requiring IRF3. Surprisingly, a remarkably similar pattern of cell signaling and gene expression was observed in TLR3- and TLR4-activated microglia, suggesting a relatively minor role for MyD88 following TLR4 activation in these cells. HIV did not activate IRF3 but rather decreased IRF3 protein, indicating that HIV does not activate TLR3 or RIG-like helicases in microglia. Taken together, these results indicate that activation of TLR3 or TLR4 will elicit antiviral immunity, in addition to inducing proinflammatory responses. We suggest that a balanced expression between inflammatory and innate immune genes might be achieved by IRF3 over-expression. PMID- 19646732 TI - Oxidation of the erythro and threo forms of the phenolic lignin model compound 1 (4-hydroxy-3-methoxyphenyl)-2-(2-methoxyphenoxy)-1,3-propanediol by laccases and model oxidants. AB - Mixtures of equal amounts of the erythro and threo forms of the phenolic arylglycerol beta-aryl ether 1-(4-hydroxy-3-methoxyphenyl)-2-(2-methoxyphenoxy) 1,3-propanediol were oxidized (i) with laccases from Trametes versicolor, Agaricus bisporus, Myceliophthora thermophila and Rhus vernicifera, (ii) with laccase-mediator systems consisting of T. versicolor laccase and ABTS or HBT, and (iii) with various model oxidants including cerium(IV) ammonium nitrate (CAN), lignin peroxidase, Fenton's reagent, and lead(IV) tetraacetate (LTA). All the laccases exhibited a similar preferential degradation of the threo form. The mediator ABTS counteracted the threo preference of laccase, but the mediator HBT did not affect it. The outer-sphere model oxidants CAN and lignin peroxidase showed a preferential degradation of the threo form. LTA and Fenton's reagent did not exhibit any stereo-preference. The results suggest that laccases of different origin, primary structure, and redox potential behave as typical outer-sphere oxidants in their interaction with the diastereomers of the arylglycerol beta aryl ether. PMID- 19646733 TI - Effects of chronic copper exposure on fluvial systems: linking structural and physiological changes of fluvial biofilms with the in-stream copper retention. AB - Long-term metal exposure is known to be responsible for a large variety of structural and functional changes in periphyton communities which allow these communities to adapt to metal-polluted conditions. This study aimed to link the changes that chronic copper (Cu) exposure causes on the structure and physiology of fluvial biofilms with the efficiency of the river systems in retaining phosphate and Cu. The effects of a chronic Cu exposure on the structure, physiology and induction of Cu tolerance of the community were evaluated by comparing this community with a non-exposed one. Results showed that periphyton chronically exposed to Cu had lower algal biomass, higher proportion of green algae, lower proportion of brown algae, and higher EPS content per unit of biomass than the un-exposed community. In addition, the chronically-exposed community showed a Cu content (both total and intracellular Cu content) ten times higher than the un-exposed community. While in-stream phosphate retention was not markedly influenced by chronic Cu exposure; Cu retention was clearly reduced, as was shown by a reduction in Cu retention efficiency (Cu-S(w)) and demand (Cu-Vf). The chronically-exposed periphyton, in spite of having high intracellular Cu concentration, showed similar photosynthetic efficiency than the un-exposed community and showed a higher Cu tolerance. It indicated that this community was acclimatized to Cu exposure and that this acclimatization was probably linked to the ability to detoxify and immobilize metals. These observations suggest that the fate of Cu in fluvial ecosystems will be influenced by the exposure history of the system. The results from this study indicate that metals will travel longer distances in metal-polluted streams compared to pristine systems having effects on water quality farther downstream. PMID- 19646734 TI - Maternal exposure to floricultural work during pregnancy, PON1 Q192R polymorphisms and the risk of low birth weight. AB - BACKGROUND: Although there is evidence from animal studies of impaired reproductive function by exposure to organophosphates (OP), the effects on birth weight have not been sufficiently evaluated in epidemiological studies. Paraoxonase (PON1) detoxifies organophosphates by cleavage of active oxons. Some PON1 gene polymorphisms could reduce the enzyme activity and increase susceptibility to OP toxicity. OBJECTIVE: To assess the association between maternal exposure to floriculture during pregnancy and the risk of low birth weight (<2500 g) in their offspring, as well as to evaluate the interaction between this exposure and maternal genotype for PON1 Q192R polymorphisms. MATERIALS AND METHODS: A cross sectional study was carried out in two Mexican states (States of Mexico and Morelos) with high frequencies of greenhouse activity. We interviewed and collected blood samples from 264 females (floriculturists or partners of floricultural workers) who became pregnant during the 10 years prior to the interview. The questionnaire measured socioeconomic characteristics, tobacco and alcohol consumption, diseases and occupational and reproductive history. We also applied a food frequency questionnaire. Information was obtained pertaining to 467 pregnancies. DNA was extracted from white cells, and PON1 genotype was determined by Restriction Fragment Length Polymorphism for Q192R polymorphisms. Results were analyzed with generalized estimating equations models. RESULTS: After adjusting for potential confounders, we detected a statistically significant interaction between maternal exposure to flower growing work during pregnancy and PON1 Q192R polymorphisms on risk of low birth weight. The risk of having a baby with LBW is nearly six times higher if a mother is a floriculture worker during pregnancy and has PON1 192RR genotype (OR 5.93, 95% CI 1.28, 27.5). CONCLUSION: These results suggest that the interaction between maternal floriculture work during pregnancy and 192RR PON1 genotype increases the probability of having children with LBW. PMID- 19646735 TI - Multivariate analysis of the spatial patterns of 8 trace elements using the French soil monitoring network data. AB - Geostatistical and spatially constrained multivariate analysis methods (MULTISPATI-PCA) have been applied at the scale of France to differentiate the influence of natural background from the pollution due to human activities on the content of 8 trace elements in the topsoil. The results of MULTISPATI-PCA evidence strong spatial structures attributed to different natural and artificial processes. The first axis can be interpreted as an axis of global richness in trace elements. Axis 2 reflects geochemical anomalies in Tl and Pb. Axis 3 exhibits on one hand natural pedogeogenic anomalies and on the other hand, it shows high values attributable to anthropogenic contamination. Finally, axis 4 is driven by anthropogenic copper contamination. At the French territory scale, we show that the main factors controlling trace elements distribution in the topsoil are soil texture, variations in parent material geology and weathering, and various anthropogenic sources. PMID- 19646736 TI - Historical accumulation rates of mercury in four Scottish ombrotrophic peat bogs over the past 2000 years. AB - The historical accumulation rates of mercury resulting from atmospheric deposition to four Scottish ombrotrophic peat bogs, Turclossie Moss (northeast Scotland), Flanders Moss (west-central), Red Moss of Balerno (east-central) and Carsegowan Moss (southwest), were determined via analysis of (210)Pb- and (14)C dated cores up to 2000 years old. Average pre-industrial rates of mercury accumulation of 4.5 and 3.7 microg m(-2) y(-1) were obtained for Flanders Moss (A.D. 1-1800) and Red Moss of Balerno (A.D. 800-1800), respectively. Thereafter, mercury accumulation rates increased to typical maximum values of 51, 61, 77 and 85 microg m(-2) y(-1), recorded at different times possibly reflecting local/regional influences during the first 70 years of the 20th century, at the four sites (TM, FM, RM, CM), before declining to a mean value of 27+/-15 microg m(-2) y(-1) during the late 1990s/early 2000s. Comparison of such trends for mercury with those for lead and arsenic in the cores and also with direct data for the declining UK emissions of these three elements since 1970 suggested that a substantial proportion of the mercury deposited at these sites over the past few decades originated from outwith the UK, with contributions to wet and dry deposition arising from long-range transport of mercury released by sources such as combustion of coal. Confidence in the chronological reliability of these core derived trends in absolute and relative accumulation of mercury, at least since the 19th century, was provided by the excellent agreement between the corresponding detailed and characteristic temporal trends in the (206)Pb/(207)Pb isotopic ratio of lead in the (210)Pb-dated Turclossie Moss core and those in archival Scottish Sphagnum moss samples of known date of collection. The possibility of some longer-term loss of volatile mercury released from diagenetically altered older peat cannot, however, be excluded by the findings of this study. PMID- 19646737 TI - Analysis of phenols and nitrophenols in rainwater collected simultaneously on an urban and rural site in east of France. AB - The behaviour of phenols and nitrophenols in the atmosphere is of concern for environmental research as these are known to be toxic to humans and wildlife. To increase the knowledge about these compounds, the concentrations of 20 phenols and nitrophenols in rainwater were studied in an urban (Strasbourg) and a rural (Erstein) site in Eastern France. The wet rain samples were collected on a weekly basis between January 2002 and July 2003, and analyzed for phenols and nitrophenols using SPME and gas chromatography coupled to mass spectrometry. The compounds were derivatized with MDBSTFA directly in the injection port of the gas chromatograph. Total concentrations ranged from 0 to 1383 microg L(-1) in Strasbourg and from 0 to 1215 microg L(-1) in Erstein. These concentrations are in the same range than those measured in other studies, but considerably higher than the concentrations measured for pesticides (about 10 times) and polycyclic aromatic hydrocarbons (about 1000 times) on the same sites and at the same period. Phenols, except for o-cresol, were generally less concentrated than nitrophenols. o-Cresol was one of the major compounds, probably due to its role as raw material in pesticide production. The concentrations of phenols and nitrophenols were found to vary with time. No seasonal trend was observed, but significant correlations with rainfall amount were identified. PMID- 19646738 TI - Prevention of venous thromboembolism in immobilized neurological patients: Guidelines of the Italian Society for Haemostasis and Thrombosis (SISET). AB - Neurological disorders are often associated with immobilization, thus placing patients at increased risk for venous thromboembolism (VTE). This risk is very high in patients with acute ischemic stroke and spinal cord injuries, and it remains poorly defined in patients with peripheral nervous disorders or degenerative disorders of the central nervous system. The benefit of prophylactic strategies remains often unclear. The Italian Society for Studies on Haemostasis and Thrombosis promoted the development of evidence- and consensus-based guidelines to help physicians involved in the management of neurological patients. After a comprehensive and systematic review of the literature, a panel of experts formulated recommendations for the prevention of VTE in adolescent or adult patients presenting with different neurological disorders. Patients with acute ischemic stroke should routinely receive pharmacological prophylaxis to be started within 48 hours and continued for approximately 14 days; patients with acute hemorrhagic stroke should routinely receive mechanical prophylaxis, pharmacological prophylaxis should be considered once the patient is stable; patients with neuro-muscular degenerative diseases and with other major risk factors for venous thrombosis should be considered for the administration of pharmacological or mechanical prophylaxis; patients with peripheral nerve diseases should receive mechanical prophylaxis while immobilized and in the presence of additional risk factors for VTE, patients with Guillain Barre should be considered for pharmacological prophylaxis with low molecular weight heparin; patients with spinal cord injury should receive combined mechanical and pharmacological prophylaxis; patients with non traumatic spinal cord diseases should be considered for pharmacological prophylaxis. PMID- 19646739 TI - A Pfannenstiel single-site nephrectomy and nephroureterectomy: a practical application of laparoendoscopic single-site surgery. AB - OBJECTIVES: To present the initial clinical experience with laparoendoscopic single-site (LESS) radical nephrectomy and nephroureterectomy performed completely through a Pfannenstiel incision. METHODS: Two patients underwent a single-site nephrectomy and nephroureterectomy for the diagnosis of an enhancing renal parenchymal mass and a renal pelvic mass, respectively. In both cases, a 7.5-cm Pfannenstiel incision was made and GelPort was inserted. Trocars were placed through the access port, and nephrectomy was performed using standard and bariatric length laparoscopic instruments. Distal ureter was resected through the Pfannenstiel incision for nephroureterectomy. No additional ports were used as both procedures were completed via the Pfannenstiel approach. RESULTS: The procedures were completed in 187 and 409 minutes, respectively, without complication. Blood loss was estimated at 50 and 200 mL, respectively. Postoperatively, the patients required minimal analgesia. Patients were discharged on postoperative days 2 and 4, respectively. CONCLUSIONS: LESS nephrectomy and nephroureterectomy using only a Pfannenstiel incision are technically feasible and reproducible in human beings if performed by surgeons with standard laparoscopic skills. Using standard and bariatric length laparoscopic instruments, the procedures were performed without complication, with minimal blood loss and minimal variance from standard laparoscopic techniques. We anticipate that this approach can be incorporated by the urologist adept at laparoscopic surgery and provides a practical application of LESS surgery for extirpative procedures. PMID- 19646740 TI - Elevated urinary levels and urothelial expression of hepatocarcinoma-intestine pancreas/pancreatitis-associated protein in patients with interstitial cystitis. AB - OBJECTIVES: To investigate the pathophysiology of interstitial cystitis (IC), we examined urinary levels and urothelial expression of human orthologue of pancreatitis-associated protein (PAP) III, namely, hepatocarcinoma-intestine pancreas (HIP)/PAP, in patients with IC. We have previously shown that PAP III is expressed with increased frequency in the bladder urothelium in a rat cystitis model (Takahara Y, et al. J Urol. 2008;179:1603-1609). METHODS: HIP/PAP levels in the urine from patients with IC were measured by enzyme-linked immunosorbent assay, and HIP/PAP expression in the bladder tissues was assessed by immunohistochemical study. RESULTS: The median concentration of urinary HIP/PAP was significantly higher in patients with IC than in controls (13.67 vs 1.86 pg/mL urine, respectively, P <.0001, with Mann-Whitney U test). HIP/PAP immunoreactivity was observed in the urothelium of 88.2% of patients with IC (15/17) and in 5.9% of bladder tissues of controls (1/17). Urinary HIP/PAP levels in patients with IC were positively correlated with urinary frequency and bladder pain (r = 0.429, 0.443) and inversely correlated with mean voided urine volume (r = -0.488). CONCLUSIONS: Urinary HIP/PAP levels were significantly higher in IC patients and the apparent HIP/PAP expression in the bladder urothelium was more frequently observed among IC patients. The involvement of HIP/PAP in the pathophysiology of IC is suggested. PMID- 19646741 TI - Sentinel node (SLN) biopsy in the management of locally advanced cervical cancer. AB - OBJECTIVES: Sentinel lymph node (SLN) biopsy can significantly contribute to the management of locally advanced cervical cancers with high risk of lymph node (LN) positivity. However, low detection rate and sensitivity were reported in larger tumors, albeit on a small number of cases. It was the aim of our study to verify the SLN reliability in large tumors, with modified dye application technique and a careful identification of side-specific lymphatic drainage. METHODS: The study involved 44 patients with tumors 3 cm in diameter or larger, stages IB1 to IIA, or selected IIB. In cases where SLN could not be detected, systematic pelvic lymphadenectomy was performed on the respective side. Systematic pelvic lymphadenectomy was performed during the second step radical procedure if not already done. RESULTS: Detection rate in the whole cohort reached 77% per patient and 59% bilaterally. No significant difference was found whether a blue dye or a combined method was used (75% vs 80%, and 55% vs 67%). Systematic pelvic lymphadenectomy was performed in cases with undetected SLN unilaterally in 8 and bilaterally in 10 women. A systematic pelvic lymphadenectomy was included in the second step radical procedure in 19 cases and no positive LN were found. There was no case of false-negative SLN result in patients who underwent surgical treatment. CONCLUSION: Detection rate in locally advanced cervical cancer could be improved by a careful dye application technique. Low false-negative SLN rate could be achieved if pelvic lymphatic drainage is evaluated on a side-specific principle by performing systematic lymphadenectomy if SLN is not detected. PMID- 19646742 TI - Abdominal radical trachelectomy as a fertility-sparing procedure in women with early-stage cervical cancer in a series of 61 women. AB - OBJECTIVE: This retrospective study was conducted as a review of a series of women who had undergone abdominal radical trachelectomy and pelvic lymphadenectomy for early-stage cervical cancer. METHODS: We performed a retrospective review of patients who had undergone an abdominal radical trachelectomy. Data regarding tumor size and histology, surgical complications, recurrences, pregnancies and live births were collected and were presented as a percentage of the total number of cases. RESULTS: A total of 61 women were followed up for a median of 27 months (range: one month--79 months). There were six recurrences (9.8%); none of the recurrences occurred in patients with a tumor diameter of <20 mm except in one case with adenocarcinoma. Twenty-nine women attempted to conceive; four of these women were successful. All four of these women had live births: two had preterm deliveries, and the remaining two had full term deliveries. The cumulative pregnancy rate among the women who attempted to conceive was 13.8% (4/29). CONCLUSION: Among selected women with early-stage cervical cancer, especially those with a tumor diameter of <20 mm, abdominal radical trachelectomy and pelvic lymphadenectomy is a fertility-sparing treatment option, even though the cumulative conception rate was not particularly high compared with that for women who had undergone a vaginal radical trachelectomy. PMID- 19646744 TI - Synchronization and resynchronization of inseminations in lactating dairy cows with the CIDR insert and the Ovsynch protocol. AB - Pregnancy per artificial insemination (AI) was evaluated in dairy cows (Bos taurus) subjected to synchronization and resynchronization for timed AI (TAI). Cows (n=718) received prostaglandin F(2alpha) (PGF) on Days -38 and -24 (Days 39 and 53 postpartum), gonadotropin-releasing hormone (GnRH) on Day -10, PGF on Day 3, and GnRH and TAI on Day 0. Between Days -10 and -3, cows received a progesterone intravaginal insert (CIDR group) or no CIDR (Control group). Between Days 14 and 23, cows received a CIDR (Resynch CIDR group) or no CIDR (Resynch control group), GnRH on Day 23, with pregnancy diagnosis on Day 30. Cows in estrus (between Days 0 and 30) were re-inseminated at detected estrus (RIDE). Nonpregnant cows received PGF on Day 30 and GnRH and TAI on Day 33. Plasma progesterone was determined to be low or high on Days -24 and -10. Pregnancy rates were evaluated 30 and 55 d after AI. The CIDR insert included in the Presynch-Ovsynch protocol did not increase overall pregnancy per AI for first service (36.1% and 33.6% for CIDR; 34.1% and 28.8% for Control) but did decrease pregnancy loss (7.0% for CIDR and 15.6% for Control). The CIDR insert increased pregnancy per AI in cows with high progesterone at the time the CIDR insert was applied. Administration of a CIDR insert between Days 14 and 23 of the estrous cycle after first service did not increase overall pregnancy per AI to second service (24.7% and 22.7% for Resynch CIDR; 28.6% and 25.3% for Resynch control). For second service, RIDE cows had lower pregnancy rates in the Resynch CIDR group than in the Resynch control group. Cows with a CL (corpus luteum) at Day 30 had higher pregnancy rates in the Resynch CIDR group than those in the Resynch control group. PMID- 19646743 TI - Identification of a physiologically relevant endogenous ligand for PPARalpha in liver. AB - The nuclear receptor PPARalpha is activated by drugs to treat human disorders of lipid metabolism. Its endogenous ligand is unknown. PPARalpha-dependent gene expression is impaired with inactivation of fatty acid synthase (FAS), suggesting that FAS is involved in generation of a PPARalpha ligand. Here we demonstrate the FAS-dependent presence of a phospholipid bound to PPARalpha isolated from mouse liver. Binding was increased under conditions that induce FAS activity and displaced by systemic injection of a PPARalpha agonist. Mass spectrometry identified the species as 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Knockdown of Cept1, required for phosphatidylcholine synthesis, suppressed PPARalpha-dependent gene expression. Interaction of 16:0/18:1-GPC with the PPARalpha ligand-binding domain and coactivator peptide motifs was comparable to PPARalpha agonists, but interactions with PPARdelta were weak and none were detected with PPARgamma. Portal vein infusion of 16:0/18:1-GPC induced PPARalpha dependent gene expression and decreased hepatic steatosis. These data suggest that 16:0/18:1-GPC is a physiologically relevant endogenous PPARalpha ligand. PMID- 19646745 TI - Postmortem recovery and cryopreservation of spermatozoa from the vas deferens of rhesus macaques (Macaca mulatta). AB - To determine whether sperm derived from the vas deferens could be retrieved and successfully cryopreserved, testes were collected from 20 rhesus macaques (Macaca mulatta). The males ranged in age from 3 to 19 yr with an average age of 8.5 yr. No sperm was obtained from three animals that were younger than 4 yr. The remaining 17 samples contained sperm with an average sperm cell number of 421.8+/ 88.7x10(6) and an average motility of 72.8+/-4.4%. After 24h of culture in TALP medium at 37 degrees C in 5% CO(2) and 95% air, the overall motility decreased significantly in all samples regardless of treatment. Freezing in TEST (TES-Tris buffer)-yolk buffer containing 6% (vol/vol) glycerol had a significant effect on sperm, reducing the immediate postthaw motility to 42.4% in nontreated samples. Treatment with dibutyryl-cAMP and caffeine further reduced sperm motility after 4h in fresh sperm (72.8% vs. 50.4%) but increased motility in sperm that had been frozen (14.0% vs. 23.2%). The age of the male did not influence sperm concentration or grade but proved to be a significant factor in determining motility of frozen-thawed treated sperm, with lower motility found in samples from older males. Overall, the study demonstrates that motile sperm can be obtained from postmortem males, although subsequent studies will be needed to determine whether the quality is sufficient to facilitate its use in assisted reproduction. PMID- 19646746 TI - Evaluation of test protocol variables for dental implant fatigue research. AB - OBJECTIVES: This work begins to explore the influence of cycling rate and environment on fatigue testing of dental implants according to the ISO protocol 14801. METHODS: Twenty-four Straumann implants (4.1 mm x 12 mm) were tested up to five million cycles per ISO 14801: loaded at either 2 or 30 Hz in room air at 25 degrees C or normal saline at 37 degrees C (n=6 per group). Implant displacements/cycle were captured during all testing. Fracture-surface features were examined using scanning electron microscopy (n=12). Two complimentary methods were developed to estimate fatigue crack growth rates. RESULTS: Failures (bulk fracture) were found to be bi-modally distributed, either <350,000 cycles or >1.5 million cycles at both cycling rates. Following initial crack formation, fatigue crack growth required merely 1100-4200 cycles to failure. Initial crack pop-in was statistically more likely under 2 Hz than 30 Hz (chi(2), p<0.05) but testing in air and normal saline were equivalent in terms of likelihood of fracture versus runout (chi(2), p>0.6). On a microscopic