title stringlengths 0 1.13k | abstract stringlengths 1 15.7k | PMID int64 22 36.5M |
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Mouse meningiocytes express Sox2 and yield high efficiency of chimeras after nuclear reprogramming with exogenous factors. | Induced pluripotent stem cell technology, also termed iPS, is an emerging approach to reprogram cells into an embryonic stem cell-like state by viral transduction with defined combinations of factors. iPS cells share most characteristics of embryonic stem cells, counting pluripotency and self-renewal, and have so far been obtained from mouse and humans, including patients with genetic diseases. Remarkably, autologous transplantation of cell lineages derived from iPS cells will eliminate the possibility of immunological rejection, as well as current ethical issues surrounding human embryonic stem cell research. However, before iPS can be used for clinical purposes, technical problems must be overcome. Among other considerations, full and homogeneous iPS reprogramming is an important prerequisite. However, despite the fact that cells from several mouse tissues can be successfully induced to iPS, the overall efficiency of chimera formation of these clones remains low even if selection for Oct4 or Nanog expression is applied. In this report, we demonstrate that cells from the mouse meningeal membranes express elevated levels of the embryonic master regulator Sox2 and are highly amenable to iPS. Meningeal iPS clones, generated without selection, are fully and homogeneously reprogrammed based on DNA methylation analysis and 100% chimera competent. Our results define a population of somatic cells that are ready to undergo iPS, thus highlighting a very attractive cell type for iPS research and application. | 18,826,945 |
The transcriptional coactivators SAGA, SWI/SNF, and mediator make distinct contributions to activation of glucose-repressed genes. | The paradigm of activation via ordered recruitment has evolved into a complicated picture as the influence of coactivators and chromatin structures on gene regulation becomes understood. We present here a comprehensive study of many elements of activation of ADH2 and FBP1, two glucose-regulated genes. We identify SWI/SNF as the major chromatin-remodeling complex at these genes, whereas SAGA (Spt-Ada-Gcn5-acetyltransferase complex) is required for stable recruitment of other coactivators. Mediator plays a crucial role in expression of both genes but does not affect chromatin remodeling. We found that Adr1 bound unaided by coactivators to ADH2, but Cat8 binding depended on coactivators at FBP1. Taken together, our results suggest that commonly regulated genes share many aspects of activation, but that gene-specific regulators or elements of promoter architecture may account for small differences in the mechanism of activation. Finally, we found that activator overexpression can compensate for the loss of SWI/SNF but not for the loss of SAGA. | 18,826,948 |
An activin/furin regulatory loop modulates the processing and secretion of inhibin alpha- and betaB-subunit dimers in pituitary gonadotrope cells. | Of all ligands of the transforming growth factor beta superfamily, inhibins and activins are a physiologically relevant pair that are functional antagonists of each other. Activin stimulates whereas inhibin blocks follicle-stimulating hormone biosynthesis and secretion from pituitary gonadotrope cells, and together, inhibin and activin control the pituitary gonadal axis essential for normal reproductive function. Sharing a similar beta-subunit, the secretion of inhibin heterodimers (alpha/beta) or activin homodimers (beta/beta) as mature bioactive ligands depends, in part, on the proteolytic processing of precursor proteins. A short loop regulatory pathway controlling precursor processing and dimer secretion was discovered. Activin stimulates endogenous inhibin alpha- and betaB-subunit mRNA, protein, and proteolytic processing. Simultaneously, activin stimulated the proconvertase furin through a Smad2/3-dependent process. The data provide a mechanism where the regulation of furin and inhibin subunits cooperates in an important positive short feedback loop. This regulatory loop augments the secretion of bioactive mature activin B, as well as inhibin B dimers, necessary for local follicle-stimulating hormone beta regulation. | 18,826,955 |
Usher syndrome and Leber congenital amaurosis are molecularly linked via a novel isoform of the centrosomal ninein-like protein. | Usher syndrome (USH) and Leber congenital amaurosis (LCA) are autosomal recessive disorders resulting in syndromic and non-syndromic forms of blindness. In order to gain insight into the pathogenic mechanisms underlying retinal degeneration, we searched for interacting proteins of USH2A isoform B (USH2A(isoB)) and the LCA5-encoded protein lebercilin. We identified a novel isoform of the centrosomal ninein-like protein, hereby named Nlp isoform B (Nlp(isoB)), as a common interactor. Although we identified the capacity of this protein to bind calcium with one of its three EF-hand domains, the interacton with USH2A(isoB) did not depend on this. Upon expression in ARPE-19 cells, recombinant Nlp(isoB), lebercilin and USH2A(isoB) were all found to co-localize at the centrosomes. Staining of retinal sections with specific antibodies against all three proteins revealed their co-localization at the basal bodies of the photoreceptor-connecting cilia. Based on this subcellular localization and the nature of their previously identified binding partners, we hypothesize that the pathogenic mechanisms for LCA and USH show significant overlap and involve defects in ciliogenesis, cilia maintenance and intraflagellar and/or microtubule-based transport. The direct association of Nlp(isoB) with USH2A(isoB) and lebercilin indicates that Nlp can be considered as a novel candidate gene for USH, LCA and allied retinal ciliopathies. | 18,826,961 |
After the master settlement agreement: targeting and exposure of youth to magazine tobacco advertising. | Targeting and exposure of youth to magazine advertising of tobacco products is associated with increased smoking initiation. National magazine advertising and youth exposure declined in the period following the Master Settlement Agreement (MSA). However, tobacco companies continued targeting youth with brands that were popular among them through magazine advertising and placement of ads in magazines with high youth readership. Existing restrictions, followed by enforcement through litigation, have achieved a marked reduction in overall magazine advertising but may be less adequate compared with pending federal legislation to fully protect youth from the marketing of tobacco products designed to appeal to them. | 18,826,968 |
Co-morbidity obese children in family practice in The Netherlands: the results of a pilot study. | The aim of this pilot study was to assess the prevalence of co-morbidity in obese children. Particular emphasis was on cardiovascular risk. In this retrospective, cross-sectional, observational study the data of 155 obese children, who visited a paediatric obesity outdoor clinic, have been studied. In all, 92% of the population had at least one cardiovascular risk factor. In all, 48% showed a high systolic and 9% a high diastolic blood pressure, while 18% had an increased fasting glucose. In 60%, we diagnosed insulin resistance: the homeostasis model assessment was elevated. The prevalence of high blood pressure, dyslipidaemia, abnormal fasting glucose and insulin resistance are high in this retrospective study. Outcomes of foreign studies on this object are difficult to compare because various populations and cut-off points are used. A new, prospective, study will be conducted to asses the prevalence of co-morbidity in obese children in general practice. | 18,826,992 |
Familial risks for hospitalization with endocrine diseases. | Familial clustering of a disease is an indicator of a possible heritable cause. In the era of genome scans, the consideration of data on heritability should be important in the assessment of the likely success of the scans. The objective of the study was to carry out a family study on nonthyroid endocrine diseases to search familial clustering of these diseases beyond the known syndromes. The Swedish Multigeneration Register on 0- to 72-yr-old subjects was linked to the Hospital Discharge Register from years 1964 to 2004. Standardized incidence ratios were calculated for offspring of affected parents and siblings by comparing with those whose relatives had no hospitalization for nonthyroid endocrine diseases. A total of 11,948 hospitalized cases and 443 familial cases were identified. The familial standardized incidence ratios were increased for parathyroid, pituitary, and adrenal hyperfunctions and hypofunctions, some findings consistent with known syndromes, most clearly that for adrenal cortical hypofunction showing recessive inheritance described for autoimmune polyendocrine syndrome 1. The sibling risks were very high for many diseases, but some of these affecting young individual may be due to bias caused by selective hospitalization. A high sibling risk observed for anterior pituitary hypofunction may represent a yet-unknown recessive syndrome. To our knowledge this is a first population-based study on nonthyroid endocrine diseases. The results call for further studies to sort out the challengingly high sibling risk for many individual nonthyroid endocrine diseases, whether they are due to bias or possible recessive effects. | 18,827,002 |
Vitamin D receptor genotype in hypophosphatemic rickets as a predictor of growth and response to treatment. | Treatment of X-linked hypophosphatemic rickets improves bone mineralization and bone deformities, but its effect on skeletal growth is highly variable. Genetic variants in the promoter region of the vitamin D receptor (VDR) gene may explain the response to treatment because this receptor mediates vitamin D action. We studied the VDR promoter haplotype structure in a large cohort of 91 patients with hypophosphatemic rickets including 62 patients receiving 1alpha-hydroxyvitamin D3 derivatives and phosphates from early childhood on. Treatment improved bone deformities and final height, but 39% of treated patients still had short stature at the end of growth (-2 sd score or below). Height was closely associated with VDR promoter Hap1 genotype. Hap1(-) patients (35% of the cohort) had severe growth defects. This disadvantageous association of Hap1(-) status with height was visible before treatment, under treatment, and on to adulthood. Gender and age at initiation of treatment could not account for the Hap1 effect. No association with growth was found with a polymorphism of the PTH receptor gene otherwise found to be associated with adult height. Compared with Hap1(+) patients, those who were Hap1(-) had a higher urinary calcium response to 1alpha-hydroxyvitamin D3 and had significantly lower circulating FGF23 levels (C-terminal assay), taking into account their phosphate and 1alpha-hydroxyvitamin D3 intakes. The present work identifies the VDR promoter genotype as a key predictor of growth under treatment with 1alpha-hydroxyvitamin D3 derivatives in patients with hypophosphatemic rickets, including those with established PHEX alterations. The VDR promoter genotype appears to provide valuable information for adjusting treatment and for deciding upon the utility of early GH therapy. | 18,827,005 |
Myofibroblast communication is controlled by intercellular mechanical coupling. | Neoformation of intercellular adherens junctions accompanies the differentiation of fibroblasts into contractile myofibroblasts, a key event during development of fibrosis and in wound healing. We have previously shown that intercellular mechanical coupling of stress fibres via adherens junctions improves contraction of collagen gels by myofibroblasts. By assessing spontaneous intracellular Ca2+ oscillations, we here test whether adherens junctions mechanically coordinate myofibroblast activities. Periodic Ca2+ oscillations are synchronised between physically contacting myofibroblasts and become desynchronised upon dissociation of adherens junctions with function-blocking peptides. Similar uncoupling is obtained by inhibiting myofibroblast contraction using myosin inhibitors and by blocking mechanosensitive ion channels using Gd3+ and GSMTx4. By contrast, gap junction uncouplers do not affect myofibroblast coordination. We propose the following model of mechanical coupling for myofibroblasts: individual cell contraction is transmitted via adherens junctions and leads to the opening of mechanosensitive ion channels in adjacent cells. The resulting Ca2+ influx induces a contraction that can feed back on the first cell and/or stimulate other contacting cells. This mechanism could improve the remodelling of cell-dense tissue by coordinating the activity of myofibroblasts. | 18,827,018 |
How does increasingly plainer cigarette packaging influence adult smokers' perceptions about brand image? An experimental study. | Cigarette packaging is a key marketing strategy for promoting brand image. Plain packaging has been proposed to limit brand image, but tobacco companies would resist removal of branding design elements. A 3 (brand types) x 4 (degree of plain packaging) between-subject experimental design was used, using an internet online method, to expose 813 adult Australian smokers to one randomly selected cigarette pack, after which respondents completed ratings of the pack. Compared with current cigarette packs with full branding, cigarette packs that displayed progressively fewer branding design elements were perceived increasingly unfavourably in terms of smokers' appraisals of the packs, the smokers who might smoke such packs, and the inferred experience of smoking a cigarette from these packs. For example, cardboard brown packs with the number of enclosed cigarettes displayed on the front of the pack and featuring only the brand name in small standard font at the bottom of the pack face were rated as significantly less attractive and popular than original branded packs. Smokers of these plain packs were rated as significantly less trendy/stylish, less sociable/outgoing and less mature than smokers of the original pack. Compared with original packs, smokers inferred that cigarettes from these plain packs would be less rich in tobacco, less satisfying and of lower quality tobacco. Plain packaging policies that remove most brand design elements are likely to be most successful in removing cigarette brand image associations. | 18,827,035 |
Sample size calculations for 3-level cluster randomized trials. | The first applications of cluster randomized trials with three instead of two levels are beginning to appear in health research, for instance, in trials where different strategies to implement best-practice guidelines are compared. In such trials, the strategy is implemented in health care units ('clusters') and aims at changing the behavior of health care professionals working in this unit ('subjects'), while the effects are measured at patient level ('evaluations'). To guide the choice of number of clusters, number of subjects per cluster, and number of evaluations per subject. We derive a sample size formula and investigate the influence of sample allocation on power or number of clusters required. The required sample size is the product of the sample size in absence of correlation and two variance inflation factors (VIFs) that describe the clustering of evaluations within subjects and of subjects within cluster, respectively. Because each VIF is expressed in terms of an interpretable Pearson correlation, subject matter knowledge can be incorporated. Moreover, these Pearson's correlations are related to intracluster correlations (ICCs) from comparable, but 2-level cluster randomized trials. Formulas are obtained to guide the sample allocation (number of clusters, subjects, and evaluations) for minimizing total sample size, minimizing the number of clusters, or maximizing power given a budget constraint. Empirical estimates of variance components or ICCs from 3-level cluster trials are scarce which limits reliably powering. When parameterized in terms of Pearson correlations, the two variance inflation factors give quantitative insight into the impact of the number of clusters, subjects and evaluations on power. Moreover, subject matter knowledge as well as ICCs from 2-level cluster randomized trials can be incorporated in the sample size calculation, when empirical estimates of variance components or ICCs from a pilot or comparable 3-level study are lacking. | 18,827,041 |
Toll-like receptors: another player in the pathogenesis of the anti-phospholipid syndrome. | The anti-phospholipid syndrome (APS) is a systemic autoimmune disease characterized by an adaptive immune response against self phospholipid (PL)--binding proteins. Although APS is considered as an autoantibody-mediated disease, there is now evidence that anti-phospholipid antibodies (aPL) are necessary but not sufficient to trigger some of the clinical manifestations of the syndrome. For example, mediators of the innate immunity are recognized to be additional second hits able to induce the thrombotic events in the presence of aPL. Finally, environmental agents - in particular infectious ones - were reported to act as triggers for the production of autoantibodies cross-reacting with PL-binding proteins as well as inflammatory stimuli that potentiate the aPL thrombogenic effect. Altogether, these findings suggest a role for the innate immunity in APS pathogenesis. Toll-like receptors (TLR) are receptors that induce prompt inflammatory responses and mediate functional activation in immune effector cells. There is evidence that aPL, and in particular anti-beta(2) glycoprotein I (beta(2)GPI) antibodies, may activate endothelial cells and monocytes through TLR-4-dependent signalling. Whether or not TLR may behave as surface receptors for beta(2)GPI is still matter of research. Drugs or molecules able to interfere with TLR involvement may represent new therapeutic approaches for APS. | 18,827,059 |
