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Selected AbstractsRecent advances in the management and prophylaxis of respiratory syncytial virus infectionACTA PAEDIATRICA, Issue 2001A Greenough Respiratory syncytial virus (RSV) infection is an important cause of morbidity, particularly in prematurely born infants who have had chronic lung disease. Current therapy is essentially supportive. Overall, the results of randomized trials do not support the use of bronchodilators, corticosteroids or Ribavirin. Nitric oxide and exogenous surfactant may improve the respiratory status of those infants who require ventilatory support. Nosocomial infection can be reduced by appropriate handwashing. There is no safe and effective vaccine for use in infants. Immunoprophylaxis reduces hospitalization and requirement for intensive care. Palivizumab, a humanized monoclonal antibody, is preferred to RSV immune globulin as the immunoprophylactic agent. Immunoprophylaxis should be reserved for infants at highest risk of severe respiratory syncytial virus infection, if this strategy is to be used most cost-effectively. [source] Pitfalls in the Diagnosis of Cerebellar InfarctionACADEMIC EMERGENCY MEDICINE, Issue 1 2007Sean I. Savitz MD Abstract Background Cerebellar infarctions are an important cause of neurologic disease. Failure to recognize and rapidly diagnose cerebellar infarction may lead to serious morbidity and mortality due to hydrocephalus and brain stem infarction. Objectives To identify sources of preventable medical errors, the authors obtained pilot data on cerebellar ischemic strokes that were initially misdiagnosed in the emergency department. Methods Fifteen cases of misdiagnosed cerebellar infarctions were collected, all seen, or reviewed by the authors during a five-year period. For each patient, they report the presenting symptoms, the findings on neurologic examination performed in the emergency department, specific areas of the examination not performed or documented, diagnostic testing, the follow-up course after misdiagnosis, and outcome. The different types of errors leading to misdiagnosis are categorized. Results Half of the patients were younger than 50 years and presented with headache and dizziness. All patients had either incomplete or poorly documented neurologic examinations. Almost all patients had a computed tomographic scan of the head interpreted as normal, and most of these patients underwent subsequent magnetic resonance imaging showing cerebellar infarction. The initial incorrect diagnoses included migraine, toxic encephalopathy, gastritis, meningitis, myocardial infarction, and polyneuropathy. The overall mortality in this patient cohort was 40%. Among the survivors, about 50% had disabling deficits. Pitfalls leading to misdiagnosis involved the clinical evaluation, diagnostic testing, and establishing a diagnosis and disposition. Conclusions This study demonstrates how the diagnosis of cerebellar infarction can be missed or delayed in patients presenting to the emergency department. [source] Practical Assessment of Maternal Cardiovascular Risk in PregnancyCONGENITAL HEART DISEASE, Issue 5 2008Nazanin Moghbeli MD ABSTRACT Cardiovascular disease in pregnancy is the most common cause of maternal mortality in the developed world and an important cause of heart failure, stroke, and arrhythmia. As more children with congenital heart disease survive into adulthood, there is a more pressing need to understand the risks that pregnancy poses for these women. Pregnancy, labor, and delivery increase the hemodynamic stress on the cardiovascular system and place women with heart disease at increased risk of cardiovascular complications, which include heart failure and death. Systematic assessment of pregnancy risk in these women, ideally before conception, is essential in optimizing maternal and fetal outcomes. This article describes the process of assessing risk of pregnancy-associated cardiovascular complications in women with structural heart disease. We review the current literature on pregnancy risk in women with complex congenital lesions, valvular heart disease, cardiomyopathy, and aortopathy, and suggest an approach to risk stratification. Based on a review of the literature, we report features that pose an increased risk of adverse maternal and fetal outcomes, which include poor maternal functional status; prior history of heart failure, arrhythmia, or cerebral vascular events; cyanosis; poor systemic ventricular function; and severe aortic or mitral stenosis. Pulmonary hypertension and Eisenmenger syndrome place women at exceedingly high risk for cardiovascular complications in pregnancy, including maternal and fetal death. [source] The epidemiology of contact allergy in the general population , prevalence and main findingsCONTACT DERMATITIS, Issue 5 2007Jacob Pontoppidan Thyssen A substantial number of studies have investigated the prevalence of contact allergy in the general population and in unselected subgroups of the general population. The aim of this review was to determine a median prevalence and summarize the main findings from studies on contact allergy in the general population. Published research mainly originates from North America and Western Europe. The median prevalence of contact allergy to at least 1 allergen was 21.2% (range 12.5,40.6%), and the weighted average prevalence was 19.5%, based on data collected on all age groups and all countries between 1966 and 2007. The most prevalent contact allergens were nickel, thimerosal, and fragrance mix. The median nickel allergy prevalence was 8.6% (range 0.7,27.8%) and demonstrates that nickel was an important cause of contact allergy in the general population and that it was widespread in both men and women. Numerous studies demonstrated that pierced ears were a significant risk factor for nickel allergy. Nickel was a risk factor for hand eczema in women. Finally, heavy smoking was associated with contact allergy, mostly in women. Population-based epidemiological studies are considered a prerequisite in the surveillance of national and international contact allergy epidemics. [source] Contact sensitization from Compositae-containing herbal remedies and cosmeticsCONTACT DERMATITIS, Issue 4 2002Evy Paulsen The Compositae (Asteraceae) family of plants is currently an important cause of allergic plant contact dermatitis in Europe. The family comprises some of the oldest and