Incidence of class 1 and 2 integrases in clinical and commensal bacteria from livestock, companion animals, and exotics

Many pathogenic and commensal organisms are multidrug resistant due to exposure to various antibiotics. Often, this antimicrobial resistance is encoded by integrons that occur on plasmids or that are integrated into the bacterial chromosome. Integrons are commonly associated with bacterial genera in the family Enterobacteriaceae. We determined that class 1 integrases were present in approximately 46% of the isolates from the family Enterobacteriaceae; class 2 integrases were present only among Escherichia coli and Salmonella isolates. Seven percent of veterinary isolates were positive for class 3 integrase by DNA-DNA hybridization but could not be confirmed to be positive by PCR. None of the veterinary isolates possessed the class 4 integrase gene. The distribution of these integrase genes was variable within the members of the family Enterobacteriaceae when some or all integrase classes were absent from a particular genus. There was also considerable variability in the distribution of these integrases within a species, depending on the animal host. Unlike the class 1 integrases, the other integrase class, intI2, appears to be more restricted in its distribution among the members of the family Enterobacteriaceae. There is also considerable variability in the distribution of the class 1 integrases within E. coli strains isolated from different food animals. The class 1 integrases are the most widely disseminated of the four classes among the members of the family Enterobacteriaceae from both the clinical and normal flora of animals. This is the first report to closely examine the distribution of class 2 integrases in members of the family Enterobacteriaceae isolated in the United States.     

基于尿动力学客观指标的神经原性膀胱概率预测模型构建

目的:建立概率预测的Logistic回归模型,分析影响神经原性膀胱尿动力学的主要危险因素和保护因素,并评价模型的灵敏度、特异度和准确性。方法:收集2004-03/2006-03在中山大学附属第一医院尿流动力学室行尿动力学检查的患者80例,对其尿动力学图的客观指标进行回顾性分析。①80例中尿流动力学图正常者29例为对照组,尿流动力学图显示神经原性膀胱者51例为病例组。②将两组资料采用统一的变量指标(包括性别、年龄以及尿流动力学仪器自动采集计算的34个数据)输入SPSS12.0版本数据库,进行主成分分析,将贡献率高的主成分进行单因素分析,取其中有统计学意义的主成分作多因素Logistic回归分析,建立Logistic回归方程,计算各因素的OR值,并计算模型的灵敏度、特异度和准确度。结果:①尿动力学34个客观指标进行主成分分析后得出8个主成分(C1～8),取贡献率高的5个主成分进行单因素分析,结果有2个主成分可以进入多因素Logistic回归分析。获得Logistic回归概率预测模型,此概率预测模型灵敏度为82.4%,特异度75.9%,准确度为80.0%。②主成分C1的OR值=4.606,C1中的首次尿意膀胱压力和逼尿肌压力、正常尿意膀胱压力和逼尿肌压力、强烈尿意膀胱压力和逼尿肌压力、尿急尿意膀胱压力和逼尿肌压力、充盈期最大逼尿肌压力的系数分别是0.823,0.834,0.781,0.913,0.924,0.932,0.883,0.916,0.857,高于C1中其他变量的系数,故可把主成分C1看作是一个“压力型”指标。③C3的OR值=0.183,C3中系数较高的变量是最大流率、平均流率、压力流率中最大流率和平均流率,分别是0.694,0.777,0.768,0.771,因此把C3看作为“流率”变量指标。结论:①成功构建了人神经原性膀胱尿流动力学图的概率预测模型,其中“压力”因子主成分是危险因素,“流率”因子主成分是保护因素。②概率预测模型的灵敏度、特异度和准确性显示其有较好的代表性。     

In vitro changes in platelet function and metabolism following increasing doses of ultraviolet-B irradiation

Ultraviolet-B (UV-B) irradiation of platelet concentrates (PCs) may prevent the development of posttransfusion HLA alloimmunization. This study evaluated the effect of increasing doses of UV-B radiation on stored PCs. Pooled PCs were irradiated at UV-B doses of 600, 2400 or 10,000 mJ per cm2 and stored up to 96 hours under standard blood bank conditions. Compared to nonirradiated room-temperature and 37 degrees C controls, the irradiated units showed no significant changes in platelet count, white cell count, discharge of lactate dehydrogenase, release of beta-thromboglobulin, metabolism of ATP, ADP, ammonia, glutamine, glutamate, hypoxanthine, pCO2, or pO2 at any time of storage following any of the three UV-B doses. However, after a dose of 10,000 mJ per cm2, there were significant decreases in in vitro assays of platelet function-specifically, osmotic recovery and morphology score. Some metabolic systems were also affected by the 10,000 mJ per cm2 radiation dose, as shown by a decline in pH and bicarbonate and an increase in glucose consumption and lactate production (p < 0.05). The changes in these latter assays appeared only after 96 hours of postirradiation storage. Such changes were not seen in either the room- temperature or 37 degrees C control groups. Thus, heat generated during irradiation, per se, did not appear responsible for the observed in vitro changes in platelet function and metabolism. On the basis of the assays analyzed, it is concluded that UV-B irradiation of PCs at doses up to 10,000 mJ per cm2 does not induce significant metabolic or functional derangements following short-term storage (24-48 hours).(ABSTRACT TRUNCATED AT 250 WORDS)     