level, fatigue crack growth rates appears to be similar at 2 and 30 Hz, but may be slower in the presence of saline versus dry at 2 Hz. SIGNIFICANCE: Implant failure under fatigue conditions involved "classic" damage mechanisms. Failure appears more likely at 2 Hz than 30 Hz for reasons that remain to be elucidated. Saline may enable chemically assisted crack growth involving grain boundaries during the stage of fatigue crack growth, but did not influence likelihood of failure. PMID- 19646748 TI - The use of a mutant TNF-alpha as a vaccine adjuvant for the induction of mucosal immune responses. AB - Safe and potent adjuvants are required in order to establish effective mucosal vaccines. Cytokines are promising adjuvants because they are human-derived safe biomaterial and display immune-modulating functions. We have created a mutant tumor necrosis factor-alpha (TNF-alpha), mTNF-K90R, that exhibits high bioactivity and resistance to proteases. Here, we examined the potential of mTNF K90R as a mucosal adjuvant. Initially, we showed that intranasal co administration of mTNF-K90R with ovalbumin (OVA) potently produced OVA-specific Immunoglobulin (Ig) G antibodies (Abs) in serum and IgA Abs both at local and distal mucosal sites compared to co-administration with wild-type TNF-alpha. The OVA-specific immune response was characterized by high levels of serum IgG1 and increased production of interleukin-4 (IL-4), IL-5 and IL-10 from splenocytes of immunized mice, suggesting a Th2 response. Furthermore, intranasal immunization with an antigen from influenza virus plus mTNF-K90R exhibited mucosal adjuvant activity for induction of both systemic and mucosal immune responses. Importantly, histopathological examination of the nasal tissue of mTNF-K90R treated mice detected no signs of toxicity. These findings suggest that mTNF-K90R is safe and effective mucosal adjuvant and this system may have potential application as a universal mucosal adjuvant system for mucosal vaccines improving the immune response to a variety of viral antigens. PMID- 19646749 TI - Intervertebral disc regeneration in an ex vivo culture system using mesenchymal stem cells and platelet-rich plasma. AB - An ex vivo degenerative intervertebral disc (IVD) organ culture system was established for the screening of disc regeneration agents. Its application was demonstrated by a stem cell and growth factor-based therapeutic approach for the amelioration of IVD. An ex vivo culture system using chymopapain to partially digest nucleus proposus tissue was established to mimic human IVD degeneration. This system was then used for the evaluation of different therapeutic regimens including: mesenchymal stem cell derived from eGFP-transgenic porcine (MSC-GFP), platelet-rich plasma (PRP) and MSC-GFP/PRP combined treatment, and confirmed in in vivo animal model. Chondrogenic-specific gene products including Col II and aggrecan were found upregulated and chondrogenic matrix deposition increased, as evident by sustained fluorescent signals over 4 weeks, in the MSC-GFP implanted group. Previously, we demonstrated in vitro stage-specific chondrogenesis of MSC by chondrocytic commitment. These same molecules upregulated for chondrogenesis were also observed in MSC-GFP group. PRP that has been shown to promote nucleus pulposus (NP) regeneration also resulted in significant increased levels of mRNA involved in chondrogenesis and matrices accumulation. The ex vivo IVD regeneration results were repeated and supported by in vivo porcine degenerative system. Moreover, the disc height index (DHI) was significantly increased in both in vivo MSC-GFP and PRP regeneration groups. Unexpectedly, the MSC-GFP/PRP combined therapy demonstrated an inclination towards osteogenesis in ex vivo system. The ex vivo degenerative IVD culture system described in this study could serve as an alternative and more accessible model over large animal model. This system also provides a high-throughput platform for screening therapeutic agents for IVD regeneration. PMID- 19646747 TI - Fluoride-containing adhesive: durability on dentin bonding. AB - OBJECTIVES: To evaluate (1) the influence of fluoride-containing adhesive on microtensile bond strength (microTBS) and (2) in vitro secondary caries inhibition at the resin-dentin interface after 24 h and 3 months water-storage and (3) the degree of conversion of different adhesives after 24h 1 month. METHODS: Flat surfaces of human teeth were ground and randomly assigned to six groups: (SBMP-24) Scotchbond Multi-Purpose control [SBMP], 24 h; (SE-24) SBMP etch and primer+Clearfil SE Bond adhesive [SE], 24h; (PB-24) SBMP etch and primer+Clearfil Protect Bond adhesive [PB], 24h; (SBMP-3) SBMP, 3 months; (SE-3) SBMP+SE, 3 months; and (PB-3) SBMP+PB, 3 months. To evaluate the effect of the adhesive resin alone, all teeth were etched with 35% phosphoric acid and primed with SBMP primer prior to applying the adhesive resin. Bonded assemblies were prepared for microTBS and stored in distilled water at 37 degrees C for 24h and 3 months. Sections of restored teeth of each group were exposed to an acid challenge. The specimens were sectioned, polished, and then observed with polarized light microscopy (PLM). Also, the degree of conversion (DC) of the adhesives was measured using Fourier Transform-Infrared spectroscopy (FTIR) at 24 h and 1 month, after polymerization. RESULTS: microTBS values obtained in MPa (24h/3m) were: (MP) 61.5+/-10.5/52.9+/-8.9, (SE) 55.5+/-11.8/55.6+/-13, and (PB) 50.3+/-9.9/61.0+/-13.6. For interface analysis by PLM, an inhibition zone (IZ) adjacent to the hybrid layer was created only when the fluoride-containing adhesive (PB) was used. The DC in percentage (24 h, 1 month) were: (MP) 60.5+/ 2.8/61.3+/-0.6, (SE) 69.6+/-1.3/70.7+/-0.05, and (PB) 53.1+/-0.4/58.3+/-1.6. SIGNIFICANCE: The fluoride-containing adhesive demonstrated significant increase of bond strength values after water-storage. This material was also able to create an acid inhibition zone in dentin. There was a significant increase of degree of conversion after 1 month only for PB. PMID- 19646750 TI - Laminar-flow immediate-overlay hepatocyte sandwich perfusion system for drug hepatotoxicity testing. AB - Drug hepatotoxicity testing requires in vitro hepatocyte culture to maintain the long-term and stable liver specific functions. We developed a drug testing platform based on laminar-flow immediate-overlay hepatocyte sandwich perfusion culture. The immediate-overlay sandwich (collagen-coated porous polymeric membrane as top overlay) protects the cells and integrity of the top collagen matrix from the impact of flow. A bioreactor was designed that allowed proper control of shear stress and mass transfer. The culture parameters such as the optimal perfusion initiation time and flow rate were systematically and mechanistically determined. The optimized system could re-establish hepatocyte polarity to support biliary excretion and to maintain other liver specific functions, such as the biotransformation enzyme activities, for two weeks that extended the usable in vitro hepatocyte-based drug testing window. When the perfusion cultured hepatocytes from days 7 or 14 were used for drug testing, the APAP-induced hepatotoxicity measurements were more sensitive and consistent over time than the static culture control, enabling further exploitations in large scale drug testing applications. PMID- 19646751 TI - Polyelectrolyte-coated gold nanorods and their interactions with type I collagen. AB - Gold nanorods (AuNRs) have unique optical properties for numerous biomedical applications, but the interactions between AuNRs and proteins, particularly those of the extracellular matrix (ECM), are poorly understood. Here the effects of AuNRs on the self-assembly, mechanics, and remodeling of type I collagen gels were examined in vitro. AuNRs were modified with polyelectrolyte multilayers (PEMs) to minimize cytotoxicity, and AuNRs with different terminal polymer chemistries were examined for their interactions with collagen by turbidity assays, rheological tests, and microscopy. Gel contraction assays were used to examine the effects of the PEM-coated AuNRs on cell-mediated collagen remodeling. Polyanion-terminated AuNRs significantly reduced the lag (nucleation) phase of collagen self-assembly and significantly increased the dynamic shear modulus of the polymerized gels, whereas polycation-terminated AuNRs had no effect on the mechanical properties of the collagen. Both polyanion- and polycation-terminated AuNRs significantly inhibited collagen gel contraction by cardiac fibroblasts, and the nanoparticles were localized in intra-, peri-, and extracellular compartments, suggesting that PEM-coated AuNRs influence cell behavior via multiple mechanisms. These results demonstrate the significance of nanoparticle ECM interactions in determining the bioactivity of nanoparticles. PMID- 19646752 TI - The control of cell adhesion and detachment on thin films of thermoresponsive poly[(N-isopropylacrylamide)-r-((3-(methacryloylamino)propyl)-dimethyl(3 sulfopropyl)ammonium hydroxide)]. AB - This paper describes the formation of poly(N-isopropylacrylamide) (PNIPAAm) and poly[(N-isopropylacrylamide)-r-((3-(methacryloylamino)propyl)-dimethyl(3 sulfopropyl)ammonium hydroxide)] (P(NIPAAm-r-MPDSAH)) films on a glass surface via surface-initiated, atom transfer radical polymerization as a cell-culture platform. The films of PNIPAAm with various thicknesses and of P(NIPAAm-r-MPDSAH) with various ratios of NIPAAm and MPDSAH are formed to investigate the behaviors of cell adhesion and detachment. In the case of the PNIPAAm-grafted glass surfaces, the optimal film thickness, achieving the effective control of both cell adhesion and detachment, is estimated to be 11-13 nm for NIH 3T3 fibroblast cells. The adhesion and detachment behaviors of NIH 3T3 fibroblast cells are further tuned by incorporating the hydrophilic and non-biofouling MPDSAH moiety into the PNIPAAm system. The cell adhesion and detachment are controlled best, when the ratio of NIPAAm and MPDSAH is 75:1 (NIPAAm:MPDSAH). PMID- 19646753 TI - Acute myeloid leukemia and ischemic heart disease successful first line treatment with clofarabine as single agent. PMID- 19646754 TI - Inflammatory myofibroblastic tumor of the bone marrow. PMID- 19646755 TI - Fludarabine, cyclophosphamide, mitoxantrone plus rituximab (FCM-R) in frontline CLL <70 Years. AB - Randomized trials demonstrated the superiority of chemoimmunotherapy over chemotherapy in the frontline treatment of CLL. Based on favorable experience with the addition of mitoxantrone (M) to fludarabine (F) plus cyclophosphamide (C), we designed a pilot study testing the combination of FCM plus rituximab (R). Thirty patients with previously untreated, symptomatic CLL, <70 years, and beta-2 microglobulin 2 units of RBC transfusions/month (65.0 vs. 35.3 months, respectively, P=0.02). Univariate statistical analysis identified the presence of disease progression to advanced MDS (chi(2)=26.4, P=0.001) and the administration of >1 or >2 units of RBC per month (chi(2)=15.9 and 14.6, respectively, P=0.001) as the most important parameters affecting survival. Nevertheless, even the administration of 1 RBC unit every 4-8 weeks had a significantly adverse impact on survival compared to non-transfused patients. Transfusion dependency itself did not affect disease progression as determined by the presence of multilineage dysplasia and adverse karyotype (expressed by the IM-1 or IM-2 score). Multivariate analysis confirmed disease progression towards leukemia as a highly significant independent variable affecting survival (P=0.0001). None of the other evaluated parameters had a significant impact on survival in patients with progressive disease. In non-transplanted patients without MDS progression, administration of >2 units of RBC transfusions/month was the only independent variable with adverse impact on survival in patients with unilineage erythroid dysplasia (P=0.02). In patients with multilineage dysplasia, only heavy transfusion dependency (>3TURBC/month) and serum ferritin >2000 microg/l adversely affected survival (P=0.03). Modification of the WPSS by replacing transfusion dependency with initial Hb level <80 g/l retained its prognostic relevance and allowed the identification of a potential risk subset of early MDS patients with intermediate and high scores and limited survival (<40% at 5 years) as early as at the time of diagnosis. Our results confirm a significant negative impact of transfusion dependency on survival in patients with early MDS without excess of blasts. The main risk subgroup is characterized by unilineage dysplasia limited to erythropoiesis in combination with dependency on >2TU of RBC per month. These patients usually have prolonged survival that leads to the development of heavy transfusion iron overload and they thus represent the most important target group for intensive chelation therapy. PMID- 19646757 TI - Differential activities of thalidomide and isoprenoid biosynthetic pathway inhibitors in multiple myeloma cells. AB - Thalidomide has emerged as an effective agent for treating multiple myeloma, however the precise mechanism of action remains unknown. Agents known to target the isoprenoid biosynthetic pathway (IBP) can have cytotoxic effects in myeloma cells. The interactions between thalidomide and IBP inhibitors in human multiple myeloma cells were evaluated. Enhanced cytotoxicity and induction of apoptosis were observed in RPMI-8226 cells. Examination of intracellular levels of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) revealed a wide variance in basal levels and response to IBP inhibitors. These findings provide a mechanism for the differential sensitivity of myeloma cells to pharmacologic manipulation of the IBP. PMID- 19646758 TI - Response of spring and summer riverine microbial communities following glyphosate exposure. AB - Seasonal variation in the response of riverine microbial communities to an environmentally relevant exposure to glyphosate (about 10 microgl(-1)) was assessed on natural communities collected in spring and summer, using two 14-day microcosm studies. The two experiments showed no major effect of glyphosate on algal biomass (chlorophyll a concentrations), bacterial activity ([(3)H]thymidine incorporation), or bacterial community diversity (16S PCR-TTGE detection). Effects on algal community composition (genus-level taxonomic identification) and eukaryotic community diversity (18S PCR-DGGE on <100 microm organisms) were only detected on the samples collected in summer. This work demonstrates that even if the effects of a short pulse of glyphosate (10 microgl(-1)) on riverine microorganisms seem to be limited, the responses of natural microbial communities to glyphosate exposure (and probably to other pesticide exposures) can clearly vary between the experiments, and can be seasonally dependent. PMID- 19646759 TI - Facilitating evaluations of innovative, competence-based assessments: creating understanding and involving multiple stakeholders. AB - Schools are held more responsible for evaluating, quality assuring and improving their student assessments. Teachers' lack of understanding of new, competence based assessments as well as the lack of key stakeholders' involvement, hamper effective and efficient self-evaluations by teachers of innovative, competence based assessments (CBAs). While evaluating two CBAs in Agricultural Vocational Education and Training institutions, two interventions in the evaluation process aimed to tackle these problems were examined: (1) starting with explicating the CBA in the teacher team using a concrete explication format and (2) qualitatively involving key stakeholders (i.e., teachers, students and employers) in the evaluation of the CBA through mixed-group interviews. Quantitative and qualitative analysis, as well as stakeholders' perceptions are used to find indications for the added value of these interventions for evaluation and further improvement of the CBAs. Results show that external facilitation is needed to make both interventions work. However, under this condition, explicating the CBA led to more complete, concrete and shared understandings of the actual CBA among teachers and mixed-groups interviews resulted in more concrete and elaborate evaluations of the CBAs' quality and more ideas for improvement. Both interventions can facilitate building up elaborate, more valid and concrete arguments for CBA quality in self-evaluations, certainly in the case of evaluating innovative assessments. Lessons learned will provide guidelines for incorporating the interventions into other evaluations of innovative programs. PMID- 19646760 TI - Comparison of penetrating keratoplasty performed with a femtosecond laser zig-zag incision versus conventional blade trephination. AB - PURPOSE: To evaluate visual outcomes and astigmatism in patients who underwent penetrating keratoplasty (PK) with 2 different incision techniques. DESIGN: Retrospective comparison of a consecutive surgical series. PARTICIPANTS: Fifty seven consecutive patients who underwent PK at the University of California, Irvine, academic referral practice. METHODS: A comparison of 49 eyes of 43 patients that underwent femtosecond laser zig-zag incision pattern PK versus 17 eyes of 14 patients that underwent conventional Barron suction trephination PK performed contemporaneously. All PKs were closed with an identical, 24-bite running nylon suture technique. MAIN OUTCOME MEASURES: Topographically determined astigmatism, best spectacle-corrected visual acuity (BSCVA), and recovery of full visual potential. RESULTS: The postoperative follow-up ranged from 1 to 12 months. There was a significant difference in average astigmatism between the groups at postoperative month 1 (P = 0.013) and 3 (P = 0.018). By month 3, the average astigmatism was 3 diopters (D) in the zig-zag group and 4.46 D in the conventional group. Of the patients with normal macular and optic nerve function (n(ZZ) = 32; n(con) = 14), a significant difference in BSCVA was seen at month 1 (P = 0.0003) and month 3 (P = 0.006) with 81% of the zig-zag group versus 45% of the conventional group achieving BSCVA of > or =20/40 by month 3 (P = 0.03). CONCLUSIONS: The femtosecond laser generated zig-zag-shaped incision results in a more rapid recovery of BSCVA and induces less astigmatism compared with conventional blade trephination PK. FINANCIAL DISCLOSURE(S): Proprietary commercial disclosure may be found after the references. PMID- 19646761 TI - Noncovalent interactions and coordination reactions in the systems consisting of copper(II) ions, aspartic acid and diamines. AB - Interactions of aspartic acid between 1,3-diaminopropane (tn) and 1,4 diaminobutane (Put) in metal-free systems as well as in the systems including copper(II) ions were studied. The composition and overall stability constants of the complexes formed were determined by the potentiometric method. The interaction centres and coordination sites were identified by spectroscopic methods. Each of the ligands has both negative and positive interaction centres. In aspartic acid such centres are carboxyl groups and amine group, while in the polyamine molecules - protonated amine groups. The centres are also the potential sites of the coordination of metal ions. Analysis of the logK(e) values of the adducts in the systems with polyamines has shown that the stability of the adducts in the metal-free systems depends on a significant degree on the steric factor that is the length of the polyamine. In some species the inversion effect, hitherto not reported in literature, was found. In the ternary systems including Cu(II) ions, only protonated species are formed, including molecular complexes with intermolecular interactions and metallation through the oxygen atoms of carboxyl groups and amine groups of the amino acid. In the adducts the protonated diamine is in the outer coordination sphere and is involved in noncovalent interactions with the anchoring CuH(Asp) or Cu(Asp) complexes. PMID- 19646762 TI - Pregnancy massage reduces prematurity, low birthweight and postpartum depression. AB - Pregnant women diagnosed with major depression were given 12 weeks of twice per week massage therapy by their significant other or only standard treatment as a control group. The massage therapy group women versus the control group women not only had reduced depression by the end of the therapy period, but they also had reduced depression and cortisol levels during the postpartum period. Their newborns were also less likely to be born prematurely and low birthweight, and they had lower cortisol levels and performed better on the Brazelton Neonatal Behavioral Assessment habituation, orientation and motor scales. PMID- 19646763 TI - CANMAT guidelines for depression: clear and user-friendly. PMID- 19646764 TI - Determinants of work outcome in schizophrenia and schizoaffective disorder: role of cognitive function. AB - Cognitive impairment has been reported to be more important than clinical symptomatology as a determinant of work and social function in schizophrenia. In a retrospective analysis of a group of 152 patients with chronic schizophrenia or schizoaffective disorder, performance on a battery of neuropsychological tests was contrasted in employed (32, 21.1%) versus unemployed subgroups. As predicted, neurocognitive performance was more important than clinical symptoms in predicting employment status. Among neurocognitive functions, verbal working memory (as reflected by the Consonant Trigram Test) was the strongest predictor of employment status. PMID- 19646765 TI - Preventing suicide and homicide in the United States: the potential benefit in human lives. AB - In order to assess the potential benefit in human lives if all geographical regions in the US (Northeast, South, Midwest, and West) achieved the lowest suicide and homicide rates observed within these regions, age-, race- and gender adjusted suicide and homicide rates for each of the four regions were calculated based on data retrieved using the Centers for Disease Control and Prevention database for 1999-2004. Data on known risk factors were retrieved from online sources. Overall suicide rates (10.42 per 100,000) exceeded homicide rates (6.97 per 100,000). Almost 27% (12,942 lives per year) of the 288,222 suicide and homicide deaths during the study period might have been avoided if all US regions achieved the mortality rate reported by the Northeast. A firearm was used in 55% of all suicides and 66% of all homicides. In the total estimate of avoidable deaths, firearm suicides (90%) and firearm homicides (75%) were overrepresented. The Northeast had the lowest access to firearms (20%) contrasted to almost double in the other regions, whereas greater firearms availability was related to unrestricted firearm legislation. Measures to restrict firearms availability should be highly prioritized in the public health agenda in order to achieve an impressive benefit in human lives. PMID- 19646766 TI - Abnormal transbilayer distribution of phospholipids in red blood cell membranes in schizophrenia. AB - Abnormalities in membrane lipids have been repeatedly reported in patients with schizophrenia. These abnormalities include decreased phosphatidylethanolamine (PE) and n-3 and n-6 polyunsaturated fatty acids in peripheral and brain cell membranes. The present study investigates the hypothesis of an overrepresentation of PE in the external leaflet of the red blood cell (RBC) membrane in patients with schizophrenia. The assumption was that this modification of PE asymmetrical distribution could explain the reported lipid membrane abnormalities. Phosphatidylethanolamine located in the external leaflet was specifically labeled in RBC membranes from 65 medicated patients with schizophrenia and 38 healthy controls. Labeled (external) and non-labeled (internal) PE and their respective fatty acid composition were analyzed by mass spectrometry. A significant increase in the percentage of external leaflet PE was found in RBC membranes in 63.1% of the patients. In this subgroup, a significant depletion of n-3 and n-6 polyunsaturated fatty acids from internally located PE was also observed. Age, sex and antipsychotic treatment were not associated with the transbilayer membrane distribution of PE. Potential mechanisms underlying these abnormalities may involve membrane phospholipid transporters or degradative enzymes involved in phospholipid metabolism. The anomaly described could characterize a subgroup among patients with schizophrenia. PMID- 19646767 TI - Glatiramer acetate improves regulatory T-cell function by expansion of naive CD4(+)CD25(+)FOXP3(+)CD31(+) T-cells in patients with multiple sclerosis. AB - Naturally occurring regulatory T-cells (Treg) exhibit impaired function in patients with relapsing-remitting multiple sclerosis (RRMS) resulting from an age inappropriate disproportion between prevalences of newly generated CD31 coexpressing naive Treg and long-lived memory Treg in the periphery. Recent evidence suggests that the immunomodulatory action of glatiramer acetate (GA) includes effects on Treg function and frequencies. We prospectively assessed suppressive activities and frequencies of Treg and Treg subsets in 15 patients with RRMS undergoing long-term therapy with GA. Treatment for up to six months reconstituted