Loss of high-affinity thrombin receptors during platelet concentrate storage impairs the reactivity of platelets to thrombin

BACKGROUND: The storage of platelet concentrates (PCs) induces a reduction in the platelet surface expression of glycoprotein (GP) Ib alpha. The location of the platelets' high-affinity binding site for thrombin has been postulated as being located on GPIb alpha. This study attempts to determine whether loss or alteration of GPIb alpha during storage of PCs is related to impairment in the reactivity of platelets to thrombin. STUDY DESIGN AND METHODS: In this study, platelet surface expression of GPIb alpha was monitored by means of flow cytometry, throughout standard storage of PCs for up to 10 days. Two thrombin- induced platelet responses, the binding of radiolabeled fibrinogen and the platelet surface expression of P-selectin, were evaluated. Thrombin- binding assays were also performed to assess the number of thrombin receptors in platelets. RESULTS: The surface expression of the GPIb/IX complex declines during storage of PCs. The thrombin-induced maximal binding of fibrinogen in platelets stored for 3, 7, and 10 days was 77 +/? 7 percent, 60 +/? 20 percent, and 34 +/? 25 percent, respectively, of that found in fresh platelets. Moreover, the concentration of thrombin needed for 50 percent of platelets to express the CD62 antigen P-selectin at the surface increased from 0.05 U per mL in fresh platelets to 0.11, 0.56, and 1.2 U per mL in platelets stored for 3, 7, and 10 days, respectively. Thrombin-binding experiments demonstrated a significant reduction in the number of high-affinity binding sites throughout storage of PCs (55 +/? 21 sites/platelet in 10-day-stored platelets vs. 73 +/? 25 in fresh platelets). A significant correlation was also observed between the number of high-affinity thrombin-binding sites and surface expression of GPIb alpha. Selective blockage of the thrombin-binding site on GPIb alpha with monoclonal antibody LJ-Ib10 also inhibited the response of fresh platelets to thrombin, up to a level equivalent to that found in 3-day-stored platelets. CONCLUSION: The loss of the GPIb alpha-located high-affinity thrombin-binding site may impair the ability of platelets to become activated by thrombin as storage time increases.     

Lack of clinical significance of "enzyme-only" red cell alloantibodies

In a retrospective study on samples from 10,000 recently transfused patients, 35 samples were found to contain an antibody that reacted with ficin-treated red cells but was not demonstrable by low-ionic- strength saline solution and indirect antiglobulin test (LISS-IAT). In those 35 patients, the specificity of the antibody was such that each patient would have been transfused with antigen-negative blood had the antibody reacted in LISS-IAT. Tests on red cells from the units already transfused showed that 19 patients had among them received, by chance, 32 antigen-positive and 74 antigen-negative units. The remaining 16 patients had among them received 57 units that were, again by chance, all antigen negative. One patient given antigen-positive blood suffered a delayed transfusion reaction; in two others the antibodies became LISS-IAT active after transfusion. However, similar changes to the LISS- IAT-active state were seen with two antibodies of patients given only antigen-negative blood. Also found in the 10,000 patients were 28 clinically insignificant antibodies, 77 sera in which the antibody was too weak to identify, and 216 autoantibodies that reacted only with ficin-treated red cells. These data support a belief, generally held in the United States but not necessarily elsewhere, that the use of protease-treated red cells for routine pretransfusion tests creates far more work than the accrued benefits justify.     

河南省5所院校学生的亚健康状况

目的:调查河南省5所院校大学生亚健康的发生情况并分析其影响因素。方法:调查于2006-03/07在河南省5所高校完成。选择郑州大学、河南农业大学、河南财经学院、新乡医学院和安阳工学院五所不同专业院校1～4年级的大学生为对象进行亚健康调查。根据大学生"亚健康"主要表现特征,参照相关文献中关于亚健康状态的各种表现,自行设计亚健康调查表。每项问题后都有很好、稍差、明显差和很差或是没有、较少、较多和经常出现4种选项,以选择明显差、很差、较多和经常出现为亚健康标准。结果:共发放调查问卷2000份,收回有效问卷1990份。郑州大学、河南农业大学、河南财经学院、新乡医学院和安阳工学院5所大学亚健康人数分别为267,235,260,274,260人,亚健康的发生率分别为66.75%,59.34%,65.98%,68.50%,65.00%。不同专业院校大学生亚健康状态发生率与学习环境、专业特点、性别、城乡有关。亚健康的主要表现形式排在前3位的分别是长期持续疲劳,注意力难以集中,记忆力减退。在调查对象中,了解、听说过和不知晓亚健康的人数分别为441,340,1209人,占总人数的比例分别为22.16%,17.08%,60.75%。结论:大学生中相当一部分人存在亚健康状况,而社会、学习环境与心理、生活方式和人际关系等是导致大学生亚健康状况的主要因素。应正确引导大学生预防和消除亚健康状态,培养和建立新的高教教学卫生理念。     