Differential selective constraints shaping codon usage pattern of housekeeping and tissue-specific homologous genes of rice and arabidopsis. | Intra-genomic variation between housekeeping and tissue-specific genes has always been a study of interest in higher eukaryotes. To-date, however, no such investigation has been done in plants. Availability of whole genome expression data for both rice and Arabidopsis has made it possible to examine the evolutionary forces in shaping codon usage pattern in both housekeeping and tissue-specific genes in plants. In the present work, we have taken 4065 rice-Arabidopsis homologous gene pairs to study evolutionary forces responsible for codon usage divergence between housekeeping and tissue-specific genes. In both rice and Arabidopsis, it is mutational bias that regulates error minimization in highly expressed genes of both housekeeping and tissue-specific genes. Our results show that, in comparison to tissue-specific genes, housekeeping genes are under strong selective constraint in plants. However, in tissue-specific genes, lowly expressed genes are under stronger selective constraint compared with highly expressed genes. We demonstrated that constraint acting on mRNA secondary structure is responsible for modulating codon usage variations in rice tissue-specific genes. Thus, different evolutionary forces must underline the evolution of synonymous codon usage of highly expressed genes of housekeeping and tissue-specific genes in rice and Arabidopsis. | 18,827,062 |
Paternity testing requested by private parties in Italy: some ethical considerations. | In Italy, judicial and extrajudicial requests for paternity testing have increased in recent years. A retrospective analysis of such private extrajudicial requests received by the legal medicine unit of the Department of Environmental Medicine and Public Health of Padua University was conducted to identify problem areas most helpful in determining whether to accept private parties' requests for paternity testing. Such testing is most delicate when a presumptive father may be seeking to disown paternity and when testing is wanted without the consent of a member of the mother-child-father triangle. Tests that could establish paternity where none has been recognised are less problematic, as the child will not lose out. Legal and ethical-deontological aspects of consent, of the protection of minors and of children's and parents' need for follow-up interviews to deal with the outcome of such testing are carefully considered by the Padua University team when deciding whether to accept a request for testing. It is argued that because such issues are not dealt with by mail-order laboratories, the use of such services is inappropriate. | 18,827,105 |
Cesarean delivery for the second twin. | To examine maternal and infant outcomes after a vaginal delivery of twin A and a cesarean delivery of twin B, and to identify whether the second twin experienced increased short-term morbidity as part of a combined route of delivery. Between January 1, 1999, and December 31, 2000, a prospective cohort study of all cesarean deliveries was conducted at 13 university centers. This secondary analysis was limited to women with twin gestations who experienced labor and underwent cesarean delivery. We compared outcomes of the second twin in women who had vaginal delivery of the first twin and a cesarean delivery of the second twin to those who had cesarean delivery of both twins. One thousand twenty-eight twin pregnancies experienced labor and underwent cesarean delivery; 179 (17%) had a combined vaginal/cesarean delivery. Gestational age at delivery was 34.6 weeks in both groups (P=.97). The rupture of membranes to delivery interval was longer in the combined group (3.2 compared with 2.3 hours, P<.001). Endometritis and culture-proven sepsis in the second twin were more common in the combined group, respectively (n=24, odds ratio 1.6, 95% confidence interval, 1.0-2.7; n=15, odds ratio 1.8, 95% confidence interval, 1.0-3.4). These differences were not significant after logistic regression analysis. There were no statistically significant differences in an arterial cord pH of less than 7.0, Apgar score less than or equal to 3 at 5 minutes, seizures, grade III or IV intraventricular hemorrhage, hypoxic ischemic encephalopathy, or neonatal death. Combined twin delivery may be associated with endometritis and neonatal sepsis when compared with a twin delivery where both are delivered by cesarean in twin pregnancies experiencing labor. More serious neonatal sequelae, including hypoxic ischemic encephalopathy and death, were not affected by the route of delivery of the second twin. | 18,827,115 |
Treatment of acne using a 3-milligram drospirenone/20-microgram ethinyl estradiol oral contraceptive administered in a 24/4 regimen: a randomized controlled trial. | To assess the efficacy of the combined oral contraceptive containing 3-mg drospirenone/20-microgram ethinyl estradiol (3-mg drospirenone/20-microgram ethinyl estradiol) administered as 24 consecutive days of active treatment after a 4-day hormone-free interval (24/4 regimen) compared with placebo for the treatment of moderate acne vulgaris. Healthy females aged 14-45 years with moderate acne were randomized in this double-blind study to 3-mg drospirenone/20-microgram ethinyl estradiol (n=270) or placebo (n=268) for six cycles of 28 days. The primary outcome measures of acne lesion counts and Investigator Static Global Assessment scale ratings were assessed at baseline and during cycles 1, 3, and 6. The percentage reduction from baseline to endpoint for total lesions is 46.3% for 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 combination oral contraceptive group and 30.6% for placebo group (P<.001). The likelihood of participants in the 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 regimen group having "clear" or "almost clear" skin as rated by the investigators at endpoint was about threefold (odds ratio 3.13, 95% confidence interval 1.69-5.81; P=.001) greater than in the placebo group. The 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 regimen was well tolerated. The low-dose combined oral contraceptive containing 3-mg drospirenone/20-microgram ethinyl estradiol administered in a 24/4 regimen significantly reduced acne lesion counts more effectively than placebo and demonstrated greater improvement in the Investigator Static Global Assessment rating of acne. The safety profile was consistent with low-dose combined oral contraceptive use. | 18,827,119 |
Postpartum screening for diabetes after a gestational diabetes mellitus-affected pregnancy. | To estimate trends in postpartum glucose testing in a cohort of women with gestational diabetes mellitus (GDM). A validated computerized algorithm using Kaiser Permanente Northwest automated data systems identified 36,251 live births or stillbirths from 1999 through 2006. The annual percentage of pregnancies complicated by gestational diabetes with clinician orders for and completion of a fasting plasma glucose (FPG) test within 3 months of delivery was calculated. Logistic regression with generalized estimating equations was used to test for statistically significant trends. The percentages of pregnancies affected by GDM increased from 2.9% in 1999 to 3.6% in 2006 (P<.01). Clinician orders for postpartum tests increased from 15.9% in 1999 to 79.3% in 2004 (P<.01), and then remained stable through 2006. Completed FPG tests increased from 9.0% in 1999 to 57.8% in 2004 (P<.01), and then remained stable through 2006. No oral glucose tolerance tests were ordered. From 2004 to 2006, the practice site where women received care was the factor most strongly associated with the clinician order, but it was not predictive of test completion. Among women with clinician orders, those who were Asian or Hispanic or who attended the 6-week postpartum examination were more likely to complete the test than their counterparts. Postpartum glucose testing in women with GDM-affected pregnancies increased over time. However, even in recent years, 42% of women with GDM-affected pregnancies failed to have a postpartum FPG test, and no test was ordered for 21% of GDM-affected pregnancies. | 18,827,130 |
Nicotine gum for pregnant smokers: a randomized controlled trial. | To estimate the safety and efficacy of treatment with 2-mg nicotine gum for smoking cessation during pregnancy. Pregnant women who smoked daily received individualized behavioral counseling and random assignment to a 6-week treatment with 2-mg nicotine gum or placebo followed by a 6-week taper period. Women who did not quit smoking were instructed to reduce the number of cigarettes smoked by substituting with gum. Measures of tobacco exposure were obtained throughout the study. Participants in the nicotine (n = 100) and placebo (n = 94) groups were comparable in age, race/ethnicity, and smoking history. Biochemically validated smoking-cessation rates were not significantly higher with nicotine gum compared with placebo (after 6 weeks of treatment: 13% compared with 9.6%, P=.45; at 32-34 weeks of gestation: 18% compared with 14.9%, P=.56). Using a completer analysis, nicotine gum significantly reduced the number of cigarettes smoked per day (nicotine gum: -5.7 [standard deviation (SD)=6.0]; placebo: -3.5 [SD=5.7], P=.035), and cotinine concentration (nicotine gum: -249 ng/mL [SD=397]; placebo: -112 ng/mL [SD=333]; P=.04). Birth weights were significantly greater with nicotine gum compared with placebo (3,287 g [SD=566] and 2,950 g [SD=653], respectively, P<.001). Gestational age was also greater with nicotine-replacement therapy than with placebo (38.9 weeks [SD=1.7] and 38.0 weeks [SD=3.3], respectively; P=.014). Although nicotine gum did not increase quit rates, use of nicotine gum increased birth weight and gestational age, two key parameters in predicting neonatal wellbeing. | 18,827,129 |
Low rates of both asymptomatic chlamydia screening and diagnostic testing of women in US outpatient clinics. | To estimate demographic characteristics of nonpregnant women who seek health care in hospital outpatient clinics, and the proportion of visits where a chlamydia test was not done in asymptomatic young women at preventive visits and in symptomatic women. We analyzed data from the 2005 National Hospital Ambulatory Medical Care Survey to estimate the number of visits made by nonpregnant women aged 15-25 years and 26-35 years. We estimated the proportion of preventive visits where young women were not screened for chlamydia and the proportion of visits where women with signs or symptoms of chlamydia were not tested. In 2005, 5.2 million visits were made by nonpregnant women aged 15-25 years to outpatient clinics: 21.3% were by black non-Hispanic women, 15.2% by Hispanic women, 41.9% by women with Medicaid/State Children's Health Insurance Program insurance, and 10.8% by women with signs or symptoms of chlamydia. These young women were not screened at 84.0% of 1.2 million asymptomatic preventive visits, and were not tested for chlamydia at 78.3% of 0.6 million visits where they presented with signs or symptoms of chlamydia. Women aged 26-35 years were not tested at 86.3% of 0.4 million visits where they presented with signs or symptoms of chlamydia. While low chlamydia screening coverage has been reported, the low level of diagnostic testing in outpatient clinics was unexpected. Simple and effective interventions are needed to increase both diagnostic testing and screening of young women for Chlamydia in outpatient clinics, a venue that provides care to at-risk populations. | 18,827,133 |
Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach. | There is poor agreement on definitions of different phenotypes of preschool wheezing disorders. The present Task Force proposes to use the terms episodic (viral) wheeze to describe children who wheeze intermittently and are well between episodes, and multiple-trigger wheeze for children who wheeze both during and outside discrete episodes. Investigations are only needed when in doubt about the diagnosis. Based on the limited evidence available, inhaled short-acting beta(2)-agonists by metered-dose inhaler/spacer combination are recommended for symptomatic relief. Educating parents regarding causative factors and treatment is useful. Exposure to tobacco smoke should be avoided; allergen avoidance may be considered when sensitisation has been established. Maintenance treatment with inhaled corticosteroids is recommended for multiple-trigger wheeze; benefits are often small. Montelukast is recommended for the treatment of episodic (viral) wheeze and can be started when symptoms of a viral cold develop. Given the large overlap in phenotypes, and the fact that patients can move from one phenotype to another, inhaled corticosteroids and montelukast may be considered on a trial basis in almost any preschool child with recurrent wheeze, but should be discontinued if there is no clear clinical benefit. Large well-designed randomised controlled trials with clear descriptions of patients are needed to improve the present recommendations on the treatment of these common syndromes. | 18,827,155 |
Time from diagnosis to treatment initiation predicts survival in younger, but not older, acute myeloid leukemia patients. | Acute myeloid leukemia (AML) is considered an oncologic emergency. Delaying induction chemotherapy until molecular testing results return, may benefit some patients but harm others. We examined the effect of time from AML diagnosis to treatment (TDT) on complete remission (CR) and overall survival (OS), using patient characteristics available at diagnosis. Regression models were applied to older (> or = 60 years) and younger (< 60 years) adults, controlling for age, baseline white blood cell count, secondary AML (sAML), and performance status. Median patient age was 60 years (range, 17-87 years), TDT 4 days (range, 1-78 days), and 45% had sAML. Cytogenetic risk distribution was: favorable, 8%; intermediate, 66%; unfavorable, 26%. CR rate was 67% and median OS was 68 weeks in patients younger than 60 years; 55% and 33 weeks in older patients, respectively. In univariate and multivariate analyses, longer TDT was associated with worse CR and OS in younger (univariate: P < .001 in both; multivariate: P < .001 and P = .001, respectively), but not older patients (univariate: P = .45, P = .19; multivariate: P = .63, P = .30, respectively). Results did not change with inclusion of cytogenetic data or in risk group subsets. AML therapy should be initiated immediately in younger patients. Delaying treatment does not seem harmful in older patients, allowing individualized approaches. | 18,827,183 |
Validation of an enzyme-linked immunosorbent assay for diagnosis of human trichinellosis. | Trichinellosis is a zoonotic disease caused by the consumption of raw or semiraw meat from different animals harboring Trichinella larvae in their muscles. Since there are no pathognomonic signs, diagnosis can be difficult; for this reason, serology is important. The objective of this study was to validate an enzyme-linked immunosorbent assay (ELISA) using excretory/secretory antigens to detect anti-Trichinella immunoglobulin G antibodies in human sera. A total of 3,505 human serum samples were tested. A receiver-operator characteristic (ROC) curve analysis was performed. The accuracy of the test was determined by calculating the area under the curve, which was equal to 0.999, indicating high accuracy. The coefficient of variation calculated for data from four serum samples in eight working sessions was no higher than 5% for the positive sera or 14% for the negative sera. Moreover, the analysis of the differences in optical density between duplicates indicated a high repeatability for the ELISA. At the ROC optimized cutoff, the sensitivity and specificity of the test were, respectively, 99.2% and 90.6% (specificity of 95.6% when excluding the samples from multiparasitized persons from Tanzania). The validated ELISA showed good performance in terms of sensitivity, repeatability, and reproducibility, whereas the specificity was limited. These results suggest that this test is suitable for detecting anti-Trichinella antibodies in human sera for diagnostic purposes, whereas its use in epidemiological surveys could be questionable. | 18,827,188 |
Effects of a reduced dose schedule and intramuscular administration of anthrax vaccine adsorbed on immunogenicity and safety at 7 months: a randomized trial. | In 1999, the US Congress directed the Centers for Disease Control and Prevention to conduct a pivotal safety and efficacy study of anthrax vaccine adsorbed (AVA). To determine the effects on serological responses and injection site adverse events (AEs) resulting from changing the route of administration of AVA from subcutaneous (s.q.) to intramuscular (i.m.) and omitting the week 2 dose from the licensed schedule. Assessment of the first 1005 enrollees in a multisite, randomized, double-blind, noninferiority, phase 4 human clinical trial (ongoing from May 2002). Healthy adults received AVA by the s.q. (reference group) or i.m. route at 0, 2, and 4 weeks and 6 months (4-SQ or 4-IM; n = 165-170 per group) or at a reduced 3-dose schedule (3-IM; n = 501). A control group (n = 169) received saline injections at the same time intervals. Noninferiority at week 8 and month 7 of anti-protective antigen IgG geometric mean concentration (GMC), geometric mean titer (GMT), and proportion of responders with a 4-fold rise in titer (%4 x R). Reactogenicity outcomes were proportions of injection site and systemic AEs. At week 8, the 4-IM group (GMC, 90.8 microg/mL; GMT, 1114.8; %4 x R, 97.7) was noninferior to the 4-SQ group (GMC, 105.1 microg/mL; GMT, 1315.4; %4 x R, 98.8) for all 3 primary end points. The 3-IM group was noninferior for only the %4 x R (GMC, 52.2 microg/mL; GMT, 650.6; %4 x R, 94.4). At month 7, all groups were noninferior to the licensed regimen for all end points. Solicited injection site AEs assessed during examinations occurred at lower proportions in the 4-IM group compared with 4-SQ. The odds ratio for ordinal end point pain reported immediately after injection was reduced by 50% for the 4-IM vs 4-SQ groups (P < .001). Route of administration did not significantly influence the occurrence of systemic AEs. The 4-IM and 3-IM regimens of AVA provided noninferior immunological priming by month 7 when compared with the 4-SQ licensed regimen. Intramuscular administration significantly reduced the occurrence of injection site AEs. Trial Registration clinicaltrials.gov Identifier: NCT00119067. | 18,827,210 |