naive Treg and increased total Treg numbers with concomitant reversion of the Treg defect. PMID- 19646768 TI - Expression of alpha1-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis. AB - The study was undertaken to explore: i) the presence of alpha(1)-adrenoceptors (AR) on thymic lymphoid and non-lymphoid cells and ii) their putative role in T cell development. The expression of alpha(1)-AR on thymic cells was assessed using both immunohistochemistry and flow cytometric analyses, while their putative role in thymopoiesis was estimated by analyses of thymocyte proliferation and apoptosis, and major thymocyte subset distribution in adult rats subjected to 14-day-long treatment with the alpha(1)-AR blocker urapidil. The presence of alpha(1)-AR was demonstrated on both thymocytes (mainly less mature CD3(-) and CD3(low) cells) and thymic non-lymphoid cells (thymic epithelial cells and CD68-positive cells). Chronic treatment with urapidil increased the thymic weight and thymocyte number. The increase in thymocyte number might, at least partly, be related to an enhanced thymocyte proliferation. In addition, an altered thymocyte subset distribution was observed in these rats. The increase in the percentage of CD4+CD8+ double positive (DP) TCRalphabeta(-) thymocytes was accompanied by the reduction in that of CD4+CD8+ (DP) TCRalphabeta(low) cells, and divergent changes in the percentage of the most mature single positive (SP) TCRalphabeta(high) thymocytes. In urapidil administered rats the percentage of CD4+CD8- SP TCRalphabeta(high) thymocytes was increased, while that of the CD4-CD8+ TCRalphabeta(high) was reduced, compared with controls. In addition, proportions of CD4+CD25+RT6.1- and CD161+TCRalphabeta+ regulatory cells were increased. Collectively, the results indicate that alpha(1)-AR are involved in complex network of neuro-thymic and intrathymic communications that provide fine tuning of both conventional effector and regulatory T-cell development. PMID- 19646769 TI - Orbital lymphatic malformation showing the symptoms of orbital complications of acute rhinosinusitis in children: a report of 2 cases. AB - Orbital lymphatic malformations are benign cystic malformations of the lymphatic system. The present report shows two cases with symptoms of orbital complications of acute rhinosinusitis with proptosis, compressive optic neuropathy, loss of vision and cellulites in children. Magnetic resonance imaging (MRI) revealed a well-demarcated intraorbital mass with heterogeneous signal conformable with lymphatic malformation in both cases. A tumor extirpation was performed via lateral orbitotomy in both cases. Postoperatively the symptoms and especially the loss of vision improved completely. Histological analysis of the surgical specimens verified lymphatic malformations of the orbit. Orbital lymphatic malformations can mimic the symptoms of orbital complications of acute rhinosinusitis. The existence of lymphatic malformation should be considered in every orbital complication of rhinosinusitis in children. PMID- 19646770 TI - Blood homocysteine and risk of depression in the elderly. AB - We studied whether increased blood homocysteine is a predictor for incident depression in a population-based cohort aged >or=65. A total of 240 men and 217 women were identified at baseline and were assessed 4 years later for depression (Geriatric Depression Scale, GDS >or=10 or use of antidepressants). Risk of incident depression was estimated for the highest gender-specific tertile of baseline plasma homocysteine compared to the other tertiles combined in a reference group. As deficiencies of B(12) and folate are the main determinant of increased blood homocysteine in old age, serum concentrations of these vitamins were also measured. In women only, the highest homocysteine tertile was associated with incident depression. However, women with combined serum B(12)/folate deficiency had the highest blood homocysteine but also a lower depression risk than vitamin-replete women. In conclusion, the data only moderately support the hypothesis that blood homocysteine is a predictor of depression. PMID- 19646771 TI - Curing Germany's health care system by mandatory health premia? AB - A current proposal for reforming the German statutory health insurance suggests replacing earnings-related contributions by per-capita health premia. Combining a computable general equilibrium analysis with abundant empirical data on heterogenous household types, we investigate both the distributional and allocative impact of such a reform proposal. Our results indicate efficiency gains in terms of GDP and employment. This is because employed households of all skill types would increase their labour supply. Yet, while these household types would benefit from introducing health premia, others, such as those including pensioners or unemployed individuals, may suffer in terms of equivalent variations, despite tax-financed compensating transfers to these low-income households. Nonetheless, such transfers are an essential part of the reform proposal in order to mitigate redistributional effects. By comparing two different compensation schemes, we find that higher transfers go along with higher GDP and employment. This result may indicate that more redistribution comes at no efficiency costs. PMID- 19646772 TI - Abnormal retinal autoregulation is detected by provoked stimulation with flicker light in well-controlled patients with type 1 diabetes without retinopathy. AB - AIMS: Investigation of retinal vasodilation under flickering light is considered a dynamic analysis in contrast to the static analysis of retinal vessel equivalents (mean retinal vessel diameter). We investigated whether dynamic analysis apart from the static one in type 1 diabetic patients without diabetic retinopathy with well-controlled diabetes could lead to additional information regarding retinal autoregulation. METHODS: 18 normotensive type 1 diabetic patients without retinopathy and 19 healthy subjects were included. Diameter of retinal vessels was measured with Dynamic Vessel Analyzer. Changes in vasodilation are expressed as percent change over baseline values. RESULTS: HbA(1c) was 7.5+/-1.0% in diabetic patients. In arteries, the response to flicker was diminished in diabetic patients compared to healthy volunteers (p<0.023). In patients flicker stimulation increased arterial diameter by +2.7% in contrast to +4.4% in controls. Venous vessel diameter increased by +3.1% in diabetic individuals and by +5.3% in the control group (p<0.002). There were no differences in static analysis between both groups. CONCLUSIONS: Diabetic patients without retinopathy with relatively good glycemic control show reduced retinal vasodilation after flicker indicating dysfunction in retinal autoregulation. The use of provocation test in conjunction with static analysis could lead to additional information regarding abnormal retinal autoregulation. PMID- 19646774 TI - A semi-automatic algorithm for measurement of basement membrane thickness in kidneys in electron microscopy images. AB - In this paper, we present a semi-automatic algorithm for measurement of the glomerular basement membrane thickness in electron microscopy kidney images. A string of sparsely spaced points are manually inputted along the central line of the basement membrane (lamina densa) to be measured. The gaps between successive input points are lineally interpolated. A nonlinear mapping is applied to straighten the curved central line. Two distance functions of edges to the central line are constructed. The smooth envelope lines are obtained by repetitive applications of a linear low-pass filtering followed by a comparing and selecting process. The boundaries of the glomerular basement membrane are obtained from the inverse mapping of the envelope functions. The average basement membrane thickness is estimated as the ratio of the basement membrane area to the length of the central line. PMID- 19646773 TI - Frequent HCV reinfection and superinfection in a cohort of injecting drug users in Amsterdam. AB - BACKGROUND/AIMS: This study investigates the occurrence of HCV reinfection and superinfection among HCV seroconverters participating in the Amsterdam Cohort Studies among drug users from 1985 through 2005. METHODS: HCV seroconverters (n=59) were tested for HCV RNA at five different time points: the last visit before seroconversion (t=-1), the first visit after seroconversion (t=1), six months after (t=2) and one year after (t=3) seroconversion, and the last visit prior to November 2005 (t=4). If HCV RNA was present, part of the NS5B region was amplified and sequenced. Additional phylogenetic analysis and cloning was performed to establish HCV reinfection and superinfection. RESULTS: Multiple HCV infections were detected in 23/59 (39%) seroconverters; 7 had HCV reinfections, 14 were superinfected, and 2 had reinfection followed by superinfection. At the moment of HCV reinfection, 7/9 seroconverters were HIV-negative: persistent HCV reinfection developed in both HIV-positive cases but also in 4/7 HIV-negative cases. In total, we identified 93 different HCV infections, varying from 1 to 4 infections per seroconverter. Multiple HCV infections were observed in 10/24 seroconverters with spontaneous HCV clearance (11 reinfections, 3 superinfections) and in 13/35 seroconverters without viral clearance (20 superinfections). CONCLUSIONS: HCV reinfection and superinfection are common among actively injecting drug users. This might further complicate the development of an effective HCV vaccine. PMID- 19646775 TI - Molecular profile in body fluids in subjects enrolled in a randomised trial for lung cancer screening: Perspectives of integrated strategies for early diagnosis. AB - The aim of this study was to evaluate the diagnostic value of a grid of molecular genetic markers detectable in sputum and plasma samples of individuals enrolled in a lung cancer screening program with low-dose CT. Subjects enrolled in the baseline screening round of the ITALUNG (randomised) screening trial were invited to provide biological specimens for molecular analysis (1356 subjects out of 1406). We included 98 subjects in this analysis. There was a highly statistically significant difference between proportion of subjects with a negative baseline CT screening test who were positive to allelic imbalance, and those with a non calcified nodule (NCN greater than or equal to 5mm), the reason of recall for all suspects at CT Scan (chi(2): 22.9; P<0.0001). Allelic imbalance showed good performance for screening of NCN > or = 5 mm. In subjects recalled for NCN > or = 5 mm, LOH, K-ras mutations and high levels of free plasma DNA (>5ng/ml plasma) might be important to support clinical decision making for further follow-up and repeated screening. This study, embedded in an early diagnosis randomised trial, suggests that a multi-screening approach integrating imaging technique and a biomolecular marker panel is worth of further investigation. PMID- 19646777 TI - Psoriasis in patients with HIV infection: from the medical board of the National Psoriasis Foundation. AB - BACKGROUND: Patients with psoriasis and HIV infection often present with more severe and treatment-refractory cutaneous disease. In addition, many of these patients have significant psoriatic arthritis. Many effective drugs for psoriasis and psoriatic arthritis are immunosuppressive. Therefore, therapy for the HIV infected patient is more challenging, requiring both careful consideration of the potential risks and benefits of treatment and more fastidious monitoring for potential adverse events. OBJECTIVE: A task force of the National Psoriasis Foundation Medical Board was convened to evaluate treatment options. Our aim was to arrive at a consensus on therapy for psoriasis in patients with HIV. METHODS: A MEDLINE search of the terms "psoriasis," "psoriatic arthritis," "human immunodeficiency virus (HIV)," and "HIV skin diseases" was performed and literature relevant to HIV-associated psoriasis and the treatment of HIV associated psoriasis were reviewed. RESULTS: Based on a review of the literature, 29 reports were included as evidence in this review. Topical therapy is the first line recommended treatment for mild to moderate disease. For moderate to severe disease, phototherapy and antiretrovirals are the recommended first-line therapeutic agents. Oral retinoids may be used as second-line treatment. For more refractory, severe disease, cautious use of cyclosporine, methotrexate, hydroxyurea, and tumor necrosis factor-alpha inhibitors may also be considered. LIMITATIONS: There are no randomized, placebo-controlled trials evaluating the therapeutic efficacy or safety of treatments for patients with HIV-associated psoriasis; consequently, the evidence supporting this review consists mainly of case reports or case series. CONCLUSIONS: HIV-associated psoriasis is often refractory to traditional treatments. Treatment is challenging and requires careful consideration and should be tailored to patients based on disease severity and the input from an infectious disease specialist. Close monitoring for potential adverse events is necessary. PMID- 19646776 TI - Costs for 5-year lung cancer survivors in a tertiary care hospital in South Korea. AB - INTRODUCTION: As the population of patients with lung cancer increases, the expenditure on lung cancer treatment will become a huge economic burden in many countries. To support public health services for the treatment of lung cancer, the calculation of lung cancer-specific costs is important. METHODS: This study included newly diagnosed 76 lung cancer patients who had survived for at least 5 years after the diagnosis in a tertiary care hospital in South Korea. Direct medical costs were calculated from health care claims obtained from Seoul National University Hospital, which included out-of-pocket expenditures. Direct non-medical and indirect costs were calculated from national statistics. RESULTS: Mean direct medical costs, direct non-medical costs, and indirect costs amounted to $21,321, $6444 and $4943 respectively, based on an exchange rate of Korean Won 1200=US $1. The average cost for treatment of one lung cancer patient for all 5 years was $32,708. This constituted 44.7% of the per capita income during the same 5-year period. CONCLUSION: The economic burden of lung cancer treatment is significant in Korea. PMID- 19646778 TI - A prospective randomized trial of topical pimecrolimus for cetuximab-associated acnelike eruption. AB - BACKGROUND: Clinical trials addressing the acneiform rash associated with epidermal growth factor receptor inhibitors are lacking. OBJECTIVE: We evaluated the ability of topical pimecrolimus to reduce the severity of cetuximab-related facial rash. METHODS: In all, 24 patients with metastatic colorectal cancer with cetuximab facial rash received twice daily pimecrolimus application for 5 weeks to half of the face. At baseline, week 2, and week 5, a dermatologist performed facial lesion counts, patients reported perceived severity of rash-related symptoms, and standardized facial photographs were obtained for blinded evaluation of global rash severity. RESULTS: Treatment sides had greater decrease in lesion counts than observation sides of face at weeks 2 (P < .001) and 5 (P = .02). However, there were no significant differences in patients' assessment of symptoms and in review of facial photographs for rash severity between treatment and observation sides. LIMITATIONS: This study was not placebo controlled. CONCLUSIONS: Pimecrolimus application did not translate into clinically meaningful benefit for patients with cetuximab-related facial rash. PMID- 19646779 TI - Are biologics safe in the treatment of atopic dermatitis? A review with a focus on immediate hypersensitivity reactions. AB - Traditional systemic agents used for the treatment of atopic dermatitis (AD) are associated with significant potential toxicities and often do not provide adequate therapeutic responses. Biologic agents hold promise for a more targeted and less toxic approach to AD systemic therapy. Patients with AD, however, may theoretically be at higher risk of developing IgE-mediated reactions to protein based therapies. We performed a review of publications reporting the use of biologics in the treatment of AD. Of the 261 patients with AD identified who were exposed to a biologic therapy, no type-I immediate hypersensitivity reactions were reported. One infusion reaction occurred with infliximab and two patients had "mild respiratory difficulty" with interferon-gamma. Thrombocytopenia may occur at a higher rate than expected in patients treated with efalizumab. Combined, these data support the safety of biologics in the treatment of AD and the further development of new biologics for this population should be encouraged. PMID- 19646780 TI - The safety of nanosized particles in titanium dioxide- and zinc oxide-based sunscreens. AB - Given the increasing incidence and prevalence of skin cancer, dermatologists are more frequently recommending sunscreens to their patients. However, the safety of titanium dioxide and zinc oxide nanosized particles in the majority of sunscreens has come under scrutiny from governments and the general public. We sought to characterize the use, safety, and regulatory state of nanosized particles in titanium dioxide and zinc oxide in sunscreens based on studies and position statements from 1980 to 2008. Although we found no evidence of significant penetration of titanium dioxide and zinc oxide nanosized particles beyond the stratum corneum, further studies must be done to simulate real-world conditions particularly in sunburned skin and under ultraviolet exposure. PMID- 19646781 TI - Livedo, dementia, thrombocytopenia, and endotheliitis without antiphospholipid antibodies: seronegative antiphospholipid-like syndrome. AB - We report a 51-year-old woman who presented with dementia, livedo racemosa, polyarthralgia, mild renal insufficiency, proteinuria, and thrombocytopenia. Cutaneous and renal biopsy specimens both showed an identical specific occlusive arteriolopathy consistent with Sneddon syndrome and antiphospholipid syndrome. However, no antiphospholipid antibodies were detected and we, therefore, diagnosed seronegative antiphospholipid-like syndrome. We discuss the nosology of this entity and its association with non-antiphospholipid antibody-related Sneddon syndrome. The common denominator of Sneddon syndrome and antiphospholipid syndrome with or without antiphospholipid antibodies seems to be the endothelial damage and occlusive arteriolopathy. Skin biopsy is useful to confirm the diagnosis of seronegative antiphospholipid-like syndrome. PMID- 19646782 TI - Treatment of MSSA bacteraemia in renal units: do we need specific guidelines? PMID- 19646783 TI - A randomised prospective comparison of Rotecno versus new Gore occlusive surgical gowns using bacterial air counts in ultraclean air. AB - Ultraclean air (UCA) in operating theatres is defined as <10 colony-forming units (cfu)/m(3). The current European standards for surgical gowns are contained in EN13795 but these do not include containment of bacterial dispersal as a standard test. A trial in 2003 found that there were bacterial air counts of 1 cfu/m(3) with Rotecno gowns and 0.5 cfu/m(3) with body exhaust suits in total knee arthroplasty (TKA). This study compared bacterial air counts using Rotecno gowns with a new type of occlusive gown made from Gore liquid-proof fabric, which were superior to the Rotecno gowns on standard EN13795 laboratory testing. Fifty-six joint replacements were allocated randomly either to Rotecno or to Gore gowns with stratification into TKA, total hip arthroplasty (THA) or revision THA. Airborne bacteria were collected from within 30 cm of the wound for the first 10 min of surgery using a Casella slit sampler. The new gowns were associated with higher air counts (3.7 cfu/m(3)) than the Rotecno gowns (1.2 cfu/m(3)) (P<0.001). Three of the Gore samples exceeded the clean air standard of 10 cfu/m(3). In TKA patients, the existing Rotecno gowns, now many years old, had higher air counts (2.0 cfu/m(3)) than in the 2003 trial (0.8 cfu/m(3)) (P<0.001). The new gowns were superior in standard laboratory tests but not superior at preventing airborne bacterial dispersal. Rotecno gowns, although many years old, were still effective. This study highlights the importance of testing new materials in a clinical environment with UCA; in-vitro testing alone is probably not an adequate assessment. PMID- 19646784 TI - Disinfection efficacy against parvoviruses compared with reference viruses. AB - Some virus species can resist harsh environmental conditions, surviving on surfaces for long periods with the possibility of being transmitted to susceptible hosts. Studies are limited on the efficacy of disinfectants against viruses dried onto surfaces, in particular, with the identification of new pathogenic non-enveloped viruses that are expected to have high resistance to disinfection, such as parvoviruses. In this study a range of commonly used biocides, including heat, was tested against porcine parvovirus (PPV), minute virus of mice (a parvovirus), poliovirus type 1, adenovirus type 5, and vaccinia virus dried onto surfaces. PPV was the most resistant species identified, since many biocides generally considered as effective against non-enveloped viruses and used for high level disinfection demonstrated limited activity. Ethanol had poor activity against all non-enveloped viruses. Effectiveness against these viruses may be important in preventing nosocomial transmission of emerging pathogenic species such as bocavirus and other parvoviruses. This work confirms the need to validate disinfection products against viruses dried onto surfaces and demonstrates that PPV is a particularly resistant surrogate. PMID- 19646785 TI - Active warming systems to maintain perioperative normothermia in hip replacement surgery: a therapeutic aid or a vector of infection? AB - Various reliable body heat-regulating systems have been designed and developed with the aim of maintaining an adequate body temperature in the course of major surgery. This is crucial to avoid the onset of potentially severe complications that are especially serious in elderly and debilitated subjects. Among these systems, the Bair Hugger blanket has demonstrated excellent efficacy. However, some reports in the literature have suggested that the use of such devices can increase the risk of nosocomial infections, particularly surgical wound infections. The aim of this study was to assess the risk of contamination of the surgical site correlated to the use of the Bair Hugger blanket during hip replacement surgery. To this end, the level of bacterial contamination of the air in the operating theatre was quantified with and without the use of the Bair Hugger, during the course of 30 total non-cemented hip implants performed in patients with osteoarthritis. Sampling was done both in the empty theatre and during surgical procedures, in different zones around the operating table and on the patient's body surface. Statistical analysis of the results demonstrated that the Bair Hugger system does not pose a real risk for nosocomial infections, whereas it does offer the advantage of preventing the potentially very severe consequences of hypothermia during major orthopaedic surgery. In addition, monitoring patients over the six months following the operation allowed us to exclude a later manifestation of a nosocomial infection. PMID- 19646786 TI - Poor utility of MRSA screening to predict staphylococcal species in orthopaedic implant infections. PMID- 19646787 TI - Role of bacterial biofilms in chronic non-healing ulcers and effect of subinhibitory concentrations of Betadine and hydrogen peroxide on biofilms. PMID- 19646788 TI - Hospital-wide surveillance of catheter-related bloodstream infection: from the expected to the unexpected. AB - Catheter-related bloodstream infections (CRBSIs) are among the most frequent healthcare-associated infections and cause considerable morbidity, mortality, and resource use. CRBSI surveillance serves quality improvement, but is often restricted to intensive care units (ICUs). We conducted a four-month prospective cohort study of all non-cuffed central venous catheters (CVCs) to design an efficient CRBSI surveillance and prevention programme. CVCs were assessed on a daily basis for ward exposure time, care parameters, and the occurrence of laboratory-confirmed CRBSI. Overall, 248 patients with 426 CVCs accounted for 3567 CVC-days (median: 5) and 15 CRBSI episodes. CVCs were inserted by anaesthetists, ICU physicians and internists in 45%, 47%, and 8% of cases, respectively. CVC utilisation rates for intensive care, internal medicine, non abdominal surgery and abdominal surgery were 29.8, 3.8, 1.7 and 4.9 per 100 patient-days, respectively. Fourteen percent of patients changed wards while having a CVC in place, so spending CVC-days at risk within multiple departments. CRBSI incidence densities for ICU, internal medicine, surgery and abdominal surgery were 5.6, 1.9, 2.4 and 7.7 per 1000 CVC-days at risk, respectively. In a univariate Cox proportional hazards model, the high CRBSI rate in abdominal surgery was associated with longer CVC duration, frequent use of parenteral nutrition and CVC insertion by anaesthetists. CRBSI