Protein S is a cofactor for activated protein C neutralization of an inhibitor of plasminogen activation released from platelets

Platelets stimulated with thrombin release an inhibitor of plasminogen activator (PAI), which has been shown previously to be neutralized by activated protein C (APC). The requirements for optimal neutralization of PAI activity were investigated. The releasate of gel-filtered human platelets stimulated with thrombin served as a source of PAI. When 6 X 10(8) platelets/mL were incubated with thrombin (1 IU/mL), the releasate contained 18 to 26 ng/mL PAI as determined by incubation of the releasate with urokinase and measurement of residual urokinase activity on plasminogen (S2251). Preincubation of PAI with up to 4 micrograms/mL APC for two hours yielded less than 20% neutralization of PAI activity. In the presence of protein S, phospholipid, and Ca2+, neutralization of PAI activity was time-dependent with 50% neutralization occurring in two hours with 1 microgram/mL APC. The cofactor effects of protein S and phospholipid were concentration- dependent with half-maximal acceleration at approximately 3 micrograms/mL protein S and 10 micrograms/mL phospholipid when the experiments were performed at 1 microgram/mL APC. Diisopropylfluorophosphate-inactivated APC, gla-domainless APC, and thrombin-cleaved protein S had no effect on PAI activity, indicating requirement for preservation of the APC active site and of the Ca2+ binding ability of both APC and protein S. These results suggest coordinate binding of APC and protein S onto phospholipid membrane as a prerequisite for optimal expression of PAI neutralized by APC.     

Using aggregate geographic data to proxy individual socioeconomic status: does size matter?

OBJECTIVES: This study assessed whether aggregate-level measures of socioeconomic status (SES) are less biased as proxies for individual-level measures if the unit of geographic aggregation is small in size and population. METHODS: National Health Interview Survey and census data were used to replicate analyses that identified the degree to which aggregate proxies of individual SES bias interpretations of the effects of SES on health. RESULTS: Ordinary least squares regressions on self-perceived health showed that the coefficients for income and education measured at the tract and block group levels were larger than those at the individual level but smaller than those estimated by Geronimus et al. at the zip code level. CONCLUSIONS: Researchers should be cautious about use of proxy measurement of individual SES even if proxies are calculated from small geographic units.     

Socioeconomic status and injury mortality: individual and neighbourhood determinants

STUDY OBJECTIVE: This study examined both individual and neighbourhood correlates of injury mortality to better understand the contribution of socioeconomic status to cause specific injury mortality. Of particular interest was whether neighbourhood effects remained after adjusting for individual demographic characteristics and socioeconomic status. DESIGN: Census tract data (measuring small area socioeconomic status, racial concentration, residential stability, urbanisation, and family structure) was merged with the National Health Interview Survey (NHIS) and a file that links the respondents to subsequent follow up of vital status and cause of death data. Cox proportional hazards models were specified to determine individual and neighbourhood effects on homicide, suicide, motor vehicle deaths, and other external causes. Variances are adjusted for the clustered sample design of the NHIS. SETTING: United States, 1987-1994, with follow up to the end of 1995. PARTICIPANTS: From a sample of 472 364 persons ages 18-64, there were 1195 injury related deaths over the follow up period. MAIN RESULTS: Individual level effects were generally robust to the inclusion of neighbourhood level variables in the models. Neighbourhood characteristics had independent effects on the outcome even after adjustment for individual variability. For example, there was approximately a twofold increased risk of homicide associated with living in a neighborhood characterised by low socioeconomic status, after adjusting for individual demographic and socioeconomic characteristics. CONCLUSIONS: Social inequalities in injury mortality exist for both persons and places. Policies or interventions aimed at preventing or controlling injuries should take into account not only the socioeconomic characteristics of people but also of the places in which they live.     

慢性粒细胞白血病异基因造血干细胞移植34例疗效及生活质量随访

目的：观察异基因造血干细胞移植治疗慢性粒细胞白血病的疗效并进行生活质量评估。 方法：选择2002-03／2007-03在解放军第四军医大学西京医院血液科接受异基因造血干细胞移植18～50岁慢性粒细胞白血病患者34例，其中HLA相合的同胞供者29例，非血缘志愿供者5例。所有患者及其家属对治疗以及研究均知情并签署同意书，医院伦理委员会知情并批准。预处理方案采用改良的马利兰联合环磷酰胺或环磷酰胺联合全身放疗方案。采用标准的环孢素联合短期氨甲喋呤方案预防移植物抗宿主病；无关供者移植加用抗人胸腺细胞球蛋白。所有患者均接受WHOQOL—BREF问卷调查其移植前后的生活质量。 结果：所有患者均获得植入。①移植物抗宿主病出现情况：14.7％（5／34）患者出现急性移植物抗宿主病，41．2％（14，34）患者出现慢性移植物抗宿主病。②移植其他并发症：合并重症肝静脉闭塞病1例；并发纯红细胞性再生障碍性贫血3例，甲状腺功能低下2例，女性雌激素水平低下9例，经积极治疗，大部分获得缓解。③长期生存情况：随访3～60个月，现存活25例（73．5％），其中在慢性期移植者，生存率达82．1％（23／28）。26．4％（9／34）患者在移植后1～50个月时死亡，4例死于白血病复发，5例死于移植并发症。（9生活质量评分：与患者移植前比较，各项指标均有显著的提高（P〈0．05）。 结论：异基因造血干细胞移植是治疗慢性粒细胞白血病的有效方法，尤其在慢性期移植效果较好。移植后长期存活患者的生活质量良好，慢性移植物抗宿主病及女性卵巢功能低下是影响患者生活质量的主要因素。     

Sickle cell trait is not associated with chronic kidney disease in adult Congolese patients: a clinic-based,cross-sectional study