most valued medicinal plants, and the increasing popularity of herbal medicine and cosmetics may theoretically result in a growing number of Compositae sensitizations from these sources. According to the literature at least 15 species, including among others arnica (Arnica montana), German and Roman chamomile (Chamomilla recutita and Chamaemelum nobile), marigold (Calendula officinalis), Echinacea and elecampane (Inula helenium), have been suspected of sensitization or elicitation of Compositae dermatitis. Epidemiological data are available for 2 species only, arnica and German chamomile, the rest of the evidence being anecdotal. Based on this, sensitization seems to occur relatively frequently with a few species such as arnica and elecampane, and occurs rarely with the majority, especially the widely used German chamomile. Sesquiterpene lactones are the most important allergens, but there are a few cases of sensitization from a coumarin, a sesquiterpene alcohol and a thiophene. The risk of elicitation of dermatitis by using Compositae-containing products in Compositae-sensitive individuals is by-and-large unknown. [source] A Case of Foul Genital Odor Treated with Botulinum Toxin ADERMATOLOGIC SURGERY, Issue 9 2004Jae-Bong Lee MD Background. Genital odor is an uncommon condition characterized by an offensive and malodorous smell in the genital area. Although the etiology of foul genital odor is multifactorial, an important cause is sweat secretion and decomposition of sweat components by bacteria. Different methods are effective in reducing body odor secondary to bromhidrosis. Conservative methods only act for a short period of time, and more invasive surgical methods carry risk of complications or are inapplicable for the genital region. Methods. A patient with localized foul odor in the genital hair bearing area was treated with botulinum toxin A. Results. Botulinum toxin A was effective in creating an odorless and anhydrous response in the genital region, and no major adverse effects were noted during a follow-up of 9 months after injection. Conclusion. Local injection of botulinum toxin A appears to be a useful treatment for foul genital odor related to sweat glands activity. [source] Brachial-ankle pulse wave velocity and cardiovascular risk factors in the non-diabetic and newly diagnosed diabetic Chinese: Guangzhou Biobank Cohort Study-CVDDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2010Lin Xu Abstract Background Increased arterial stiffness is an important cause of cardiovascular disease (CVD). We examined determinants of arterial stiffness in subjects across strata of glycaemic status. Methods A total of 1249 subjects from a sub-study of the Guangzhou Biobank Cohort Study (GBCS-CVD) had brachial-ankle pulse wave velocity (baPWV) measured by automatic oscillometric method. Major cardiovascular risk factors including glycosylated haemoglobin A1c (HbA1c), high sensitivity C-reactive protein (hsCRP), fasting triglyceride, low- and high-density lipoprotein cholesterol and both fasting and post 2-h oral glucose-load glucose, systolic and diastolic blood pressure were assessed. Results In all, 649, 479 and 121 subjects were classified into normoglycaemia, impaired glucose metabolism (IGM) and newly diagnosed diabetes groups, respectively. Both age and systolic blood pressure were significantly associated with increased baPWV in all three groups (all p < 0.001). In both normoglycaemic and IGM groups, hsCRP and HbA1c were positively associated with baPWV (p from 0.04 to < 0.001), whereas current smoking and triglyceride were associated with baPWV in the normoglycaemic and IGM group, respectively (p = 0.04 and 0.001). No gender difference in baPWV was observed in the normoglycaemic or IGM groups. However, in the newly diagnosed diabetes group, men had higher baPWV than women (p = 0.01). Conclusions In the normoglycaemic and IGM subjects, after adjusting for age, blood pressure and other confounders, increasing HbA1c was associated with increased baPWV, suggesting a pathophysiological role of chronic glycaemia that can contribute to vascular disease risk in persons without diabetes. Copyright © 2010 John Wiley & Sons, Ltd. [source] An update on cyathostomins: Anthelmintic resistance and worm controlEQUINE VETERINARY EDUCATION, Issue 10 2008J. B. Matthews Summary Intestinal nematodes are an important cause of equine disease. Of these parasites, the Cyathostominae are the most important group, both in terms of their prevalence and their pathogenicity. Cyathostomin infections are complex and control is further complicated by ever-increasing levels of resistance to some of the commonly used anthelmintics. There are no new equine anthelmintics under development, so it is imperative that the efficacy of any currently-effective drug classes be maintained for as long as possible. It is believed that the proportion of refugia (i.e. the percentage of parasites not exposed to a drug at each treatment) is one of the most crucial factors in determining the rate at which anthelmintic resistance develops. It is important, therefore, that levels of refugia be taken into account when designing nematode control programmes for horses. This can be assisted by knowledge of the local epidemiology of the infection, supplemented by faecal egg count analysis to identify those animals that are making the major contribution to pasture contamination. This type of rational nematode control requires equine veterinary surgeons to get involved in designing and implementing deworming programmes. The advice given must be based on a combination of knowledge of cyathostomin biology and epidemiology as well as an awareness of the parasite population's current drug sensitivity and a sound history of husbandry at the establishment. As anthelmintic resistance will be the major constraint on the future control of cyathostomins, researchers are now actively investigating this area. Studies are underway to develop tests that will enable earlier detection of anthelmintic resistance and an assay that will help identify those horses that require anthelmintic treatments targeted at intestinal wall larvae. [source] The application of a scintigraphic grading system to equine tibial stress fractures: 42 casesEQUINE VETERINARY JOURNAL, Issue 4 2003P. H. L. RAMZAN Summary Reasons for performing study: Tibial stress fractures are an important cause of lameness in the Thoroughbred racehorse. While it