Clostridium difficile-associated diarrhea from a general hospital in Argentina

Clostridium difficile is responsible for 15-25% of all cases of antibiotic associated diarrhea. The incidence of infection with this organism is increasing in hospitals worldwide, consequent to the widespread use of broad-spectrum antibiotics. Although the clinical and financial impact of nosocomial C. difficile infection is believed to be significant, only limited information is available on the importance of C. difficile as a cause of diarrhea in Argentina. The aim of the study was to evaluate the impact and diagnosis methods of CDAD from symptomatic patients in a general hospital from Argentina. Consecutive diarrheal stool samples from symptomatic patients from a General Hospital in Argentina were screened for toxigenic C. difficile between April 2000 and April 2001. Toxins were detected in stools by the Premier Cytoclone A+B EIA. Each specimen was examined for toxigenic C. difficile strains by culture. From 104 specimens, 40 (38.5%) [32 of 87 patients (36.8%)] were positive and 64 (61.5%) [55 of 87 patients (63.2%)] were negative by stool toxin assay and/or toxigenic culture. In 11 of 40 positives samples C. difficile toxins were detected only by toxigenic culture. Five (15.6%) patients presented with symptomatic recurrences. Toxin-negative strains were not isolated. This data indicates that the high prevalence of toxigenic strains of C. difficile is of concern in routine diagnostic testing for C. difficile toxins in our study population. Detection of toxins in stools by EIA, coupled with testing strains for toxigenicity only in those cases in which direct toxin assay produces negative results, may be a satisfactory strategy. CDAD is an emerging nosocomial problem in our hospital. It will be necessary to evaluate the epidemiology and measures to control nosocomial spread.     

上海部分地区儿童艰难梭菌相关性腹泻的临床分析

本文旨在监测儿童腹泻中艰难梭菌相关性腹泻(CDAD)的发病情况,并对其进行回顾性临床分析。对复旦大学附属儿科医院2007年2月～9月111例腹泻患儿的粪便标本进行艰难梭菌毒素A检测及粪便厌氧菌培养,对所有患儿进行回顾性病史采集及分析,并对粪便培养所得的4株艰难梭菌菌株用多位点可变数目串联重复序列分析(MLVA)技术进行同源性分析。111例患者中,艰难梭菌毒素A检测及艰难梭菌培养均为阳性者无,艰难梭菌毒素A阳性而艰难梭菌培养阴性者16例,艰难梭菌毒素A阴性而艰难梭菌培养阳性者4例,艰难梭菌毒素A及艰难梭菌培养均阴性者91例。比较院内、院外组3种不同病程腹泻CDAD的发病率,无显著差异。MLVA分析发现粪便培养得到的4株艰难梭菌菌株有部分同源性。结果提示,目前上海部分地区儿童CDAD发病情况为散发,但彼此之间有部分同源性;院内、外获得性腹泻的CDAD发病率无显著差异;艰难梭菌毒素A阳性或艰难梭菌培养阳性的病例在临床表现上与艰难梭菌毒素A阴性且艰难梭菌培养阴性的腹泻病例无显著差异。     

Probiotic therapy for the prevention and treatment of Clostridium difficile-associated diarrhea: a systematic review