Effectiveness of long-term psychodynamic psychotherapy: a meta-analysis. | The place of long-term psychodynamic psychotherapy (LTPP) within psychiatry is controversial. Convincing outcome research for LTPP has been lacking. To examine the effects of LTPP, especially in complex mental disorders, ie, patients with personality disorders, chronic mental disorders, multiple mental disorders, and complex depressive and anxiety disorders (ie, associated with chronic course and/or multiple mental disorders), by performing a meta-analysis. Studies of LTPP published between January 1, 1960, and May 31, 2008, were identified by a computerized search using MEDLINE, PsycINFO, and Current Contents, supplemented by contact with experts in the field. Only studies that used individual psychodynamic psychotherapy lasting for at least a year, or 50 sessions; had a prospective design; and reported reliable outcome measures were included. Randomized controlled trials (RCTs) and observational studies were considered. Twenty-three studies involving a total of 1053 patients were included (11 RCTs and 12 observational studies). Information on study characteristics and treatment outcome was extracted by 2 independent raters. Effect sizes were calculated for overall effectiveness, target problems, general psychiatric symptoms, personality functioning, and social functioning. To examine the stability of outcome, effect sizes were calculated separately for end-of-therapy and follow-up assessment. According to comparative analyses of controlled trials, LTPP showed significantly higher outcomes in overall effectiveness, target problems, and personality functioning than shorter forms of psychotherapy. With regard to overall effectiveness, a between-group effect size of 1.8 (95% confidence interval [CI], 0.7-3.4) indicated that after treatment with LTPP patients with complex mental disorders on average were better off than 96% of the patients in the comparison groups (P = .002). According to subgroup analyses, LTPP yielded significant, large, and stable within-group effect sizes across various and particularly complex mental disorders (range, 0.78-1.98). There is evidence that LTPP is an effective treatment for complex mental disorders. Further research should address the outcome of LTPP in specific mental disorders and should include cost-effectiveness analyses. | 18,827,212 |
Late-life anxiety and cognitive impairment: a review. | Emerging research implicates a consistent reciprocal relationship between late-life anxiety and cognition. Understanding this relationship may clarify pathophysiological substrates of cognitive impairment and why co-occurring anxiety and cognitive impairment relates to poorer treatment prognosis for both conditions. This article critically reviews evidence of more prevalent anxiety in cognitively impaired older adults, elevated anxiety related to poorer cognitive performance, and more severe anxiety symptoms predicting future cognitive decline. It considers pathophysiologic mediators and moderators, and the influence of comorbid depression or medical illness in anxiety. Identified directions for future research includes use of in-depth anxiety assessment comparing normal and mild cognitively impaired older adults and use of challenging neuropsychological tests to determine if specific cognitive domains suffer in anxious older adults. | 18,827,225 |
The surgical anatomy of the blood supply to the femoral head: description of the anastomosis between the medial femoral circumflex and inferior gluteal arteries at the hip. | The inferior gluteal artery is described in standard anatomy textbooks as contributing to the blood supply of the hip through an anastomosis with the medial femoral circumflex artery. The site(s) of the anastomosis has not been described previously. We undertook an injection study to define the anastomotic connections between these two arteries and to determine whether the inferior gluteal artery could supply the lateral epiphyseal arteries alone. From eight fresh-frozen cadaver pelvic specimens we were able to inject the vessels in 14 hips with latex moulding compound through either the medial femoral circumflex artery or the inferior gluteal artery. Injected vessels around the hip were then carefully exposed and documented photographically. In seven of the eight specimens a clear anastomosis was shown between the two arteries adjacent to the tendon of obturator externus. The terminal vessel arising from this anastomosis was noted to pass directly beneath the posterior capsule of the hip before ascending the superior aspect of the femoral neck and terminating in the lateral epiphyseal vessels. At no point was the terminal vessel found between the capsule and the conjoined tendon. The medial femoral circumflex artery receives a direct supply from the inferior gluteal artery immediately before passing beneath the capsule of the hip. Detailed knowledge of this anatomy may help to explain the development of avascular necrosis after hip trauma, as well as to allow additional safe surgical exposure of the femoral neck and head. | 18,827,238 |
Total knee replacement for patients with ankylosed knees. | The purpose of this study was to determine objectively the outcome of total knee replacement in patients with ankylosed knees. There were 82 patients (99 knees) with ankylosed knees who underwent total knee replacement with a condylar constrained or a posterior stabilised prosthesis. Their mean age was 41.9 years (23 to 60) and the mean follow-up was for 8.9 years (6.6 to 14). Pre- and post-operative data included the Hospital for Special Surgery (HSS), the Knee Society (KS) and the Western Ontario and McMaster University Osteoarthritis index (WOMAC) scores. The mean HSS, KS and WOMAC scores improved from 60, 53, and 79 pre-operatively to 81, 85, and 37 at follow-up. These improvements were statistically significant (p = 0.018, 0.001 and 0.014 respectively). The mean physical, social and emotional WOMAC scores also improved significantly (p = 0.032, p = 0.023 and p < 0.001 respectively). The mean satisfaction score was 8.5 (SD 1.5). Total knee replacement gives good mid-term results in patients with ankylosed knees. | 18,827,240 |
Transphyseal reconstruction of the anterior cruciate ligament in prepubescent children. | We present the results of 17 children of Tanner stage 1 or 2 who underwent reconstruction of the anterior cruciate ligament between 1999 and 2006 using a transphyseal procedure, employing an ipsilateral four-strand hamstring graft. The mean age of the children was 12.1 years (9.5 to 14). The mean follow-up was 44 months (25 to 100). Survival of the graft, the functional outcome and complications were recorded. There was one re-rupture following another injury. Of the remaining patients, all had good or excellent results and a normal International Knee Documentation Committee score. The mean post-operative Lysholm score was 97.5 (SD 2.6) and the mean Tegner activity scale was 7.9 (SD 1.4). One patient had a mild valgus deformity which caused no functional disturbance. No other abnormality or discrepancy of leg length was seen. Measurements with a KT1000 arthrometer showed no significant difference between the normal and the operated legs. In this small series, transphyseal reconstruction of the anterior cruciate ligament appeared to be safe in these young children. | 18,827,241 |
Prognostic factors and outcome of treatment in Perthes' disease: a prospective study of 368 patients with five-year follow-up. | This nationwide prospective study was designed to determine prognostic factors and evaluate the outcome of different treatments of Perthes' disease. A total of 28 hospitals in Norway were instructed to report all new cases of Perthes' disease over a period of five years and 425 patients were reported and followed for five years. Of these, 368 with unilateral disease were included in the present study. The hips were classified radiologically according to a modified two-group Catterall classification and the lateral pillar classification. A total of 358 patients (97%) attended the five-year follow-up, when a modified three-group Stulberg classification was used as a radiological outcome measure. For patients over six years of age at diagnosis and with more than 50% necrosis of the femoral head (152 patients), the surgeons at the different hospitals had chosen one of three methods of treatment: physiotherapy (55 patients), the Scottish Rite abduction orthosis (26), and proximal femoral varus osteotomy (71). Of these hips, 146 (96%) were available for the five-year follow-up. The strongest predictor of outcome was femoral head involvement of more or less than 50% (odds ratio (OR) = 7.76, 95% confidence interval (CI) 2.82 to 21.37), followed by age at diagnosis (OR = 0.98, 95% CI 0.92 to 0.99) and the lateral pillar classification (OR = 0.62, 95% CI 0.40 to 0.98). In children over six years at diagnosis with more than 50% of femoral head necrosis, proximal femoral varus osteotomy gave a significantly better outcome than orthosis (p = 0.001) or physiotherapy (p = 0.001). There was no significant difference between the physiotherapy and orthosis groups (p = 0.36), and we found no difference in outcome after any of the treatments in children under six years (p = 0.73). We recommend proximal femoral varus osteotomy in children aged six years and over at the time of diagnosis with hips having more than 50% femoral head necrosis. The abduction orthosis should be abandoned in Perthes' disease. | 18,827,249 |
In vivo local administration of osteogenic protein-1 increases structural properties of the overstretched anterior cruciate ligament with partial midsubstance laceration: a biomechanical study in rabbits. | We report the effects of local administration of osteogenic protein-1 on the biomechanical properties of the overstretched anterior cruciate ligament in an animal model. An injury in the anterior cruciate ligament was created in 45 rabbits. They were divided into three equal groups. In group 1, no treatment was applied, in group II, phosphate-buffered saline was applied around the injured ligament, and in group III, 12.5 microg of osteogenic protein-1 mixed with phosphate-buffered saline was applied around the injured ligament. A control group of 15 rabbits was assembled from randomly-selected injured knees from among the first three groups. Each rabbit was killed at 12 weeks. The maximum load and stiffness of the anterior cruciate ligament was found to be significantly greater in group III than either group 1 (p = 0.002, p = 0.014) or group II (p = 0.032, p = 0.025). The tensile strength and the tangent modulus of fascicles from the ligament were also significantly greater in group III than either group I (p = 0.002, p = 0.0174) or II (p = 0.005, p = 0.022). The application of osteogenic protein-1 enhanced the healing in the injured anterior cruciate ligament, but compared with the control group the treated ligament remained lengthened. The administration of osteogenic protein-1 may have a therapeutic role in treating the overstretched anterior cruciate ligament. | 18,827,254 |
Impact of neurofibromatosis type 1 on school performance. | School functioning of 86 Dutch neurofibromatosis type 1 children (7-17 years) using teacher questionnaires was analyzed to determine the impact of neurofibromatosis type 1 on school performance. In all, 75% of the neurofibromatosis type 1 children performed more than 1 standard deviation below grade peers in at least one of the domains of spelling, mathematics, technical reading or comprehensive reading. Furthermore, neurofibromatosis type 1 children had a 4-fold increased risk for attending special education and a 6-fold increased risk for receiving remedial teaching for learning, behavior, speech, or motor problems. Children without apparent learning disabilities still frequently displayed neuropsychological deficits. Only 10% of the children did not show any school-functioning problems. Finally, it was found that the clinical severity of neurofibromatosis type 1 correlated with the cognitive deficits. Taken together, it was shown that neurofibromatosis type 1 has profound impact on school performance. Awareness of these problems may facilitate timely recognition and appropriate support. | 18,827,266 |
Clinical observation of self-injurious behavior correlated with changes in scalp morphology in a child with congenital hydrocephalus. | We report the case of a 12-year-old girl born with cerebral dysgenesis and congenital hydrocephalus first shunted shortly after birth. She had severe tissue-damaging self-injurious behavior, profound mental retardation, quadriparesis, as well as multiple cranial anomalies including turricephaly. After stage 1 cranial remodeling, a bone window was left pending second stage remodeling. Episodic changes in fluctuation of the scalp overlying the bone window were easily observed. During the course of a behavioral assessment for her self-injury, it was observed that the overall frequency of occurrence of self-injury increased significantly (P < .01) when the scalp was protruding and bulging compared with when the scalp was flush with the skull table. Periods of increased scalp protrusion were also associated with higher scores on a pain scale developed for children with communicative impairments associated with severe neurological impairment. After shunt replacement, there was remarkable improvement in functional status and decreased episodic self-injury. | 18,827,271 |
Epstein-Barr virus-associated meningoencephalomyelitis: intrathecal reactivation of the virus in an immunocompetent child. | Neurologic complications, including meningoencephalitis, transverse myelitis, and peripheral neuropathy, have been reported in patients with acute infectious mononucleosis. Chronic active Epstein-Barr virus and human immunodeficiency virus infections occasionally induce central nervous system lymphoma. On the other hand, central nervous system disease alone associated with Epstein-Barr virus rarely occurs in previously healthy individuals. A 15-year-old girl who developed acute disseminated encephalomyelitis-like disease presenting fever, anuresis, diplopia, and muscle weakness is described here. Clinical and neuroimaging studies led to the diagnosis of encephalomyelitis. Despite the absence of infectious mononucleosis-like symptoms, anti-Epstein-Barr virus antibody titers in serum and cerebrospinal fluid showed the virus reactivation. The copy number of Epstein-Barr virus DNA increased in cerebrospinal fluid but not in peripheral blood. Ganciclovir and repeated methyl-prednisolone pulse therapy resulted in complete resolution. Central nervous system disease on the limited intrathecal reactivation of Epstein-Barr virus in immunocompetent children should be differentiated from acute disseminated encephalomyelitis. | 18,827,273 |
Melatonin and its agonists: an update. | The pineal hormone melatonin is able to shift the timing of circadian rhythms, including the sleep-wake cycle, and to promote sleep. Melatonin agonists with similar properties have therapeutic potential for the treatment of circadian rhythm sleep disorders. Depression is specifically targeted by agomelatine, which is also a serotonin-2C (5-HT(2C)) antagonist. | 18,827,285 |
Schizophrenia and offspring's risk for adverse pregnancy outcomes and infant death. | Women with schizophrenia are at increased risk for adverse pregnancy outcomes. It is not known whether offspring born to fathers with schizophrenia also have an increased risk. To evaluate paternal and maternal influences on the association between schizophrenia and pregnancy outcomes. A record linkage including 2 million births was made using Swedish population-based registers. The risk for adverse pregnancy outcomes was evaluated through logistic regression. Offspring with a mother or father with schizophrenia faced a doubled risk of infant mortality, which could not be explained by maternal behaviour alone during pregnancy. Excess infant death risk was largely attributable to post-neonatal death. Maternal factors (e.g. smoking) explained most of the other risks of adverse pregnancy outcomes among both mothers and fathers with schizophrenia. The risks to offspring whose fathers had schizophrenia suggest that, in addition to maternal risk behaviour, non-optimal social and/or parenting circumstances are of importance. | 18,827,293 |