numbers were insufficient to perform a multivariate analysis. Our surveillance revealed similar CRBSI rates in both ICU and non-ICU departments, and when frequent ward transfers occurred. Hospital-wide CRBSI surveillance is advisable when a large proportion of CVC-days occur outside the ICU. PMID- 19646790 TI - [User satisfaction: a tool to evaluate the results of the care service in a primary care emergency department]. PMID- 19646789 TI - [Implicit memory in normal aging and in Alzheimer's disease: a cognitive neuroscience approach]. PMID- 19646792 TI - [Hospital antibiotic use and resistance: a relationship that is difficult to measure and complex to interpret]. PMID- 19646791 TI - [Analysis of the doubts of primary care doctors]. AB - OBJECTIVE: To determine the doubts, their number and type that doctors have during routine clinics in primary care, as well as establishing methods that may be used to resolve them. DESIGN: Prevalence study. SETTING: Health centres in the provinces of A Coruna and Lugo. PARTICIPANTS: A total of 81 primary care doctors, selected by simple random sampling. The sample size was calculated to obtain a total of 500 doubts. Only 2 doctors refused to take part. MEASUREMENTS: Number and types of doubts. Systems used to resolve them and when they were carried out. RESULTS: A mean of 1.7 doubts were detected (95% confidence interval; 1.59-1.82) for every 10 patients, of which 92% were seen as clinical problems. The 12 most frequent doubts made up 75% of all those that arose, with the interpretation of a clinical sign and treatment indications being the most common. In 51.6% of cases an attempt was made to resolve the doubt either during the consultation or during that day. A total of 35.7% of the doubts led to new appointments, either in the clinic itself or as a referral (23%). A total of 81.5% of those surveyed never used the Internet during the consultation and only 6.2% did this daily or often. CONCLUSIONS: The number of doubts that primary care doctor has is relatively small (1.7 for every 10 patients). The most common way to try to resolve them is by referral to a specialist. PMID- 19646794 TI - [Fever and abdominal pain in a patient with multiple hepatic masses]. PMID- 19646793 TI - [Hepatitis C outbreak in an oncology ward]. AB - INTRODUCTION: Study of an outbreak of hepatitis C virus (HCV) infection. METHODS: Case-control study. Odds ratios for various risk factors were studied in patients with acute hepatitis C and an appropriate control group. RESULTS: Seven cases and 46 controls were included. Implantation of a central catheter was found to be an independent risk factor for hepatitis C (OR=35; 95% CI: 16.0-62.0). CONCLUSION: Inadequate manipulation of central catheters with heparinized saline solution, which was likely to be HCV-contaminated, caused the outbreak. PMID- 19646795 TI - [Impact of morbidity, resource use and costs on maintenance of remission of major depression in Spain: a longitudinal study in a population setting]. AB - OBJECTIVE: To determinate the impact of comorbidity, resource use and cost (healthcare and lost productivity) on maintenance of remission of major depressive disorder in a Spanish population setting. METHODS: We performed an observational, prospective, multicenter study using population databases. The inclusion criteria were age > or = 18 years, first depressive episode between January 2003 and March 2007, with antidepressant prescription >60 days after the first prescription and a follow-up of at least 18 months (study: 12 months; continuation: 6 months). Two subgroups were considered: patients with/without remission. MAIN MEASURES: sociodemographic data, episodes, resource utilization bands, healthcare costs (direct) and lost productivity (indirect). Logistic regression and analysis of covariance (Bonferroni correction) were used for analysis. RESULTS: A total of 4,572 patients were analyzed and 54.6% (95% confidence interval: 53.2-56.0%) were considered in remission. Patients in remission were younger (52.6 vs. 60.7), with a lower proportion of women (71.7% vs. 78.2%), and showed less general morbidity (6.2 vs. 7.7 episodes/year), lower resource utilization bands/year (2.7 vs. 3.0), fewer sick leave days (31.0 vs. 38.5) and shorter treatment duration (146.6 vs. 307.7 days); p<0.01. Lack of remission was associated with fibromyalgia (odds ratio [OR]=2.5), thyroid alterations (OR=1.3) and hypertension (OR=1.2); p<0.001. The annual healthcare cost was euro706.0 per patient in remission vs. euro1,108.3 without remission (p <0.001) and lost productivity was euro1,631.5 vs. euro2,024.2, respectively (p <0.001). CONCLUSIONS: Patients not achieving remission showed higher morbidity, resources use, healthcare costs and, especially, productivity losses. PMID- 19646796 TI - [Induced abortion in immigrant women in a urban setting]. AB - OBJECTIVE: Given the new reality of foreign immigration in Barcelona, the aim is to describe the rate of legal abortion in the city in the years 2005 and 2006 according to women's place of origin. METHODS: The rates of legal abortion of women residing in Barcelona were computed by country of origin and age group, grouping 2005 and 2006 and using data from the abortions register and the municipal continuous register. RESULTS: Immigrant women from developing countries had a combined abortion rate of 25.4 per 1,000 women of 15-49 years, surpassing that of native women (8.9 per 1,000). The relationship is maintained in all age groups. Rates vary substantially between countries (range 5.8-82.0). CONCLUSION: In Barcelona, immigrant women from disadvantaged countries have the highest rates of abortion. Socioeconomic level and knowledge and practices in the use of contraception could generate these differences. PMID- 19646797 TI - Antioxidant and antibacterial studies of arylazopyrazoles and arylhydrazonopyrazolones containing coumarin moiety. AB - A series of novel 1-(4-methylcoumarinyl-7-oxyacetyl)-3,5-dimethyl 4(arylazo)pyrazoles and 1-(4-methylcoumarinyl-7-oxyacetyl)-3-methyl-4 (substituted phenyl) hydrazono-2-pyrazolin-5-ones were synthesised and evaluated for antibacterial and antioxidant activities. Compounds 3b, 3g, 5b, 5d and 5g showed good antibacterial activity and compound 5e was found to be the most active antioxidant in the series, and thus represent a new class of promising lead compounds. PMID- 19646798 TI - A golden age? Response to paper "Writing-up and writing-as: rediscovering nursing scholarship by Gary Rolfe". PMID- 19646799 TI - Access to and support for continuing professional education amongst Queensland nurses: 2004 and 2007. AB - This paper reports on the findings of a prospective exploratory study related to nurses' self-reports of continuing professional education access and support. The data were gathered by two postal surveys undertaken in 2004 and 2007 each which sampled 3000 nurses of the 30,000 nurse members of the industrial body - Queensland Nurses' Union. The response rates were 44.9% and 39.7% for 2004 and 2007, respectively. Over 85% of the nurses reported they had access to continuing professional education activities. However, it is apparent that the majority of these activities are either partially or completely self-funded. Further, between 2004 and 2007 the amount of financial support provided by employers for continuing education and training activities has decreased significantly. While there were differences between 2004 and 2007, the major barrier to be able to attend continuing professional education were financial (could not afford the fee involved; could not afford to take unpaid leave to attend). Another major barrier in both 2004 and 2007 was having the time to undertake the activity. Analysis for differences between nurses in different geographical locations indicated that distance remains a major barrier for nurses in rural and remote areas. These quantitative findings were supported by the qualitative findings on nurses' work where 'education and training' was, overall, the fifth highest ranked issue requiring further attention. PMID- 19646800 TI - Dynamics of mercury fluxes and their controlling factors in large Hg-polluted floodplain areas. AB - Environmental pollution by mercury (Hg) is a considerable environmental problem world-wide. Due to the occurrence of Hg volatilization from their soils, floodplains can function as an important source of volatile Hg. Soil temperature and soil water content related to flood dynamics are considered as important factors affecting seasonal dynamics of total gaseous mercury (TGM) fluxes. We quantified seasonal variations of TGM fluxes and conducted a laboratory microcosm experiment to assess the effect of temperature and moisture on TGM fluxes in heavily polluted floodplain soils. Observed TGM emissions ranged from 10 to 850 ng m(-2) h(-1) and extremely exceeded the emissions of non-polluted sites. TGM emissions increased exponentially with raised air and soil temperatures in both field (R(2): 0.49-0.70) and laboratory (R(2): 0.99) experiments. Wet soil material showed higher TGM fluxes, whereas the role of soil water content was affected by sampling time during the microcosm experiments. PMID- 19646801 TI - Effects of exercise training on noninvasive cardiac measures in patients undergoing long-term hemodialysis: a randomized controlled trial. AB - BACKGROUND: Noninvasive screening studies may identify hemodialysis (HD) patients at increased risk of sudden cardiac death. Interventions that improve the findings of such screening studies may reduce sudden cardiac death. STUDY DESIGN: Randomized and controlled clinical trial. SETTING & PARTICIPANTS: 59 HD patients were randomly assigned to an exercise training group (group A; 30 patients) or control group (group B; 29 patients). INTERVENTION: Group A participated in a 10 month supervised exercise training program during the HD sessions (3 times weekly). OUTCOMES: Each risk factor separately and the composite risk score. Patients were considered high risk according to the criteria (aerobic capacity: peak oxygen consumption [Vo(2)peak] < or = 14 mL/kg/min, left ventricular ejection fraction < or = 30%, SD of normal RR intervals [SDNN] < or = 70 milliseconds, positive T-wave alternans, or positive late potentials). Statistical analysis included a 2-group comparison of change scores and analysis of covariance adjusting for baseline. MEASUREMENTS: At entry and end of the study, Vo(2)peak and left ventricular ejection fraction were estimated, heart rate variability was calculated (measurement of SDNN, mean RR intervals), and the ratio between low- (LF) to high-frequency (HF) components (LF/HF) and late potentials and T-wave alternans were detected. RESULTS: Baseline measurements were similar between the 2 groups. At follow-up, 9 patients from group A and 20 from group B (P = 0.003) were considered high risk. The change in number of risk markers over time was significantly different between groups (-0.5 +/- 0.7 in group A versus 0.07 +/- 0.3 in group B; P < 0.001). Additionally, the change in Vo(2)peak over time was 3.5 +/- 3.2 in group A and -0.2 +/- 3.5 mL/kg/min in group B (P < 0.001), left ventricular ejection fractions were 3.4% +/- 3.9% and 0.2% +/- 7.7% (P < 0.05), SDNNs were 12.6 +/- 16.3 and -1.1 +/- 10.2 milliseconds (P < 0.001), and LF/HF ratios were 0.3 +/- 0.4 and -0.1 +/- 0.3 (P < 0.001), respectively. Change in numerical score of the signal-averaged electrocardiogram also was found to be statistically different (P < 0.05) between groups. LIMITATIONS: Clinical outcomes, including survival, were not assessed. CONCLUSIONS: Exercise training improves aerobic capacity and ameliorates some indicators of risk of sudden cardiac death in HD patients. PMID- 19646802 TI - Expressing yourself: a feminist analysis of talk around expressing breast milk. AB - Recent feminist analyses, particularly from those working within a poststructuralist framework, have highlighted a number of historically located and contradictory socio-cultural constructions and practices which women are faced with when negotiating infant feeding, especially breastfeeding, within contemporary western contexts. However, there has been little explicit analysis of the practice of expressing breast milk. The aim of this article is to explore the embodied practice of expressing breast milk. This is done by analysing, from a feminist poststructuralist perspective, discourse surrounding expressing breast milk in sixteen first time mothers' accounts of early infant feeding. Participants were recruited from a hospital in the South Midlands of England. The data are drawn from the first phase of a larger longitudinal study, during which mothers kept an audio diary about their breastfeeding experiences for seven days following discharge from hospital, and then took part in a follow-up interview. Key themes identified are expressing breast milk as (i) a way of managing pain whilst still feeding breast milk; (ii) a solution to the inefficiencies of the maternal body; (iii) enhancing or disrupting the 'bonding process'; (iv) a way of managing feeding in public; and (v) a way to negotiate some independence and manage the demands of breastfeeding. Links between these and broader historical and socio-cultural constructions and practices are discussed. This analysis expands current feminist theorising around how women actively create the 'good maternal body'. As constructed by the participants, expressing breast milk appears to be largely a way of aligning subjectivity with cultural ideologies of motherhood. Moreover, breastfeeding discourses and practices available to mothers are not limitless and processes of power restrict the possibilities for women in relation to infant feeding. PMID- 19646803 TI - The relationship between household income and childhood respiratory health in the United Kingdom. AB - Growing empirical evidence on the association between household income and adverse child health outcomes has generated mixed results with some North American studies showing a significant inverse relationship and some British studies identifying a much weaker association. We use data from the rich UK Millennium Cohort Study (MCS) dataset and check the robustness of these recent findings by focusing on the impact of household income on adverse childhood respiratory outcomes (i.e. asthma and wheezing). We also identify pathways, such as mother's child-health-related behaviours, parental health and grandparental socioeconomic status, through which income might influence child health. Our econometric strategy is to use, both in a cross-sectional and in a panel data context, detailed information in the MCS dataset to directly account for as many potential confounding factors as possible that might bias the income-child health nexus. Overall our results show that household income has a weak direct effect on child health after we control for potential mechanisms that mediate the income child health association. We argue that our evidence should inform government health and broader fiscal policies aimed at reducing health inequalities in childhood. PMID- 19646804 TI - On using Vernier acuity to assess magnocellular sensitivity. AB - A recent study [Keri, S., & Benedek, G. (2009). Visual pathway deficit in female fragile x premutation carriers: A potential endophenotype. Brain and Cognition, 69, 291-295] has found Vernier acuity deficiencies together with contrast sensitivity defects consistent with a magnocellular deficit in female fragile x premutation carriers. This may appear to support the notion that Vernier acuity may serve as a test of magnocellular sensitivity. However, Vernier acuity deficiencies have been reported in other conditions (e.g., schizophrenia, amblyopia and cortical visual impairment) where there is little evidence for magnocellular deficits. The observation that Vernier acuity deficiencies can occur without magnocellular deficits indicates that Vernier acuity is not a reliable test of magnocellular sensitivity. PMID- 19646806 TI - Adiponectin suppresses tumorigenesis in Apc(Min)(/+) mice. AB - Recent reports have shown that adiponectin has a suppressive effect on various types of malignancy. In order to clarify the role of adiponectin in colorectal carcinogenesis, we examined the effect of exogenous administration of adiponectin on intestinal polyp formation in C57BL/6J-Apc(Min)(/+) mice, which possess a point mutation in the Apc gene. And we found that adiponectin treatment significantly decreased the number of adenomatous polyps, especially polyps larger than 2mm in diameter, in the small intestine. Two major receptors for adiponectin, AdipoR1 and AdipoR2, were expressed in adenomatous polyps, and their expression levels were not altered by adiponectin injection. In conclusion, adiponectin suppresses the growth of intestinal adenomas in the Apc(Min)(/+) mice. Increasing the adiponectin level may be a new strategy for the prevention of colorectal cancer at an early step of carcinogenesis. PMID- 19646805 TI - Effectiveness of simplified chest compression-only CPR training program with or without preparatory self-learning video: a randomized controlled trial. AB - OBJECTIVES: To evaluate the effectiveness of 1-h practical chest compression-only cardiopulmonary resuscitation (CPR) training with or without a preparatory self learning video. METHODS: Participants were randomly assigned to either a control group or a video group who received a self-learning video before attending the 1 h chest compression-only CPR training program. The primary outcome measure was the total number of chest compressions during a 2-min test period. RESULTS: 214 participants were enrolled, 183 of whom completed this study. In a simulation test just before practical training began, 88 (92.6%) of the video group attempted chest compressions, while only 58 (64.4%) of the control group (p<0.001) did so. The total number of chest compressions was significantly greater in the video group than in the control group (100.5+/-61.5 versus 74.4+/ 55.5, p=0.012). The proportion of those who attempted to use an automated external defibrillator (AED) was significantly greater in the video group (74.7% versus 28.7%, p<0.001). After the 1-h practical training, the number of total chest compressions markedly increased regardless of the type of CPR training program and inter-group differences had almost disappeared (161.0+/-31.8 in the video group and 159.0+/-35.7 in the control group, p=0.628). CONCLUSIONS: 1-h chest compression-only CPR training makes it possible for the general public to perform satisfactory chest compressions. Although a self-learning video encouraged people to perform CPR, their performance levels were not sufficient, confirming that practical training as well is essential. (UMIN000001046). PMID- 19646807 TI - The pharmacological NFkappaB inhibitors BAY117082 and MG132 induce cell arrest and apoptosis in leukemia cells through ROS-mitochondria pathway activation. AB - A growing body of evidence suggests the inhibition of NFkappaB as a strategy to induce cell death in tumor cells. In this work, we evaluated the effects of the pharmacological NFkappaB inhibitors BAY117082 and MG132 on leukemia cells apoptosis. BAY117082 and MG132 presented potent apoptotic effects compared to inhibitors of MAPKs, EGFR, PI3K/Akt, PKC and PKA signaling pathways. Non-tumor peripheral blood cells were insensitive to BAY117082 and MG132 apoptotic effects. BAY117082 and MG132-induced apoptosis was dependent on their ability to increase ROS as a prelude to mitochondria membrane potential (MMP) depolarization, permeability transition pore opening and cytochrome c release. Antioxidants blocked MG132 and BAY117082 effects on ROS, MMP and cell death. Although apoptotic markers as phosphatidylserine externalization, chromatin condensation and sub-G1 were detected in BAY117082-treated cells, caspases activation did not occur and apoptosis was insensitive to caspase inhibitors, suggesting a caspase independent mechanism. In contrast, MG132 induced classical apoptosis through ROS mitochondria and subsequent caspase-9/caspase-3 activation. At sub-apoptotic concentrations, BAY117082 and MG132 arrested cells in G2/M phase of the cell cycle and blocked doxorubicin-induced NFkappaB, which sensitized doxorubicin resistant cells. Data suggest that the NFkappaB inhibitors MG132 and BAY117082 are potential anti-leukemia agents. PMID- 19646808 TI - Mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) in carcinogenesis. AB - The cation-independent mannose-6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R) is a multifunctional receptor. It is involved in a variety of cellular processes which become dysregulated in cancer. Its tumor suppressor role was recognized a long time ago. However, due to its multifunctionality, it is not easy to understand the extent of its relevance to normal cellular physiology. Accordingly, it is even more difficult understanding its role in carcinogenesis. This review presents critical and focused highlights of data relating to M6P/IGF2R, obtained during more than 25 years of cancer research. PMID- 19646809 TI - SOCS6, down-regulated in gastric cancer, inhibits cell proliferation and colony formation. AB - Members of the suppressor of cytokine-induced signaling (SOCS) family are negative regulators of cytokine signaling pathways. By mRNA differential display, we showed that SOCS6 was frequently down-regulated in gastric cancer (GC). Our data showed that allelic loss and promoter hypermethylation may account for the major mechanisms leading to SOCS6 inactivation. Ectopic expression of SOCS6 suppressed cell growth and colony formation, in part through eliciting intrinsic apoptotic pathway, accompanied with decreased mitochondrial membrane potential. Taken together, this study provides molecular and functional data supporting the importance of loss-of-function of SOCS6 as a frequent event in gastric tumorigenesis. PMID- 19646810 TI - Ultrasound-induced apoptosis in the presence of Sonazoid and associated alterations in gene expression levels: a possible therapeutic application. AB - Ultrasound (US) has been shown to induce apoptosis and cell lysis in cancer cells. In this study, we report on the potential of using Sonazoid, a new echo contrast agent, that is chemically more stable and US-resistant in combination with US in cancer therapy. The biological effects and their mechanisms in the presence or absence of ultrasonic exposure in vitro were investigated. In addition, the impact of the agent on the expression levels of genes responsive to US was studied using global-scale microarrays and computational gene expression analysis tools. Our results show that the combination led to enhanced cell killing in the presence of 1 MHz acoustic field. The apoptosis induction was shown to be mediated by the mitochondrial pathway. The occurrence of US-induced DNA damage was also observed. Despite these findings, the agent at concentrations similar to those clinically used can be considered as well tolerated. Furthermore, Sonazoid enhanced expression of genes that related to apoptosis and are responsive to US, although it alone had almost no effect. These results indicate the potential of Sonazoid for US contrast enhancement as well as the possibility of its use in US-aided therapies. PMID- 19646812 TI - Simultaneous preconcentration of copper, zinc, cadmium, and nickel in water samples by cloud point extraction using 4-(2-pyridylazo)-resorcinol and their determination by inductively coupled plasma optic emission spectrometry. AB - A procedure for simultaneous separation/preconcentration of copper, zinc, cadmium, and nickel in water samples, based on cloud point extraction (CPE) as a prior step to their determination by inductively coupled plasma optic emission spectrometry (ICP-OES), has been developed. The analytes reacted with 4-(2 pyridylazo)-resorcinol (PAR) at pH 5 to form hydrophobic chelates, which were separated and preconcentrated in a surfactant-rich phase of octylphenoxypolyethoxyethanol (Triton X-114). The parameters affecting the extraction efficiency of the proposed method, such as sample pH, complexing agent concentration, buffer amount, surfactant concentration, temperature, kinetics of complexation reaction, and incubation time were optimized and their respective values were 5, 0.6 mmol L(-1), 0.3 mL, 0.15% (w/v), 50 degrees C, 40 min, and 10 min for 15 mL of preconcentrated solution. The method presented precision (R.S.D.) between 1.3% and 2.6% (n=9). The concentration factors with and without dilution of the surfactant-rich phase for the analytes ranged from 9.4 to 10.1 and from 94.0 to 100.1, respectively. The limits of detection (L.O.D.) obtained for copper, zinc, cadmium, and nickel were 1.2, 1.1, 1.0, and 6.3 microg L(-1), respectively. The accuracy of the procedure was evaluated through recovery experiments on aqueous samples. PMID- 19646811 TI - Cathepsin G-mediated enhanced TGF-beta signaling promotes angiogenesis via upregulation of VEGF and MCP-1. AB - Transforming growth factor (TGF)-beta signaling makes a significant contribution to the pathogenesis of breast cancer bone metastasis. In other tumor types, TGF beta has been shown to promote tumor vascularity. Here, we report that inhibition of TGF-beta significantly reduces microvessel density in mammary tumor-induced bone lesions, mediated by decreased expression of both vascular endothelial