is recognised that these injuries can vary in clinical presentation and radiographic or scintigraphic appearance, little has been done to quantify lesion severity. By contrast the scintigraphic grading of tibial stress fractures in human athletes is widely reported and assists in the selection of appropriate management regimes. Objectives: To determine the relationship between scintigraphic grade, clinical severity and radiographic appearance of tibial stress fractures. Methods: The current study involved the retrospective analysis of records from 42 Thoroughbreds with abnormal tibial scintigraphic activity. Results: There was a significant association between lesion site and scintigraphic grade and good correlation of scintigraphic scoring between investigators. No significant association was found between scintigraphic grade and either radiographic grade or degree of lameness. Conclusions: The study confirmed that radiographic appearance is an unreliable measure of clinical severity or stage of progression of lesions. The scintigraphic grading system used in the study was not of use in defining stress fracture severity in the equine tibia. Potential relevance: Despite this finding, there is clearly a need for prospective investigations to explore the potential for targeted management regimes for tibial injuries based on lesion site or clinical criteria. [source] Hypertrophic cardiomyopathy: from genetics to treatmentEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 4 2010Ali J. Marian Eur J Clin Invest 2010; 40 (4): 360,369 Abstract Background, Hypertrophic cardiomyopathy (HCM) is the prototypic form of pathological cardiac hypertrophy. HCM is an important cause of sudden cardiac death in the young and a major cause of morbidity in the elderly. Design, We discuss the clinical implications of recent advances in the molecular genetics of HCM. Results, The current diagnosis of HCM is neither adequately sensitive nor specific. Partial elucidation of the molecular genetic basis of HCM has raised interest in genetic-based diagnosis and management. Over a dozen causal genes have been identified. MYH7 and MYBPC3 mutations account for about 50% of cases. The remaining known causal genes are uncommon and some are rare. Advances in DNA sequencing techniques have made genetic screening practical. The difficulty, particularly in the sporadic cases and in small families, is to discern the causal from the non-causal variants. Overall, the causal mutations alone have limited implications in risk stratification and prognostication, as the clinical phenotype arises from complex and often non-linear interactions between various determinants. Conclusions, The clinical phenotype of ,HCM' results from mutations in sarcomeric proteins and subsequent activation of multiple cellular constituents including signal transducers. We advocate that HCM, despite its current recognition and management as a single disease entity, involves multiple partially independent mechanisms, despite similarity in the ensuing phenotype. To treat HCM effectively, it is necessary to delineate the underlying fundamental mechanisms that govern the pathogenesis of the phenotype and apply these principles to the treatment of each subset of clinically recognized HCM. [source] Aggregative adherence of uropathogenic Proteus mirabilis to cultured epithelial cellsFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2007Sérgio P.D. Rocha Abstract Proteus mirabilis is an important cause of urinary tract infection (UTI) in patients with complicated urinary tracts. Thirty-five strains of P. mirabilis isolated from UTI were examined for the adherence capacity to epithelial cells. All isolates displayed the aggregative adherence (AA) to HEp-2 cells, a phenotype similarly presented in LLC-MK2 cells. Biofilm formation on polystyrene was also observed in all strains. The mannose-resistant Proteus -like fimbriae (MR/P), Type I fimbriae and AAF/I, II and III fimbriae of enteroaggregative Escherichia coli were searched by the presence of their respective adhesin-encoding genes. Only the MR/P fimbrial subunits encoding genes mrpA and mrpH were detected in all isolates, as well as MR/P expression. A mutation in mrpA demonstrated that MR/P is involved in aggregative adherence to HEp-2 cells, as well as in biofilm formation. However, these phenotypes are multifactorial, because the mrpA mutation reduced but did not abolish both phenotypes. The present results reinforce the importance of MR/P as a virulence factor in P. mirabilis due to its association with AA and biofilm formation, which is an important step for the establishment of UTI in catheterized patients. [source] Gastric inflammatory markers and interleukins in patients with functional dyspepsia, with and without Helicobacter pylori infectionFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 2 2005Leif P. Andersen Abstract Helicobacter pylori is the most important cause of gastritis, peptic ulcers and the development of gastric cancer. The chronic active inflammation is dominated by neutrophils, macrophages, lymphocytes and plasma cells. Several interleukins (IL-8, IL-10 and IFN-,) are involved in the inflammatory process in the gastric mucosa. The aim of this study was to investigate the gastric inflammation in patients with functional dyspepsia. Fifty-three consecutive patients were included and antral biopsies were obtained for histology, culture and immunohistochemistry. The sections were examined for the interleukins IL-4, IL-6, IL-8, IL-10 and IFN-, as well as for the cell markers CD4, CD8, CD14, Cd19, CD25 and CD30. Only CD4 and CD19 were significantly increased in patients with increased gastric inflammation and increased density of H. pylori. However, several of the examined markers (IFN-,, IL-8, IL-10 and CD14) showed a non-significant trend to be increased in patients with extensive gastric inflammation and high density of H. pylori. Therefore, an arbitrary index (IM11) for all the 11 immunological markers was made as an average value for each of the four morphological groups. For the four morphologically different groups of patients the values were 0.49, 0.77, 0.86 and 1.25, respectively. Significant increases in the index from none to moderate antral inflammation as well as the density of H. pylori were found (p < 0.001). By using an index of inflammatory markers trends can be summarized and thereby significant which may be of importance when gastric inflammation is investigated in children and patients with functional dyspepsia. [source] Catchment urbanisation and increased benthic algal biomass in streams: linking mechanisms to managementFRESHWATER BIOLOGY, Issue 6 2004Sally L. Taylor Summary 1. Urbanisation is an important cause of eutrophication in waters draining urban areas. We determined whether benthic algal biomass in small streams draining urban areas was explained primarily by small-scale factors (benthic light, substratum type and nutrient concentrations) within a stream, or by catchment-scale variables that incorporate the interacting multiple impacts of urbanisation (i.e. variables that describe urban density and the intensity of drainage or septic tank systems). 