FPGA design and implementation for EIT data acquisition. | OXBACT-5 was designed to meet the challenges involved in working in the intensive care hospital environment focussed particularly on thoracic imaging of patients with respiratory distress and chronic heart failure (CHF). The FPGA-based wireless LAN linked multi-channel EIT data acquisition system (DAS) providing 16 programmable excitation current channels and 64 voltage measurement channels is presented. It contains function modules of a PCI bus interface, direct digital synthesizers, dual-port memory blocks, digital demodulation and all the command and control logic in the FPGA. The whole EIT data acquisition system is fully programmable and reconfigurable from the host PC. The excitation frequency, excitation patterns, the measuring sequence and the gain of each measurement channel can be set from the host PC before each measurement. The demodulation is implemented in the FPGA chip to reduce the data rate between the DAS and the host PC. In addition, measurement process management is achieved in this FPGA chip. Complemented by analogue devices such as ADCs, DACs, analogue buffers and analogue multiplexers, the new FPGA-based EIT DAS system is implemented in a very compact way for bedside use in intensive care units of hospitals. It is intended for applications such as continuous respiration monitoring with data collection at 25 frames per second. Image reconstruction times depend on the choice of 2D or 3D imaging algorithms and the available processing power. | 18,827,313 |
A model of speckle contrast in optical coherence tomography for characterizing the scattering coefficient of homogenous tissues. | We present a theoretical model for analyzing the speckle contrast of optical coherence tomography (OCT). This model is based on the addition of noise and an OCT signal in the logarithmic scale. The theoretical model reveals that, for the superficial layer of homogenous tissue, the contrast ratio is a linear function of the location of the coherence gate in the sample and the slope of this linear dependence is proportional to the scattering coefficient. The theoretical model is consistent with the experimental results, suggesting that the slope can be useful to characterize the scattering coefficient of the homogenous samples. | 18,827,323 |
Planning lung radiotherapy using 4D CT data and a motion model. | This work is a feasibility study to use a four-dimensional computed tomography (4D CT) dataset generated by a continuous motion model for treatment planning in lung radiotherapy. The model-based 4D CT data were derived from multiple breathing cycles. Four patients were included in this retrospective study. Treatment plans were optimized at end-exhale for each patient and the effect of respiratory motion on the dose delivery investigated. The accuracy of the delivered dose as determined by the number of intermediate respiratory phases used for the calculation was considered. The time-averaged geometry of the anatomy representing the mid-ventilation phase of the breathing cycle was generated using the motion model and a treatment plan was optimized for this phase for one patient. With respiratory motion included, the mid-ventilation plan achieved better target coverage than the plan optimized at end-exhale when standard margins were used to expand the clinical target volume (CTV) to planning target volume (PTV). Using a margin to account for set-up uncertainty only, resulted in poorer target coverage and healthy tissue sparing. For this patient cohort, the results suggest that conventional three-dimensional treatment planning was sufficient to maintain target coverage despite respiratory motion. The motion model has proved a useful tool in 4D treatment planning. | 18,827,322 |
Changes in deep abdominal muscle thickness during common trunk-strengthening exercises using ultrasound imaging. | Cross-sectional study design. To characterize changes in muscle thickness in the transversus abdominis (TrA) and internal oblique (IO) muscles during common trunk-strengthening exercises, and to determine whether these changes differ based on age. Although trunk-strengthening exercises have been found to be useful in treating those with low back pain (LBP), our understanding of the relative responses of the TrA and IO muscles during different exercises is limited. Six commonly prescribed trunk-strengthening exercises were performed by 120 subjects (40 subjects per age group: 18-30, 31-40, and 41-50 years). Ultrasound imaging was used to measure the thickness of the TrA and IO during the resting and contracted state of each exercise. The average thickness of the muscles while in the contracted position was divided by the thickness values in the resting position for each exercise, based on 2 performances of each exercise. Two 3-by-6 repeated-measures analyses of variance were used to determine significant changes in muscle thickness of the TrA and IO, based on age group and exercise performed. For both muscles, the trunk exercise-by-age interaction effect (TrA, P = .358; IO, P = .217) and the main effect for age (TrA, P = .615; IO, P = .219) were not significant. A significant main effect for trunk exercise for both muscles (P<.001) was found. The horizontal side-support (mean +/- SD contracted-rest thickness ratio: TrA, 1.95 +/- 0.69; IO, 1.88 +/- 0.52) and the abdominal crunch (mean +/- SD contracted-rest thickness ratio: TrA, 1.74 +/- 0.48; IO, 1.63 +/- 0.41) exercises resulted in the greatest change in muscle thickness for both muscles. The abdominal drawing-in maneuver (mean +/- SD contracted-rest thickness ratio: TrA, 1.73 +/- 0.36; IO, 1.14 +/- 0.33) and quadruped opposite upper and lower extremity lift (mean +/- SD contracted-rest thickness ratio: TrA, 1.59 +/- 0.49; IO, 1.25 +/- 0.36) exercises resulted in changes in TrA muscle thickness with minimal changes in IO muscle thickness. Changes in TrA and IO muscle thickness differed across 6 commonly prescribed trunk-strengthening exercises among healthy subjects without LBP. These differences did not vary by age. This information may be useful for informing exercise prescription. | 18,827,329 |
Development and evaluation of a novel gene delivery vehicle composed of adenovirus serotype 35. | The capacity of gene delivery vehicles is considered to be a critical factor determining the success of gene therapy. To date, various types of gene delivery vehicle have been developed. Among them, recombinant adeno-virus (Ad) vectors have potential that has favored their worldwide use in vitro and in vivo. Conventional Ad vectors are composed of subgroup C Ad serotype 5 (Ad5), although it has been clarified that the drawbacks of Ad5 vectors are a high seroprevalence of Ad5 in adults and low transduction efficiencies in cells lacking the primary receptor for Ad5, coxsackievirus and adenovirus receptor. To overcome these problems, we developed a novel Ad vector fully composed of Ad serotype 35 (Ad35). Ad35 vectors show a wide tropism for human cells because Ad35 binds to human CD46, which is ubiquitously expressed on almost all human cells, as a primary receptor. In addition, anti-Ad5 antibodies do not inhibit Ad35 vector-mediated transduction and the seroprevalence of Ad35 in adults is lower than that of Ad5. This paper reviews our studies on the development and evaluation of Ad35 vectors. Ad vectors derived from other Ad serotypes different from Ad5, including Ad35, are expected to be gene delivery vehicles alternative to conventional Ad5 vectors. | 18,827,334 |
Anti-inflammatory and immunomodulatory properties of 2-amino-3H-phenoxazin-3-one. | Accumulating evidence suggests that nitric oxide (NO) and prostaglandin E(2) (PGE(2)) are involved in the pathogenesis of various chronic inflammatory diseases and cancer. During the course of a screening program to identify natural anti-inflammatory substances, we isolated the compound 2-amino-3H-phenoxazin-3-one (APO) from an extract of the edible brown mushroom Agaricus bisporus IMBACH. APO inhibited NO production by mouse peritoneal macrophages in response to the pro-inflammatory stimuli lipopolysaccharide (LPS) and interferon (IFN)-gamma (LPS/IFN-gamma) at low concentrations (IC(50)=1.5 microM) through reduced inducible NO synthase protein expression. PGE(2) production by LPS/IFN-gamma-stimulated macrophages was inhibited by APO at much lower concentrations (IC(50)=0.27 microM) than those required for the inhibition of NO production. Mechanistic analysis showed that APO inhibited both cyclooxygenase (COX)-1 and COX-2 enzyme activities with almost equal selectivity. Secretion of NO and the pro-inflammatory cytokine IL-6 by IFN-gamma-activated RAW264.7 cells, a murine macrophage-like cell line, was also dose-dependently reduced by APO. Furthermore, APO increased the secretion of the anti-inflammatory cytokine IL-4 by antigen-stimulated T cells and promoted the polarization of CD4(+) Th cells toward the anti-inflammatory Th2 phenotype at equimolar concentrations that inhibited NO production. Our results suggested that APO induced polarization toward the Th2 subset, at least in part through the down-regulation of IL-12 production. Thus, APO appears to have potent anti-inflammatory and immunoregulatory properties that may provide a promising therapeutic strategy for the treatment of T cell-mediated inflammatory autoimmune diseases as well as for bacteria-induced chronic-inflammatory diseases. | 18,827,359 |
Development of novel fast-disintegrating tablets by direct compression using sucrose stearic acid ester as a disintegration-accelerating agent. | It was attempted to produce novel furosemide (FS) fast-disintegrating tablets by direct compression. The combination of FS, microcrystalline cellulose, croscarmellose sodium and xylitol was used as the basic formulation, and sucrose stearic acid ester (SSE) was chosen as an additional additive. The tablets with SSE were prepared by the simple addition of SSE, using a lyophilized mixture of FS and SSE or using a FS/SSE mixture obtained by evaporation of their ethanol solution. Only the tablets, produced using the FS/SSE mixture obtained by organic solvent (ethanol) evaporation, showed hardness of more than 30 N and a disintegration time of less than 20 s, which were the properties suitable for fast-disintegrating tablets. These properties were considered to result from well-mixed and fine-powdered SSE and FS. | 18,827,375 |
New organoselenium compounds active against pathogenic bacteria, fungi and viruses. | Different N-substituted benzisoselenazol-3(2H)-ones, analogues of ebselen were designed as new antiviral and antimicrobial agents. We report their synthesis, chemical properties as well as study on biological activity against broad spectrum of pathogenic microorganisms (Staphylococcus aureus, Staphylococcus simulans, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Candida albicans, Aspergillus niger) and viruses (herpes simplex virus type 1 (HSV-1), encephalomyocarditis virus (EMCV), vesicular stomatitis virus (VSV)), in vitro. Most of them exhibited high activity against viruses (HSV-1, EMCV) and gram-positive bacteria strains (S. aureus, S. simulans), while their activity against gram-negative bacteria strains (E. coli, P. aeruginosa, K. pneumoniae) was substantially lower. Some of tested compounds were active against yeast C. albicans and filamentous fungus A. niger. | 18,827,382 |
Sesquiterpenes from the roots of Cichorium endivia. | Twelve new sesquiterpene and sesquiterpene glycosides were obtained along with eleven known compounds from the roots of Cichorium endivia (Compositae). The compounds were identified as guaianolide, germacrenolide and elemanolide, based on spectroscopic methods and chemical evidence. | 18,827,387 |
Cytotoxic and anti-oxidant activities of lanostane-type triterpenes isolated from Poria cocos. | A new lanostane-type triterpene, 29-hydroxypolyporenic acid C (8), was isolated from the dried sclerotia of Poria cocos together with eight other known compounds pachymic acid (1), dehydropachymic acid (2), 3-acetyloxy-16alpha-hydroxytrametenolic acid (3), polyporenic acid C (4), 3-epi-dehydropachymic acid (5), 3-epi-dehydrotumulosic acid (6), tumulosic acid (7), and dehydrotumulosic acid (9). The compounds were identified by spectral analysis and comparison with spectroscopic data reported in the literatures. Although none of the nine (1 to 9) compounds showed promising antioxidant activity, 1 through 6 and 8 showed good cytotoxicity against human lung cancer cell line A549 and human prostate cancer cell line DU145. Interestingly, all these compounds exhibited better cytotoxicity towards A549 than DU145 cells. | 18,827,390 |
Migratory localization of cyclin D2-Cdk4 complex suggests a spatial regulation of the G1-S transition. | The association of the cyclin D-Cdk (DC) complex with retinoblastoma protein (pRb) is required for the G1-S transition of the cell cycle. Cyclin synthesis, nuclear localization and degradation are control mechanisms for the transition, but regulation of the DC complex nuclear import also contributes to the transition. Analysis of the timing of the G1-S transition in mammalian cell lines revealed acceleration with overexpression of cyclin D2 and Cdk4. Immunolocalization assays revealed that cyclin D2 and Cdk4 formed a complex in the cytoplasm and approached the nucleus. They accumulated on the cytosolic surfaces of the nuclear pores and then were arrested at the nuclear membrane before the nucleus reached a critical size. Finally, the complex was released into the nucleus and colocalized with pRb there, which led to pRb phosphorylation and DNA synthesis. The translocalization depended on the G1-S transition. In contrast, a truncated cyclin D2 that was not able to fully associate with Cdk4 lost the ability for release into the nucleus. This pattern of translocalization suggests a spatial separation of the cyclin D-Cdk complex from pRb and DNA in the nucleus to regulate the G1-S transition. | 18,827,403 |
SYP71, a plant-specific Qc-SNARE protein, reveals dual localization to the plasma membrane and the endoplasmic reticulum in Arabidopsis. | SNAREs ('Soluble N-ethyl-maleimide sensitive factor attachment protein receptors') play a critical role in the membrane fusion step of the vesicular transport system in eukaryotes. The number of the genes encoding SNARE proteins is estimated to be 64 in Arabidopsis thaliana. This number is much larger than those in other eukaryotes, suggesting a complex membrane trafficking in plants. The Arabidopsis SNAREs, the SYP7 group proteins, SYP71, SYP72, and SYP73, form a plant-specific SNARE subfamily with not-yet-identified functions. We have previously reported that the SYP7 subfamily proteins are predominantly localized to the endoplasmic reticulum in the Arabidopsis suspension cultured cells under transient expression condition. However, several proteomic analyzes indicated the plasma membrane localizations of one of SYP7 subfamily proteins, SYP71. In order to confirm the expression patterns and subcellular localization of SYP7, we performed combination analyses including promoter GUS analysis, a sucrose density gradient centrifugation analysis, as well as an observation on transgenic Arabidopsis plants expressing GFP-fused SYP71 under control of its native promoter. From these analyses, we concluded that one of the SYP7 subfamily proteins, SYP71, is predominantly expressed in all vegetative tissues and mainly localized to the plasma membrane. We also found that SYP71 is localized to the endoplasmic reticulum in the dividing cells of various types of tissues. | 18,827,404 |
MicroRNA-206 is highly expressed in newly formed muscle fibers: implications regarding potential for muscle regeneration and maturation in muscular dystrophy. | miR-1, miR-133a, and miR-206 are muscle-specific microRNAs expressed in skeletal muscles and have been shown to contribute to muscle development. To gain insight into the pathophysiological roles of these three microRNAs in dystrophin-deficient muscular dystrophy, their expression in the tibialis anterior (TA) muscles of mdx mice and CXMD(J) dogs were evaluated by semiquantitative RT-PCR and in situ hybridization. Their temporal and spatial expression patterns were also analyzed in C2C12 cells during muscle differentiation and in cardiotoxin (CTX)-injured TA muscles to examine how muscle degeneration and regeneration affect their expression. In dystrophic TA muscles of mdx mice, miR-206 expression was significantly elevated as compared to that in control TA muscles of age-matched B10 mice, whereas there were no differences in miR-1 or miR-133a expression between B10 and mdx TA muscles. On in situ hybridization analysis, intense signals for miR-206 probes were localized in newly formed myotubes with centralized nuclei, or regenerating muscle fibers, but not in intact pre-degenerated fibers or numerous small mononucleated cells, possibly proliferating myoblasts and inflammatory infiltrates. Similar increased expression of miR-206 was also found in C2C12 differentiation and CTX-induced regeneration, in which differentiated myotubes or regenerating fibers showed abundant expression of miR-206. However, CXMD(J) TA muscles contained smaller amounts of miR-206, miR-1, and miR-133a than controls. They exhibited more severe and more progressive degenerative alterations than mdx TA muscles. Taken together, these observations indicated that newly formed myotubes showed markedly increased expression of miR-206, which might reflect active regeneration and efficient maturation of skeletal muscle fibers. | 18,827,405 |
A boy with growth disturbance caused by hypothalamic damage associated with intracranial hypotension syndrome following a motor vehicle accident: case report. | We examined the endocrine profile of a boy aged 10 years and 4 months with intracranial hypotension syndrome (IHS) following a motor vehicle accident. His complaint was growth disturbance. GH secretion gradually decreased and finally was lost in spite of an epidural blood patch procedure. His height velocity was restored by GH replacement therapy. MRI and SPECT revealed damage to the hypothalamic and pituitary gland. We concluded that growth disturbance is an important sign in pediatric patients with hypothalamic damage associated with IHS. | 18,827,408 |