BackgroundThe recent increase in the number and severity of cases of nosocomial Clostridium difficile-associated diarrhea (CDAD) has prompted interest in the use of probiotics for the prevention and treatment of this disease. We performed a systematic review of randomized controlled trials to assess the effectiveness of probiotic therapy.MethodsWe searched the PubMed, EMBASE, INAHTA, HEN and Cochrane Collaboration databases to identify trials in which the prevention or treatment of CDAD with probiotic therapy was the primary or secondary outcome. We extracted data on the number of patients randomly assigned to receive probiotic or placebo, the number of patients with CDAD, the type of probiotic, criteria for diagnosing CDAD, persistence of infection after treatment, compliance and adverse effects.ResultsWe identified 4 eligible studies in which prevention (n = 1) or treatment (n = 3) of CDAD was the primary outcome. The benefit of probiotic therapy seen in 2 of the studies was restricted to subgroups characterized by severe CDAD and increased use of vancomycin. The remaining 2 studies were too methodologically flawed for us to draw meaningful conclusions. We also identified 4 trials in which prevention of antibiotic-associated diarrhea with probiotics was the primary outcome and prevention of CDAD a secondary outcome. These studies were limited primarily by too few CDAD cases and provided no evidence of effective prophylaxis. Overall, heterogeneity in choice and dose of probiotic and in criteria for diagnosing CDAD makes it difficult to synthesize information from the 8 studies.InterpretationStudies conducted to date provide insufficient evidence for the routine clinical use of probiotics to prevent or treat CDAD. Better designed and larger studies are needed.Both the incidence and severity of Clostridium difficile-associated diarrhea (CDAD) have increased in hospitals across North America.^1,2,3,4 Recent outbreaks in Montreal and Sherbrooke resulted in a 4-fold increase in the number of CDAD cases as well as an increase in the number of attributable deaths.^1,5,6,7 CDAD is a debilitating and costly illness, particularly among patients with recurring episodes. Probiotics, or naturally occurring “good bacteria,” have been suggested as a means of both preventing and treating the disease.^8,9,10,11 The disturbance of normal gastrointestinal flora, particularly after antibiotic use, is believed to predispose patients to colonization by C. difficile;² probiotics, by delivering bacteria to the gastrointestinal tract, are believed to restore equilibrium in the altered gastrointestinal flora and thus protect against colonization.⁸ Probiotics that have been proposed for prevention and treatment of antibiotic-associated diarrhea and CDAD include various bacteria (Bifidobacterium, Lactobacillus GG, L. rhamnosus, L. casei, L. plantarum 299v, Enteroccus faecium [SF68]) and yeasts (Saccharomyces boulardii, S. cerevisiae). They are commonly available as lyophilized capsules or in the form of a fermented drink. We performed a systematic review of randomized controlled trials of probiotic therapy for the prevention and treatment of CDAD.     

Relapses or reinfections: Analysis of a case of Clostridium difficile-associated colitis by two typing systems

Immunoblotting and pulsed-field gel electrophoresis of Clostridium difficile isolates were employed to differentiate reinfection by a newly acquired strain from relapse by an original strain in a 10-year-old patient with four episodes of C. difficile-associated colitis. Immunoblot typing demonstrated subserogroup K-1 of serogroup K for the first and second organisms, subserogroup A-1 of serogroup A for the third organism, and subserogroup G-4 of serogroup G for the fourth organism. PFGE analysis revealed consistent results with immunoblot analysis except that the strains from the fourth episode, whose DNA constantly degraded, were nontypable by this method. Five separate isolates of C. difficile from a specimen of each episode showed identical PFGE patterns, indicating that infections of multiple strains probably did not occur in this patient. These typing results suggested that the second episode after a 17-day course of vancomycin therapy represented a relapse by the strain causing the first episode, and that the third and fourth episodes after tapering vancomycin therapy were reinfections by other strains. Both immunoblot and PFGE typing systems are promising tools for analyzing recurrence of C. difficile infection. Received: 27 November 1995 / Revised: 1 January 1996 / Accepted: 22 March 1996     

The changing pattern of neoplastic disease in Canadian Eskimos.

The records of the two main referral centres for the western and central Arctic were reviewed for Eskimo patients with cancer diagnosed between 1949 and 1974 inclusive. To these were added the records for the past 6 years of patients from the eastern Arctic, giving the toatal of 180 histologically proved cases of malignant disease. Athe data were analysed for prevalence, relative frequency, geographic distribution and changes with time of the various neoplasms. Salivary gland and renal neoplasms have in recent years been displaced by cancer of the lung and uterine cervix as the most common malignant tumours in Canadian Eskimos. The prevalence of lung cancer in Eskimo women, particularly of the central Artic, is striking. Cancer of the nasopharynx kept the same relative position during early and late years of the survey period. Breast cancer is still uncommon in Eskimos. Lactation rather than gestation history appeared to be an important protective factor. Cases of cervical cancer outnumbered those of breast cancer by 18 to 4, in sharp contrast to the relative proportions of these tumours in all Canadian women.     