growth factor (VEGF) and monocyte chemotactic protein (MCP)-1, both known angiogenic factors. Cathepsin G upregulation at the tumor-bone interface has been linked to increased TGF-beta signaling, and we also report that inhibition of Cathepsin G reduced tumor vascularity, as well as VEGF and MCP-1 expression. PMID- 19646813 TI - High effective adsorption of organic dyes on magnetic cellulose beads entrapping activated carbon. AB - Maghemite (gamma-Fe(2)O(3)) nanoparticles were created with a submerged circulation impinging stream reactor (SCISR) from FeCl(3) x 6H(2)O and FeCl(2).4H(2)O by using precipitation followed by oxidation. Subsequently, by blending cellulose with the Fe(2)O(3) nanoparticles and activated carbon (AC) in 7 wt% NaOH/12 wt% urea aqueous solution pre-cooled to -12 degrees C, millimeter scale magnetic cellulose beads, coded as MCB-AC, was fabricated via an optimal dropping technology. The cellulose beads containning Fe(2)O(3) nanoparticles exhibited sensitive magnetic response, and their recovery could facilitate by applying a magnetic field. The adsorption and desorption of the organic dyes on MCB-AC were investigated to evaluate the removal of dyes (methyl orange and methylene blue) with different charges from aqueous solution. Their adsorption kinetics experiments were carried out and the data were well fitted by a pseudo second-order equation. The results revealed that the MCB-AC sorbent could efficiently adsorb the organic dyes from wastewater, and the used sorbents could be recovered completely. Therefore, we developed a highly efficient sorbent, which were prepared by using simple and "green" process, for the applications on the removal of hazardous materials. PMID- 19646814 TI - Adsorption of platinum(IV) and palladium(II) from aqueous solution by thiourea modified chitosan microspheres. AB - The chitosan microparticles were prepared using the inverse phase emulsion dispersion method and modified with thiourea (TCS). TCS was characterized by scanning electron microscope (SEM), the Fourier transform infrared (FT-IR) spectra, sulfur elemental analysis, specific surface area and pore diameter. The effects of various parameters, such as pH, contact time, initial concentration and temperature, on the adsorption of Pt(IV) and Pd(II) by TCS were investigated. The results showed that the maximum adsorption capacity was found at pH 2.0 for both Pt(IV) and Pd(II). TCS can selectively adsorb Pt(IV) and Pd(II) from binary mixtures with Cu(II), Pb(II), Cd(II), Zn(II), Ca(II), and Mg(II). The adsorption reaction followed the pseudo-second-order kinetics, indicating the main adsorption mechanism of chemical adsorption. The isotherm adsorption equilibrium was well described by Langmuir isotherms with the maximum adsorption capacity of 129.9 mg/g for Pt(IV) and 112.4 mg/g for Pd(II). The adsorption capacity of both Pt(IV) and Pd(II) decreased with temperature increasing. The negative values of enthalpy (DeltaH degrees ) and Gibbs free energy (DeltaG degrees ) indicate that the adsorption process is exothermic and spontaneous in nature. The adsorbent was stable without loss of the adsorption capacity up to at least 5 cycles and the desorption efficiencies were above 95% when 0.5 M EDTA-0.5M H2SO4 eluent was used. The results also showed that the preconcentration factor for Pt(IV) and Pd(II) was 196 and 172, respectively, and the recovery was found to be more than 97% for both precious metal ions. PMID- 19646815 TI - Fluoride sorption by nano-hydroxyapatite/chitin composite. AB - In this study the fluoride adsorption potential of novel nano hydroxyapatite/chitin (n-HApCh) composite was explored. The sorbent was characterized using FTIR studies. The effects of pH, interfering anions and contact time were studied. The sorption data obtained under optimized conditions were subjected to Langmuir and Freundlich isotherms. Kinetic studies indicate that the rate of sorption of fluoride on n-HApCh composite follows pseudo-second order and pore diffusion patterns. n-HApCh composite possesses higher defluoridation capacity (DC) of 2840 mg F(-)kg(-1) than nano-hydroxyapatite (n HAp) which showed a DC of 1296 mg F(-) kg(-1). Field trials were conducted with the sample collected from a nearby fluoride endemic area. PMID- 19646816 TI - Biogenic amine depletion causes chronic muscular pain and tactile allodynia accompanied by depression: A putative animal model of fibromyalgia. AB - Fibromyalgia is a prevalent and burdensome disorder characterized by chronic widespread pain and complex comorbid symptoms. To develop better treatments for pain-centered fibromyalgia symptoms, there is still a need for animal models which mimic the features of fibromyalgia patients. In the present study, we have established a fibromyalgia animal model by utilizing a never-before-published pharmacological effect of reserpine. Repeated administration of reserpine (1mg/kg s.c., once daily, for three consecutive days) causes a significant decrease in the muscle pressure threshold and tactile allodynia, which are sustained for 1week or more in both male and female rats. This treatment regimen decreases the amount of biogenic amines (dopamine, norepinephrine, and 5-hydroxytryptamine) in the spinal cord, thalamus, and prefrontal cortex, which are deeply involved in pain signal processing. It also significantly increases immobility time in the forced swim test, which is indicative of depression, a common comorbid symptom of fibromyalgia. Pregabalin, duloxetine, and pramipexole significantly attenuated the reserpine-induced decrease in muscle pressure threshold, but diclofenac did not. The validity of the use of this reserpinized animal as a fibromyalgia model is demonstrated from three different aspects, i.e., face validity (manifestation of chronic pain and comorbid symptoms), construct validity (dysfunction of biogenic amine-mediated central nervous system pain control is involved), and predictive validity (similar responses to treatments used in fibromyalgia patients). This animal model is expected to contribute to the better understanding of fibromyalgia pathophysiology and the evaluation of drugs, especially those which would activate biogenic amine system. PMID- 19646818 TI - Association of BoLA DRB3 and DQA1 alleles with susceptibility to Neospora caninum and reproductive outcome in Quebec Holstein cattle. AB - The BoLA DRB3 and DQA1 genes are part of the major histocompatibility complex (MHC) class II in cattle. These genes are highly polymorphic and have been associated with resistance to several diseases, such as mastitis, Bovine Leukemia Virus (BLV) and dermatophilis. Sequenced based typing of these genes has been carried out extensively from blood samples; however it is often impractical or expensive to obtain such samples. Repositories of well-characterized serum from cattle are readily available in many veterinary research facilities. This paper reports a retrospective analysis of BoLA class II genotypes of cattle obtained from stored serum samples from Holstein cattle from Quebec dairy farms, which were obtained as part of a previous study on bovine neosporosis. It was possible to genotype 56 cattle with known infection status for Neospora caninum. We identified 14 different DRB3 and 10 different DQA1 alleles in this population. The allele frequency distribution was consistent with previously studied cattle populations, and alleles known to be associated with BLV and mastitis were present. No association was found between allele frequency distribution of DRB3 or DQA genes and infection with N. caninum. However, an association of allele DRB3*1001 and allele DRB3*2703 with resistance and susceptibility to pregnancy loss, irrespective of infection status, was identified. PMID- 19646817 TI - Electroacupuncture suppresses capsaicin-induced secondary hyperalgesia through an endogenous spinal opioid mechanism. AB - Central sensitization, caused either by tissue inflammation or peripheral nerve injury, plays an important role in persistent pain. An animal model of capsaicin induced pain has well-defined peripheral and central sensitization components, thus is useful for studying the analgesic effect on two separate components. The focus of this study is to examine the analgesic effects of electroacupuncture (EA) on capsaicin-induced secondary hyperalgesia, which represents central sensitization. Capsaicin (0.1%, 20 microl) was injected into the plantar side of the left hind paw, and foot withdrawal thresholds in response to von Frey stimuli (mechanical sensitivity) were determined for both primary and secondary hyperalgesia in rats. EA (2 Hz, 3 mA) was applied to various pairs of acupoints, GB30-GB34, BL40-BL60, GV2-GV6, LI3-LI6 and SI3-TE8, for 30 min under isoflurane anesthesia and then the effect of EA on mechanical sensitivity of paw was determined. EA applied to the ipsilateral SI3-TE8, but to none of the other acupoints, significantly reduced capsaicin-induced secondary hyperalgesia but not primary hyperalgesia. EA analgesic effect was inhibited by a systemic non specific opioid receptor (OR) antagonist or an intrathecal mu- or delta-OR antagonist. EA analgesic effect was not affected by an intrathecal kappa-OR antagonist or systemic adrenergic receptor antagonist. This study demonstrates that EA produces a stimulation point-specific analgesic effect on capsaicin induced secondary hyperalgesia (central sensitization), mediated by activating endogenous spinal mu- and delta-opioid receptors. PMID- 19646820 TI - How are lifetime polytobacco users different than current cigarette-only users? Results from a Canadian young adult population. AB - Current cigarette smoking combined with ever use of other tobacco products (lifetime polytobacco use) is important to examine as users may be at greater risk for illicit drug use, nicotine addiction, and adverse health outcomes. We determined estimates and patterns of lifetime polytobacco use and conducted multivariable analyses to determine demographic, family and friend, psychosocial, and lifestyle factors associated with use among a sample of Canadian young adults. Overall prevalence was 36.3% for current cigarette use; 10.1% for current cigarette use only and 26.2% for lifetime polytobacco use. Among polytobacco users, current cigarette use and ever cigar use was most frequent (67.2%). For males, the final model contained demographic, family and friends, and lifestyle factors. For females, the final model also included psychosocial factors. Illicit drug use was the strongest significant predictor for lifetime polytobacco use among males. We found gender specific differences when comparing lifetime polytobacco users to current cigarette-only users, in particular; male lifetime polytobacco users were more likely to use drugs and alcohol. Interventions focusing on individual substances should consider addressing combinations of use. PMID- 19646819 TI - Effect of vagus nerve stimulation on thermal injury in rats. AB - OBJECTIVE: To investigate the effects of vagus nerve stimulation on haemodynamics, pulmonary histopathology, arterial blood gas and pro-inflammatory responses to thermal injury. INTERVENTIONS: Forty-eight male Sprague-Dawley (SD) rats were randomly divided into six equal groups: normal control (NC) group; thermal injury (TEM) group subjected to 40% total body surface area (%TBSA) third degree thermal injury; vagotomy (VGX) group subjected to bilateral cervical vagotomy after thermal injury; electrical stimulation (STM) group subjected to bilateral cervical vagotomy plus the left vagus nerve trunk electrical stimulation (5 V, 2 ms and 1 Hz) after thermal injury; the antagonist of muscarinic acetylcholine receptor (MRA) group administrated with atropine (0.1 mg kg(-1)) before electrical stimulation and the antagonist of nicotinic acetylcholine receptor (NRA) group administrated with hexamethonium (10 mg kg( 1)) before electrical stimulation. MEASUREMENTS AND MAIN RESULTS: The haemodynamics, histopathology of lung tissue, arterial blood gas, lactic acid, tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) levels were measured. Vagus nerve electrical stimulation not only significantly increased the mean arterial pressure (MAP) and heart rate (HR), but also decreased the infiltration of inflammatory cells into interstitial and alveolar spaces after thermal challenge and attenuated TNF-alpha and IL-6 production. Hexamethonium pre treatment significantly reversed the effects of vagal electrical stimulation, but atropine administration before electrical stimulation had no such effects. CONCLUSIONS: Direct electrical stimulation of the vagus nerve might produce therapeutic effect on thermal injury. The effect may be realised by limiting the inflammatory response via nicotinic acetylcholine receptors in rats. PMID- 19646821 TI - A new method for inducing bone tissue regeneration: negative pressure membrane technology. AB - With the advances of medical molecular biology in recent years, our understanding of the process of fracture healing has deepened and the development of new technologies for guided bone regeneration has emerged. Here, with the recent discoveries of membrane-based as well as negative pressure-induced tissue regeneration, we suggest an innovative method of bone regeneration using negative pressure membrane technology. Polymeric membrane materials are implanted around the fracture site using in vitro devices. The container of the membrane between the fracture ends can induce effective negative pressure in order to attain both membrane and negative pressure-induced bone regeneration. The key to this technology is the use of semi-permeable membranes, which prevent the collapse of membranous structures and the loss of a variety of bone marrow cells and larger proteins during the induction of negative pressure. PMID- 19646822 TI - Histological patterns and associated PSA levels for prostatic adenocarcinoma following brachytherapy. AB - Changes in morphologic patterns over a time course following radiation and their corresponding PSA levels were investigated. A total of 60 patients with prostatic adenocarcinoma treated with brachytherapy between 1993 and 2003, who had at least one positive post-radiation biopsy, were evaluated for their morphologic patterns as well as the associated PSA levels. A total of 86 positive post-radiation biopsies were performed. There were 17 patients with more than 1 positive post radiation biopsy and 43 patients with single positive biopsy. Among the 17 with more than 1 positive biopsy, the morphologic patterns of treatment effect were commonly followed by patterns without treatment effect on subsequent biopsies. The morphology without treatment effect followed by treatment effect was infrequent. Furthermore, over a time course, the later the positive post radiation biopsy, the much more common the morphologic pattern without treatment effect was observed. Compared to the morphologic pattern with treatment effect, the morphology without treatment effect was associated with a significantly higher PSA level (mean 0.69 versus 2.78 ng/ml, p<0.05). An increase in the Gleason's score in recurrent carcinoma was also noted in 14% of the cases. Multiple factors were likely involved in the variability of the changes in post radiation morphologic patterns. A new neoplastic process was particularly considered in some of our cases, which may merit clinical attention. The significant difference in PSA levels between carcinomas without treatment effect and those with treatment effect also suggested a post-radiation variation of tumor biology and a potential role of these patterns in monitoring and managing the patients treated with brachytherapy. PMID- 19646823 TI - Obligate basal cell component in salivary oncocytoma facilitates distinction from acinic cell carcinoma. AB - The differential diagnosis between benign salivary oncocytoma (ONC) and low-grade malignant acinic cell carcinoma (ACC) can be difficult due to a significant histomorphological overlap of the structural and cytological presentation of both tumor types. To the best of our knowledge a comprehensive study comparing (immuno )histological markers in cases of difficult differential diagnosis between ONC and ACC has not yet been performed. We investigated a panel of different immunohistochemical (CK5/6, CK14, CK7, CK18, p63 and Ki67) and histochemical (PAS, alpha-amylase) markers in 12 cases of ONC and 19 cases of ACC. The statistically significant stronger expression of CK7 in ONC and stronger expression of PAS and alpha-amylase in ACC in routine practice each is hampered by a pronounced overlap between both tumor groups. The obligate presence of an additional small basal cell component in all cases of ONC, demonstrable with p63 and CK5/6, enables a straightforward distinction from ACC, being constantly devoid of a basal cell component. Unexpectedly, CK14 is not a suitable marker for a reliable proof of these basal cells. The detection of this basal cell component in ONC in routine Hematoxylin-eosin stain is difficult and in some cases not possible; therefore, immunohistochemistry with p63 or CK5/6 is recommended for selected cases. PMID- 19646824 TI - Whole-field simultaneous integrated-boost intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma. AB - PURPOSE: To retrospectively review the outcomes of our patients with newly diagnosed nondisseminated nasopharyngeal carcinoma treated with intensity modulated radiotherapy using a whole-field simultaneous integrated-boost technique. METHODS AND MATERIALS: A total of 175 patients treated with WF-SIB between mid-2004 and 2005 were eligible for study inclusion. The distribution of disease by stage was Stage IA in 10.9%, Stage IIA in 2.3%, Stage IIB in 21.7%, Stage III in 41.1%, Stage IVA in 14.9%, and Stage IVB in 9.1%. Of the 175 patients, 2 (1.2%), 10 (5.7%), and 163 (93.1%) had World Health Organization type I, II, and III histologic features, respectively. We prescribed 70 Gy, 60 Gy, and 54 Gy delivered in 33 fractions within 6.5 weeks at the periphery of three planning target volumes (PTV; PTV70, PTV60, and PTV54, respectively). Of the 175 patients, 46 with early T-stage disease received a brachytherapy boost, and 127 with advanced local or regional disease received chemotherapy. RESULTS: The median follow-up period was 34 months. The overall 3-year local failure-free survival, regional failure-free survival, distant failure-free survival, and overall survival rate was 93.6%, 93.3%, 86.6%, and 87.2%, respectively. Cox regression analysis showed Stage N2-N3 disease (p = .029) and PTV (p = .024) to be independent factors predicting a greater risk of distant failure and poor overall survival, respectively. Grade 3 acute mucositis/pharyngitis occurred in 23.4% of patients, and Stage T4 disease was the only significant predictor of mucositis/pharyngitis (p = .021). CONCLUSION: Whole-field simultaneous integrated boost intensity-modulated radiotherapy with a dose >70 Gy achieved excellent locoregional control, without an excess incidence of severe, acute mucositis/pharyngitis, in the present study. Strategies for using such highly conformal treatment for patients with a large tumor and late N-stage disease are potential areas of investigation for future studies. PMID- 19646825 TI - Accurate prediction of pathological rectal tumor response after two weeks of preoperative radiochemotherapy using (18)F-fluorodeoxyglucose-positron emission tomography-computed tomography imaging. AB - PURPOSE: To determine the optimal time point for repeated (18)F fluorodeoxyglucose-positron emission tomography (PET)-CT imaging during preoperative radiochemotherapy (RCT) and the best predictive factor for the prediction of pathological treatment response in patients with locally advanced rectal cancer. METHODS AND MATERIALS: A total of 30 patients referred for preoperative RCT treatment were included in this prospective study. All patients underwent sequential PET-CT imaging at four time points: prior to therapy, at day 8 and 15 during RCT, and shortly before surgery. Tumor metabolic treatment responses were correlated with the pathological responses by evaluation of the tumor regression grade (TRG) and the pathological TN (ypT) stage of the resected specimen. RESULTS: Based on their TRG evaluations, 13 patients were classified as pathological responders, whereas 17 patients were classified as pathological nonresponders. The response index (RI) for the maximum standardized uptake value (SUV(max)) on day 15 of RCT was found to be the best predictive factor for the pathological response (area under the curve [AUC] = 0.87) compared to the RI on day 8 (AUC = 0.78) or the RI of presurgical PET imaging (AUC = 0.66). A cutoff value of 43% for the reduction of SUV(max) resulted in a sensitivity of 77% and a specificity of 93%. CONCLUSIONS: The SUV(max)-based RI calculated after the first 2 weeks of RCT provided the best predictor of pathological treatment response, reaching AUCs of 0.87 and 0.84 for the TRG and the ypT stage, respectively. However, a few patients presented with peritumoral inflammatory reactions, which led to mispredictions. Exclusion of these patients further enhanced the predictive accuracy of PET imaging to AUCs of 0.97 and 0.89 for TRG and ypT, respectively. PMID- 19646826 TI - Molecular biological characterization of avian poxvirus strains isolated from different avian species. AB - Fifteen strains of Avipoxvirus from different avian species were isolated and molecular biologically characterized. Most strains did not produce evident pocks on the chorioallantoic membranes of commercial and specific-pathogen free embryonated chicken eggs where, on the contrary, microscopic signs of viral growth were always detected. Polymerase chain reaction of highly conserved P4b gene was positive for all cases confirming to be a reliable diagnostic method for Avipoxvirus. Sequencing of these amplicons confirmed most strains clustered either with Fowlpox virus or with Canarypox virus whereas a possible new clade could be hypothesized for one strain from Japanese quail. Classification of Avipoxvirus strains by amplification of the newly identified locus fpv140 revealed major limitations as only five samples were positive. These results underline the importance to undertake similar studies on higher numbers of Avipoxvirus isolates and on wider genomic regions of this large viral group. PMID- 19646827 TI - Development and use of real-time PCR to detect and quantify Mycoplasma haemocanis and "Candidatus Mycoplasma haematoparvum" in dogs. AB - Two canine haemoplasma species have been recognised to date; Mycoplasma haemocanis (Mhc), which has been associated with anaemia in splenectomised or immunocompromised dogs, and "Candidatus Mycoplasma haematoparvum" (CMhp), recently described in an anaemic splenectomised dog undergoing chemotherapy. The study aim was to develop quantitative real-time PCR assays (qPCRs) incorporating an endogenous internal control to detect Mhc and CMhp and to apply these assays to DNA samples extracted from canine blood collected in Northern Tanzania (n=100) and from dogs presented to a Trinidadian veterinary hospital (n=185). QPCRs specific for Mhc and CMhp were designed using 16S rRNA gene sequence data, and each was duplexed with an assay specific for canine glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The assays detected < or =10 copies of a sequence-specific haemoplasma plasmid per reaction and neither assay showed cross-reactivity with 10(6) copies of the sequence-specific plasmid from the non-target canine haemoplasma species. Nineteen of the 100 Tanzanian samples (19%) were positive for Mhc alone and one (1%) was dually infected. One Trinidadian sample was negative for canine GAPDH DNA and was excluded from the study. Of the 184 remaining Trinidadian samples, nine (4.9%) were positive for Mhc alone, five (2.7%) for CMhp alone, and two (1.1%) dually infected. This is the first report of canine haemoplasma qPCR assays that use an internal control to confirm the presence of amplifiable sample DNA, and their application to prevalence studies. Mhc was the most commonly detected canine haemoplasma species. PMID- 19646828 TI - Time-lapse resistivity surveys over simulated clandestine graves. AB - The aim of this study was to develop a better understanding of how electrical resistivity surveys can be used to locate clandestine graves. Resistivity surveys were conducted regularly over three simulated clandestine graves containing a pig cadaver, no cadaver and a pig cadaver wrapped in tarpaulin, respectively. Additionally, soil and groundwater samples were collected from two more simulated graves outside the survey area. The grave containing a pig cadaver was detectable from a low resistivity anomaly in the survey data. Groundwater data suggest that the resistivity anomaly associated with the surveyed pig grave was caused by a localised increase in groundwater conductivity. Wrapping a cadaver was found to initially change the resistivity response of a grave to a high resistivity anomaly. Resistivity surveys did not detect the disturbed soil in the grave that did not contain a cadaver. Although soil samples showed grave soil to be more porous than undisturbed soil, the lack of response from the grave that did not contain a cadaver suggests that disturbed soil was not responsible for the resistivity anomalies observed in this study. Resistivity