Transfusion-associated graft-versus-host disease in immunocompetent patients: report of a fatal case associated with transfusion of blood from a second-degree relative, and a survey of predisposing factors

A patient without evident immune deficiency who received a transfusion of blood from a second-degree family member developed fatal transfusion- associated graft-versus-host disease (TA-GVHD). The donor was homozygous for an HLA haplotype for which the recipient was heterozygous (one-way HLA match). All 39 reported cases of TA-GVHD in immunocompetent patients were reviewed to ascertain the predisposing factors and to define the indications for irradiating blood for this population. HLA typing was described in 15 cases; in 13, including seven related and six unrelated donors, a one-way HLA match was present. Thirty-one (79%) of the 39 cases were reported from Japan (and 196 other cases are cited in the Japanese literature), but a one-way HLA match among unrelated donors at HLA-A, -B, -DR loci is only approximately two to four times more likely in Japanese persons than in whites. Fresh blood (< 96 hours old) was used in 29 (94%) of the 31 cases reported from Japan and in 33 (87%) of 38 cases overall (in one case, the age of the blood used was not reported). Thus, factors that appear to predispose to TA-GVHD in immunocompetent patients are a one- way HLA match, fresh blood, and, possibly, Japanese ancestry. Irradiating cellular blood components from all blood relatives of transfusion recipients will not completely eliminate the risk of TA- GVHD.     

低氧训练对下丘脑-垂体-肾上腺皮质轴内分泌相关激素的影响

目的:总结低氧训练对下丘脑-垂体-肾上腺皮质轴内分泌相关激素的影响,为科学运动训练提供依据。资料来源:应用计算机检索中国期刊全文数据库1994-01/2006-10的相关文章,检索词"低氧,低氧训练,下丘脑-垂体-肾上腺,激素",并限定文章语言种类为中文。并应用计算机检索美国国立医学图书馆NCBI1980-01/2006-10的相关文章,检索词"Hypoxic Training,organism endocrine system,hormone",并限定文章语言种类为English。资料选择:对资料进行初审,选取低氧训练与下丘脑-垂体-肾上腺分泌的相关激素有关的文献,并作初步分类,同类文献首选近年发表的核心期刊文章。排除重复及综述类文献。资料提炼:共收集到95篇相关文章,其中56篇属于重复及综述类文献,对符合标准38篇文献进行分析整理。资料综合:①高海拔状态下机体对低氧产生应激反应,表现为下丘脑-垂体-肾上腺皮质轴的适应性运转,血中促肾上腺皮质激素浓度增加,以调节机体对应激刺激的适应能力,同时使促肾上腺皮质激素释放因子分泌增加。②高原训练后,睾酮和皮质醇的变化都较明显,其总体变化均趋于降低,睾酮/皮质醇值有升有降,从一定意义上反映了机体的机能状况与疲劳积累程度。③低氧还引起大鼠血浆β-内啡肽浓度升高,可使心房钠尿素增加、前列腺素增加、血管内皮素分泌增加及抑制血管内皮舒张因子的分泌。结论:激素对机体的新陈代谢、生长发育、各种功能活动以及维持内环境稳态等方面发挥重要的调节作用,低氧训练对机体激素的影响一直应该受到人们的关注。     

Hormone therapy effects on social behavior and activity levels of surgically postmenopausal cynomolgus monkeys