2. Benthic algal biomass was assessed as chlorophyll a density (chl a) in 16 streams spanning a rural,urban gradient, with both a wide range of urban density and of piped stormwater infrastructure intensity on the eastern fringe of metropolitan Melbourne, Australia. The gradient of urban density among streams was broadly correlated with catchment imperviousness, drainage connection (proportion of impervious areas connected to streams by stormwater pipes), altitude, longitude and median phosphorus concentration. Catchment area, septic tank density, median nitrogen concentration, benthic light (photosynthetically active radiation) and substratum type were not strongly correlated with the urban gradient. 3. Variation in benthic light and substratum type within streams explained a relatively small amount of variation in log chl a (3,11 and 1,13%, respectively) compared with between-site variation (39,54%). 4. Median chl a was positively correlated with catchment urbanisation, with a large proportion of variance explained jointly (as determined by hierarchical partitioning) by those variables correlated with urban density. Independent of this correlation, the contributions of drainage connection and altitude to the explained variance in chl a were significant. 5. The direct connection of impervious surfaces to streams by stormwater pipes is hypothesised as the main determinant of algal biomass in these streams through its effect on the supply of phosphorus, possibly in interaction with stormwater-related impacts on grazing fauna. Management of benthic algal biomass in streams of urbanised catchments is likely to be most effective through the application of stormwater management approaches that reduce drainage connection. [source] Ischemic nephropathy in an elderly patientGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 2 2008Satoshi Hoshide Congestive heart failure often occurs in patients with bilateral renal artery stenosis. Recently, Jacobson and Breyer, and Jacobson introduced the term "ischemic nephropathy", which implies critical bilateral involvement or global ischemia. Ischemic nephropathy is not only a cause of hypertension but also an important cause of end-stage renal disease. However, the aging kidney often show that the renal artery does not demonstrate stenosis of the main trunks, but stenosis of an atherosclerotic branch. We present a case of multiple atherosclerotic peripheral renal arteries, which might have caused ischemic nephropathy in an elderly hypertensive patient with advanced atherosclerosis. [source] Co-morbidity in the ageing haemophilia patient: the down side of increased life expectancyHAEMOPHILIA, Issue 4 2009E. P. MAUSER-BUNSCHOTEN Summary., Because of an increased life expectancy, (age-related) co-morbidity is becoming a common occurrence in haemophilia patients. In this review, haemophilia-related and non-haemophilia-related medical problems, treatment recommendations and psychosocial consequences in ageing haemophilia patients are discussed. Haemophilic arthropathy is an important cause of pain and disability, and a frequent indication for surgery in haemophilia patients. In addition, many adult patients are infected with hepatitis C or HIV, the consequences and treatment of which can add to physical and mental discomfort. Moreover, inhibitors against factor VIII can also develop in adulthood, especially in patients with mild haemophilia. Hypertension is reported to occur more often in haemophilia patients than in the general population. Other internal problems, like renal abnormalities, overweight, diabetes mellitus and hypercholesterolemia are discussed. Haemophilia seems to protect against cardiovascular disease, although the incidence is increasing. Recommendations are given on dealing with tooth extractions, surgical interventions and sexuality problems in patients with haemophilia. In addition to haemophilia in itself, co-morbidity has a major psychological impact, and an important effect on quality of life. It can also result in complex treatment regimens, in which coordination between health care workers is essential. [source] Cool dialysate reduces asymptomatic intradialytic hypotension and increases baroreflex variabilityHEMODIALYSIS INTERNATIONAL, Issue 2 2009Lindsay J. CHESTERTON Abstract Intradialytic hypotension (IDH) remains an important cause of morbidity and mortality in chronic hemodialysis (HD) patients and can be ameliorated by cool temperature HD. The baroreflex arc is under autonomic control and is essential in the short-term regulation of blood pressure (BP). This study aimed to investigate if the baroreflex sensitivity (BRS) response to HD differed between standard and cool-temperature dialysate. Ten patients (mean age 67±2 years) prone to IDH were recruited into a randomized, crossover study to compare BRS variation at dialysate temperatures of 37 °C (HD37) and 35 °C (HD35). Each patient underwent continuous beat-to-beat BP monitoring during a dialysis session of HD37 and HD35. During HD37 2 patients developed symptomatic IDH, as opposed to 1 with HD35. However, asymptomatic IDH occurred with a frequency of 0.4 episodes per session with HD35 and 6.2 episodes per session during HD37 (odds ratio15.5; 95%CI 5.6,14.2). Although absolute BRS measurements did not differ between the 2 modalities, BRS variability increased during HD35. Our study has demonstrated that in IDH-prone patients, cool HD resulted in a reduction in heart rate and a greater reduction in cardiac output and stroke volume. Mean arterial pressure was maintained through a significantly greater increase in total peripheral resistance. Furthermore, although absolute BRS values during HD were not