氧化应激对糖尿病肾病时细胞、细胞外基质及血管通透性的影响机制

目的:糖尿病肾病及其引起的终末期肾病近年来在全球的发病情况逐年提高,该病预后差、治疗费用高,成为世界范围内严重危害人类健康的公共卫生问题。糖尿病肾病发病机制错综复杂,氧化应激被认为是重要的共同的机制之一。本文探讨氧化应激对糖尿病肾病的影响。资料来源:应用计算机检索MEDLINE,CBM,CNKI数据库及手工检索1997-01/2006-11期间的相关文献。包括临床研究(不限研究对象的年龄、性别、种族。)和基础研究,不限体内或体外研究。中文检索词包括“氧化应激”,“活性氧类”,“糖尿病肾病”和“发病机制”;英文检索词有“diabetic nephropathies”,“oxidative stress”,“reactive oxygen species”,“PKC”和“TGF-β”。资料选择:共收集到相关文献991篇,阅读全部文章的文题和大部分文章的摘要。选择文献所述内容与糖尿病肾病时氧化应激作用相关的文献。排除重复性研究和Meta分析类文章。资料提炼:共得到符合纳入条件的文献142篇,排除849篇。选择其中30篇进行分析,其中英文25篇,中文5篇,英文有1篇为手工检索的增刊。资料综合:糖尿病肾病的发病机制错综复杂,肾脏的结构和功能变化包括高滤过、肾脏和肾小球的肥大、细胞外基质的堆积、肾小球基底膜的增厚和肾小球滤过屏障功能的异常。这些变化是多因素共同作用的结果,在众多发病机制中,氧化应激被认为是共同机制之一。在正常情况下,活性氧的产生和抗活性氧水平二者处于平衡状态,当活性氧蓄积过多就会攻击机体,即氧化应激。氧化应激的产生主要是活性氧类产生过多和清除减少以及糖尿病肾病患者体内氧化应激水平增加导致的。氧化应激对糖尿病肾病的影响包括活性氧类可以增加细胞膜的通透性;使肾细胞内的谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶等抗氧化酶发生糖化或氧化,肾组织抗氧化能力降低,细胞内关键酶和转运蛋白Na-K-ATP酶失活等。结论:氧化应激作用可以增加细胞膜的通透性,使肾组织抗氧化能力降低,是糖尿病肾病的重要发病机制之一。     

Hepatitis C virus among blood donors: follow-up study

BACKGROUND: The exact significance of antibodies to hepatitis C virus (HCV) in blood donors remains unknown. Confirmatory tests of anti-HCV- reactive serum and HCV RNA by polymerase chain reaction (PCR) are used to refute a large proportion of false-positive results. STUDY DESIGN AND METHODS: Ninety-two blood donors who were anti-HCV reactive in a first-generation enzyme-linked immunosorbent assay (ELISA) were reevaluated 10 months later with a second-generation ELISA (ELISA-2) as well as with second-generation recombinant immunoblot assay (RIBA-2) and by PCR. RESULTS: Twenty-five (43.9%) of the 57 ELISA-2-positive donors were confirmed as positive by RIBA-2; of these, 84 percent were HCV RNA positive in PCR. Of the 57 who were still anti-HCV positive, 46 were followed up and tested again in the same manner 2 years after the first screening. At that time, the pattern was little changed: 94 percent of RIBA-2- and PCR-positive donors remained positive. Of RIBA-2- and PCR-positive blood donors, 62 percent had abnormal alanine aminotransferase levels in at least one of the three evaluations. Among the anti-HCV-positive donors confirmed by RIBA-2, 60 percent, versus 12.6 percent in the control group, had a significantly (p < 0.001) more frequent risk factor for HCV infection, due to parenteral exposure to blood. CONCLUSION: These data confirm a good correlation between RIBA-2 reactivity and the detection of HCV RNA in a population of anti-HCV- positive blood donors.     

