Cardiac troponin I release and cytokine response during experimental human endotoxaemia

Objective To study the relationship between cytokine levels and cardiac troponin I (cTnI).Design Prospective experimental study.Setting Intensive care unit of a university hospital.Participants Six healthy male volunteers.Interventions Endotoxin, 4 ng/kg, was given as a 1-min intravenous infusion.Measurements and results Circulating cardiac troponin I levels and proinflammatory cytokines tumour necrosis factor- (TNF-), interleukin-6 (IL-6) and interleukin-8 (IL-8) were analysed at various time points during a 24-h period. TNF- appeared in the circulation 30 min after injection (T=0.5 h), reaching peak levels (5,665±1,910 pg/ml) 2 h after infusion. At T=24 h TNF- was still elevated in the circulation compared to T=0. None of the six volunteers had a cTnI value higher than 0.1 g/l at T=0, 6 h or 24 h.Conclusion The presence of significant amounts of TNF-, IL-6 and IL-8 in the systemic circulation does not lead to increased levels of cTnI in experimental human endotoxaemia.     

Validation of risk adjustment models for in-hospital percutaneous transluminal coronary angioplasty mortality on an independent data set.

OBJECTIVES: We sought to validate recently proposed risk adjustment models for in-hospital percutaneous transluminal coronary angioplasty (PTCA) mortality on an independent data set of high risk patients undergoing PTCA. BACKGROUND: Risk adjustment models for PTCA mortality have recently been reported, but external validation on independent data sets and on high risk patient groups is lacking. METHODS: Between July 1, 1994 and June 1, 1996, 1,476 consecutive procedures were performed on a high risk patient group characterized by a high incidence of cardiogenic shock (3.3%) and acute myocardial infarction (14.3%). Predictors of in-hospital mortality were identified using multivariate logistic regression analysis. Two external models of in-hospital mortality, one developed by the Northern New England Cardiovascular Disease Study Group (model NNE) and the other by the Cleveland Clinic (model CC), were compared using receiver operating characteristic (ROC) curve analysis. RESULTS: In this patient group, an overall in-hospital mortality rate of 3.4% was observed. Multivariate regression analysis identified risk factors for death in the hospital that were similar to the risk factors identified by the two external models. When fitted to the data set, both external models had an area under the ROC curve >0.85, indicating overall excellent model discrimination, and both models were accurate in predicting mortality in different patient subgroups. There was a trend toward a greater ability to predict mortality for model NNE as compared with model CC, but the difference was not significant. CONCLUSIONS: Predictive models for PTCA mortality yield comparable results when applied to patient groups other than the one on which the original model was developed. The accuracy of the two models tested in adjusting for the relatively high mortality rate observed in this patient group supports their application in quality assessment or quality improvement efforts.     

Microdeletion 9q22.3 syndrome includes metopic craniosynostosis, hydrocephalus, macrosomia, and developmental delay

Basal cell nevus syndrome (BCNS), also known as Gorlin syndrome (OMIM #109400) is a well-described rare autosomal dominant condition due to haploinsufficiency of PTCH1. With the availability of comparative genomic hybridization arrays, increasing numbers of individuals with microdeletions involving this locus are being identified. We present 10 previously unreported individuals with 9q22.3 deletions that include PTCH1. While 7 of the 10 patients (7 females, 3 males) did not meet strict clinical criteria for BCNS at the time of molecular diagnosis, almost all of the patients were too young to exhibit many of the diagnostic features. A number of the patients exhibited metopic craniosynostosis, severe obstructive hydrocephalus, and macrosomia, which are not typically observed in BCNS. All individuals older than a few months of age also had developmental delays and/or intellectual disability. Only facial features typical of BCNS, except in those with prominent midforeheads secondary to metopic craniosynostosis, were shared among the 10 patients. The deletions in these individuals ranged from 352 kb to 20.5 Mb in size, the largest spanning 9q21.33 through 9q31.2. There was significant overlap of the deleted segments among most of the patients. The smallest common regions shared among the deletions were identified in order to localize putative candidate genes that are potentially responsible for each of the non-BCNS features. These were a 929 kb region for metopic craniosynostosis, a 1.08 Mb region for obstructive hydrocephalus, and a 1.84 Mb region for macrosomia. Additional studies are needed to further characterize the candidate genes within these regions.     