significantly altered by a reduction in dialysate temperature, there was a greater percentage increase in BRS values during cool HD. Understanding the varied causes of, and categorizing impaired hemodynamic responses to HD will enable further individualization of HD prescriptions according to patient need. [source] Chronic viral hepatitis in hemodialysis patientsHEMODIALYSIS INTERNATIONAL, Issue 2 2005Sydney Tang Abstract Ever since the first outbreaks of hepatitis in hemodialysis units in the late 1960s, a number of hepatotropic viruses transmitted by blood and other body fluids have been identified. This review summarizes the current state of knowledge regarding these blood-borne agents from an epidemiologic and preventive perspective. Data source and study selection were obtained from research and review articles related to the epidemiology of viral hepatitis in hemodialysis and indexed on Medline and Embase from 1965 to 2004. Hepatitis B virus (HBV) was the first significant hepatotropic virus to be identified in hemodialysis centers. HBV infection has been effectively controlled by active vaccination, screening of blood donors, the use of erythropoietin, and segregation of HBV carriers. To date, HBV remains an important cause of morbidity in endemic areas. Hepatitis delta virus is a defective virus that can only infect HBV-positive individuals. Hepatitis C virus is the most significant cause of non-A, non-B hepatitis and is mainly transmitted by blood transfusion. The introduction in 1990 of routine screening of blood donors for HCV contributed significantly to the control of HCV transmission. An effective HCV vaccine remains an unsolved challenge, however. Pegylation of interferon-, has made it possible to treat HCV-positive dialysis patients. Unexplained sporadic outbreaks of hepatitis by the mid-1990s prompted the discovery of hepatitis G virus and hepatitis GB virus C in 1995 and the TT virus in 1997. Although epidemiologic analyses revealed high prevalence rates of both viruses in the hemodialysis population, their exact role in liver disease has yet to be determined. The vigilant observation of guidelines on universal precaution and regular virologic testing are the cornerstones of the effective control of chronic hepatitis in the setting of hemodialysis. [source] Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: Selected practical issues in their evaluation and management,HEPATOLOGY, Issue 1 2009Raj Vuppalanchi Nonalcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease in the western world. It is now recognized that these patients have myriad of important co-morbidities (e.g., diabetes, hypothyroidism and metabolic syndrome). The workup of patients with suspected NAFLD should consist of excluding competing etiologies and systemic evaluation of metabolic comorbidities. NAFLD is histologically categorized into steatosis and steatohepatitis, two states with fairly dichotomous natural history. While significant progress has been made in terms of noninvasively predicting advanced fibrosis, insufficient progress has been made in predicting steatohepatitis. Currently, liver biopsy remains the gold standard for the histological stratification of NAFLD. While sustained weight loss can be effective to treat NASH, it is often difficult to achieve. Foregut bariatric surgery can be quite effective in improving hepatic histology in selected patients without liver failure or significant portal hypertension. Thiazolidinediones have shown promise and the results from the ongoing, large multicenter study should become available soon. Large multicenter studies of CB, receptor anatagonists are also underway but their results will not be available for several years. Several recent studies have highlighted that cardiovascular disease is the single most important cause of morbidity and mortality in this patient population. Conclusion: Health care providers should not only focus on liver disease but also concentrate on aggressively modifying and treating their cardiovascular risk factors. (HEPATOLOGY 2009;49:306-317.) [source] A mouse model for cystic biliary dysgenesis in autosomal recessive polycystic kidney disease (ARPKD),HEPATOLOGY, Issue 5 2005Markus Moser Autosomal recessive polycystic kidney disease (ARPKD) is an important cause of liver- and renal-related morbidity and mortality in childhood. Recently, PKHD1, the gene encoding the transmembrane protein polyductin, was shown to be mutated in ARPKD patients. We here describe the first mouse strain, generated by targeted mutation of Pkhd1. Due to exon skipping, Pkhd1ex40 mice express a modified Pkhd1 transcript and develop severe malformations of intrahepatic bile ducts. Cholangiocytes maintain a proliferative phenotype and continuously synthesize TGF-,1. Subsequently, mesenchymal cells within the hepatic portal tracts continue to synthesize collagen, resulting in progressive portal fibrosis and portal hypertension. Fibrosis did not involve the hepatic lobules, and we did not observe any pathological changes in morphology or function of hepatocytes. Surprisingly and in contrast to human ARPKD individuals, Pkhd1ex40 mice develop morphologically and functionally normal kidneys. In conclusion,our data indicate that subsequent to formation of the embryonic ductal plate, dysgenesis of terminally differentiated bile ducts occurs in response to the Pkhd1ex40 mutation. The role of polyductin in liver and kidney may be functionally divergent, because protein domains essential for bile duct development do not affect nephrogenesis in our mouse model. Supplementary material for this article can be found on the HEPATOLOGYwebsite (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html). (HEPATOLOGY 2005.) [source] SUCCESS, TRUTH, AND MODERNISM IN HOLOCAUST HISTORIOGRAPHY: READING SAUL FRIEDLÄNDER THIRTY-FIVE YEARS AFTER THE PUBLICATION OF METAHISTORY,HISTORY AND THEORY, Issue 2 2009WULF KANSTEINER ABSTRACT This essay provides a close reading of Saul Friedländer's exceptionally successful comprehensive history of the Holocaust from the theoretical perspective of Hayden White's philosophy of history. Friedländer's The Years of Extermination has been celebrated as the first synthetic history of the "Final Solution" that acknowledges the experiences of the victims of Nazi genocide. But Friedländer has not simply added the voices of the victims to a conventional historical account of the Holocaust. Instead, by displacing