Hepatocarcinogenesis following HCV RNA eradication by interferon in chronic hepatitis patients. | Interferon (IFN) therapy reduces the incidence of hepatocarcinogenesis in patients with hepatitis C viral (HCV) infection who achieve a sustained virological response (SVR). The aim of the present study was to determine the rate of hepatocarcinogenesis and the risk factor in sustained virological responders. The study subjects were 1,193 patients with HCV-related chronic liver disease and IFN- or IFN plus ribavirin-induced SVR. The age, male/female ratio, and liver fibrosis stage [(F0-F3)/LC] were 15-83 years, 808/385, and 1106/41, respectively. Patients were followed-up for 8.3 years (range, 0 to 19.0 years) and the incidence of hepatocellular carcinoma was recorded. Hepatocellular carcinogenesis was detected in 23 patients during the follow-up. The crude rates of hepatocarcinogenesis at 5, 10, and 15 years were 1.5%, 2.4% and 4.1%, respectively. Multivariate analysis identified cirrhosis, male sex and age older than 50 years as determinants of hepatocarcinogenesis with hazard ratios of 12.9 (p<0.001), 6.45 (p=0.012), and 20.2 (p=0.004), respectively. Long-term follow-up of patients with chronic HCV infection is necessary even in those who show SVR, especially in male elderly patients with cirrhosis. | 18,827,409 |
The anatomical distribution of colorectal cancer in Korea: evaluation of the incidence of proximal and distal lesions and synchronous adenomas. | The incidence of colorectal cancer throughout the Republic of Korea has been rising over the last 25 years. The change in incidence is supposed to be due to the westernized life style. We evaluated the anatomical distribution of colorectal cancer and the properties of synchronous adenomatous polyps in the Korean population which were known to be different from those in Western countries. From January 1997 to December 2006, 896 cases of colorectal cancer were reviewed retrospectively. A total of 25.1% were proximally located cancer with a modest female predominance (odds ratio 1.5). Synchronous adenomatous lesions were accompanied in 31.9% of all colorectal cancer cases. In the distal colorectal cancer patients, 18.8% had proximally located synchronous adenomas. In those with proximal colon cancer, only 20.5% of patients had distally located adenomas. The likelihood of a proximal colon cancer without distal sentinel lesions was higher in females (odds ratio 3.0). There has been a steep rise in the incidence of colorectal cancer in Korea and distal colon cancer is more prevalent than in Western countries. However, as over 20% of proximal colon cancers can exist without distal colonic synchronous or sentinel lesions, a total colonoscopic examination should be considered first in surveillance. | 18,827,411 |
Removal of a foreign body (artificial tooth) from the bronchial tree: a new method. | A 70-year-old man who had aspirated an artificial tooth during treatment at a dental clinic visited our hospital. His symptoms and physical condition were not remarkable. CT of chest revealed a foreign body in the right middle bronchus; bronchoscopy revealed it was wedged there. First, the authors tried to remove it using a suction device attached to a bronchoscope, as well as by using a forcep; however, the attempt failed. Therefore, a second effort was made using a cap constructed of a nasogastric tube, based on the concept of attaching an endoscopic cap to a bronchoscope. The latter was successful. | 18,827,418 |
Severe respiratory failure and torsades de pointes induced by disopyramide in a patient with myasthenia gravis. | Class 1a anti-arrhythmic drugs are often used for the treatment of atrial fibrillation (AF), but it is not well known that myasthenia gravis (MG)-like symptoms can be generated by their anti-cholinergic effects. We had a patient with MG who developed symptomatic MG aggravation after AF treatment with disopyramide. Symptomatic MG aggravation was followed by Takotsubo-shaped cardiomyopathy, QT prolongation, and torsades de pointes. We suggest that the anti-cholinergic effects of disopyramide can induce MG crisis and should therefore be carefully considered when disopyramide is used to treat AF in patients with MG. | 18,827,420 |
Strain differences in hepatic cytochrome P450 1A and 3A expression between Sprague-Dawley and Wistar rats. | Expression of hepatic cytochrome P450 (CYP) isoforms was compared in Sprague-Dawley (SD) and Wistar (WI) rats, which are commonly used strains in preclinical studies. Basal CYP1A1, CYP1A2, and CYP3A2 mRNA levels were higher in WI rats than in SD rats (by 8-, 3- and 2-fold, respectively). Treatment with phenobarbital, a potent CYP inducer, increased the predominance of expression of these three mRNAs in WI rats (by 26-, 4-, and 2-fold, respectively) along with the predominance of increased microsomal total P450 contents and smooth-surface endoplasmic reticulum in the centrilobular hepatocytes. CYP1A enzymatic activity was also higher in WI rats than in SD rats. No strain differences were observed in phenobarbital induction of CYP2B1/2, CYP2C6, or CYP3A1. CYP3A2 mRNA was more strongly induced by dexamethasone, a typical inducer of CYP3A, together with CYP3A1 mRNA, in WI rats than in SD rats (by 2-fold), whereas the CYP1A1 and CYP1A2 mRNA expression induced by beta-naphtoflavone, a typical inducer of CYP1A, did not differ between the two strains. Furthermore, WI rats exhibited predominantly arylhydrocarbon receptor, pregnane X receptor, and constitutive androstane receptor mRNAs, responsible for CYP1A or CYP3A induction, with phenobarbital or dexamethasone induction. In conclusion, significant, predominant expression of hepatic CYP1A and CYP3A mRNAs in WI rats was observed, possibly related to nuclear receptor-mediated induction. Considering the pharmacokinetic and toxicological importance of CYP1A and CYP3A, different outcomes might arise depending on the rat strains used in preclinical studies of drugs metabolized typically or mainly by both isoforms. | 18,827,444 |
Expression of sonic hedgehog regulates morphological changes of rat developing cerebellum in hypothyroidism. | Although thyroid hormones are crucial for cerebellar development, and several thyroid hormone-dependent genes are known to be correlated with morphological development of the cerebellum, the precise mechanisms of morphological cerebellar changes in hypothyroidism (HT) remain unknown. To investigate these mechanisms in experimental rat HT induced by the anti-thyroid drug methimazole (MMI-HT rat), we carried out gene expression analysis (sonic hedgehog (Shh), reelin, and Bax) using quantitative real-time PCR. Histological examination revealed cerebellar abnormalities, including reductions in the thickness of the molecular layer and delayed disappearance of the external granular layer (EGL), as well as excess bulges or sublobules in the internal granular layer (IGL). At Postnatal Day (P) 6, Shh expression in MMI-HT rat was comparable to that in controls, thus suggesting that Shh expression was sufficient to form the lobes in the initial phase. However, Shh expression decreased in the later phases, as compared with age-matched controls. This demonstrated that stronger and sustained signaling is necessary for partitioning of the cardinal lobes into lobes and sublobes. Although reelin expression was not clearly different from that in controls, Bax expression decreased at P 15. The attrition of Bax at P 15 as well as Shh in the later phase may be related to irregularities in the IGL and the relatively large numbers of internal granular cells. Taken together, these results suggest that Shh expression is related to the morphological cerebellar changes in experimental hypothyroidism and that sustained signaling by Shh may play a key role in normal development, particularly lobulation, in the cerebellum. | 18,827,446 |
Chinese dumpling scare hits Japan--a case of methamidophos food poisoning. | An outbreak of food poisoning that affected at least ten people in various regions of Japan was traced to exposure to Chinese dumplings contaminated with the organophosphate insecticide Methamidophos. We experienced the most serious case, a five years old girl, who suffered coma. She presented with features of cholinergic overactivity and her serum cholinesterase activity was 9 U/l. We started intravenous treatment with pralidoxime iodide, atropine sulfate, and midazolam. Her symptoms improved gradually and she was discharged on day 25 without any sequelae. Though poisoning attributed to organophosphate insecticides has become less common in recent years, it is even more important to diagnose the problem rapidly based on the characteristic symptoms and to start specific treatment at the earliest possible stage after poisoning. | 18,827,448 |
[Inhibitory effects of hybrid liposomes on the growth of gastric tumor cells established from cotton rats]. | We established cell-line (CoRa 622 G6) of gastric carcinoma using cotton rats with spontaneous malignant gastric carcinoma with hypergastrinaemia. Inhibitory effects of hybrid liposomes (HL) composed of dimyristoylphosphatidylcoline (DMPC) and polyoxyethylene (n) dodecyl ether (C(12)(EO)(n): n=21, 23, 25) on the growth of CoRa 622 G6 cells were clarified on the basis of WST-1 assay. Fusion and accumulation of HL including fluorescence probe into CoRa 622 G6 cell membrane were clarified using confocal laser microscopy and total internal reflection fluorescence microscopy. Induction of apoptosis of CoRa 622 G6 cells after the treatment with HL was observed in fluorescence micrographs on the basis of Annexin-V binding assay and TUNEL method using confocal laser microscopy. The results in this study could contribute to the chemotherapy for patients with gastric carcinoma. | 18,827,469 |
[NMR analysis of a contaminant in heparin]. | Recently, it has been reported that certain lots of heparin are associated with an acute, rapid onset of serious side effects indicative of allergic reaction, and (1)H NMR is one of the convenience but strong analytical methods to identify a contaminant in heparin. However, an NMR signal from the contaminant in some cases is overlapped with a satellite peak from heparin, leading a misunderstanding of the presence of the contaminant. Here, we show the satellite peak observed close to the NMR signal of the contaminant, and recommend the (13)C decoupling NMR to discriminate the satellite peak from the contaminant. | 18,827,473 |
Pegylated interferon plus ribavirin combination therapy for chronic hepatitis C in patients with congenital coagulation disorders. | Chronic hepatitis C (CHC) and end-stage liver disease are becoming an increasingly common cause of mortality in patients with congenital bleeding disorders, especially in the HIV-coinfected group. Combination of pegylated interferon (Peg-IFN) and ribavirin has recently become the treatment of choice for CHC. In this study, we evaluated the safety and efficacy of combination therapy with Peg-IFN plus ribavirin for the treatment of CHC in human immunodeficiency virus (HIV)- and HIV+ patients with congenital bleeding disorders. Between 2000 and 2004, 50 (18-68 years old) patients with CHC (19 HIV+) from two hemophilia centers were included in the study. They were treated with weekly subcutaneous administration of Peg-INF-alpha combined with 800-1,200 mg ribavirin daily, for 24-48 weeks depending on viral genotype. Response was evaluated at weeks 12, 24, 48 (end of treatment response) and 72 had sustained virological response). Overall, 22/50 patients (43.8%) had end of treatment response and 20/50 (40%) sustained virological response. HIV- patients responded similarly to the general population (58.1%), while HIV+ patients had very low response rates (10.5%). The high rate of discontinuation (36.9%) as a result of side effects contributed to the observed low response rate in the HIV+ group. The only factor strongly associated with sustained virological response in the HIV- patients was the reduction of HCV RNA at 12 weeks (p = 0.001). Patients with viral genotypes other than 1 had higher SVR rates, but this was not found to be statistically significant. Peg-INF plus ribavirin is safe for the treatment of CHC monoinfected patients with inherited bleeding disorders, with similar response rates to nonhemophiliacs. On the contrary, in HIV coinfected hemophilic patients under highly active antiretroviral therapy it is associated with severe toxicity and very poor sustained virological response rates. Careful evaluation and several considerations are needed before starting treatment in this population. | 18,827,474 |
Auditory brainstem correlates of basilar membrane nonlinearity in humans. | A behavioral measure of the basilar membrane response can be obtained by comparing the growth in forward masking for maskers at, and well below, the signal frequency. Since the off-frequency masker is assumed to be processed linearly at the signal place, the difference in masking growth with level is thought to reflect the compressive response to the on-frequency masker. The present experiment used an electrophysiological analog of this technique, based on measurements of the latency of wave V of the auditory brainstem response elicited by a 4-kHz, 4-ms pure tone, presented at 65 dB SPL. Responses were obtained in quiet and in the presence of either an on-frequency (4 kHz) or an off-frequency (1.8 kHz) pure-tone forward masker. Wave V latency increased with masker level, although the increase was greater for the off-frequency masker than for the on-frequency masker, consistent with a more compressive response to the latter. Response functions generated from the data showed the characteristic shape, with a nearly linear response at lower levels and 4:1 compression at higher levels. However, the breakpoint between the linear region and the compressive region was at about 60 dB SPL, higher than expected on the basis of previous physiological and psychophysical measures. | 18,827,479 |
Role of AIB1 for tamoxifen resistance in estrogen receptor-positive breast cancer cells. | The p160 nuclear receptor coactivator, AIB1 (amplified in breast cancer 1), is frequently overexpressed in human breast cancer and has been shown to be associated with tamoxifen resistance. The present study aimed to investigate the role of AIB1 in tamoxifen resistance of breast cancer cells. We reconstructed the RNA interference expression vector, pGenesil-1-U6, specially targeting AIB1 mRNA, and it was stably transfected into the human breast cancer cell line BT474. Cell proliferation and cell cycle distribution were assessed in the cells transfected with scramble control shRNA (BT474/shControl) and AIB1 shRNA (BT474/shAIB1) to explore the possible functions of AIB1 in breast cancer progression. The expression of AIB1, ERalpha, HER2 and pS2 was analyzed in the presence of 17beta-estradiol or 4-hydroxytamoxifen (Tam) by Western blot analysis. Compared with the parental BT474 and the BT474/shControl cells, the levels of AIB1 mRNA and protein were significantly reduced in BT474/shAIB1 cells. A knockdown of AIB1 levels restored the inhibitory effect of tamoxifen on cell proliferation. Tam behaves like an estrogen agonist in ER-positive breast cancer cells that express high levels of AIB1 and HER2, resulting in de novo resistance. Knockdown of AIB1 can eliminate this cross talk and restore the antitumor effects of tamoxifen. | 18,827,493 |
[Comparisons of health inequalities in small areas with using the standardized mortality ratios in Korea]. | This study was performed to compare the standardized mortality ratios among different small areas and to explore the usefulness of standardized mortality ratios in South Korea. To calculate the standardized mortality ratio (SMR), we obtained the national deaths certificate data (2004-2006) and national registration population data (2003-2006), and these were provided by the National Statistical Office. The small areas (Eup.Myoun.Dong) were based on the subdivisions of counties. Among the 3,580 small areas classified by the National Statistical Office, 3,571 areas were included in this study. The basic statistics and decile distributions of the SMRs for all the regional levels were calculated, and the small area maps were also produced for some selected regions. To evaluate the precision of SMR, we calculated the 95% confidence intervals of the SMR in selected small areas. The mean and the standard deviation of the SMRs among all small areas were 100.8 and 17.0, respectively. The range was 30.6-211.7 and the inter-quartile range was 20.7. Seoul metropolitan city displayed the lowest mean SMR among 16 regions in South Korea, and 34.6 percent of the small area SMRs belonged to the first decile (the lowest group). On the contrary, the mean SMR of Gyeongsangnam province was highest, and 26.1 percent of the small area SMRs belonged to the tenth decile(the highest group). In some areas, the precision of the SMR, which was calculated by the 95% confidence intervals, remained questionable, yet it was quite stable for almost areas. The standardized mortality ratios can be useful for allocating health resources at the small area level in Korea. | 18,827,497 |