Efficacy and safety of fidaxomicin compared with oral vancomycin for the treatment of adults with Clostridium difficile-associated diarrhea: data from the OPT-80-003 and OPT-80-004 studies

Clostridium difficile is emerging as one of the most important and devastating pathogens affecting hospitalized populations around the world. The incidence of C. difficile infection is increasing and disease severity is worsening. Thus, an effective alternative to metronidazole and oral vancomycin is urgently needed. Two Phase III trials, OPT-80-003 and OPT-80-004, showed that oral fidaxomicin for 10 days was noninferior compared with treatment with oral vancomycin among adult patients with toxin-positive C. difficile-associated diarrhea (CDAD). Furthermore, fidaxomicin was associated with a lower rate of recurrence of CDAD within 4 weeks of completion of therapy. The safety and tolerability of fidaxomicin was consistent with earlier studies and established that fidaxomicin is an efficacious and well-tolerated treatment option for CDAD. Despite these potential advantages, the cost-effectiveness of this expensive agent remains poorly understood.     

1991-2017年叶尔羌河流域冰川景观格局时空演变

冰川景观变化是全球环境和气候变化的共同"指示器"。随着全球气候变化加剧,干旱和半干旱地区的冰川景观将进一步变化。科学评估冰川景观格局时空演变特征,为应对冰川景观变化及其影响提供科学参考。基于1991-2017年Landsat TM/ETM+/OLI遥感影像,采用监督分类方法获取叶尔羌河流域冰川景观时空格局及变化数据,利用景观格局指数、质心迁移模型、分形维数等方法分析近26年叶尔羌河流域冰川景观格局时空演变特征。结果表明：（1）1991-2017年叶尔羌河流域冰川斑块面积呈消减趋势,但有所减缓,共减少799.50 km²（-13.09%）。冰川斑块面积消减主要集中在海拔5400-5800 m之间,相较之下,海拔4400 m以下的区域冰川斑块面积消减率最高,达63.68%;不同坡度冰川景观消减率存在差异,陡坡冰川斑块面积消减率最高（15.98%）,急陡坡消减率最低（2.87%）;阴阳两坡冰川景观均呈消减趋势,阳坡冰川斑块面积消减速率显著高于阴坡。（2）近26年来,叶尔羌河流域冰川斑块数量、最大斑块指数均减小,而平均形状指数、平均周长面积比、分裂指数均增加,表明冰川景观不断消减,破碎化程度增加。（3）研究期间,叶尔羌河流域冰川景观质心发生迁移,整体呈现东北偏移趋势。（4）通过分形理论对叶尔羌河流域冰川景观空间结构特征进行分析表明,该流域冰川景观消减率略微降低,但仍然处于持续消融状态。     

A methodology to evaluate disease severity: a case study of chestnut blight in El Bierzo region (northwestern Spain)

Correct knowledge of the incidence and severity of disease is essential for implementation of timely and effective management control strategies. In this article, multiple correspondence analysis (MCA) is applied to evaluate the severity of chestnut blight incited by the ascomyceteous fungus Cryphonectria parasitica. This economically important bark disease leads to the loss of an important part of the chestnut production and the progressive death of the tree. A total of 7240 living European chestnut (Castanea sativa) trees across 452 plots were surveyed in El Bierzo, NW Spain. For each tree, the main stem and canopy were visually assessed for signs of the pathogen and/or symptoms of the disease and the extent of the disease was classified on a qualitative ordinal scale consisting of six levels. The statistical procedure is useful because it quickly analyses measurable, discrete observations from assessed individuals to provide a disease severity measure related to tree features and disease extension inside the tree. The results indicated that the penetration of the pathogen is located in the lower part of the crown and spreads to the tips of the branches in the upper part of the crown. Thus, our results suggest that man‐made wounds, when the tree was grafted or pruned, are the main channel of pathogen penetration in El Bierzo region. Disease severity estimates and incidence data for C. parasitica across the region were compared. From the perspective of the management and control of the disease, a disease severity value provides a more accurate indication of the scenario of the disease in a region than presence or absence data alone.     