linear notions of time and space and subtly deconstructing conventional concepts of causality, he has invented a new type of historical prose that performs rather than analyzes the victims' point of view. Friedländer's innovation has particularly radical consequences for the construction of historical explanations. On the one hand, Friedländer explicitly argues that anti-Semitism was the single most important cause of the Holocaust. On the other hand, his transnational, multifaceted history of the "Final Solution" provides a wealth of data that escapes the conceptual grasp of his explicit model of causation. Friedländer chooses this radically self-reflexive strategy of historical representation to impress on the reader the existential sense of disbelief with which the victims experienced Nazi persecution. To Friedländer, that sense of disbelief constitutes the most appropriate ethical response to the Holocaust. Thus the narratological analysis of The Years of Extermination reveals that the exceptional quality of the book, as well as presumably its success, is the result of an extraordinarily creative act of narrative imagination. Or, put into terms developed by White, who shares Friedländer's appreciation of modernist forms of writing, The Years of Extermination is the first modernist history of the Holocaust that captures, through literary figuration, an important and long neglected reality of the "Final Solution." [source] Validation of microarray-based resequencing of 93 worldwide mitochondrial genomes,HUMAN MUTATION, Issue 1 2009Anne Hartmann Abstract The human mitochondrial genome consists of a multicopy, circular dsDNA molecule of 16,569 base pairs. It encodes for 13 proteins, two ribosomal genes, and 22 tRNAs that are essential in the generation of cellular ATP by oxidative phosphorylation in eukaryotic cells. Germline mutations in mitochondrial DNA (mtDNA) are an important cause of maternally inherited diseases, while somatic mtDNA mutations may play important roles in aging and cancer. mtDNA polymorphisms are also widely used in population and forensic genetics. Therefore, methods that allow the rapid, inexpensive and accurate sequencing of mtDNA are of great interest. One such method is the Affymetrix GeneChip® Human Mitochondrial Resequencing Array 2.0 (MitoChip v.2.0) (Santa Clara, CA). A direct comparison of 93 worldwide mitochondrial genomes sequenced by both the MitoChip and dideoxy terminator sequencing revealed an average call rate of 99.48% and an accuracy of ,99.98% for the MitoChip. The good performance was achieved by using in-house software for the automated analysis of additional probes on the array that cover the most common haplotypes in the hypervariable regions (HVR). Failure to call a base was associated mostly with the presence of either a run of ,4,C bases or a sequence variant within 12 bases up- or downstream of that base. A major drawback of the MitoChip is its inability to detect insertions/deletions and its low sensitivity and specificity in the detection of heteroplasmy. However, the vast majority of haplogroup defining polymorphism in the mtDNA phylogeny could be called unambiguously and more rapidly than with conventional sequencing. Hum Mutat 0,1,8, 2008. © 2008 Wiley-Liss, Inc. [source] Costs and benefits of breeding in human-altered landscapes for the Eagle Owl Bubo buboIBIS, Issue 4 2002Luigi Marchesi We studied a population of 23,25 Eagle Owl Bubo bubo pairs between 1994 and 2000 in a 1330-km2 study plot in the central-eastern Italian Alps. Compared to random sites, territories were located at lower elevation and closer to intensively cultivated-urbanized valley floors. Early laying was associated with low elevation and negatively affected productivity. Diet was dominated by rats, hedgehogs and dormice (n = 978 prey items), all of them typical of low-elevation habitats. Higher productivity was associated with a higher proportion of rats in the diet of individual pairs. Low availability of rats resulted in a more diverse diet, in turn associated with low productivity. Territories were occupied every year in a non-random fashion, and those most occupied were characterized by higher productivity and higher occurrence of the favoured prey types in the diet, suggesting they were of superior quality. Eagle Owls also paid a cost associated with nesting near human-altered habitats: the main cause of mortality reported to local authorities was electrocution. This is an increasing cause of death for many European populations and may be a cause for conservation concern. Human persecution is also an important cause of mortality in some parts of the European range. Apart from such costs, the study population appeared to have adapted well to the proximity of humans: estimates of density and productivity were comparable to those recorded elsewhere in Europe. The pattern found in our population also held at higher spatial scales: data from 17 European populations showed density to be highest in low-elevation, human-altered landscapes. [source] Influenza-associated hospitalization in urban Thai childrenINFLUENZA AND OTHER RESPIRATORY VIRUSES, Issue 5-6 2007Piyarat Suntarattiwong Background, Studies in North America and Europe have shown that young children are at increased risk of serious complications and hospitalization from influenza infection. In Thailand, however, influenza is commonly considered a mild infection that rarely requires hospitalization. An improved understanding of the burden of serious complications from influenza infection in young children is needed to inform clinical treatment and vaccination guidelines. Methods, We conducted a prospective study of children 0,5 years of age with lower respiratory tract infection or influenza-like illness admitted to a pediatric tertiary-care hospital in Bangkok, Thailand during July 2004 to July 2005. All respiratory specimens were tested for influenza using a rapid antigen test and tissue cell culture. Results, Thirty-nine of 456 (8.6%) hospitalized children had culture-positive influenza. Eighty percent of hospitalized influenza patients had no underlying chronic illnesses. Nineteen (49%) influenza patients required hospital stays of 5 days or more and two patients required mechanical ventilation. Influenza activity demonstrated bimodal seasonal variation with peak activity from August to October and January to April. Cough was present in 38 (97%) cases and fever >38.5°C