surveys successfully detected all graves containing cadavers throughout the study, whilst also showing the potential to eliminate the need for mass excavation in a genuine search. PMID- 19646829 TI - Determination of malathion levels and its effect on the development of Chrysomya megacephala (Fabricius) in South China. AB - The present study determines the concentration of Malathion in rabbit tissues and Dipteral larvae feeding on those tissues. Malathion was found in all muscle and liver samples of the test rabbit, as well as larvae fed on it. Samples from the control rabbit and pupae from all colonies were negative for Malathion. Correlations were found between administered dosage, tissue concentrations and younger or prepuparial larvae. Effects of Malathion on the development rate of Chrysomya megacephala (Fabricius) were also reported. C. megacephala is the most common fly species found on corpses in South China during the early stages of decomposition. Significant differences in larval growth rate were both observed among the colonies fed on muscle and liver. The presence of Malathion in both muscle and liver appears to retard the normal growth rate of C. megacephala in larval stage. Larvae from all colonies fed on tissues from rabbits treated with Malathion were smaller and attained maximum length later than those from the control colony. Duration of the larval and pupal stages was both significantly prolonged for larvae on tissues from rabbit receiving Malathion than those from the control colony. The difference of the duration of the larval and pupal stages together from the muscle colonies would alter the postmortem interval estimation by up to 36h. As for liver colonies, it would alter the postmortem interval estimation by up to 28h. A significantly different duration of the larval and pupal stages from the muscle colonies would alter a postmortem estimate by up to 28h relative to the liver colonies. PMID- 19646830 TI - Sexual dimorphism of ossified costal cartilage. Radiograph scan study on Caucasian men and women (Czech population). AB - The aim of our study was to evaluate differences between males and females based on patterns of costal cartilage ossification and also with respect to ageing. We provided diagnosis of ossifications from two files of radiograms. The first group consisted of 1044 chest and abdominal radiograms of patients (537 men and 507 women), ranging in age from 10 to 95 years obtained by using conventional X-ray technique. The second group was a set of 55 radiograms of chest plate fragments of cadavers (29 men and 26 women) aged from 15 to 98, obtained by using soft X ray imaging in the skiagraphic-skiascopic unit. Ossifications were identified in more than 80% of the cases. They appear in puberta and their occurrence increases with age. The peripheral ossification pattern, typically the male pattern, is characterized by subperichondral deposits which contour the upper and lower margin of cartilage. The female, central lingual ossification pattern, is characterized by the pyramidal (lingual) shape of ossifications with a peak towards the sternum. The existence of another typical female central globular model of ossification was not confirmed in the file of cadavers. Central globular foci were found in both sexes (62% of women and 34% of men) from the 3rd decade. In the sample of Caucasian men and women (Czech population) we detected a frequent occurrence of costal cartilage ossification. Peripheral and central lingual patterns are highly predictive for sex determination. Globular loci of ossifications can be used for age estimation. PMID- 19646831 TI - Forensic evidence in apparel fabrics due to stab events. AB - Stab injuries and fatalities have been reported to be the most common crimes of violence in several countries, particularly in those where access to firearms is restricted [J.M. Taupin, F.-P. Adolf, J. Robertson, Examination of damage to textiles, in: J. Robertson, M. Grieve (Eds.), Forensic Examination of Fibres, CRC Press, United States of America, 1999, pp. 65-87; A.C. Hunt, R.J. Cowling, Murder by stabbing, Forensic Sci. Int. 52 (1991) 107-112; D.A. Rouse, Patterns of stab wounds: a six year study, Med. Sci. Law 34 (1994) 67-71]. Analysis of damaged apparel may provide important information about the cause of death and the events leading up to and after the victim's final moments [M.T. Pailthorpe, N.A.G. Johnson, The private forensic scientist and the criminal justice system, in: D. Biles, J. Vernon (Eds.), Private Sector and Community Involvement in the Criminal Justice System: Conference Proceedings, vol. 23, Australian Institute of Criminology, Wellington, 1994, 231-240]. A high proportion of stab wounds occur in the chest and as this area is generally clothed many sharp force cases involve damage to fabrics [J.M. Taupin, F.-P. Adolf, J. Robertson, Examination of damage to textiles, in: J. Robertson, M. Grieve (Eds.), Forensic Examination of Fibres, CRC Press, United States of America, 1999, pp. 65-87; A.C. Hunt, R.J. Cowling, Murder by stabbing, Forensic Sci. Int. 52 (1991) 107-112; D.A. Rouse, Patterns of stab wounds: a six year study, Med. Sci. Law 34 (1994) 67-71]. The structural stabilisation and degradation of fabric due to laundering significantly alters fabric properties [S.E. Gore, R.M. Laing, C.A. Wilson, D.J. Carr, B.E. Niven, Standardizing a pre-treatment cleaning procedure and effects of application on apparel fabrics, Text. Res. J. 76 (2006) 455-464], yet the effect of such on severance morphology does not appear to have been investigated. In this work the effect of blade type (hunting knife, kitchen knife, screwdriver) on new and laundered apparel fabrics was investigated. Two approaches were used (i) a human participant trial, and (ii) guided drop testing (using an impact rig). Force-time plots from the human participant trials were matched to those from the impact rig. Information on severance morphology was obtained using visual analysis techniques. Blades could be differentiated and directionality estimated by observing differences in severance shape and size, the degree of fabric distortion, the position of severed yarn ends, loop snippets, curled yarns, planar array and the morphology of fractured fibres. Fabric construction had a visible effect on severance morphology. Pre-impact degradation via laundering hindered the ability to link fractured fibre ends to a source of damage by altering morphology and increasing the variability. The correlation between blade height and severance length was weak, attributed to elastic deformation and recovery. The impact rig was a valuable tool in the reconstruction of textile damage. Damage was consistent when inflicted using a human participant trial and the impact rig, although more variable in the former. The advantage of the impact rig lies in the ability to produce a severance typical of the blade in question, under controlled conditions, in a reproducible manner. PMID- 19646832 TI - Metformin plus pentoxifylline versus prescriptive diet in non-alcoholic steatohepatitis (NASH): a randomized controlled pilot trial. PMID- 19646833 TI - [Magnetic resonance spectroscopy: a new standard for quantification of liver steatosis?]. PMID- 19646834 TI - Liver biopsy in alcoholic and non-alcoholic steatohepatitis patients. AB - Alcoholic liver disease and non-alcoholic liver disease share a similar histological spectrum that starts with 'simple' steatosis, and may be accompanied by inflammation. Alcoholic steatohepatitis and non-alcoholic steatohepatitis (NASH) are progressive forms of alcoholic liver disease and non-alcoholic liver disease, respectively, and can evolve into cirrhosis. The currently accepted minimum diagnostic criteria for steatohepatitis include steatosis, lobular inflammation and hepatocellular injury, but not fibrosis. Steatosis involving more than 5% of hepatocytes is required for the diagnosis of non-alcoholic fatty liver disease, but is not necessary for the diagnosis of alcoholic liver disease. Lobular inflammation is usually mild and frequently consists of a mixed, acute and chronic, inflammatory cell infiltrate composed of neutrophils and mononuclear cells. The presence of large numbers of neutrophils favors an alcoholic etiology. Hepatocellular injury in fatty liver disease usually occurs in the form of ballooning, but it can also present as apoptotic (acidophilic) bodies and lytic necrosis. The characteristic pattern of fibrosis in non-cirrhotic steatohepatitis is pericellular/perisinusoidal and is the result of deposition of collagen in the space of Disse. In both alcoholic steatohepatitis and NASH, sinusoidal collagen formation is the result of hepatic stellate cell activation that, in NASH, has been correlated with the grade of steatosis and fibrosis. PMID- 19646835 TI - Oxygen-enhanced MRI vs. quantitatively assessed thin-section CT: pulmonary functional loss assessment and clinical stage classification of asthmatics. AB - PURPOSE: The purpose of this study was to prospectively compare the efficacy of oxygen-enhanced MR imaging (O(2)-enhanced MRI) and CT for pulmonary functional loss assessment and clinical stage classification of asthmatics. MATERIALS AND METHODS: O(2)-enhanced MRI, CT and %FEV(1) measurement were used 34 consecutive asthmatics classified into four stages ('Mild Intermittent [n=7]', 'Mild Persistent [n=8], 'Moderate Persistent [n=14]' and 'Severe Persistent [n=5]'). Relative enhancement ratio maps for every subject were generated, and determine mean relative enhancement ratios (MRERs). Mean lung density (MLD) and the airway wall area (WA) corrected by body surface area (WA/BSA) were also measured on CT. To compare the efficacy of the two methods for pulmonary functional loss assessment, all indexes were correlated with %FEV(1). To determine the efficacy of the two methods for clinical stage classification, all parameters for the four clinical stages were statistically compared. RESULTS: %FEV(1) showed fair or moderate correlation with all parameters (0.15<=r(2)<=0.30, p<0.05). WA, WA/BSA and MRER of the 'Severe Persistent' group were significantly larger than those of 'Mild Intermittent' and 'Mild Persistent' groups (p<0.05), and MRER of the 'Moderate Persistent' group significantly lower than that of the 'Mild Intermittent' group (p<0.05). CONCLUSION: O(2)-enhanced MRI is as effective as CT for pulmonary functional loss assessment and clinical stage classification of asthmatics. PMID- 19646836 TI - Imaging parameter effects in apparent diffusion coefficient determination of magnetic resonance imaging. AB - PURPOSE: Although an apparent diffusion coefficient (ADC) value is often used for differential diagnosis of tumours, it varies with scanning parameters. The present study was performed to investigate the influence of imaging parameters, i.e., b value, repetition time (TR) and echo time (TE), on ADC value. METHODS: The phantoms were scanned using diffusion weighted imaging (DWI) with changing b values (b=0-3000 s/mm(2)), TR and TE to determine the influence on ADC. Moreover, ADC of the brain in normal volunteers was determined with varying b values (b=0 1000 s/mm(2)). RESULTS: Diffusion decay curves were obtained by biexponential fitting in all phantoms. The points where fast and slow components of the biexponential decay crossed were called turning points. The b values of turning points that crossed from the biexponential curve were different in each phantom. The b values of turning points depended on ADC of fast diffusion component. When ADC is calculated using two b values of front and back for the turning point, the ADC value may be different. Therefore, it was necessary to perform calculations by b value until the turning point to obtain the ADC value of the fast component. In addition, b>=100 was recommended to avoid the influence of perfusion by blood. Furthermore, the choice of long TR and short TE was effective for accurate measurement of ADC. CONCLUSION: It is important to determine the turning point for measuring ADC. PMID- 19646837 TI - Development and validation of a high-performance liquid chromatography/tandem mass spectrometry method for the determination of artemether and its active metabolite dihydroartemisinin in human plasma. AB - To study the pharmacokinetic profile of artemether in children and in the context of antiviral drugs for HIV infected patients co-infected with malaria, an LC MS/MS method was developed and validated to simultaneously determine artemether and its metabolite dihydroartemisinin in human plasma. Using artemisinin as the internal standard, 0.5 mL samples were processed with solid phase extraction (Waters Oasis HLB column), the elutes were directly injected onto a C18 LC column (Waters, Symmetry, 150 mm x 4.6 mm, 5 microm). Mass detection utilized ESI+ as the ionization mode and MRM as the quantitation mode. In respect to the low ionization capacity of artemether, ammonium formate was added to the LC mobile phase to facilitate ionization (M+NH4+). The calibration range was 2-200 ng/mL. The recovery was 73-81% for artemether and 90-99% for dihydroartemisinin. The validated method was applied to analysis of clinical samples with results in good agreement with an existing method. PMID- 19646838 TI - Effects of immunization against alpha-inhibin using two adjuvants on daily sperm production and hormone concentrations in ram lambs. AB - Twenty-five ram lambs were immunized against alpha-inhibin peptide emulsified in Freund's adjuvant (FRA), Emulsigen (EML) containing an oligodeoxynucleotide as an immunostimulant, or adjuvant without alpha-inhibin antigen (control). Four immunizations were administered during an 85-d period, after which testes were obtained for determination of daily sperm production (DSP) and histological evaluation. alpha-Inhibin antibody (Ab) titers were 70-fold greater in lambs treated with FRA than in EML-treated ram lambs. alpha-Inhibin immunization had no effect on testes weight or on plasma concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Mean DSP/g tended (P=0.1) to be greater in alpha-inhibin-immunized (EML=17.6x10(6); FRA=15.8x10(6)) ram lambs than in control animals (14.4x10(6)). One of the 8 control ram lambs had an elevated DSP/g, which was a statistical outlier. Without data from this lamb, DSP/g was increased (P<0.01) in alpha-inhibin-immunized ram lambs by 28% over controls. No association was found between the titer of alpha-inhibin Ab developed and DSP/g. Histologically, the percentage of testicular area occupied by seminiferous tubules differed (P=0.01) by treatment and was greatest (82%) in EML-treated ram alpha-inhibin-immunized lambs and lowest (74%) in control animals. Percentage tubular area and DSP/g were correlated (r=0.57, P=0.003). Findings show that (1) the extent of the increase in DSP/g is not dependent on the titer of alpha-inhibin Ab; (2) the increase in DSP/g is achieved through an increase in the mass of seminiferous tubules; and (3) FRA elicits a greater alpha inhibin Ab titer than EML containing an oligodeoxynucleotide. PMID- 19646839 TI - Dermatofibrosarcoma protuberans: recurrence is related to the adequacy of surgical margins. AB - INTRODUCTION: The aim of the study was to investigate the results of surgical treatment in primary and recurrent dermatofibrosarcoma protuberans (DFSP), with respect to local tumor control. PATIENTS AND METHODS: Thirty-eight patients were treated between 1971 and 2005 at the University Medical Center Groningen (UMCG). Thirty patients presented with primary disease (79%) and 8 patients with locally recurrent disease (21%). The treatment consisted of surgical resection and in case of marginal or positive resection margins (R1 resection) adjuvant radiotherapy. RESULTS: Adequate surgical margins as a single modality was associated with 100% local control in all primary DFSPs. Two patients whose resection specimens had microscopically positive resection margins had withdrawn from adjuvant radiotherapy and developed local recurrence (LF rate 7%). Two of the 8 patients referred with a local recurrence developed a second recurrence (LF rate 25%); one of these patients developed distant disease and ultimately died of systemic disease. None of the five patients with DFSP-FS developed LF after treatment at the UMCG. After a median follow-up of 89 (12-271) months, the 10 year disease-free survival was 85% and the 10-year disease specific survival was 100%. CONCLUSION: After wide surgical resection of a DFSP or DFSP-FS, or an R1 resection combined with adjuvant radiotherapy the risk of local recurrence is extremely low. PMID- 19646840 TI - Perioperative tumor cell dissemination in patients with primary or metastatic colorectal cancer. AB - INTRODUCTION: Although there is general correlation between the TNM stage of colorectal cancer (CRC) and its prognosis, there is often significant variability of tumor behaviour and individual patient outcome, which is unaccounted for by pathologic factors alone. Our aim was to estimate perioperative tumor cell dissemination in patients with primary or CRC liver metastases as a possible factor influencing the outcome. METHODS: Forty patients were prospectively enrolled in the study from the year 2007 to 2008. Eighteen patients had histologically proven CRC (50% rectal, 44% colonic, 6% colonic and rectal). Sixteen patients (47%) had CRC liver metastases only. The remaining six patients who underwent colon or liver resection for benign conditions, acted as the control group. All patients with malignant pathologies had R0 resections. Blood samples were taken before the surgical incision (T0), immediately after tumor resection (T1) and at the end of the surgical intervention (T2). Data acquisition was performed using a dual-laser FACSCalibur flow cytometer. Circulating malignant cells were identified as being CD45-/cytokeratin+. RESULTS: The analysis of patients overall (CRC resection subgroup and hepatectomy subgroup) revealed that there was no statistically significant difference of the tumoral cell count in the blood per million of hematopoietic cells at T0, T1 and T2. CONCLUSIONS: This study demonstrates no differences in the detected circulating numbers of tumor cells at different stages of surgical intervention. PMID- 19646841 TI - Carcinoma within solitary ductal papilloma of the breast. AB - BACKGROUND: Solitary ductal papilloma of the breast, traditionally considered a benign disorder, was recently found to have malignant potential, especially when associated with atypical ductal hyperplasia. METHODS: All patients diagnosed with solitary ductal papilloma at a tertiary medical center from 1994 to 2004 were identified by a database search. Background, clinical and pathological data were collected for those with a carcinoma within the papilloma, and their pathological specimens were revised. RESULTS: Of the 3849 breast biopsies performed in our medical center during the study period, 77 (2%) yielded a solitary ductal papilloma. In 12 cases (15.6% of all solitary ductal papillomas; 0.3% of all breast biopsies), a carcinoma was found within the papilloma. Ten were diagnosed as carcinoma in situ and 2 as microinvasive carcinoma. CONCLUSION: In the present series, the incidence of carcinoma within solitary ductal papilloma was 15.6%, indicating that solitary ductal papillomas have malignant potential. SUMMARY: Carcinoma within solitary ductal papilloma of the breast was found in 15.6% of all papillomas. This seems to indicate a malignant potential of papillomas and the need for surgical excision. PMID- 19646843 TI - The use of allograft prosthesis composite for extensive proximal femoral bone deficiencies: a 2- to 9.8-year follow-up study. AB - We report here results for 15 hips that we repaired using allograft prosthesis composite (APC) and monitored for a mean of 4.2 years. Two hips underwent repeat revisions with new APCs after a mean of 83.7 months. The average Harris Hip Score improved from 21.8 before revision surgery to 83.2 afterward, and 12 stems showed good stability. Of the 15 hips repaired with APC, 13 had good junctional union. One of the 2 remaining hips showed nonunion, which was repaired with an onlay graft 3.3 years later, and the other hip showed both infection and nonunion. There was 1 dislocation, and 2 hips had complications related to the greater trochanter. Our findings demonstrate that the use of APC produces satisfactory results. PMID- 19646842 TI - [Anaphylaxis in terminal pregnancy: two case studies and review of the literature]. AB - Anaphylaxis is a relative uncommon event in pregnancy that can have serious implications for both mother and foetus. Two cases of grade 3 anaphylactic shock occurring at the end of the third trimester of pregnancy are reported; the causal agents were respectively amoxicillin and suxamethonium. Maternal and foetal outcome was good after adequate resuscitation and caesarean section performed in both cases because of severe bradycardia. A review of the literature confirms the good maternal outcome; neurologic damage in the newborn is frequent. On the basis of physiologic findings degranulation of placental mast cell is evoked in the genesis of birth asphyxia. PMID- 19646845 TI - Sleepiness, on-task behavior and attention in children with epilepsy who visited a school for special education: a comparative study. AB - Children with epilepsy are at risk for problems in daytime functioning. We assessed daytime sleepiness, on-task behavior and attention in 17 children (aged between 7 and 11 years) with epilepsy who visited a school for special education and compared these to 17 children from a control group who visited a regular school. Within the group of children with epilepsy, we explored whether behavioral and cognitive functioning varied across days of the week and times of the day. Data were collected during four consecutive school days. Children with epilepsy had more daytime sleepiness, less on-task behavior and less attention than controls. Furthermore, sleepiness and on-task behavior varied cross days of the week and times of the day, an effect that was not found in controls. Implications for educational practice are discussed. PMID- 19646844 TI - Factors influencing the improvement of gait ability after total hip arthroplasty. AB - We aimed to investigate the factors influencing gait improvement in the patients who had undergone total hip arthroplasty. We performed gait analysis on 43 female patients with unilateral hip osteoarthritis. All the patients were analyzed before and at 2, 6, and 12 months after the surgery. There were significant reductions in spatiotemporal parameters in the patients with hip osteoarthritis compared with the control group. The mean values of the spatiotemporal parameters of the patients showed considerable improvement by 12 months after surgery; however, they did not reach the same values as those observed in the healthy subjects. The stage of osteoarthritis and the changes in the leg-length discrepancies were the factors that most influenced gait improvement after total hip arthroplasty throughout the follow-up period. PMID- 19646846 TI - Dopamine-modulated dynamic cell assemblies generated by the GABAergic striatal microcircuit. AB - The striatum, the principal input structure of the basal ganglia, is crucial to both motor control and learning. It receives convergent input from all over the neocortex, hippocampal formation, amygdala and thalamus, and is the primary recipient of dopamine in the brain. Within the striatum is a GABAergic microcircuit that acts upon these inputs, formed by the dominant medium-spiny projection neurons (MSNs) and fast-spiking interneurons (FSIs). There has been little progress in understanding the computations it performs, hampered by the non-laminar structure that prevents identification of a repeating canonical microcircuit. We here begin the identification of potential dynamically-defined computational elements within the striatum. We construct a new three-dimensional model of the striatal microcircuit's connectivity, and instantiate this with our dopamine-modulated neuron models of the MSNs and FSIs. A new model of gap junctions between the FSIs is introduced and tuned to experimental data. We introduce a novel multiple spike-train analysis method, and apply this to the outputs of the model to find groups of synchronised neurons at multiple time scales. We find that, with realistic in vivo background input, small assemblies of synchronised MSNs spontaneously appear, consistent with experimental observations, and that the number of assemblies and the time-scale of synchronisation is strongly dependent on the simulated concentration of dopamine. We also show that feed-forward inhibition from the FSIs counter-intuitively increases the firing rate of the MSNs. Such small cell assemblies forming spontaneously only in the absence of dopamine may contribute to motor control problems seen in humans and animals following a loss of dopamine cells. PMID- 19646847 TI - Glomerular microcircuits in the olfactory bulb. AB - Microcircuits in the olfactory bulb have long received particular attention from both experimentalists and theoreticians, due in part to an abundance of dendrodendritic interactions and other specialized modifications to the canonical cortical circuit architecture. Recent experimental and theoretical results have elucidated the mechanisms and function of these circuits and their presumed