Chronic kidney disease (CKD) and end-stage renal disease (ESRD) are associated with significant cardiovascular (CV) and renal morbidity and mortality rates, with substantial economic burden.1,2 Therefore, early identification of CKD patients at high risk of progression is urgently needed for early and targeted treatment to improve patient care.1-3 Diabetes and hypertension are the primary risk factors for CKD and ESRD but do not fully account for CKD and ESRD risk.1-3 Marked variability in the incidence of CKD suggests that factors other than diabetes and hypertension contribute to its aetiology.4Family studies have suggested a genetic component to the aetiology of CKD and ESRD.5 In African Americans, high-risk common variants in the Apol1/MYH9 locus may explain up to 70% of the differences in ESRD rates between European and African Americans.5 While this finding has great implications for ESRD, the identification of additional risk factors for CKD, including genetic loci in association with estimated glomerular filtration rate (eGFR), may help to advance our understanding of the underpinnings of CKD in African Americans.5 In this era of identifying genetic risk factors for kidney disease, it may be appropriate to revisit one of the most common genetic disorders: sickle cell haemoglobinopathies.5In this regard, sickle cell trait (SCT), present in approximately 7–9% of African Americans, has been reported to be a potential candidate gene.6 However, conflicting reports exist as to whether SCT is a risk factor for the progression of nephropathy.6,7 Haemoglobin S (HbS) was selected for in Africa because of the protection it affords from malarial infection, a scenario similar to the protection from trypanosomal infection provided by heterozygosity for APOL1 nephropathy risk variants.6Whereas APOL1 contributes to risk for nephropathy in an autosomal recessive inheritance pattern, HbS reportedly had a dominant effect on risk, with SCT being associated with ESRD.6 In line with this finding, a few small studies on African Americans reported HbS as an independent risk factor for CKD and ESRD.8 However, other studies using a large sample of African Americans stated that SCT was not independently associated with susceptibility to ESRD in African Americans,6 highlighting the need for further studies in other populations such as those of sub-Saharan Africa where SCT is prevalent.Although SCT is very prevalent in black Africans,9 few studies have been conducted to assess the association between SCT and CKD.10 In Democratic Republic of Congo (DRC), the prevalence of CKD and SCT has been reported to be 12% and 17–24%, respectively.11-13 No study has evaluated the frequency of SCT among CKD patients to assess its association with reduced kidney function. Therefore, the aim of this clinic-based, cross-sectional study was to assess the potential association between SCT and CKD among adult Congolese patients.     

Evaluation of antibacterial,antifungal and modulatory activity of methanol and ethanol extracts of Padina sanctae-crucis

Background

Multi-resistantmicroorganisms such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida tropicalis e Candida krusei are the main causes of microbial infections. Padina sanctae-crucis is a seaweed often used to check the contamination of ecosystems by materials such as heavy metals, but studies of the antimicrobial activity of the same seaweed were not found.

Methods

The tests for the minimum inhibitory concentration and modulation of microbial resistance, with the use of ethanolic and methanolic extracts of Padina Sanctae-cruces combined with drugs of the class of aminoglycosides and antifungal were used to evaluate the activity against the cited microorganisms.

Results

Was observed a modulation of antibiotic activity between the natural products and the E. coli and S. aureus strains, indicating a synergism and antagonism respectively.

Conclusions

The results showed a moderate modulatory effect against some microorganisms studied.     

Presentation,management,and outcome of newly diagnosed glioblastoma in elderly patients

OBJECT: Optimum management for elderly patients with newly diagnosed glioblastoma(GBM) in the temozolomide(TMZ) era is not well defined.The object of this study was to clarify outcomes in this population.METHODS: The authors retrospectively reviewed 105 consecutive cases involving elderly patients(age ≥ 65 years) with newly diagnosed GBM who were treated at the Mayo Clinic between 2003 and 2008.RESULTS: The patients’ median age was 74 years(range 66-87 years),and the median Karnofsky Performance Status(KPS) score was 80(range 40-90).Half of the patients underwent biopsy and half underwent resection.Patients with deep-seated lesions(19 patients [18%]) or multifocal lesions(34 patients [32%]) were more likely to have biopsy than resection(p = 0.0001 and 0.0009,respectively).New persistent neurological deficits developed in 7 patients(6.7%).Postoperative hemorrhage occurred in 6 patients(5.7%),all of whom underwent biopsy.Complete follow-up data regarding adjuvant treatment was available in 84 patients.Forty-one(49%) were treated with chemotherapy(mostly TMZ) and radiation therapy(RT),and 23(27%) with RT alone.Nineteen(23%) received only palliative care after surgery(more common with biopsy,p = 0.03).Chemotherapy complications occurred in 28.6%(Grade 3 or 4 hematological complications in 11.9%).The median values for progression-free survival(PFS) and overall survival(OS) were 3.5 and 5.5 months.In a multivariate analysis,younger age(p = 0.03,risk ratio [RR] 0.34,95% CI 0.13-0.89),single lesion(p = 0.02,RR 0.51,95% CI 0.30-0.89),resection(p = 0.04,RR 0.54,95% CI 0.31-0.94),and adjuvant treatment(p = 0.0001,RR 0.24,95% CI 0.11-0.49) were associated with better OS.Only adjuvant treatment was significantly associated with prolonged PFS(p = 0.0007,RR 0.27,95% CI 0.13-0.57).With combined therapy with resection,RT,and chemotherapy,the median PFS and OS were 8 and 12.5 months,respectively.CONCLUSIONS: The prognosis for GBM worsens with increasing age in elderly patients.With important risks,resection and adjuvant treatment are associated with prolonged survival.Although selection bias cannot be excluded in this retrospective study,advanced age alone should not necessarily preclude optimal resection followed by adjuvant radiochemotherapy.