[Study on the health status of the residents near military airbases in Pyeongtaek City]. | We conducted an epidemiologic survey to evaluate the effect of the aircraft noise exposure on the health of the residents near the military airbases in Pyeongtaek City. The evaluation of environmental noise level, questionnaire survey, and health examination were performed for 917 residents. The study population consisted of four groups: subjects who lived in the village close to the fighter airbase (high exposure), subjects who lived along the course of fighters (intermediate exposure), and subjects near a helicopter airbase, and the control group. The prevalence of the aircraft noise related accident and irritable bowel syndrome in the exposure groups were higher than that of the control group. The risks of noise induced hearing loss, hypertension and diabetes mellitus were higher in the exposed groups than in the control group. The prevalence of anxiety disorder and primary insomnia were higher in the exposed groups than in the control group. Prevalence odd ratios of the risk for primary insomnia after adjusting age, sex, agricultural noise, and occupation were 4.03 [95% confidence interval (95% CI) 1.56-10.47] for the subject near the helicopter airbase, 1.23 (95% CI 0.40-3.76) for those intermediately exposed to fighter noise, and 4.99 (95% CI 2.14-11.64) for those highly exposed to fighter noise. The results of the present study suggest that the aircraft noise may have adverse effects on hearing function, cardiovascular health and mental health. Therefore, it seems to be needed to take proper measures including the control of the aircraft noise and the management of the exposed people's health. | 18,827,498 |
Lead hazards for pregnant women and children: part 1: immigrants and the poor shoulder most of the burden of lead exposure in this country. Part 1 of a two-part article details how exposure happens, whom it affects, and the harm it can do. | Poor, urban, and immigrant populations are at far greater risk for lead exposure than are other groups in the United States. Children with even slightly elevated blood lead levels are at increased risk for significant neurobehavioral problems that can extend through adolescence. Research has shown that elevated blood lead levels in pregnant women, even those well below 10 micrograms per deciliter-the Centers for Disease Control and Prevention's "level of concern"-can cause miscarriage, premature birth, low birth weight, and subsequent developmental delays in their children. Despite these well-established dangers, routine prenatal lead screening and lead education is not a standard of care. Part 1 of this two-part article presents a short case example of a pregnant mother with lead poisoning and describes the epidemiology of lead exposure in the United States, the main sources of lead exposure, and the effects of lead on the pregnant mother and the developing fetus and child. Prevention is crucial. Treatment options such as chelation must be used selectively and will not reverse damage once it's occurred. Part 2 will describe recommendations for screening, education, nutrition, reducing environmental exposures, and treatment. | 18,827,541 |
Activity of lipoplatin in tumor and in normal cells in vitro. | Lipoplatin is a novel liposomal cisplatin formulation with reduced adverse side effects compared with its parental compound, cisplatin. The aims of this preclinical study were to compare lipoplatin and cisplatin cytotoxicity in vitro in established cell lines derived from non-small cell lung cancer, renal cell carcinoma, and in normal hematopoietic cell precursors, and to identify biological markers associated with sensitivity and resistance. Our results showed a superior cytotoxicity in all tumor cell models and a much lower toxicity in normal cells for lipoplatin compared with cisplatin, suggesting a higher therapeutic index for the liposomal compound. Moreover, RT-PCR analysis of molecular markers known to be related to cisplatin resistance showed a direct correlation between cisplatin and lipoplatin resistance and ERCC1 and LRP expression. In conclusion, lipoplatin showed a higher antitumor activity in both tumor histotypes investigated and was found to be safer than the parent compound, cisplatin. Moreover, ERCC1 and LRP expression levels would seem to be valid predictors of sensitivity or resistance to these drugs. | 18,827,563 |
Nonalcoholic fatty liver disease: the potential role of nutritional management. | To review available data pertaining to dietary imbalances and metabolic alterations leading to the development of fatty liver disease and nutritional managements. The importance of treating fatty liver disease is now firmly recognized not only because of the risk of progression toward a more aggressive liver disease but also because the fatty liver is an important provider of cardiovascular risks. The ideal diet for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis patients should reduce fat mass and inflammation in the adipose tissue, restore insulin sensitivity, and provide low amounts of substrates for de-novo lipogenesis, but scientific evidence to recommend specific diets is currently lacking. Moderate weight loss, low-calorie diets, reduction in saturated fatty acids intake, together with an increase in monosaturated and n-3 polyunsaturated fatty acids appear to be beneficial. Excessive consumption of high glycemic index carbohydrates appears deleterious, as it favors hyperglycemia and hyperinsulinemia and stimulates de-novo lipogenesis. Physical exercise is an important component of the approach, as it improves insulin sensitivity. Behavioral therapy promotes long-term compliance to lifestyle modifications. One panacea is unlikely to be found, the more useful approach is probably multimodal and includes tailored lifestyle modifications. Randomized controlled trials are needed to establish dietary recommendations. While awaiting such trials, reduced consumption of simple sugar, especially sweetened beverages, and incremental increase in physical activity must be encouraged. | 18,827,582 |
Inhibition of Hsp90 leads to cell cycle arrest and apoptosis in human malignant pleural mesothelioma. | Heat shock protein 90 (Hsp90) is an abundant molecular chaperone that mediates the maturation and stability of a variety of proteins associated with the promotion of cell growth and survival. Inhibition of Hsp90 function leads to proteasomal degradation of its mis-folded client proteins. Recently, Hsp90 has emerged as being of prime importance to the growth and survival of cancer cells and its inhibitors have already been used in phase I and II clinical trials. We investigated how 17-allylamino-17-demethoxygeldanamycin (17-AAG), a small molecule inhibitor of Hsp90, is implicated in human malignant pleural mesothelioma (MM). We found that 17-AAG led to significant G1 or G2/M cell cycle arrest, inhibition of cell proliferation, and decrease of AKT, AKT1, and survivin expression in all human malignant pleural mesothelioma cell lines examined. We also observed significant apoptosis induction in all MM cell lines treated with 17-AAG. Furthermore, 17-AAG induced apoptosis in freshly cultured primary MM cells and caused signaling changes identical to those in 17-AAG treated MM cell lines. These results suggest that Hsp90 is strongly associated with the growth and survival of MM and that inhibition of Hsp90 may have therapeutic potential in the treatment of MM. | 18,827,603 |
Community-acquired methicillin-resistant staphylococcus aureus: diagnosis and treatment update for plastic surgeons. | : After studying this article, the participant should be able to: 1. Identify risk factors associated with community-acquired methicillin-resistant Staphylococcus aureus. 2. Recognize the clinical presentation of patients with community-acquired methicillin-resistant S. aureus. 3. Understand the treatment and indications for decolonization of patients who have community-acquired methicillin-resistant S. aureus infections. : Community-acquired methicillin-resistant Staphylococcus aureus has evolved over the past 10 years as a new health threat seen by plastic surgeons and is an increasing cause of soft-tissue infections. This pathogen has several distinct virulence factors and unique antimicrobial susceptibilities that distinguish methicillin-resistant S. aureus from traditional hospital-acquired methicillin-resistant S. aureus. This article reviews the epidemiology, risk factors, clinical presentation, and treatment of community-acquired methicillin-resistant S. aureus. | 18,827,629 |
Radiation effects and radioprotection in MC3T3-E1 mouse calvarial osteoblastic cells. | Little is known about the mechanisms and treatment of radiation-induced inhibition of craniofacial bone growth. In an earlier study, the radioprotector amifostine (WR-2721) administered to rabbits before irradiation radioprotected cultured orbitozygomatic complex periosteal osteoblast-like cells. This study assessed the effects of amifostine and its active metabolite on the radiation survival, function, and phenotype of mouse calvarial osteoblast-like cells in a cell culture model. MC3T3-E1 newborn mouse calvarial osteoblast-like cells underwent gamma-radiation (0 to 10 Gy) in the presence or absence of either WR-2721 or WR-1065, its active metabolite (10 to 10 M). The effects of radiation with and without drugs were assessed using endpoints of colony-forming ability, cell viability, alkaline phosphatase activity, and expression of osteoblastic phenotype genes (alkaline phosphatase, collagen type I, osteocalcin, and osteopontin). All experiments were replicated at least in triplicate. Irradiation resulted in a dose-dependent inhibition of clonogenic cell survival. Pretreatment with WR-1065, but not WR-2721, resulted in a significant improvement of osteoblast-like cell survival. Specifically, maximum radioprotection was observed with 10 M WR-1065 at a clinically relevant 2-Gy dose of irradiation. No significant radioprotection was observed at the lower (5 x 10 M) concentration of WR-1065. Furthermore, radiation seemed to suppress the expression of osteoblastic phenotype-related genes in a dose-dependent manner. This study reveals improved survival after irradiation in osteoblast-like cells treated with WR-1065 in vitro and corroborates previous findings from animal models. Further studies using this agent and similar drugs are important for devising strategies to prevent radiation-induced inhibition of craniofacial bone growth. | 18,827,633 |
Role of TGF-beta and FGF in the treatment of radiation-impaired wounds using a novel drug delivery system. | Despite refinements in radiotherapy, radiation-impaired wound healing continues to be a major source of postoperative morbidity with few treatment options. The application of polypeptide growth factors has been investigated in both the clinical and laboratory settings. The authors used a novel sustained-release delivery system to examine the effect of transforming growth factor (TGF)-beta and fibroblast growth factor (FGF) on radiation-impaired wound healing in a rodent model. Eighty Sprague-Dawley rats underwent dorsal skin surface irradiation of 2500 cGy using a medical linear accelerator producing energy of 6 MeV followed by creation of a full-thickness skin incision. Six groups of 16 animals underwent either sham irradiation (irradiation control); irradiation only; irradiation and unimpregnated delivery system only; or irradiation and either TGF-beta, FGF, or TGF-beta plus FGF combined. Four animals from each group were euthanized at 4, 7, 14, and 28 days, and the harvested specimens underwent ultimate tensile strength testing and histologic evaluation. All five irradiated groups had significantly lower ultimate tensile strength than the sham-irradiated control group at all time points (p < 0.05), thus validating the authors' model of radiation-impaired wound healing. Functional analysis demonstrated that all three growth factor-treated groups had significantly higher tensile strengths than either of the untreated irradiated groups at 14 days after wounding (p < 0.05). Histologic evaluation of the irradiated groups revealed increased cellularity and more organized collagen architecture of all treated groups when compared with the untreated groups, with the most pronounced differences seen at 7 days and 14 days after wounding. This study effectively demonstrates that TGF-beta and FGF act individually and synergistically when delivered locally by means of a sustained release system to improve ultimate tensile strength in an acute postirradiation impaired wound-healing model. | 18,827,634 |
Scars: a review of emerging and currently available therapies. | With the investigation and potential introduction of several novel scar-reducing therapies to the market within the next several years, it is germane to review both the pathophysiology of scarring and the safety and efficacy of currently available and emerging therapeutic agents. An extensive review of the English-language literature was conducted using the MEDLINE database. A comprehensive review of the pathophysiology of scarring and scar management, including both emerging and currently available therapies, was completed. Current clinical studies are limited by small sample sizes, lack of well-designed controls, and lack of standardized scar outcome measurement parameters. A prominent challenge in the study of scar management is the paucity of well-designed, large, randomized, controlled studies examining existing scar-reducing techniques. The greatest improvement in scar-reducing protocols likely entails a polytherapeutic strategy for management. Further investigation into the role of inflammation in scarring is paramount to the development of improved scar-reducing agents. There is a need for large controlled trials using a polytherapeutic strategy that combines existing and novel agents to provide a standardized evidence-based evaluation of efficacy. | 18,827,639 |
Spinal cord injury without radiological abnormality in an infant with delayed presentation of symptoms after a minor injury. | We present a very rare case of an infant with delayed presentation of spinal cord injury without radiologic abnormality (SCIWORA) after a minor injury. To emphasize the importance of spinal evaluation with MRI in selected cases, even after minor injuries, especially in infants. SCIWORA arises mainly in infants and children during accidental trauma or after sport injury. However, it has been very rare for a 6-day-delayed infant SCIWORA after a minor injury. An infant presented with transient nausea and vomiting after falling from a baby-rocking horse of less than 30-cm height. The patient demonstrated right hemiparesis 6 days later. Plain cervical radiographs and brain and cervical spine computed tomograms (CT) were normal, but the cervical magnetic resonance imaging (MRI) demonstrated a high signal in the T2-weighted image of the lower cervical cord, and a neck collar was applied. A follow-up cervical MRI 1 month later showed that the high signal of the lower cervical cord had disappeared. Another follow-up cervical MRI 12 months later also showed normal radiographic findings but there still remained mild weakness of the right lower extremities. The authors present a rare case of infant SCIWORA who developed delayed neurologic symptoms 6 days after a minor injury and suggest that spinal evaluation with MRI could be warranted in the selected case even after minor injuries, especially in infants. | 18,827,684 |
Lumbar epidural capillary hemangioma presenting as lumbar disc herniation disease: case report. | A case of lumbar spinal epidural hemangioma is presented. To present the first reported lumbar spinal epidural hemangioma patient clinically mimicking the lumbar disc herniation disease. Capillary hemangiomas are benign endothelial cell neoplasms that are believed to be hamartomatous proliferations of vascular endothelial cells. The occurrence of spinal epidural capillary hemangiomas is exceedingly rare. There are only 3 reported epidurally located cases of capillary hemangiomas in the spinal channel in literature. Lumbar spinal epidural capillary hemangioma in a patient has not been previously reported. Radiologic features, pathology, and clinical course were documented. L4 hypoesthesia and back pain of the patient was caused by an epidurally located capillary hemangioma. The neurologic symptoms of the patient were markedly improved after surgery. We have reported for the first lumbar epidural capillary hemangioma patient in literature. These lesions are benign and surgical treatment is curative. | 18,827,685 |
The use of traction in the treatment of severe spinal deformity. | Multicenter, retrospective, nonrandomized comparison group study of patients with severe scoliosis and kyphosis treated after 1995 with halo-gravity traction and without halo-gravity traction before definitive fusion. Compare surgical correction of severe spine deformity with preoperative halo traction and without preoperative traction. Prior studies have demonstrated that halo traction is a safe, well-tolerated method of applying gradual, sustained traction to maximize operative correction in patients with severe idiopathic scoliosis (IS) and kyphosis. However, these studies lack a comparison control group and study only a relatively small number of patients with IS. Fifty-three patients with severe scoliosis or kyphosis were studied using hospital records, standing preoperative, traction, postoperative, and final radiographs. Thirty were treated with traction and 23 were treated without traction. Patients within each group were analyzed based on demographics, diagnosis, perioperative, and radiographic data. In addition, patients were evaluated based on diagnosis, specifically whether patients had adolescent idiopathic scoliosis. Within the entire study population, there was no statistically significant difference in main coronal curve correction (62% vs. 59%), operative time, blood loss, and total complication rate (27% vs. 52%). However, the nontraction group underwent vertebral column resection more often (30% vs. 3%, P = 0.015). The traction group had a statistically significant increase in average hospital stay (36 vs. 14 days) (P = 0.011). Analysis of the 23 patients with adolescent idiopathic scoliosis also showed no statistically significant differences in curve correction, blood loss, or complications. Our study shows that patients with halo traction less frequently had a vertebral body resection, but achieved comparable deformity correction. | 18,827,696 |