was significantly associated with influenza. Conclusion, Influenza is an important cause of hospitalization in children <5 years of age in Thailand. Children <5 years should be considered as a target group when establishing clinical guidelines for antiviral treatment and influenza vaccination. [source] A regional frequency analysis of United Kingdom extreme rainfall from 1961 to 2000INTERNATIONAL JOURNAL OF CLIMATOLOGY, Issue 11 2003H. J. Fowler Abstract Multi-day rainfall events are an important cause of recent severe flooding in the UK, and any change in the magnitude of such events may have severe impacts upon urban structures such as dams, urban drainage systems and flood defences and cause failures to occur. Regional pooling of 1-, 2-, 5- and 10-day annual maxima for 1961 to 2000 from 204 sites across the UK is used in a standard regional frequency analysis to produce generalized extreme value growth curves for long return-period rainfall events for each of nine defined climatological regions. Temporal changes in 1-, 2-, 5- and 10-day annual maxima are examined with L-moments using both a 10 year moving window and the fixed decades of 1961,70, 1971,80, 1981,90 and 1991,2000. A bootstrap technique is then used to assess uncertainty in the fitted decadal growth curves and to identify significant trends in both distribution parameters and quantile estimates. There has been a two-part change in extreme rainfall event occurrence across the UK from 1961 to 2000. Little change is observed at 1 and 2 days duration, but significant decadal-level changes are seen in 5- and 10-day events in many regions. In the south of the UK, growth curves have flattened and 5- and 10-day annual maxima have decreased during the 1990s. However, in the north, the 10-day growth curve has steepened and annual maxima have risen during the 1990s. This is particularly evident in Scotland. The 50 year event in Scotland during 1961,90 has become an 8-year, 11-year and 25-year event in the East, South and North Scotland pooling regions respectively during the 1990s. In northern England the average recurrence interval has also halved. This may have severe implications for design and planning practices in flood control. Copyright © 2003 Royal Meteorological Society [source] Association between ICAM-1 Gly-Arg polymorphism and renal parenchymal scarring following childhood urinary tract infectionINTERNATIONAL JOURNAL OF IMMUNOGENETICS, Issue 1 2006R. A. Gbadegesin Summary Renal parenchymal scarring (RPS) following urinary tract infection (UTI) is an important cause of renal morbidity in children. Studies have shown that the intensity of the inflammatory response following infection is related to the risk of RPS. However, genetic variability in this response has not been studied. Adhesion molecules play a crucial role in leucocyte recruitment following infection, and polymorphisms have been reported in the genes for key cell adhesion molecules. We have investigated the possibility that children who develop RPS following UTI may exhibit altered genotype or allele frequencies for polymorphisms of the intercellular adhesion molecule-1 (ICAM-1) (exons 4 and 6), E-selectin (exons 2 and 4), platelet endothelial cell adhesion molecule-1 (PECAM-1) (exon 3) and CD11b (3,UTR) genes, which may predict outcome of UTI. DNA was isolated from 99 children shown to have developed RPS, 43 children with no evidence of scarring (NS) following UTI and 170 healthy controls. Genotyping was performed by restriction fragment length polymorphism (RFLP) analysis. When the RPS group was compared with the NS group, there was a significant reduction in the frequency of the ICAM-1 exon 4 A allele (10.6 vs. 21.3%, respectively, ,2= 6.01, P= 0.014). There was no significant difference in either allele or genotype frequency for any of the other polymorphisms studied. These data suggest that the A allele of the ICAM-1 exon 4 polymorphism may protect against the risk of RPS following UTI and may participate in the regulation of the inflammatory response following UTI. [source] Nursing Home Capabilities and Decisions to Hospitalize: A Survey of Medical Directors and Directors of NursingJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2006Joan L. Buchanan PhD OBJECTIVES: To obtain information from decision makers about attitudes toward hospitalization and the factors that influence their decisions to hospitalize nursing home residents. DESIGN: Cross-sectional survey. SETTING: Four hundred forty-eight nursing homes, 76% of which were nonprofit, from 25 states. PARTICIPANTS: Medical directors and directors of nursing (DONs). MEASUREMENTS: Participants were surveyed about resource availability, determinants of hospitalization, causes of overhospitalization, and nursing home practice. RESULTS: The survey response rate was 81%, with at least one survey from 93% of the facilities. Medical directors and DONs agreed that resident preference was the most important determinant in the decision to hospitalize, followed by quality of life. Although both groups ranked on-site doctor/nurse practitioner evaluation within 4 hours as the least accessible resource, they did not rank doctors not being quickly available as an important cause of overhospitalization. Rather, medical directors perceived the lack of information and support to residents and families around end-of-life care and the lack of familiarity with residents by covering doctors as the most important causes of overhospitalization. DONs agreed but reversed the order. Medical directors and DONs expressed confidence in provider and staff ability, although DONs were significantly more positive. CONCLUSION: Medical directors and DONs agree about most factors that influence decisions to hospitalize nursing home residents. Patient-centered factors play the largest roles, and the most important causes of overhospitalization are potentially modifiable. [source] Cutaneous marginal zone B-cell lymphoma in the setting of fluoxetine therapy: a hypothesis regarding pathogenesis based on in vitro suppression of T-cell-proliferative responseJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2006Thomas S. Breza Jr Introduction:, Drugs may be an important cause of atypical lymphocytic infiltration. Oftentimes, these infiltrates are in the context of pseudolymphomata. We report a patient who developed lymphocytoma cutis temporally associated with initiation of fluoxetine therapy that later