contributions to olfactory stimulus processing and odor perception. We here review the architecture and functionality of a prominent olfactory bulb microcircuit: the glomerular network. PMID- 19646848 TI - Na VPA-induced acute ischemic stroke in an epileptic patient with methylenetetrahydrofolate reductase gene polymorphism. AB - A 23-year-old man using Na-Valproic acid (VPA) was admitted to our clinic due to convulsion. The neurological examination revealed right hemiparesis. From the exitus notes, we learned that his two siblings had died from status epilepticus. Magnetic resonance imaging (MRI), MRI spectroscopy, and diffusion-weighted investigations (DWI) showed acute-subacute ischemic stroke in the left temporo parieto-occipital region. The patient had an ischemic stroke. Heterozygote methylenetetrahydrofolate reductase (MTHFR) 677C/T polymorphism was determined on genetic examination. The homocysteine (Hcy) level was 18.2 mmol/l (5-15 mmol/l). So VPA treatment was stopped and oxcarbazepine treatment was started. MTHFR 677C/T polymorphism is associated with the risk of vascular diseases due to hyperhomocysteinemia. Heterozygote (MTHFR) 677C/T polymorphism has not been reported to be associated with epilepsy. In patients with heterozygote (MTHFR) 677C/T polymorphism and under long-term use of certain drugs the determination of Hcy plasma levels may be useful to prevent the development of atherothrombotic disease. PMID- 19646849 TI - Treadmill running improves long-term potentiation (LTP) defects in streptozotocin induced diabetes at dentate gyrus in rats. AB - OBJECTIVES: It has been demonstrated that exercise has neuroprotective effects in the central nervous system (CNS), especially in hippocampus. Previous studies have indicated that diabetes mellitus affects synaptic plasticity in the hippocampus leading to impairments in learning and memory. The aim of this study was to evaluate the effects of treadmill running on synaptic plasticity at dentate gyrus (DG) of streptozotocin-induced diabetic rats. STUDY DESIGN: Experimental groups were the control, the diabetes and the diabetes-exercise groups. Long-term potentiation (LTP) in perforant path-DG synapses was assessed (by 400Hz tetanization) in order to investigate the effect of exercise on synaptic plasticity. Field excitatory post-synaptic potential (fEPSP) slope and population spike (PS) amplitude were measured. RESULTS: With respect to the control group, fEPSP were significantly decreased in the diabetes group. However, there were no differences between responses of the diabetes-exercise group and the control. CONCLUSION: The present results suggest that LTP induction in the dentate gyrus is affected under diabetic conditions and that treadmill running prevents these effects. The data suggest that treadmill running protect against diabetes-induced decrease of learning ability and memory function of the hippocampus. PMID- 19646850 TI - Innate-like recognition of microbes by invariant natural killer T cells. AB - Invariant natural killer T cells (iNKT cells) express a restricted T cell antigen receptor (TCR) repertoire and they respond rapidly to glycolipid antigens presented by CD1d. These glycolipid antigens have hexose sugars in alpha-linkage to two types of lipids that can bind to CD1d. Recent work has shown that the responses of iNKT cells to antigen-bearing microbes can have a profound impact on the development of inflammatory diseases. iNKT cells overcome the limitation of their limited TCR diversity by also responding in a foreign antigen-independent fashion to some infectious agents, similar to NK cells. Recent results demonstrate several mechanisms for the indirect activation of iNKT cells by viruses or TLR ligands, dependent on self-antigen recognition and/or different cytokines produced by antigen presenting cells. The means by which iNKT cells influence other cell types and overall host defense are likewise diverse, illustrating the flexibility and functional diversity of this T lymphocyte sublineage. PMID- 19646852 TI - Fine-tuning of T cell responses during infection. AB - Adequate control of infection relies on development of a tailored immune response according to the requirements of a given infection. This is achieved by the continuous crosstalk between innate and adaptive immunity. Pathogen diversity is deciphered via a plethora of receptors converging signals to adaptor molecules; tissue sites and environment generate additional signals that further influence T cell lineage decisions. Within this continuum of interactions, fine-tuning of the ensuing T cell responses together with plasticity of the committed T cells ensure development of balanced immune responses maintaining homeostasis. This review focuses on the multiple mechanisms that govern T cell differentiation during infection. PMID- 19646851 TI - T cells in mycobacterial infection and disease. AB - There has been an increase in our understanding of the complexity of the T cell response to mycobacterial infection recently. Improved tools have allowed the determination of the location and kinetics of naive T cell activation in the mouse as well the variety of function of mycobacteria-specific cells in humans. There is also an increased appreciation of the balance required during mycobacterial infection between anti-bacterial activity and control of the immunopathologic response. The integration of the T cell functional data with the consequences of infection should improve rational vaccine design. PMID- 19646853 TI - CD8+ T cells in Trypanosoma cruzi infection. AB - CD8(+) T cells have emerged as crucial players in the control of a number of protozoan pathogens, including Trypanosoma cruzi, the agent of human Chagas disease. The recent identification of the dominant targets of T. cruzi-specific T cells has allowed investigators to follow the generation of and document the functionality of T cell responses in both mice and humans. Although slow to develop in the early stages of the infection, T. cruzi-specific CD8(+) T cells reach prodigious levels and remain highly functional throughout chronic infections in mice. Following drug-induced cure during either the acute or chronic stage, these immunodominant T cells persist as stable, antigen independent memory populations. T. cruzi-specific CD8(+) T cells in humans are less-well-studied but appear to lose functionality and decline in numbers in these decades-long infections. Changes in the frequency of parasite-specific T cell upon therapeutic treatment in humans may provide a new metric for determining treatment efficacy. PMID- 19646855 TI - Spinal manipulation for asthma: a systematic review of randomised clinical trials. AB - Some clinicians believe that spinal manipulation is an effective treatment for asthma. The aim of this systematic review was to critically evaluate the evidence for or against this claim. Four electronic databases were searched without language restrictions from their inceptions to September 2008. Bibliographies and departmental files were hand-searched. The methodological quality of all included studies was assessed with the Jadad score. Only randomised clinical trials of spinal manipulation as a treatment of asthma were included. Three studies met these criteria. All of them were of excellent methodological quality (Jadad score 5) and all used sham-manipulation as the control intervention. None of the studies showed that real manipulation was more effective than sham-manipulation in improving lung function or subjective symptoms. It is concluded that, according to the evidence of the most rigorous studies available to date, spinal manipulation is not an effective treatment for asthma. PMID- 19646854 TI - Neutrophilic inflammation is associated with altered airway hydration in stable asthmatics. AB - BACKGROUND: Airway dehydration is a potential trigger of bronchoconstriction in exercise-induced asthma; however, its role in stable asthma has not been explored. Using sputum percent solids, as an indicator of airway hydration, we sought relationships between airway hydration and other known markers of neutrophilic (TH1) and allergic (TH2) inflammation in stable asthma. METHODS: Thirty-seven atopic subjects with stable asthma and 15 healthy controls underwent sputum induction. Sputum was analyzed for percent solids, cell counts, cellular and biochemical markers of inflammation and purines. RESULTS: Sputum percent solids was significantly elevated in stable asthmatics vs. controls and positively correlated with markers of neutrophilic/TH1-type inflammation (neutrophils, IL-8 and AMP). Sputum percent solids were not correlated with markers of allergic/TH2-type inflammation. These data suggest a direct relationship between neutrophil inflammation and airway hydration in stable asthmatics. PMID- 19646856 TI - Critical view on diagnosing muscle wasting by single-frequency bio-electrical impedance in COPD. AB - BACKGROUND: Assessment of muscle wasting in COPD is relevant as it is independently associated with metabolic and functional consequences and even survival. Muscle wasting can be approached by assessing fat free mass (FFM), but it is already demonstrated that FFM measured by bio-electrical impedance analysis (BIA) underestimates FFM measured by dual energy X-ray absorptiometry (FFM(DExA)) in a relatively small COPD group. OBJECTIVE: To evaluated critical points for defining muscle wasting in a large cohort of moderate to severe COPD patients and with DEXA scan as reference. DESIGN: FFM by BIA was compared with FFM(DExA) in 1087 COPD patients (641 male symbol, FEV1: 44.8+/-17.5%pred). In a subgroup (n=422), FFM(DExA) was predicted by multivariate analysis and a new formula to calculate FFM by BIA was developed. The new formula was compared with FFM(DExA) in the remaining subgroup (n=665). Muscle wasting was defined according to the cut-offs of Schols et al. (FFM index (FFMI)<16 kg/m(2) for men, 15 kg/m(2) for women), Vestbo et al. (FFMI<17.1 kg/m(2) for men, 14.6 kg/m(2) for women), and Coin et al. (FFMI<17.8 kg/m(2) for men, 14.6 kg/m(2) for women). RESULTS: There was an underestimation of FFM by BIA when compared to FFM(DExA) by the Bland Altman. Comparing the new formula with FFM(DExA), the mean underestimation almost disappeared but the variation remained. The proportion of muscle wasting was largely dependent on the used cut-offs, especially in men. CONCLUSION: The results of the present study emphasize the importance to accurately bare in mind the technique and cut-offs to establish muscle wasting before implementing it in the clinical practice. PMID- 19646857 TI - Dielectric constants are not enough: principal component analysis of the influence of solvent properties on molecularly imprinted polymer-ligand rebinding. AB - The influence of the physical properties of incubation medium on the rebinding of template to bupivacaine molecularly imprinted and non-imprinted methacrylic acid ethylene dimethacrylate co-polymers has been studied. Principal component analysis (PCA) was employed to identify the factors with the greatest influence on binding. While the dielectric constant (D) made a significant contribution to describing the observed binding, the influence of polarity as reflected in the Snyder polarity index (SPI) was also demonstrated to make a significant contribution. The use of solvents containing hydroxyl functionality in particular was observed to exert unique effects on recognition. The variation in solvent influence on binding at constant D motivates more complex analyses when studying MIP-ligand recognition. PMID- 19646858 TI - Computational design of affinity and specificity at protein-protein interfaces. AB - The computer-based design of protein-protein interactions is a rigorous test of our understanding of molecular recognition and an attractive approach for creating novel tools for cell and molecular research. Considerable attention has been placed on redesigning the affinity and specificity of naturally occurring interactions. Several studies have shown that reducing the desolvation costs for binding while preserving shape complimentarity and hydrogen bonding is an effective strategy for improving binding affinities. In favorable cases specificity has been designed by focusing only on interactions with the target protein, while in cases with closely related off-target proteins it has been necessary to explicitly disfavor unwanted binding partners. The rational design of protein-protein interactions from scratch is still an unsolved problem, but recent developments in flexible backbone design and energy functions hold promise for the future. PMID- 19646859 TI - Membrane protein structure determination using cryo-electron tomography and 3D image averaging. AB - The vast majority of membrane protein complexes of biological interest cannot be purified to homogeneity, or removed from a physiologically relevant context without loss of function. It is therefore not possible to easily determine the 3D structures of these protein complexes using X-ray crystallography or conventional cryo-electron microscopy. Newly emerging methods that combine cryo-electron tomography with 3D image classification and averaging are, however, beginning to provide unique opportunities for in situ determination of the structures of membrane protein assemblies in intact cells and nonsymmetric viruses. Here we review recent progress in this field and assess the potential of these methods to describe the conformation of membrane proteins in their native environment. PMID- 19646860 TI - A prokaryotic perspective on pentameric ligand-gated ion channel structure. AB - The X-ray structures of two prokaryotic pentameric ligand-gated ion channels have recently provided detailed insight into this important family of neurotransmitter receptors. These prokaryotic homologs share the overall architecture of their eukaryotic counterparts with conservation in functionally important residues. Although both structures are similar they show distinct conformations of the ion conduction pore. One structure depicts a nonconducting state of the channel with a narrow transmembrane pore that is interrupted by conserved hydrophobic residues. The second structure reveals a conducting conformation where the hydrophobic constriction has opened to an aqueous funnel-shaped channel. The two structures thus suggest a novel gating mechanism for the family, where pore opening proceeds by a change of the tilt of the pore-forming helices. PMID- 19646861 TI - CXCL12/SDF1 expression by breast cancers is an independent prognostic marker of disease-free and overall survival. AB - The cytokine C-X-C motif chemokine 12 (CXCL12) is synthesised by metastasis target tissues and has been shown to attract tumour cells that express the receptor, C-X-C chemokine receptor type 4 (CXCR4). However, epigenetic silencing of CXCL12 has recently been reported to increase the metastatic potential of breast cancer cells and the reintroduction of the cytokine gene into MDA-MB-231 breast carcinoma cells decreases the number of metastases formed in vivo. We therefore wished to know whether CXCL12 expression correlates with relapse-free and overall survival in human breast cancer patients. The expression of C-X-C motif chemokine 12 (CXCL12) and C-X-C chemokine receptor type 4 (CXCR4) was analysed in 100 archival breast cancer samples by immunohistochemistry and in two breast cancer microarray datasets of 408 cases. Data were analysed by univariate and multivariate COX regression analyses. CXCL12 and CXCR4 are expressed by epithelial tumour cells and by stromal and endothelial cells. Microarray gene expression analysis and immunohistochemistry revealed that expression of CXCL12 but not of CXCR4 significantly correlates with disease-free and overall survival in oestrogen receptor-positive and -negative cancers. The expression of the oestrogen receptor alpha and that of CXCL12 do not correlate. CXCL12 is a strong, independent prognostic marker. We propose that saturation of the receptor through autocrine CXCL12 production reduces chemotaxis towards CXCL12-releasing metastasis target tissues. PMID- 19646862 TI - What is the impact of antithrombotic therapy and risk factors on the frequency of thrombovascular events in patients with metastatic breast cancer receiving epoetin beta? AB - PURPOSE, PATIENTS AND METHODS: This retrospective analysis of the BRAVE study evaluated the impact of baseline risk factors and antithrombotic therapy on the risk of thrombovascular events (TVEs) in patients receiving epoetin compared to patients not receiving epoetin. RESULTS: Baseline risk factors have a significant impact on TVE risk under epoetin therapy. More than 2 risk factors increased the risk of TVEs in patients receiving epoetin (hazard ratio [HR] 2.89, confidence interval [CI] 1.04-8.02, p value [p]=0.04). In patients on epoetin without antithrombotic therapy, the risk for TVEs was higher (HR 4.11, CI 1.37-12.4, p=0.01) compared to those who received antithrombotics (HR 1.37, CI 0.59-3.18, p=0.45). CONCLUSIONS: Our analysis has identified several risk factors which may impact the risk of TVEs under epoetin therapy. These data suggest that antithrombotic therapy may have the potential to reduce the risk of TVEs under epoetin therapy. These findings are hypothesis-generating and need to be confirmed in a prospective, randomised study. PMID- 19646863 TI - Chemical composition of acid-base fractions separated from biooil derived by fast pyrolysis of chicken manure. AB - Our earlier investigations on the chemical composition of biooils derived by the fast pyrolysis of chicken manure revealed the presence of more than 500 compounds. In order to simplify this heterogeneous and complex chemical system, we produced four biooil fractions namely strongly acidic fraction A, weakly acidic fraction B, basic fraction C and neutral fraction D on the basis of their solubilities in aqueous solutions at different pHs. The yield (wt/wt.%) for fraction A was 3%, for fraction B 21.3%, for fraction C 2.4% and for fraction D 32.4%, respectively. The four fractions were analyzed by elemental analyses, Fourier Transform infrared spectrophotometry (FTIR), (1)H and (13)C nuclear magnetic spectroscopy (NMR), and electrospray ionization mass spectrometry (ESI MS). The major components of the four fractions were saturated and unsaturated fatty acids, N-heterocyclics, phenols, sterols, diols and alkylbenzenes. The pH separation system produced fractions of enhanced chemical homogeneity. PMID- 19646864 TI - Characterization of alpha-nitromethyl ketone as a new zinc-binding group based on structural analysis of its complex with carboxypeptidase A. AB - Zinc-binding groups (ZBGs) are exhaustively applied in the development of the new inhibitors against a wide variety of physiologically and pathologically important zinc proteases. Here the alpha-nitro ketone was presented as a new ZBG, which is a transition-state analog featured by the unique bifurcated hydrogen bonds at the active site of carboxypeptidase A based on the structural analysis. Introduction of a nitro group at the alpha-position of the ketone could provide more non covalent interactions without loss of the abilities to form a tetrahedral transition-state analog. PMID- 19646865 TI - Discovery of a novel azepine series of potent and selective 5-HT2C agonists as potential treatments for urinary incontinence. AB - A range of heterocycle fused azepines were synthesized in order to find a CNS penetrant, selective 5-HT(2C) agonist for the treatment of incontinence. The pyridazo-azepines such as compound 11 were shown to be potent 5-HT(2C) agonists and have potential for CNS penetration and good in vitro ADME properties but lacked selectivity against 5-HT(2B). Fusing a further heterocycle gave the selective triazolopyrimido-azepines. An example of this series, compound 36, was shown to be potent, selective, metabolically stable in vitro and efficacious in an in vivo model of stress urinary incontinence. PMID- 19646866 TI - 2-Aminobenzimidazoles as potent Aurora kinase inhibitors. AB - This Letter describes the discovery and key structure-activity relationship (SAR) of a series of 2-aminobenzimidazoles as potent Aurora kinase inhibitors. 2 Aminobenzimidazole serves as a bioisostere of the biaryl urea residue of SNS-314 (1c), which is a potent Aurora kinase inhibitor and entered clinical testing in patients with solid tumors. Compared to SNS-314, this series of compounds offers better aqueous solubility while retaining comparable in vitro potency in biochemical and cell-based assays; in particular, 6m has also demonstrated a comparable mouse iv PK profile to SNS-314. PMID- 19646867 TI - Synthesis and antibacterial activity of 7-(1,2,3,4-tetrahydropyrrolo[1,2 a]pyrazin-7-yl) quinolones. AB - A novel series of 7-(1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-yl) quinolones has been designed and synthesized in which the heterocyclic side chain is attached to the quinolone core through a carbon-carbon linkage. The antibacterial activity of the compounds was determined against a panel of Gram-positive and Gram-negative pathogens. Compounds 1b and 1e, bearing an 8-methoxy group as well as unsubstituted and (3S)-methyl substituted 1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin 7-yl side chains, respectively, demonstrated notable activity against ciprofloxacin-resistant clinical isolates of Streptococcus pneumoniae. PMID- 19646868 TI - Design, synthesis and analgesic properties of novel conformationally-restricted N acylhydrazones (NAH). AB - A set of six azaheterocycles were designed as conformationally-constrained N acylhydrazones and tested as analgesics. PMID- 19646869 TI - Discovery of N-(3-(morpholinomethyl)-phenyl)-amides as potent and selective CB2 agonists. AB - Recently sulfamoyl benzamides were identified as a novel series of cannabinoid receptor ligands. Replacing the sulfonamide functionality and reversing the original carboxamide bond led to the discovery of N-(3-(morpholinomethyl)-phenyl) amides as potent and selective CB(2) agonists. Selective CB(2) agonist 31 (K(i)=2.7; CB(1)/CB(2)=190) displayed robust activity in a rodent model of postoperative pain. PMID- 19646870 TI - Arylcarboxyamino-substituted diaryl ureas as potent and selective FLT3 inhibitors. AB - A series of diaryl ureas with an amide substitution at the 4-position was prepared and found to be potent and selective FLT3 inhibitors with good oral bioavailability and efficacy in a tumor xenograft model. PMID- 19646871 TI - Mechanosensing through cooperative interactions between myosin II and the actin crosslinker cortexillin I. AB - BACKGROUND: Mechanosensing governs many processes from molecular to organismal levels, including during cytokinesis where it ensures successful and symmetrical cell division. Although many proteins are now known to be force sensitive, myosin motors with their ATPase activity and force-sensitive mechanical steps are well poised to facilitate cellular mechanosensing. For a myosin motor to experience tension, the actin filament must also be anchored. RESULTS: Here, we find a cooperative relationship between myosin II and the actin crosslinker cortexillin I where both proteins are essential for cellular mechanosensory responses. Although many functions of cortexillin I and myosin II are dispensable for cytokinesis, all are required for full mechanosensing. Our analysis demonstrates that this mechanosensor has three critical elements: the myosin motor where the lever arm acts as a force amplifier, a force-sensitive bipolar thick-filament assembly, and a long-lived actin crosslinker, which anchors the actin filament so that the motor may experience tension. We also demonstrate that a Rac small GTPase inhibits this mechanosensory module during interphase, allowing the module to be primarily active during cytokinesis. CONCLUSIONS: Overall, myosin II and cortexillin I define a cellular-scale mechanosensor that controls cell shape during cytokinesis. This system is exquisitely tuned through the enzymatic properties of the myosin motor, its lever arm length, and bipolar thick-filament assembly dynamics. The system also requires cortexillin I to stably anchor the actin filament so that the myosin motor can experience tension. Through this cross-talk, myosin II and cortexillin I define a cellular-scale mechanosensor that monitors and corrects shape defects, ensuring symmetrical cell division. PMID- 19646872 TI - Ecdysone receptor acts in fruitless- expressing neurons to mediate drosophila courtship behaviors. AB - In Drosophila melanogaster, fruitless (fru) encodes male-specific transcription factors (FRU(M); encoded by fru P1) required for courtship behaviors (reviewed in). However, downstream effectors of FRU(M) throughout development are largely unknown. During metamorphosis the nervous system is remodeled for adult function, the timing of which is coordinated by the steroid hormone 20-hydroxyecdysone (ecdysone) through the ecdysone receptor, a heterodimer of the nuclear receptors EcR (isoforms are EcR-A, EcR-B1, or EcR-B2) and Ultraspiracle (USP) (reviewed in). Here, we show that genes identified as regulated downstream of FRU(M) during metamorphosis are significantly overrepresented with genes known to be regulated in response to ecdysone or EcR. FRU(M) and EcR isoforms are coexpressed in neurons in the CNS during metamorphosis in an isoform-specific manner. Reduction