Rheumatic disease and complementary-alternative treatments: a qualitative study of patient's experiences. | Complementary-alternative medicine (CAM) has been widely used by rheumatic patients for many years, but doctors are often unaware of the actual use. This study aimed at patients' experience and perceptions of CAM as a way for long-term coping with illness. Fifteen in-depth interviews were conducted with patients sampled by contact with voluntary patient-driven rheumatic disease societies, outside of any treatment settings. Strategically, the sampling included a variety of rheumatic diseases and CAM-treatments, but strived otherwise to be typical of CAM-users. Interviews were taped and fully transcribed; coding and analysis of themes were assisted by computer software. Rheumatic disease patients expressed use of CAM as methods of regulation of discomforts, the feeling of the body, and self-empowerment, not for unrealistic healing of their rheumatic disease. They experienced a variety of effects, most often expressed in terms of mind-body interrelated experiences, such as "lightness of the body" rather than relief in specific symptoms. They expressed the feeling of "have been helped" when leaving a CAM-session and appreciated to have more than 1 way to understand their disease and symptoms. They were usually not naive, but were critical consumers. The patients typically believed in the alternative viewpoints of "natural is best" and in "energy meridians," but they were otherwise not believers in any alternative, "new age"-type worldview. These findings suggest that clinical practice may be enriched by listening to or asking rheumatic disease patients' CAM-experiences in a nonpatronizing way. | 18,827,715 |
Hemoglobin vesicles and red blood cells as carriers of carbon monoxide prior to oxygen for resuscitation after hemorrhagic shock in a rat model. | Hemoglobin vesicles (HbVs) are artificial oxygen (O2) carriers that encapsulate concentrated hemoglobin (Hb) solution in phospholipid vesicles (liposomes). Recent reports on cytoprotective effects of exogenous carbon monoxide (CO) urged us to test infusion of CO-bound HbV (CO-HbV) and red blood cells (CO-RBC) in hemorrhagic-shocked rats to improve tissue viability over that of O2-bound HbV (O2-HbV) and O2-bound RBC (O2-RBC). Male Wistar rats were anesthetized with 1.5% sevoflurane inhalation (FiO2 = 21%) while spontaneous breathing was maintained. Shock was induced by 50% blood withdrawal from femoral artery. Fifteen minutes later, they received CO-HbV, CO-RBC, O2-HbV, O2-RBC, or empty vesicles (EV) suspended in 5% recombinant albumin. All groups showed prompt recovery of blood pressure and blood gas parameters just after resuscitation and survived for 6 h of observation period. However, only the EV group showed significant hypotension at 3 and 6 h. Plasma enzyme levels were elevated at 6 h, especially in the O2-HbV, O2-RBC, and EV groups. They were significantly lower in the CO-HbV and CO-RBC groups than in the O2-bound fluids. Immunohistochemical staining of 3-nitrotyrosine exhibited less oxidative damage in the liver and lung for CO-HbV and CO-RBC groups. Blood carbonyl Hb levels (26%-39% immediately after infusion) decreased to less than 3% at 6 h while CO was exhaled through the lung. Both HbV and RBC gradually gained the O2 transport function. Collectively, both CO-HbV and CO-RBC showed a resuscitative effect for hemorrhagic-shocked rats. They reduced oxidative damage to organs in comparison to O2-HbV and O2-RBC. Adverse and poisonous effects of CO gas were not evident for 6 h in this experimental model. Further study is necessary to clarify the neurological impact of a longer observation period for eventual clinical applications. | 18,827,742 |
Metabolic syndrome and schizophrenia from integrative medicine perspective. | There has been a growing interest in the effect that comorbid schizophrenia and metabolic syndrome may have on each other. To examine metabolic syndrome from integrative medicine point of view including prevalence of metabolic syndrome in patients with schiziphrenia compared to their first-degree relatives, healthy volunteers without schizophrenia in close family, and patients with PTSD, as well as the percentage patients with schizophrenia without any component of metabolic syndrome. Metabolic syndrome according to NCEP/ATP III criteria and number of its components were analysed in 205 patients with schizophrenia, 140 healthy volunteers and 105 patients with combat PTSD. Metabolic syndrome was identified in 45.9% of the patients with schizophrenia, 38.1% of the war veterans with PTSD, 36.7% of the first-degree relatives of patients with schizophrenia and 16.2% of the healthy volunteers without schizophrenia in close family. Only 21.5% of the patients with schizophrenia were without any metabolic syndrome component. The comorbidity of schizophrenia and metabolic syndrome is very important for theory and practice of integrative medicine. Almost 80% of the patients with schizophrenia have increased risk or developed cardiovascular disorders,. | 18,827,767 |
Association of cholesterol and socio-demographic parameters with suicidality in the male patients with schizophrenia. | Suicidal behavior is a major health risk in schizophrenia. The aim of this study was to evaluate serum cholesterol concentrations and some socio-demographic parameters in suicidal and non-suicidal men suffering from schizophrenia. Results of this study show that there were no differences in socio-demographic parameters between suicidal and non-suicidal schizophrenic patients but there was a difference in the level of cholesterol (lower in suicidal patients). Duration of untreated psychosis was higher in suicidal patients, which could means that suicidality is a process determined by many different factors including time of treatment. Suicidal patients in our study have been more seriously ill than non-suicidal (had higher scores on PANNS and HDRS-17) and we explained these findings by the fact of damage associated to higher time of non-treatment. Our results show that cholesterol has an important role in distinguishing suicidal from non-suicidal patients, which, if confirmed on a higher number of patients and in more studies, may be of considerable clinical significance. Clinical management of suicidal states is based on integrative approach and includes ensuring immediate safety, the use of psychosocial techniques to address depression and psychosocial stressors, and targeted pharmacotherapy for psychotic and depressive symptoms. | 18,827,768 |
Pharamacogenetics and antidepressant treatment in integrative psychiatry perspective. | The concept of individualized drug therapy on the basis of pharmacogenetics has become a central focus in the treatment of depression. There is an increasing agreement about the importance of polymorphisms in cytochrome P450 enzymes and the effects of drug-drug interactions in relation to the incidence of adverse effects. There has been also increasing focus on the role of the drug transporter P-glycoprotein (P-gp) with regard to drug penetration into the brain. P-gp at the blood-brain barrier can exert a profound effect on the ability of some antidepressants to enter the brain. In addition, genetic polymorphism of the serotonin transporter has been investigated in relationship to the therapeutic response to several antidepressants, especially SSRIs. However, prediction of response on the basis of variants of candidate genes is incipient and remains elusive. | 18,827,770 |
Metabolic syndrome and depression in war veterans with post-traumatic stress disorder. | Post-traumatic stress disorder (PTSD), depression and metabolic syndromes are growing public health problems in post-war countries. Understanding the co-morbidity among PTSD, depression and metabolic syndrome has an important clinical and theoretical issue. To examine the relationship between combat-related PTSD, co-morbid depression and metabolic syndrome as well as between severity of depression and metabolic syndrome. Metabolic syndrome and co-morbid depression were investigated in 100 male war veterans with combat PTSD and in 79 males who needed medical attention in dispensary of family medicine. Metabolic syndrome according NCEP: ATP III was found in 25 % of war veterans with PTSD. Metabolic syndrome was identified more frequently in PTSD patients with co-morbid depression (47.8 %) compared to those without depression (9.1%). PTSD with moderate and severe co-morbid depression was associated with higher rates of metabolic syndrome (78.6% and 90.9% respectively) in comparison with mild depression (26.2%). PTSD is frequently comorbid with depression, and when the two disorders co-occur, the risk for metabolic syndrome is increased. Treatment of war veterans with PTSD should address co-morbid depression and metabolic syndrome as well as the clinical features of PTSD. | 18,827,772 |
The role and importance of consulting psychiatry in paediatric surgery. | The main aim of this study was to point on role and importance of consulting psychiatry in paediatric population of patients particularly in branch of paediatric surgery. This study is a view to a few years research on biopsychosocial aspect of treatment of long bones fractures in children and adolescents realized in Departments for paediatric surgery of three hospitals, in Zagreb and Rijeka, Croatia, as well as in Mostar, Bosnia and Herzegovina, in period 2003.-2007. There have been investigated 135 patients, both gender, 10-18 years of age differently treated for long bones limbs' fractures. Basic methods of work were self-reported questionnaires to evaluate the degree of self-esteem, depression, anxiety, quality of life and perception of social support in mentioned patients. Our results pointed at the influence of type of treatment of long bones fractures on psychological variables, mostly on self-esteem and self-perception of quality of life. As a conclusion, we suggest the possibility of psychological preparation of the patients in order to diminish the psychological reaction to the surgical treatment, as well as individual consulting (liaison) psychiatric intervention during the treatment of fractures of long bones according to the individual needs. | 18,827,776 |
What is imatinib-resistant chronic myeloid leukemia? Identifying and managing loss of response. | Imatinib is widely recognized as the standard of care in the first-line treatment of chronic myeloid leukemia (CML); however, resistance can limit its long-term benefits. Early identification of the loss of response to imatinib is therefore important for the optimal management of patients with this type of leukemia. Cytogenetic and molecular responses during the first 12 months of treatment have been shown to predict future responses (complete cytogenetic response and major molecular response) and reduce disease progression. The degree of early reduction in BCR-ABL levels after commencing imatinib therapy is a good indicator of subsequent response. Monitoring for kinase domain mutations should also be considered in patients with suboptimal response or in those who demonstrate resistance. Modification of the treatment strategy is required if there is a loss of response. Dasatinib and nilotinib are the most extensively studied second-generation BCR-ABL tyrosine kinase inhibitors, and are currently approved for treating patients following imatinib failure. | 18,827,790 |
Preservation of the kidney by carbon monoxide: a black swan phenomenon. | Nakao and colleagues demonstrate that carbon monoxide added to organ preservation solution reduces donor-kidney injury that occurs after cold storage and transplantation and improves the survival of the recipient. These findings are important because they highlight the role of the cytochrome P450 system in the pathogenesis of donor-kidney injury and they suggest a strategy for preserving the donor kidney, namely, the addition of carbon monoxide to organ preservation solution. | 18,827,798 |
The impact of sodium chloride and volume depletion in the chronic kidney disease of congenital chloride diarrhea. | Congenital chloride diarrhea is due to mutations in the intestinal Cl(-)/HCO(3)(-) exchange (SLC26A3) which results in sodium chloride and fluid depletion leading to hypochloremic and hypokalemic metabolic alkalosis. Although treatment with sodium and potassium chloride offers protection from renal involvement in childhood, the long-term renal outcome remains unclear. Here we describe two cases of congenital chloride diarrhea-associated end-stage renal disease with transplantation. Further, we show that there is a high incidence of mild chronic kidney disease in 35 other patients with congenital chloride diarrhea. The main feature of the renal injury was nephrocalcinosis, without hypercalciuria or nephrolithiasis with small sized kidneys and commensurately reduced glomerular filtration rates. This suggests that diarrhea-related sodium chloride and volume depletion, the first signs of non-optimal salt substitution, promote urine supersaturation and crystal precipitation. The poor compliance with salt substitution along with long-lasting hypochloremic and hypokalemic metabolic alkalosis is likely to induce progressive calcification and renal failure. Both our patients developed nephrocalcinosis in the transplanted kidneys suggesting that this complication is a consequence of intestinal SLC26A3 deficiency. Interestingly, the transporter is expressed in the distal nephron but the recurrence of nephrocalcinosis in the transplanted kidney suggests that it does not play a significant renal role in this syndrome. | 18,827,800 |
Integrative approach for differentially overexpressed genes in gastric cancer by combining large-scale gene expression profiling and network analysis. | Gene expression profiling is a valuable tool for identifying differentially expressed genes in studies of disease subtype and patient outcome for various cancers. However, it remains difficult to assign biological significance to the vast number of genes. There is an increasing awareness of gene expression profile as an important part of the contextual molecular network at play in complex biological processes such as cancer initiation and progression. This study analysed the transcriptional profiles commonly activated at different stages of gastric cancers using an integrated approach combining gene expression profiling of 222 human tissues and gene regulatory dynamic mapping. We focused on an inferred core network with CDKN1A (p21(WAF1/CIP1)) as the hub, and extracted seven candidates for gastric carcinogenesis (MMP7, SPARC, SOD2, INHBA, IGFBP7, NEK6, LUM). They were classified into two groups based on the correlation between expression level and stage. The seven genes were commonly activated and their expression levels tended to increase as disease progressed. NEK6 and INHBA are particularly promising candidate genes overexpressed at the protein level, as confirmed by immunohistochemistry and western blotting. This integrated approach could help to identify candidate players in gastric carcinogenesis and progression. These genes are potential markers of gastric cancer regardless of stage. | 18,827,816 |
Sirtuins--novel therapeutic targets to treat age-associated diseases. | Sirtuins post-translationally modulate the function of many cellular proteins that undergo reversible acetylation-deacetylation cycles, affecting physiological responses that have implications for treating diseases of ageing. Potent small-molecule modulators of sirtuins have shown efficacy in preclinical models of metabolic, neurodegenerative and inflammatory diseases, and so hold promise for drug discovery efforts in multiple therapeutic areas. Here, we discuss current knowledge and data that strengthens sirtuins as a druggable set of enzymes for the treatment of age-associated diseases, including activation of SIRT1 in type 2 diabetes. | 18,827,827 |
Therapeutic application of histone deacetylase inhibitors for central nervous system disorders. | Histone deacetylases (HDACs)--enzymes that affect the acetylation status of histones and other important cellular proteins--have been recognized as potentially useful therapeutic targets for a broad range of human disorders. Pharmacological manipulations using small-molecule HDAC inhibitors--which may restore transcriptional balance to neurons, modulate cytoskeletal function, affect immune responses and enhance protein degradation pathways--have been beneficial in various experimental models of brain diseases. Although mounting data predict a therapeutic benefit for HDAC-based therapy, drug discovery and development of clinical candidates face significant challenges. Here, we summarize the current state of development of HDAC therapeutics and their application for the treatment of human brain disorders such as Rubinstein-Taybi syndrome, Rett syndrome, Friedreich's ataxia, Huntington's disease and multiple sclerosis. | 18,827,828 |
Genetic structure of Oryza rufipogon Griff. in China. | Oryza rufipogon Griff. (common wild rice; CWR) is the ancestor of Asian cultivated rice (Oryza sativa L.). Investigation of the genetic structure and diversity of CWR in China will provide information about the origin of cultivated rice and the grain quality and yield. In this study, we used 36 simple sequence repeat (SSR) markers to assay 889 accessions, which were highly representative of whole germplasm in China. The analysis revealed a hierarchical genetic structure within CWR. First, CWR has diverged into two ecotypic populations, a south subtropical population (SSP) and a middle subtropical population (MSP), probably owing to natural selection by the different climates. The distribution of specific alleles and haplotypes indicated that Chinese CWR had both indica-like and japonica-like variations; the SSP was an indica-like type, whereas the MSP was more japonica-like. The SSP and MSP further diverged into five (HN, GD-GX1, GX2, FJ and YN) and two (JX-HuN1 and HuN2) geographical populations, respectively. The genetic data suggest the isolation by distance, although water systems also appear to play an important role in the formation of homogenous populations, and occasionally landscape was also involved. The population GD-GX1, which grew widely in Guangdong and Guangxi provinces, was the largest geographical population in China. It had a high level of genetic diversity (GD) and the closest genetic relationship with other inferred populations. The population HN, with the smallest SSR molecular weights and the highest level of GD, may be the most ancestral population. | 18,827,837 |