红壤丘陵区土地利用方式变更后土壤有机碳动态变化的模拟

采用双组分模型模拟土地利用方式变更后土壤有机碳储量的变化,并用一些调查和监测数据进行了初步验证．此双组分模型将土壤有机碳分为新形成有机碳和原有有机碳两个组分．每个组分有机碳的形成转化用一级动力学方程描述．本文用此模型对亚热带土壤开垦利用为马尾松林地、湿地松林地、柑桔园和牧草地４种方式１０年来土壤有机碳储量的变化过程进行了模拟,初步结果表明,模拟值与实测值拟合较好．可见,此方法适于用来模拟不同土壤类型下土地利用系统变更初期的土壤有机碳储量动态变化过程．     

Virus disease in wheat predicted to increase with a changing climate

Current atmospheric CO₂ levels are about 400 μmol mol^?1 and are predicted to rise to 650 μmol mol^?1 later this century. Although the positive and negative impacts of CO₂ on plants are well documented, little is known about interactions with pests and diseases. If disease severity increases under future environmental conditions, then it becomes imperative to understand the impacts of pathogens on crop production in order to minimize crop losses and maximize food production. Barley yellow dwarf virus (BYDV) adversely affects the yield and quality of economically important crops including wheat, barley and oats. It is transmitted by numerous aphid species and causes a serious disease of cereal crops worldwide. This study examined the effects of ambient (aCO₂; 400 μmol mol^?1) and elevated CO₂ (eCO₂; 650 μmol mol^?1) on noninfected and BYDV‐infected wheat. Using a RT‐qPCR technique, we measured virus titre from aCO₂ and eCO₂ treatments. BYDV titre increased significantly by 36.8% in leaves of wheat grown under eCO₂ conditions compared to aCO₂. Plant growth parameters including height, tiller number, leaf area and biomass were generally higher in plants exposed to higher CO₂ levels but increased growth did not explain the increase in BYDV titre in these plants. High virus titre in plants has been shown to have a significant negative effect on plant yield and causes earlier and more pronounced symptom expression increasing the probability of virus spread by insects. The combination of these factors could negatively impact food production in Australia and worldwide under future climate conditions. This is the first quantitative evidence that BYDV titre increases in plants grown under elevated CO₂ levels.     

Physostigmine effects in Alzheimer's disease: relationship to dementia severity

Eleven demented patients were administered .004, .009, and .013 mg/kg physostigmine intramuscularly, and placebo, double-blind, in Phase 1. The most effective dose, in terms of showing the best memory score as compared to saline, was repeated during Phase 2. Five patients improved their verbal memory scores in both Phases 1 and 2 after the most effective dose of physostigmine; these five "responders" were found to be significantly more demented than the six "nonresponders." Drug-induced increases in memory scores were significantly correlated with illness severity. Intrusions, which were not a factor in selection of the most effective dose, were reduced in the group as a whole, with the responders showing the most improvement and the nonresponders the least. The association between physostigmine effect and degree of dementia suggests to us that the severe cases may have more permeable blood-brain barriers, and that drug availability to the brain is an important factor in evaluating treatment of SDAT with cholinergic substances.     

Public health: the control of meningococcal disease in Quebec

A first outbreak of serogroup C meningococcal disease occurred in the province of Quebec in 1990-1992 and lead to a mass immunization campaign using polysaccharide vaccines. In 2001, a second outbreak was identified and a mass vaccination campaign was carried out, using the newly licensed conjugate vaccine. Clinical, epidemiological, economic and social studies were instrumental in the decision making for implementing these control programs.     