of EcR-A levels in fru P1-expressing neurons of males caused a significant increase in male-male courtship activity and significant reduction in size of two antennal lobe glomeruli. Additional genes were identified that are regulated downstream of EcR-A in fru P1-expressing neurons. Thus, EcR-A is required in fru P1-expressing neurons for wild-type male courtship behaviors and the establishment of male-specific neuronal architecture. PMID- 19646873 TI - The conserved NDR kinase Orb6 controls polarized cell growth by spatial regulation of the small GTPase Cdc42. AB - The conserved NDR kinase regulates cell morphogenesis and polarized cell growth in different eukaryotic cells ranging from yeast to neurons. Although studies have unraveled the mechanism of regulation of NDR kinase activity, the mechanism of morphology control by NDR and the effectors that mediate NDR function are unknown. Via a chemical genetic approach, we show that the fission yeast NDR homolog, Orb6 kinase, maintains polarized cell growth at the cell tips by spatially regulating the localization of Cdc42 GTPase, a key morphology regulator. Loss of Orb6 kinase activity leads to the recruitment of Cdc42 GTPase and the Cdc42-dependent formin For3, normally found only at the cell tips, to the cell sides. Furthermore, we show that loss of Orb6 kinase activity leads to ectopic lateral localization of the Cdc42 guanine nucleotide exchange factor (GEF) Gef1, but not of the other Cdc42 GEF, Scd1. Consistent with these observations, gef1 deletion suppresses the increased cell diameter phenotype of orb6 mutants. In contrast, the microtubule cytoskeleton and the localization of the microtubule-dependent polarity markers Tea1 and Tea4 are not altered by loss of Orb6 kinase activity. Our findings indicate that the conserved NDR kinase Orb6 regulates cell polarity by spatially restricting the localization and activity of Cdc42 GTPase. PMID- 19646874 TI - Repression of apical homeobox genes is required for embryonic root development in Arabidopsis. AB - Development of seed plant embryos is polarized along the apical-basal axis. This polarization occurs in the absence of cell migration and culminates in the establishment of two distinct pluripotent cell populations: the shoot apical meristem (SAM) and root meristem (RM), which postembryonically give rise to the entire shoot and root systems of the plant. The acquisition of genetic pathways that delimit root from shoot during embryogenesis must have played a pivotal role during land plant evolution because roots evolved after shoots in ancestral vascular plants and may be shoot-derived organs. However, such pathways are very poorly understood. Here we show that RM establishment in the model plant Arabidopsis thaliana requires apical confinement of the Class III HOMEODOMAIN LEUCINE ZIPPER (HD-ZIP III) proteins PHABULOSA (PHB) and PHAVOLUTA (PHV), which direct both SAM development and shoot lateral organ polarity. Failure to restrict PHB and PHV expression apically via a microRNA-dependent pathway prevents correct elaboration of the embryonic root development program and results in embryo lethality. As such, repression of a fundamental shoot development pathway is essential for correct root development. Additionally, our data suggest that a single patterning process, based on HD-ZIP III repression, mediates both apical basal and radial polarity in the embryo and lateral organ polarity in the shoot. PMID- 19646875 TI - A blood-borne PDGF/VEGF-like ligand initiates wound-induced epidermal cell migration in Drosophila larvae. AB - Epidermal cell migration is critical for restoration of tissue structure and function after damage. However, the mechanisms by which differentiated cells neighboring the wound sense the wound and assume a motile phenotype remain unclear. Here, we show that Pvr, a receptor tyrosine kinase (RTK) related to platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) receptors, and one of its ligands, Pvf1, are required for epidermal wound closure. Morphological comparison of wound-edge cells lacking Pvr or the Jun N terminal kinase (JNK) signaling pathway previously implicated in larval wound closure suggests that Pvr signaling leads wound-margin epidermal cells to extend actin-based cell processes into the wound gap while JNK mediates transient dedifferentiation of cells at the wound margin. Genetic epistasis experiments reinforce the conclusion that the JNK and Pvr signaling pathways act in parallel. Tissue-specific knockdown and rescue experiments suggest that epidermally derived Pvf1 may be sequestered in the blood and that tissue damage exposes blood-borne Pvf1 to Pvr receptors on wound-edge epidermal cells and initiates the extension of cell processes into the wound gap. These results uncover a novel mechanism of sensing tissue damage and suggest that PDGF/VEGF ligands and receptors may play a conserved autocrine role in epidermal wound closure. PMID- 19646876 TI - ANXUR1 and 2, sister genes to FERONIA/SIRENE, are male factors for coordinated fertilization. AB - In sexual reproduction, proper communication and cooperation between male and female organs and tissues are essential for male and female gametes to unite. In flowering plants, female sporophytic tissues and gametophytes direct a male pollen tube toward an egg apparatus, which consists of an egg cell and two synergid cells. The cell-cell communication between the pollen tube and the egg apparatus makes the tip of pollen tube rupture to release the sperm cell. To detect male factors involved in this communication, we screened mutants of receptor-like kinases expressed in pollen tubes and characterized ANXUR1 (ANX1) and ANXUR2 (ANX2) genes. Here we report that pollen tubes of anx1/anx2 mutants ruptured before arriving at the egg apparatus, suggesting that ANX1 and ANX2 are male factors controlling pollen tube behavior by directing rupture at proper timing. Furthermore, ANX1 and ANX2 were the most closely related paralogs of a female factor, FERONIA/SIRENE, controlling pollen tube behavior expressed in synergid cells. Our findings show that the coordinated behaviors of female and male reproductive apparatuses are regulated by these sister genes, whose duplication might play a role in the evolution of the fertilization system in flowering plants. PMID- 19646877 TI - A robust network of double-strand break repair pathways governs genome integrity during C. elegans development. AB - To preserve genomic integrity, various mechanisms have evolved to repair DNA double-strand breaks (DSBs). Depending on cell type or cell cycle phase, DSBs can be repaired error-free, by homologous recombination, or with concomitant loss of sequence information, via nonhomologous end-joining (NHEJ) or single-strand annealing (SSA). Here, we created a transgenic reporter system in C. elegans to investigate the relative contribution of these pathways in somatic cells during animal development. Although all three canonical pathways contribute to repair in the soma, in their combined absence, animals develop without growth delay and chromosomal breaks are still efficiently repaired. This residual repair, which we call alternative end-joining, dominates DSB repair only in the absence of NHEJ and resembles SSA, but acts independent of the SSA nuclease XPF and repair proteins from other pathways. The dynamic interplay between repair pathways might be developmentally regulated, because it was lost from terminally differentiated cells in adult animals. Our results demonstrate profound versatility in DSB repair pathways for somatic cells of C. elegans, which are thus extremely fit to deal with chromosomal breaks. PMID- 19646878 TI - Ska3 is required for spindle checkpoint silencing and the maintenance of chromosome cohesion in mitosis. AB - The mitotic spindle checkpoint monitors proper bipolar attachment of chromosomes to the mitotic spindle. Previously, depletion of the novel kinetochore complex Ska1/Ska2 was found to induce a metaphase delay. By using bioinformatics, we identified C13orf3, predicted to associate with kinetochores. Recently, three laboratories independently indentified C13orf3 as an additional Ska complex component, and therefore we adopted the name Ska3. We found that cells depleted of Ska3 by RNAi achieve metaphase alignment but fail to silence the spindle checkpoint or enter anaphase. After hours of metaphase arrest, chromatids separate but retain robust kinetochore-microtubule attachments. Ska3-depleted cells accumulate high levels of the checkpoint protein Bub1 at kinetochores. Ska3 protein accumulation at kinetochores in prometaphase is dependent on Sgo1 protein. Sgo1, which accumulates at the centromeres earlier, in prophase, is not dependent on Ska3. Sgo1-depleted cells show a stronger premature chromatid separation phenotype than those depleted of Ska3. We hypothesize that Ska3 functions to coordinate checkpoint signaling from the microtubule binding sites within a kinetochore by laterally linking the individual binding sites. We suggest that this network plays a major role in silencing the spindle checkpoint when chromosomes are aligned at metaphase to allow timely anaphase onset and mitotic exit. PMID- 19646880 TI - CRISPR-based adaptive and heritable immunity in prokaryotes. AB - The recently discovered CRISPR (clustered regularly interspaced short palindromic repeat) defense system protects bacteria and archaea against mobile genetic elements. This immunity system has the potential to continuously adjust its reach at the genomic level, implying that both gain and loss of information is inheritable. The CRISPR system consists of typical stretches of interspaced repetitive DNA (CRISPRs) and associated cas genes. Three distinct stages are recognized in the CRISPR defense mechanism: (i) adaptation of the CRISPR via the integration of short sequences of the invaders as spacers; (ii) expression of CRISPRs and subsequent processing to small guide RNAs; and (iii) interference of target DNA by the crRNA guides. Recent analyses of key Cas proteins indicate that, despite some functional analogies, this fascinating prokaryotic system shares no phylogenetic relation with the eukaryotic RNA interference system. PMID- 19646879 TI - Short- and long-term memory in Drosophila require cAMP signaling in distinct neuron types. AB - BACKGROUND: A common feature of memory and its underlying synaptic plasticity is that each can be dissected into short-lived forms involving modification or trafficking of existing proteins and long-term forms that require new gene expression. An underlying assumption of this cellular view of memory consolidation is that these different mechanisms occur within a single neuron. At the neuroanatomical level, however, different temporal stages of memory can engage distinct neural circuits, a notion that has not been conceptually integrated with the cellular view. RESULTS: Here, we investigated this issue in the context of aversive Pavlovian olfactory memory in Drosophila. Previous studies have demonstrated a central role for cAMP signaling in the mushroom body (MB). The Ca(2+)-responsive adenylyl cyclase RUTABAGA is believed to be a coincidence detector in gamma neurons, one of the three principle classes of MB Kenyon cells. We were able to separately restore short-term or long-term memory to a rutabaga mutant with expression of rutabaga in different subsets of MB neurons. CONCLUSIONS: Our findings suggest a model in which the learning experience initiates two parallel associations: a short-lived trace in MB gamma neurons, and a long-lived trace in alpha/beta neurons. PMID- 19646881 TI - Anti-tumor-initiating effects of phenolic compounds isolated from the bark of Picea jezoensis var. jezoensis. AB - We have previously reported the isolation of nine phenolic compounds including three new flavonostilbenes, jezonocinols A, B, and C, from the MeOH extract of the bark of Picea jezoensis var. jezoensis. Further investigation of the MeOH extract led to the isolation of three new stilbene-type compounds and one new 1,4 benzodioxane-type compound, together with seven known phenolic compounds. These compounds were tested for their inhibitory effects on the activation of (+/-)-(E) methyl-2-[(E)-hydroxy-imino]-5-nitro-6-methoxy-3-hexemide (NOR 1), a nitric oxide (NO) donor, as a primary screening test for anti-tumor initiators. All compounds tested exhibited potent inhibitory effects on NOR 1 activation. Furthermore, jezonocinol B, the most potent inhibitor of NOR 1 activation, showed remarkable anti-tumor-initiating activity in the in vivo two-stage mouse skin carcinogenesis test using peroxynitrite (ONOO(-); PN) as the initiator and 12-O tetradecanoylphorbol-13-acetate (TPA) as the promoter. PMID- 19646882 TI - Novel delta opioid receptor agonists exhibit differential stimulation of signaling pathways. AB - A novel family of 1,3,5-trisubstituted 1,2,4-triazoles was discovered as potent and selective ligands for the delta opioid receptor by rational design. Compound 5b exhibited low-nanomolar in vitro binding affinity (IC(50)=5.8 nM), excellent selectivity for the delta opioid receptor over the alternative mu and kappa opioid receptors, full agonist efficacy in receptor down-regulation and MAP kinase activation assays, and low-efficacy partial agonist activity in stimulation of GTPgammaS binding. The apparent discrepancy observed in these functional assays may stem from different signaling pathways involved in each case, as found previously for other G-protein coupled receptors. More biological studies are underway to better understand the differential stimulation of signaling pathways by these novel compounds. PMID- 19646883 TI - Different chromatin fractions of tomato (Solanum lycopersicum L.) and related species. AB - Conventional chromosome staining has suggested that more than 75% of the tomato chromosomes are constituted by heterochromatin. In order to determine whether more deeply stained proximal regions are classic heterochromatin, the distributions of C-bands and chromomycin A(3) (CMA) bands, and the prophase condensation patterns, were analysed in tomato. In this and most other species of the tomato clade, the 5S and 45S rDNA sites were also localised. In tomato, CMA banding was similar to C-banding. After conventional staining, all species displayed large condensed heteropycnotic regions that did not correspond to C bands or CMA bands. Analyses of the CMA banded karyotypes revealed a low heterochromatin content. Around 12-17% of the chromatin of tomato was CMA(+) and 1/4 to 1/5 of this heterochromatin corresponded to 45S rDNA. In other species, the CMA(+) heterochromatin showed extensive variation (8-35%), but was never near the values found in the literature for tomato. These data suggest the existence of three principal fractions of chromatin in tomato and related species: the late condensed euchromatin corresponding to the terminal regions of the chromosomes, the precocious condensed euchromatin that occupies the major part of the chromosomes and the constitutive heterochromatin that represents those regions revealed by C-bands. PMID- 19646885 TI - Substoichiometric extraction of silver(I) by S-benzyl dithiocarbazate into chloroform. AB - This paper reports on a substoichiometric extraction of Ag(I) by S-benzyl dithiocarbazate into chloroform. The method has been applied to the estimation of silver in different rock samples, adopting the principle of isotope dilution analysis. PMID- 19646884 TI - Characterizing the initial encounter complex in cadherin adhesion. AB - Cadherins are Ca(2+)-dependent cell-cell adhesion proteins with an extracellular region of five domains (EC1 to EC5). Adhesion is mediated by "strand swapping" of a conserved tryptophan residue in position 2 between EC1 domains of opposing cadherins, but the formation of this structure is not well understood. Using single-molecule fluorescence resonance energy transfer and single-molecule force measurements with the atomic force microscope, we demonstrate that cadherins initially interact via EC1 domains without swapping tryptophan-2 to form a weak Ca(2+) dependent initial encounter complex that has 25% of the bond strength of a strand-swapped dimer. We suggest that cadherin dimerization proceeds via an induced fit mechanism where the monomers first form a tryptophan-2 independent initial encounter complex and then undergo subsequent conformational changes to form the final strand-swapped dimer. PMID- 19646886 TI - Differential expression of cellulose synthase (CesA) gene transcripts in potato as revealed by QRT-PCR. AB - Two transgenic potato lines, csr2-1 and csr4-8 that contained two different antisense cellulose synthase (CesA) genes, csr2 and csr4, respectively were crossed. The aim, amongst others, was to investigate the possibility of generating double transformants to validate a hypothetical presence of the proteins of the two CesA genes in the same cellulose synthase enzyme complex. SYBR-Green quantitative real-time reverse transcription polymerase chain reaction (RT-PCR) assays were carried out on four CesA gene transcripts (CesA1, 2, 3, and 4) in the wild type genetic background, and on the two antisense CesA gene transcripts (CesA2 and 4) in the progeny resulting from the cross between the two transgenic potato lines. The quantitative RT-PCR analyses revealed different expression patterns of the two CesA genes. The CesA2 mRNA was shown to be relatively more abundant than CesA4 mRNA, regardless of the genetic background, suggesting that the two proteins are not present in the same enzyme complex. PMID- 19646887 TI - Surgical management of congenital heart disease: evaluation according to the Aristotle score. AB - OBJECTIVE: The Aristotle basic complexity (ABC) score (1.5-15 points) is the sum of potentials for early mortality, morbidity and anticipated surgical technique difficulty. The Aristotle comprehensive complexity (ACC) score (1.5-25 points) is the sum of ABC score and patient-adjusted complexity score; it comprises six complexity levels. We used the ACC score to evaluate quality in surgical management of congenital heart disease. METHODS: Procedures performed in year 2002 and 2007 were analysed. Proportion of procedures requiring at least 1 week of stay in the intensive care unit was chosen as the marker of morbidity. We adopted threshold duration of 120 min for cardio-pulmonary bypass (CPB) cases and the same duration for operations without CPB as surrogate of surgical technical difficulty. The ACC scores were correlated to mortality, morbidity and technical difficulty. RESULTS: This study included 758 patients who underwent 787 primary procedures. The mean ABC and ACC scores amounted to 7.61+/-2.46 and 9.51+/-3.84. Early mortality was 3.05% (24/787), 95% confidence interval (CI): 1.97-4.51%. Zero at ACC levels 1 and 2, it increased from 1.2% (2/161) for level 3 up to 22.2% (2/9) for level 6. Morbidity index was evaluated at 25.9% (204/787), 95% CI: 22.9-29.1%. 1.9% at level 1, it escalated up to 77.8% at level 6. Index of technique difficulty was estimated at 35.2% (277/787), 95% CI: 31.8-38.6%, ranging from 4.8% for level 1 to 66.7% for level 6. A high correlation was found between the ACC scores and mortality, indices of morbidity and technique difficulty, Spearman's correlation coefficient r being 0.9856, 1 and 0.9429, respectively. Mortality (p=0.037) and morbidity (p=0.041) were lower in year 2007 than in 2002 with ABC (p=0.18) and ACC (p=0.37) surgical performance being not significantly different. CONCLUSIONS: The Aristotle score is still under development. Morbidity evaluation should be ideally based on observed postoperative complications; estimation of surgical technical difficulty chosen in this study may not be generalised. Nevertheless, the actual Aristotle comprehensive complexity score, as evaluated in its three components, accurately determined the outcome of surgical management of congenital heart disease. It appears to be an adequate tool to evaluate quality in paediatric cardiac surgery, over time. PMID- 19646888 TI - Fast-track paediatric cardiac surgery: the feasibility and benefits of a protocol for uncomplicated cases. AB - OBJECTIVE: Fast-track patient pathways for cardiac surgery are used in adult practice and by necessity is a mainstay in the developing world. We aimed to introduce a fast-track protocol for uncomplicated paediatric open-heart surgery cases and to subsequently review the results of this change in practice. METHODS: A fast-track protocol co-ordinated by the Advanced Nurse Practitioners was introduced in January 2006 for children aged over 6 months undergoing uncomplicated open-heart procedures. We conducted a review of prospectively collected data on all included patients. The setting was a tertiary paediatric cardiac surgical centre in the UK. The outcome measures for audit were: patient fitness to leave the intensive care unit (ICU) on the day of surgery and hospital length of stay. RESULTS: Included children had a mean age 6 (standard deviation (SD) 4.9) years and mean weight 22.7 (SD 17.6) kg. Of the 194 patients included, 153 (79%) were fit to leave the ICU on the day of surgery. Patients undergoing surgery for ventricular septal defect: odds ratio (OR) 2.8 (95% CI: 1.2-5.6) P=0.01 and left ventricular outflow tract obstruction: OR 5.5 (95% CI: 1.4-21.2) P=0.01, were more likely to be unfit than atrial septal defect and right ventricular outflow tract obstruction. Patients undergoing surgery in the afternoon were more likely to be unfit than those undergoing surgery in the morning: OR 2.3 (95% CI: 1.2-4.8) P=0.03. No relationship was found between age or weight and fitness to fast track. Median length of hospital stay for the whole cohort was 3 (range: 2-11) days. After adjustment for case mix, there was significant evidence that length of hospital stay reduced as experience with the protocol increased over the series of patients RC -0.02 (95% CI: -0.01 to -0.03) P<0.01. CONCLUSION: A fast-track programme can be implemented safely and effectively if the appropriate support including a step-down ward area is put in place. Greater experience with this type of protocol leads to reductions in the length of hospital stay for children aged over 6 months undergoing uncomplicated open-heart surgery. Fast-track cases should be performed in the morning. PMID- 19646889 TI - Accuracy of dual-source computed tomography coronary angiography: evaluation with a standardised protocol for cardiac surgeons. AB - BACKGROUND: This study assesses the accuracy of the new dual-source computed tomography (DSCT) for detection of coronary artery disease (CAD) compared with invasive coronary angiography (ICA) with a specifically designed data presentation protocol for cardiac surgeons. METHODS: Forty patients (30 males/10 females) underwent ICA and DSCT. Best-quality images were prepared by radiologists. Evaluation of 12 segments of significant coronary stenosis was done by two cardiac surgeons with a data presentation protocol including different coronary views in two-/three-dimensional (2D/3D) images. No beta-blockers were administered prior to DSCT. RESULTS: ICA revealed CAD in 21 patients and valvular disease but no CAD in 19 patients. In DSCT, 20/21 patients were diagnosed with CAD (at least one significant stenosis per patient). In 11/21 patients, all 12 segments were assessed correctly; in 7/21 patients one segment and in 3/21 patients two segments were evaluated incorrectly. Of all 21 patients with CAD, 239/252 segments (95%) were correctly evaluated. In 18/19 patients without CAD, DSCT correctly ruled-out the ICA results in 226/228 segments (99%). In total, 465/480 segments were correctly assessed (97%). Of 480 segments, only six were considered not assessable. DSCT assessments of the segments showed a sensitivity of 91%, specificity of 99%, a positive predictive value of 92% and a negative predictive value of 99%. CONCLUSIONS: The accuracy of DSCT coronary angiography especially for exclusion of CAD is promising. The introduced data presentation protocol allows for the independent evaluation by cardiac surgeons after pre arrangement from the radiologists. PMID- 19646890 TI - The laparoscopically harvested omental flap for deep sternal wound infection. AB - OBJECTIVE: To report our experience with the laparoscopically harvested omental flap in the treatment of deep sternal wound infection, and to present a modification and introduce two supportive techniques in the perioperative management. METHODS: Between June 2005 and September 2007, six patients with grade IV (El Oakley-Wright classification) deep sternal wound infection following a median sternotomy for coronary artery bypass grafting underwent a reconstruction with a laparoscopically harvested omental flap. The median age of the cohort of six, consisting of one female and five males, was 67 years (range: 61-77 years). In five patients, an unilateral internal thoracic artery had been used. Considerable preoperative risk factors were present: one patient suffered from severe chronic obstructive pulmonary disease (COPD) Forced expiratory volume in 1s (FEV1)1L; two from moderate chronic obstructive airway disease, three from insulin-dependent diabetes mellitus and three were on glucocorticoid steroid therapy preoperatively. Abdominal surgery had previously been performed in four patients. In all cases, the mediastinal wound was prepared with vacuum-assisted (