APOE ε4 differentially influences change in memory performance depending on age. The SMART-MR study

The apolipoprotein E (APOE) gene may act differently in young and old persons, known as antagonistic pleiotropy. We therefore examined the prospective associations between the APOE ε4 allele and cognitive functioning, and the modifying effect of age, in 375 nondemented adults (mean age 57 ± 10 years; follow-up period 3.8 ± 0.2 years) with available data on APOE genotype and cognitive functioning, within the SMART-MR (Second Manifestations of ARTerial disease-Magnetic Resonance) cohort study. Neuropsychological tests assessing memory performance and executive functioning were performed at baseline and follow-up, and composite z-scores were calculated. Age significantly modified the association of APOE ε4 with change in memory performance (p interaction = 0.02). In persons ≤ 57 years (median split), an APOE ε4 allele was associated with an increase in immediate recall (B = 0.42; 95% confidence interval [CI], 0.17 to 0.66) and delayed recall (B = 0.37; 95% CI, 0.09 to 0.64), while in persons > 57 years, an APOE ε4 allele was associated with decline in immediate recall (B = -0.25; 95% CI, -0.52 to 0.01). Our findings suggest that the APOE ε4 allele has a differential effect on change in verbal memory performance depending on age, consistent with the hypothesis of antagonistic pleiotropy.     

Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs

Dendritic cells (DCs) are known to induce the growth and function of natural killer (NK) cells. Here, we address the capacity of DCs to interact with NK cells in human lymphoid organs and identify the role of specific DC-derived cytokines. We demonstrate that DCs colocalize with NK cells in the T cell areas of lymph nodes. In culture, DCs from either blood or spleen primarily stimulate the CD56(bright)CD16- NK cell subset, which is enriched in secondary lymphoid tissues. Blocking of IL-12 abolished DC-induced IFN-gamma secretion by NK cells, whereas membrane-bound IL-15 on DCs was essential for NK cell proliferation and survival. Maturation by CD40 ligation promoted the highest IL-15 surface presentation on DCs and led to the strongest NK cell proliferation induced by DCs. These results identify secondary lymphoid organs as a potential DC/NK cell interaction site and identify the distinct roles for DC-derived IL-12 and IL-15 in NK cell activation.     

间充质干细胞的来源

目的:间充质干细胞具有强大的增殖能力和多向分化潜能,文章对其主要的来源途径予以综述。资料来源:应用计算机检索Medline1991-01/2006-01期间的相关文章,检索词为“mesenchyma stem cells,origin,research progress”,并限定文章语言种类为English。同时计算机检索中国期刊全文数据库1998-01/2006-10期间的相关文章,检索词为“间充质干细胞,来源,研究进展”,并限定文章语言种类为中文。资料选择:对资料进行初审,并查看每篇文献后的引文。纳入标准:①间充质干细胞的起源。②间充质干细胞研究进展、干细胞的分离及鉴定。排除标准:重复研究、个案报告或Meta分析类文章。资料提炼:共收集到96篇相关文献,40篇文献符合纳入标准,排除的56篇文献为内容陈旧或重复。符合纳入标准的40篇文献中,分别涉及骨髓、肌肉、脐血、胎盘、外周血、脂肪组织、血管及其他来源的间充质干细胞。资料综合:间充质干细胞是属于中胚层的一类多能干细胞,具有强大的增殖能力和多向分化潜能,动物模型试验和临床应用研究也取得了一定的效果。间充质干细胞来源广泛,易于获得,临床上为神经损伤及其他系统的损伤修复提供了更为广泛的途径。结论:间充质干细胞主要来源于骨髓、肌肉、脐血、外周血、胎盘等组织,具有广阔的应用前景。     

Obesity and the risk of death after acute myocardial infarction

Background

In the general population, obesity is associated with an increased risk of all-cause death. However, the importance of obesity in patients with established coronary heart disease is less well defined.