went on to develop cutaneous marginal zone B-cell lymphoma. The response of peripheral blood lymphocytes to fluoxetine and other drugs was examined in an attempt to ascertain the potential role for drugs in the propagation of these infiltrates. Materials and Methods:, Routine light microscopic analysis and phenotypic studies were performed on tissue obtained from a skin biopsy. Lymphocyte mitogenic studies were carried out using increasing concentrations of fluoxetine, bupropion, and two anticonvulsants. Results:, An initial biopsy was consistent with lymphocytoma cutis. The patient stopped fluoxetine associated with lesional regression. The lesions recurred despite being off fluoxetine; a repeat biopsy was compatible with marginal zone lymphoma. Lymphocyte proliferation assays revealed a suppressive effect on T-lymphocyte proliferation at physiologic concentrations. Other tested drugs did not have a similar suppressive effect. Conclusion:, Fluoxetine may be associated with pseudolymphomata and marginal zone lymphoma. The inhibitory effects on T-lymphocyte function and more specifically T-suppressor function may lead to excessive antigen-driven B-cell proliferation. [source] Quantification of mitochondrial DNA mutation loadAGING CELL, Issue 5 2009Laura C. Greaves Summary Mitochondrial DNA (mtDNA) mutations are an important cause of genetic disease and have been proposed to play a role in the ageing process. Quantification of total mtDNA mutation load in ageing tissues is difficult as mutational events are rare in a background of wild-type molecules, and detection of individual mutated molecules is beyond the sensitivity of most sequencing based techniques. The methods currently most commonly used to document the incidence of mtDNA point mutations in ageing include post-PCR cloning, single-molecule PCR and the random mutation capture assay. The mtDNA mutation load obtained by these different techniques varies by orders of magnitude, but direct comparison of the three techniques on the same ageing human tissue has not been performed. We assess the procedures and practicalities involved in each of these three assays and discuss the results obtained by investigation of mutation loads in colonic mucosal biopsies from ten human subjects. [source] Nest predators of Lance-tailed Manakins on Isla Boca Brava, PanamáJOURNAL OF FIELD ORNITHOLOGY, Issue 2 2009Jennifer L. Reidy ABSTRACT Nest predation is often the primary cause of nest failure for passerines. Despite this, little is known about predation rates and the nest predators of birds in the tropics. I used video cameras to monitor seven Lance-tailed Manakin (Chiroxiphia lanceolata) nests on Isla Boca Brava, Panamá. One nest fledged young and six nests failed due to predation. I recorded five predation events involving four avian predators and one mammalian predator. Crested Oropendolas (Psarocolius decumanus) predated two nests and a Roadside Hawk (Buteo magnirostris) and a Black-chested Jay (Cyanocorax affinis) each predated one. The mammalian predator was a common opossum (Didelphis marsupialis). All avian predation was diurnal; the mammalian predation was nocturnal. My results suggest that tropical birds are subject to a diverse suite of nest predators, and that avian predators may be an important cause of nest failure at my study site. RESUMEN La depredación de nidos es usualmente la primera causa del fracaso de lo nidos de los paserinos. A pesar de esto, poco se conoce sobre la tasa de depredación y los depredadores de nidos de aves neotropicales. Yo use cámaras de video para monitorear siete nidos del Lance-tailed Manakins (Chiroxiphia lanceolata) en la isla Boca brava, Panamá. De un nido salieron polluelos y seis nidos fracasaron debido a la depredación. Yo documente cinco eventos de depredación de los cuales cuatro fueron por aves y uno por mamíferos. Crested Oropendolas (Psarocolius decumanus) depredo dos nidos y Roadside Hawk (Buteo magnirostris) y el Black-chested Jay (Cyanocorax affinis) depredaron uno cada uno. El depredador mamífero fue un marsupial común (Didelphis marsupialis). Todas las depredaciones de aves fueron diurnas y la del mamífero fue nocturna. Mis resultados sugieren que las aves neotropicales están sujetas a una diversa gama de depredadores de nidos y posiblemente la depredación por aves puede ser una causa importante del fracaso de las nidadas en mi lugar de estudio. [source] Underlying mechanism of portal hypertensive gastropathy in cirrhosis: A hemodynamic and morphological approachJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2009Lílian Amorim Curvêlo Abstract Background and Aim:, Portal hypertensive gastropathy (PHG) is an important cause of bleeding in patients with cirrhosis associated with portal hypertension. Histologically, the condition is characterized by dilation of the mucosal and submucosal vessels of the stomach; however, its mechanisms remain unclear. The aim of the present cross-sectional study was to evaluate the role of portal and systemic hemodynamic features, humoral factors and hepatocellular function in the development and severity of PHG in patients with cirrhosis. Methods:, Forty-six patients with cirrhosis of different etiologies underwent endoscopy. Portal hypertension was evaluated by hepatic venous pressure gradient (HVPG). The gastric mucosa was analyzed using two diagnostic methods: endoscopy according to the McCormack criteria and histological by histomorphometric analysis. Results:, The prevalence of PHG according to the endoscopic and histomorphometric methods was 93.4% and 76.1%, respectively. There were no statistically significant differences in HVPG measurements between the patients with mild (16.0 ± 5.9 mmHg) and severe PHG (16.9 ± 6.5 mmHg; P = 0.80) or between patients who did not have (15.2 ± 8.0 mmHg) and those who had PHG (16.3 ± 5.7 mmHg). No correlation was found between the presence or severity of PHG and systemic vascular resistance index (P = 0.53 and 0.34, respectively), Child,Pugh classification (P = 0.73 and 0.78, respectively) or glucagon levels (P = 0.59 and 0.62, respectively). Conclusions:, The present data show no correlation between the presence or the severity of PHG and portal pressure, Child,Pugh classification or systemic hemodynamics, suggesting that other factors may be involved in the physiopathology of PHG, such as local gastric mucosal factors or other underlying factors. [source] | |||||||||||||||||||||||||