上海地区部分婴幼儿腹泻标本中诺如病毒基因分析

目的了解2006年上海哨点医院婴幼儿疑似病毒性腹泻散发病例中诺如病毒基因型别和基因特征。方法应用反转录-聚合酶链反应(RT-PCR)扩增标本中诺如病毒核酸,测序后使用DNAstar基因分析软件与Genbank中的参考株进行核酸序列分析。结果13份测序结果均属于诺如病毒GⅡ遗传组,以GⅡ.4基因型为主。其中2份核酸序列与2006年德国汉堡毒株序列同源性相近,分别为86.2%和88.2%;2份核酸序列与2006年荷兰乌得勒支毒株序列同源性相近,均为83.9%;其余9份核酸序列与2004年中国广西、2004年和2005年日本东京毒株序列同源性相近,为87.3%～97.5%。结论2006年上海哨点医院婴幼儿疑似病毒性腹泻标本中存在诺如病毒GⅡ.4基因型散发病例,不同病毒株之间差异较大。     

The changing chromatome as a driver of disease: A panoramic view from different methodologies

Chromatin-bound proteins underlie several fundamental cellular functions, such as control of gene expression and the faithful transmission of genetic and epigenetic information. Components of the chromatin proteome (the “chromatome”) are essential in human life, and mutations in chromatin-bound proteins are frequently drivers of human diseases, such as cancer. Proteomic characterization of chromatin and de novo identification of chromatin interactors could, thus, reveal important and perhaps unexpected players implicated in human physiology and disease. Recently, intensive research efforts have focused on developing strategies to characterize the chromatome composition. In this review, we provide an overview of the dynamic composition of the chromatome, highlight the importance of its alterations as a driving force in human disease (and particularly in cancer), and discuss the different approaches to systematically characterize the chromatin-bound proteome in a global manner.     

Gender distribution in irritable bowel syndrome is proportional to the severity of constipation relative to diarrhea

Background: A significant gender disparity has been observed in individuals with irritable bowel syndrome (IBS), with females outnumbering males, especially in constipation-predominant IBS (C-IBS). However, this observation is based on Rome criteria categorization and does not take into account the severity of constipation or diarrhea.Objective: In a large prospective data set, gender differences across the severity of constipation and diarrhea were examined in patients with IBS.Methods: Consecutive adult patients with Rome I positive IBS who were referred to a tertiary care medical center (Cedars-Sinai Medical Center, Los Angeles, California) in 1999–2003 were given a questionnaire. The questionnaire asked subjects to rate their constipation and diarrhea according to perceived severity using a scale from 0 (none) to 5 (very severe). C-IBS was determined to be present if the severity of constipation was greater than the severity of diarrhea (sevC > sevD). If sevD > sevC, subjects were considered to have diarrhea-predominant IBS (D-IBS). To further categorize their symptoms, subjects were then grouped by the difference between the severity of constipation and diarrhea, creating a range of values from ?5 to +5. For each of these 11 constipation/diarrhea severity values, the female:male ratio was determined. The severity of constipation to diarrhea was compared by Spearman rank correlation.Results: A total of 429 subjects with IBS (325 women: mean [SD] age, 42.5 [0.8] years; 104 men: mean age, 42.2 [1.7] years) completed the questionnaire. Constipation occurred more frequently in women (79.7%) compared with men (61.5%) (odds ratio [OR] = 2.49; 95% CI, 1.55–4.02). The prevalence of diarrhea was similar between the sexes. Whereas C-IBS was more common in women (31.8%) than in men (26.0%) (OR = 2.03; 95% CI, 1.24–3.30), D-IBS was more prevalent in men (62.5%) than in women (36.3%) (OR = 2.39; 95% CI, 1.53–3.75). When the female:male ratio was evaluated across the 11 severity score categories of constipation and diarrhea, the greater the sevC — sevD score, the higher the proportion of women (R = 0.80; P = 0.003).Conclusion: In this study of patients with IBS, the observation of the association of constipation and gender in IBS is extended to indicate that the female:male ratio significantly increases according to the severity of constipation relative to the severity of diarrhea.