Opportunistic infections and organ‐specific diseases in HIV‐1‐infected children: a cohort study (1990–2006)

Objectives

Highly active antiretroviral therapy (HAART) has dramatically changed the natural history of HIV infection in children, but there are few studies in the literature about the incidence of clinical manifestations after HAART in this population, compared with adults. The aim of this study was to describe the influence of the widespread use of HAART on the development of opportunistic infections and organ‐specific diseases in HIV‐infected children.

Methods

An observational study of a cohort of 366 vertically HIV‐infected children followed from 1990 to 2006 was carried out. According to the main antiretroviral protocol used, three calendar periods (CPs) were defined and compared: CP1 (1990–1996: no patients on HAART), CP2 (1997–1999: <60% on HAART) and CP3 (2000–2006: >60% on HAART).

Results

Children experienced a progressive increase in CD4 T cell count (P<0.05) and a decrease in HIV viral load from 1996 onwards (P<0.05). Similarly, rates of death, AIDS, opportunistic infections (bacteraemia, candidosis, cryptosporidiosis and bacterial pneumonia) and organ‐specific diseases (wasting syndrome, thrombocytopenia, cardiomyopathy, lymphoid interstitial pneumonia and HIV‐associated encephalopathy) were lower in CP2 and CP3 than in CP1.

Conclusions

This study provides evidence of improved clinical outcomes in HIV‐infected children over time and shows that mortality, AIDS, opportunistic infections and organ‐specific diseases declined as HAART was progressively instituted in this population.

     

Choosing event‐driven and daily HIV pre‐exposure prophylaxis – data from two European PrEP demonstration projects among men who have sex with men

IntroductionDaily and event‐driven PrEP are both efficacious in reducing the risk for HIV infection. However, the practice of event‐driven PrEP (edPrEP) is less well studied, in particular when provided as an alternative to daily PrEP. We studied regimen preferences and switches, and sexually transmitted infection (STI) incidence.MethodsWe analysed pooled data from two prospective cohort studies among MSM: Be‐PrEP‐ared, Belgium and AMPrEP, the Netherlands. In both projects, participants could choose between daily and edPrEP at three‐monthly study visits, when they were also screened for sexually transmitted infections including hepatitis C (HCV). We assessed the proportion choosing each regimen, and the determinants of choosing edPrEP at baseline. Additionally, we compared the incidence rates (IRs) of HCV, syphilis and chlamydia or gonorrhoea between regimens using Poisson regression. The study period was from 3 August 2015 until 24 September 2018.Results and discussionWe included 571 MSM, of whom 148 (25.9%) chose edPrEP at baseline. 31.7% of participants switched regimen at least once. After 28 months, 23.5% used edPrEP. Older participants (adjusted odds ratio (aOR) = 1.38 per 10 years, 95% confidence interval (CI) = 1.15 to 1.64) and those unemployed (aOR = 1.68, 95% CI = 1.03 to 1.75) were more likely to initially choose edPrEP. IR of HCV and syphilis did not differ between regimens, but the IR of chlamydia/gonorrhoea was higher among daily users (adjusted incidence rate ratio = 1.61, 95% CI = 1.35 to 1.94).ConclusionsA quarter of participants chose edPrEP at baseline and at 28 months this proportion was similar. Although the IR of HCV and syphilis were similar in the two regimens, the lower incidence of chlamydia and gonorrhoea among edPrEP users may suggest that less frequent STI testing of this group could be considered.     

Clinical features of chromosome 22q11.2 microdeletion syndrome in 208 Chilean patients

Patients with chromosome 22q11 deletion syndrome exhibit significant phenotypic variability. Epidemiologic data suggest a higher incidence in Hispanics, but limited clinical information is available from Latin-American patients. We describe the clinical features of Chilean patients with 22q11 deletion syndrome and compare their findings with those reported in large European, Japanese and US series. Data were obtained from 208 patients from five medical centers. Mean age at diagnosis was 5.2 years, with a median of 2.3 years. Congenital heart defects were present in 59.6%, lower than other large series that averaged 75.8%. Palate abnormalities were present in 79%, higher than previous reports averaging 56%. Patients with congenital heart disease were diagnosed earlier (median 0.3 years of age) than those without heart defects (median 5.6 years) and had greater mortality attributable to the syndrome (9.8% vs 2.4%, respectively). The differences in frequencies of major anomalies may be due to growing awareness of more subtle manifestations of the syndrome, differences in clinical ascertainment or the presence of modifier factors. These observations provide additional data useful for patient counseling and for the proposal of health care guidelines.