The purpose of the experiments reported here was to investigate central nervous system effects of commonly prescribed postmenopausal hormone therapies in a primate model, the cynomolgus monkey (Macaca fascicularis). The results of two experiments are reported. In the first, ovariectomized adult cynomolgus monkeys were treated for eight weeks each with oral micronized 17beta-estradiol (E2) (n=23), E2+medroxyprogesterone acetate (MPA) (n=23), E2+progesterone (P4) (n=23), and placebo (n=23) using a crossover design. In the second, ovariectomized adult cynomolgus monkeys were treated for eight weeks with oral micronized E2+oral micronized P4 (n=10), or E2+intravaginal micronized P4 delivered via a Silastic ring (n=8), or oral placebo and intravaginal placebo (n=5), using a parallel arm design. Behavior was recorded during weeks two through four. Cerebrospinal fluid (CSF) and blood were sampled, and 24h heart rate recorded by telemetry during weeks five through seven. Monoaminergic metabolites were assayed in CSF, and cortisol was assayed in serum. There were no significant effects of treatment on CSF monoaminergic metabolites or heart rate. E2+MPA increased cortisol concentrations. While there were some differences in effects between experiments, both progestogens and both routes of administration increased time spent resting, particularly resting in body contact, resulting in increased passive affiliative interaction. Thus, synthetic progestogens appear to be as sedating as progesterone, and the ring delivery system does not appear to protect the central nervous system from effects of progestogens. Further research is needed to explore social context as an important feature of behavioral response to steroid hormone regimens and to verify and extend knowledge of systemic effects of vaginal ring-delivered progestogens.     

Serious infection following anti-tumor necrosis factor alpha therapy in patients with rheumatoid arthritis: lessons from interpreting data from observational studies

OBJECTIVE: In a recent observational study, we found that the risk of serious infection following anti-tumor necrosis factor alpha (anti-TNFalpha) therapy in patients with rheumatoid arthritis (RA) was not importantly increased compared with the background risk in routinely treated RA patients with similar disease severity. Observational data sets are, however, subject to a number of important biases related to selection factors for the timing of starting and stopping therapy. Infection risk is also likely to vary with duration of therapy. This study was undertaken to examine the influences of these biases and of the method of analysis on the risk of infection. METHODS: We compared the risk of serious infection in 8,659 patients treated with anti-TNFalpha with that in 2,170 patients treated with traditional disease-modifying antirheumatic drugs (DMARDs) recruited to the British Society for Rheumatology Biologics Register. We applied a number of statistical models in which we varied the length of the followup period by using different definitions of the date of discontinuation of treatment and different lag periods of risk following drug cessation. RESULTS: When the at-risk period was defined as "receiving treatment", the adjusted incidence rate ratio comparing patients receiving anti-TNFalpha therapy with patients receiving DMARD therapy was 1.22 (95% confidence interval [95% CI] 0.88-1.69). Limiting followup to the first 90 days, however, revealed an adjusted incidence rate ratio of 4.6 (95% CI 1.8-11.9). Rates of infection were increased in the 90 days immediately following drug discontinuation and beyond, explained by selection factors for drug discontinuation. CONCLUSION: These findings show that overall, the way in which UK rheumatologists select patients for starting and discontinuing anti-TNFalpha therapy explains our previous finding of no increase in risk. However, there may be important increases in true risk, notably early in the course of treatment, that would become more evident depending on the definition of at-risk period.     

Outcomes after switching from one anti-tumor necrosis factor alpha agent to a second anti-tumor necrosis factor alpha agent in patients with rheumatoid arthritis: results from a large UK national cohort study

OBJECTIVE: Patients with rheumatoid arthritis (RA) who experience treatment failure with one anti-tumor necrosis factor (anti-TNF) agent, due to either inefficacy or toxicity, are frequently switched to a second anti-TNF agent, although the benefits of switching are unknown. The present study was undertaken to compare drug continuation rates between the first course and second course of anti-TNF therapy. METHODS: The study involved a prospective cohort of RA patients from a UK national register of new anti-TNF treatment starts (n = 6,739; 876 starting adalimumab, 2,826 starting etanercept, and starting 3,037 infliximab). Over a mean 15 months of followup, 841 patients stopped taking the first drug due to inefficacy and 1,023 stopped the first drug due to toxicity, of whom 503 and 353, respectively, were switched to a second anti-TNF agent. Kaplan-Meier survival curves were plotted to determine continuation rates for each course, and Cox regression was used to compare each course for the risk of stopping and the reason for stopping (inefficacy or toxicity). RESULTS: Overall, 73% of patients who switched to a second anti-TNF agent remained on the new therapy by the end of followup. First drug discontinuation due to inefficacy was associated with an increased rate of second drug discontinuation due to inefficacy (hazard ratio [HR] 2.7, 95% confidence interval [95% CI] 2.1-3.4) but not toxicity (HR 1.1, 95% CI 0.9-1.5). Similarly, first drug discontinuation due to toxicity was associated with an increased rate of second drug discontinuation due to toxicity (HR 2.3, 95% CI 1.9-2.9) but not inefficacy (HR 1.2, 95% CI 0.8-1.6). CONCLUSION: RA patients who are switched to a second anti-TNF drug have high rates of continuation, although among those who must discontinue treatment, the reasons for stopping a second drug are related to the reasons for stopping the first drug. This large data set from the UK provides the first estimates of the magnitude of these effects in patients with long-standing severe RA.