Genome-wide analysis of protein-protein interactions and involvement of viral proteins in SARS-CoV replication. | Analyses of viral protein-protein interactions are an important step to understand viral protein functions and their underlying molecular mechanisms. In this study, we adopted a mammalian two-hybrid system to screen the genome-wide intraviral protein-protein interactions of SARS coronavirus (SARS-CoV) and therefrom revealed a number of novel interactions which could be partly confirmed by in vitro biochemical assays. Three pairs of the interactions identified were detected in both directions: non-structural protein (nsp) 10 and nsp14, nsp10 and nsp16, and nsp7 and nsp8. The interactions between the multifunctional nsp10 and nsp14 or nsp16, which are the unique proteins found in the members of Nidovirales with large RNA genomes including coronaviruses and toroviruses, may have important implication for the mechanisms of replication/transcription complex assembly and functions of these viruses. Using a SARS-CoV replicon expressing a luciferase reporter under the control of a transcription regulating sequence, it has been shown that several viral proteins (N, X and SUD domains of nsp3, and nsp12) provided in trans stimulated the replicon reporter activity, indicating that these proteins may regulate coronavirus replication and transcription. Collectively, our findings provide a basis and platform for further characterization of the functions and mechanisms of coronavirus proteins. | 18,827,877 |
Treprostinil for pulmonary hypertension. | Treprostinil is a stable, long-acting prostacyclin analogue which can be administered as a continuous subcutaneous infusion using a portable miniature delivery system. Subcutaneous treprostinil has been shown in a large multicenter randomized controlled trial to improve exercise capacity, clinical state, functional class, pulmonary hemodynamics, and quality of life in patients with pulmonary arterial hypertension, an uncommon disease of poor prognosis. Side effects include facial flush, headache, jaw pain, abdominal cramping, and diarrhea, all typical of prostacyclin, and manageable by symptom-directed dose adjustments, and infusion site pain which may make further treatment impossible in 7%-10% of the patients. Long-term survival in pulmonary arterial hypertension patients treated with subcutaneous treprostinil is similar to that reported with intravenous epoprostenol. There are uncontrolled data suggesting efficacy of subcutaneous treprostinil in chronic thromboembolic pulmonary hypertension. Treprostinil can also be administered intravenously, although increased doses, up to 2-3 times those given subcutaneously, appear to be needed to obtain the same efficacy. Preliminary results of a randomized controlled trial of inhaled treprostinil on top of bosentan and sildenafil therapies have shown significance on the primary endpoint, which was exercise capacity as assessed by the distance walked in 6 minutes. Trials of oral formulations of treprostinil have been initiated. | 18,827,901 |
Cardiovascular co-morbidity in rheumatic diseases. | Patients with rheumatic disorders have an increased risk of cardiovascular disease (CVD). This excess co-morbidity is not fully explained by traditional risk factors. Disease severity is a major risk factor for CVD in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Shared disease mechanisms in atherosclerosis and rheumatic disorders include immune dysregulation and inflammatory pathways, which are potential targets for therapy. Lessons from RA and SLE may have implications for future research on the pathogenesis of atherosclerotic vascular disease in general. Recent data indicate that suppression of inflammation reduces the risk of CVD morbidity and mortality in patients with severe RA. The modest, but clinically relevant, efficacy of atorvastatin treatment in RA adds to the evidence for important anti-inflammatory properties for statins. There is increased recognition of the need for structured preventive strategies to reduce the risk of CVD in patients with rheumatic disease. Such strategies should be based on insights into the role of inflammation in CVD, as well as optimal management of life style related risk factors. In this review, the research agenda for understanding and preventing CVD co-morbidity in patients with rheumatic disorders is discussed. | 18,827,910 |
The influence of polymorbidity, revascularization, and wound therapy on the healing of arterial ulceration. | An ulcer categorized as Fontaine's stage IV represents a chronic wound, risk factor of arteriosclerosis, and co-morbidities which disturb wound healing. Our objective was to analyze wound healing and to assess potential factors affecting the healing process. 199 patients were included in this 5-year study. The significance levels were determined by chi-squared and log-rank tests. The calculation of patency rate followed the Kaplan-Meier method. Mean age and co-morbidities did not differ from those in current epidemiological studies. Of the patients with ulcer latency of more than 13 weeks (up to one year), 40% required vascular surgery. Vascular surgery was not possible for 53 patients and they were treated conservatively. The amputation rate in the conservatively treated group was 37%, whereas in the revascularizated group it was only 16%. Ulcers in patients with revascularization healed in 92% of cases after 24 weeks. In contrast, we found a healing rate of only 40% in the conservatively treated group (p<0.001). Revascularization appeared more often in diabetic patients (n=110; p<0.01) and the wound size and number of infections were elevated (p=0.03). Among those treated conservatively, wound healing was decelerated (p=0.01/0.02; chi(2) test). The success of revascularization, presence of diabetes mellitus, and wound treatment proved to be prognostic factors for wound healing in arterial ulcers. | 18,827,918 |
Digital vasculitis: a late complication of anti-tumour necrosis factor alpha therapy. | Anti-tumour necrosis factor alpha therapy has led to significant advancement in the treatment of rheumatological disease. Rarely, anti-TNFalpha antagonists have been associated with vasculitis, predominantly cutaneous leukocytoclastic vasculitis. We present the first case of angiographically-confirmed digital vasculitis occurring as a late complication of etanercept therapy. Our case adds to the limited repertoire of case reports of anti-TNFalpha induced vasculitis and highlights the potential risk of this serious complication occurring up to several years after initiation of these agents. | 18,827,960 |
Flip-the-tip: automated patch clamping based on glass electrodes. | A conventional borosilicate glass patch pipette is glued into a plastic jacket, forming the entity of a FlipTip. One or two three-channel modules of recording tip sockets are mounted on a liquid handler platform to take up FlipTips. The tip sockets are connected to preamplifiers (HEKA) and to a suction system. The inner chamber of the tip sockets is filled with intracellular solution (IS), and FlipTips are prefilled with extracellular solution (ES) immediately before use. The FlipTips are then inserted into the recording tip sockets, and suspended cells are taken out of a cell hotel and dispensed into the open back of the FlipTips. Simply by gravity, the cells move down toward the end of the pipette. Continuous gentle suction draws a single cell into the very end of the tip, forming a classical GigaSeal of 1-5GOmega. Stronger suction pulses are then applied to establish the open whole-cell configuration. Under voltage-clamp conditions, the response of an ion channel is measured simultaneously in three to six recording sockets. Alternatively, the perforated patch method is used with Amphoterecine B as the pore-forming agent. Compound delivery is accomplished with a fused silica quartz pipette through the open back of the FlipTip directly onto the cell. All these tasks are performed automatically and completely unattended by the Flyscreen 8500 automated patch-clamp robot. A data throughput of several hundred data points per day can be accomplished with the system. | 18,827,988 |
Mechanosensitive ion channels investigated simultaneously by scanning probe microscopy and patch clamp. | Mechanosensitive ion channels play an important role for the perception of mechanical signals such as touch, balance, or sound. Here, a new experimental strategy is presented providing well-defined access to single mechanosensitive ion channels in living cells. As a representative example, the investigation of mechanosensitive transduction channels in cochlear hair cells is discussed in detail including all essential technical aspects. Three different techniques were combined: atomic force microscopy (AFM) as a device for local mechanical stimulation, patch clamp for recording the current response of mechanosensitive ion channels, and differential interference contrast (DIC) microscopy equipped with an upright water-immersion objective lens. A major challenge was to adapt the mechanical design of the AFM setup to the small working distance of the light microscope and the electrical design of the AFM electronics. Various protocols for the preparation and investigation of the organ of Corti with AFM are presented. | 18,827,992 |
Estimation of quantal parameters with multiple-probability fluctuation analysis. | The functional properties of central synapses are difficult to study because they can be modulated either presynaptically or postsynaptically, each connection has multiple contacts and release at each contact is stochastic. Moreover, studying central synapses with electrophysiology is complicated by the fact that synapses are often remote from the recording site and signals are often difficult to resolve above the noise. This together with the fact that central synapses often have few release sites and have nonuniform quantal parameters makes classical quantal analysis methods difficult to apply. Here, we discuss an alternative approach, multiple-probability fluctuation analysis (MPFA), which can be used to estimate nonuniform quantal parameters from fits of the relationship between the variance and mean amplitude of postsynaptic responses, recorded at different release probabilities. We illustrate the experimental protocols and the analysis procedure that should be followed to perform MPFA and interpret the estimated parameters. | 18,828,002 |
Mercury speciation and total trace element determination of low-biomass biological samples. | Current approaches to mercury speciation and total trace element analysis require separate extraction/digestions of the sample. Ecologically important aquatic organisms--notably primary consumers such as zooplankton, polychaetes and amphipods--usually yield very low biomass for analysis, even with significant compositing of multiple organisms. Individual organisms in the lower aquatic food chains (mussels, snails, oysters, silversides, killifish) can also have very low sample mass, and analysis of whole single organisms is important to metal uptake studies. A method for the determination of both methyl Hg and total heavy metal concentrations (Zn, As, Se, Cd, Hg, Pb) in a single, low-mass sample of aquatic organisms was developed. Samples (2 to 50 mg) were spiked with enriched with (201)MeHg and (199)Hg, then leached in 4 M HNO(3) at 55 degrees C for extraction of MeHg. After 16 h, an aliquot (0.05 mL) was removed to determine mercury species (methyl and inorganic Hg) by isotope dilution gas chromatography inductively coupled plasma mass spectrometry (ICP-MS). The leachate was then acidified to 9 M HNO(3) and digested in a microwave at 150 degrees C for 10 min, and total metal concentrations were determined by collision cell ICP-MS. The method was validated by analyzing five biological certified reference materials. Average percent recoveries for Zn, As, Se, Cd, MeHg, Hg(total) and Pb were 99.9%, 103.5%, 100.4%, 103.3%, 101%, 97.7%, and 97.1%, respectively. The correlation between the sum of MeHg and inorganic Hg from the speciation analysis and total Hg by conventional digestion of the sample was determined for a large sample set of aquatic invertebrates (n = 285). Excellent agreement between the two measured values was achieved. This method is advantageous in situations where sample size is limited, and where correlations between Hg species and other metals are required in the same sample. The method also provides further validation of speciation data, by corroborating the sum of the Hg species concentrations with the total Hg concentration. | 18,828,006 |
Thyroid uptake of 67Ga-citrate is associated with thyroid autoimmunity and hypothyroidism in patients with sarcoidosis. | To evaluate the association of gallium-67 ((67)Ga)-citrate thyroid uptake with the presence of thyroid disorders in patients with sarcoidosis (S patients). Eighty-four S patients were evaluated by a complete thyroid work-up (neck ultrasound, circulating thyroid hormones and anti-thyroid antibodies, fine-needle aspiration). In S patients with (67)Ga thyroid uptake (respect those without): serum thyroid-stimulating hormone, the titre of anti-thyroid peroxidase (AbTPO) and/or anti-thyroglobulin antibodies (AbTg), and the prevalence of S patients with hypothyroidism or with positive AbTg or AbTPO was significantly higher; a thyroid hypoechoic pattern was more frequent. The prevalence of thyroid nodules was not significantly different between the two groups. Two cases of papillary thyroid cancer were observed in S patients without (67)Ga thyroid uptake, whilst no case in those with (67)Ga thyroid uptake. (67)Ga thyroid uptake is associated with the presence of aggressive autoimmune thyroiditis and hypothyroidism in S patients; thyroid function and ultrasonography should be performed in the presence of (67)Ga thyroid uptake. | 18,828,014 |
Phase II trial of S-1 and concurrent radiotherapy in patients with locally advanced pancreatic cancer. | S-1 has a favorable effect in unresectable pancreatic cancer and a potential radiosensitizer. In addition, daily oral administration of S-1 is more convenient than continuous infusion of 5-fluorouracil. This study was designed to evaluate the efficacy and safety of S-1 and concurrent radiotherapy in patients with locally advanced pancreatic cancer. Eligibility criteria were histologically proven pancreatic adenocarcinoma, locally advanced disease, and no previous treatment. S-1 was administered orally at a dose of 40 mg/m(2) twice daily from day 1 to 14 and from day 22 to 35, and concurrent radiotherapy (a total dose of 50.4 Gy) was delivered in 28 fractions. One month after treatment completion, tumor response was evaluated by computed tomography (CT). A total of 25 patients were evaluable for efficacy and toxicity on the basis of the intention-to-treat analysis. The response rate and disease control rate were 24.0 and 68.0%, respectively. There was no treatment-related death or grade 4 toxicity. The most common grade 3 hematologic and non-hematologic toxicities were thrombocytopenia (4.0%) and anorexia (20%), respectively. All toxicities were tolerable and transient. The median time-to-progression and median overall survival were 6.5 months (95% confidence interval, 4.1-9.0 months) and 12.9 months (95% confidence interval, 6.7-19.0 months), respectively, and the 1-year survival rate was estimated to be 43%. S-1 and concurrent radiotherapy shows favorable efficacy for disease control against locally advanced pancreatic cancer and was well tolerated with no severe toxicities. | 18,828,020 |
Infantile hypertrophic pyloric stenosis: a comparative study of incidence and other epidemiological characteristics in seven European regions. | The objective of this study was to present epidemiologic data on infantile hypertrophic pyloric stenosis (IHPS) from seven well-defined European regions, and to compare incidence and changes in incidence over time between these regions. This was a population-based study using data from registries of congenital malformations (EUROCAT) for a period of more than two decades (1980-2002). A total of 2534 infants were diagnosed with IHPS during the study period, giving an overall incidence of IHPS of 2.0 per 1000 live births (LB), ranging from 0.86 per 1000 LB to 3.96 per 1000 LB in the seven regions. A significant decrease in incidence was observed in two regions and a significant increase in incidence was observed in two other regions. Young maternal age (<20 years) significantly increased the risk of IHPS by 29% (adjusted by region; p < 0.01), and at maternal age of 30 years and older the risk decreased significantly (p < 0.01). There were significant differences in the incidence of IHPS in the seven European populations. No uniform pattern of change in incidence was observed as the populations also differed in relation to trend over time with both significant increases and decreases over time. There is evidence that young maternal age is a risk factor for IHPS. | 18,828,050 |
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