Methods

As part of the Determinants of Myocardial Infarction Onset Study, we performed a prospective cohort study of 1898 patients hospitalized with confirmed acute myocardial infarction between 1989 and 1994, with a median follow-up of 3.8 years. We assessed all-cause death through December 1995, using the National Death Index. We categorized patients according to WHO criteria for body mass index (BMI). We compared long-term death according to BMI (kg/m²) by using Cox proportional hazards regression.

Results

Of the 1898 eligible patients, 607 (32%) were normal weight (18.5 to 24.9 kg/m²), 832 (44%) were overweight (25.0 to 29.9 kg/m²), 331 (17%) were class I obese (30.0 to 34.9 kg/m²), and 128 (7%) were class II or more obese (≥35.0 kg/m²). A total of 311 patients died during follow-up. After adjustment for potentially confounding risk factors and excluding patients with noncardiac comorbidity, the risk for death appeared to increase linearly, with increasing BMI across all categories (P for trend = .08). The relative risk of death in all obese patients (≥30 kg/m²) was 1.46, compared with those with normal weight (95% CI, 0.98 to 2.17).

Conclusions

We found that BMI appeared to have a positive, graded relation with post-myocardial infarction death. Whether weight reduction and secondary prevention strategies would reverse this effect in obese population remains to be seen.     

Caffeinated coffee consumption and mortality after acute myocardial infarction

Background

Previous studies have generally suggested no effect of coffee consumption on the risk of acute myocardial infarction. The effect of coffee consumption on prognosis after acute myocardial infarction is uncertain.

Methods

In an inception cohort study, we observed 1935 patients who were hospitalized with a confirmed acute myocardial infarction between 1989 and 1994 at 45 community hospitals and tertiary care centers in the United States, as part of the Determinants of Myocardial Infarction Onset Study. Trained interviewers assessed self-reported caffeinated coffee consumption before infarction with a standardized questionnaire. We analyzed survival censored at December 31, 1995, using Cox proportional hazards regression.

Results

Of the 1902 patients for whom we had information on coffee intake, 315 (17%) died during a median follow-up period of 3.8 years. Coffee drinkers tended to be men, younger, and free of comorbidity, and they were more likely to be current smokers. Coffee consumption was not associated with an overall change in long-term post-infarction mortality rate. However, we did observe an unexpected and unexplained variation in the association between coffee consumption and mortality with time, with an apparent inverse association in the first 90 days after infarction.

Conclusions

Self-reported coffee consumption has no overall association with post-infarction mortality. The unexpected time variation in the effect of coffee intake requires evaluation in other studies.     

Characterization of hepatitis B virus strains from the Central African Republic: preliminary results

Objectives

Genotyping of Hepatitis B virus (HBV) strains from patients in Central African Republic and comparison with results obtained in other African countries.

Patients and methods

Sera were collected from patients admitted with symptoms of acute or chronic hepatitis to the “Hôpital de l’Amitié de Bangui”, Central African Republic (CAR). The complete sequence of preS2/S gene has been defined for determining genotypes.

Results

Hundred and ninety-six sera were collected from 112 men and 84 women. Ninety-two percent of patients had contact with HBV (anti-HBc postitive) and the HBsAg prevalence was about 62%. HBV DNA was detected in 66% of HBsAg positive sera. No HBV-DNA was evidenced among patients with negative HBsAg. Ninety-three percent of the HBV strains belonged to genotype E; one (3.4%) belonged to genotype A1, and one (3.4%) belonged to genotype D.

Conclusions

The high prevalence of HBV infection in the studied population is due to their recruitment. The genotype E is predominant in CAR and the intragroup variability of HBV genotype E reached only 1.8%. Genotypes A and D were less common in CAR their presence may be explained by importation.