An analysis of tumor necrosis factor alpha gene polymorphisms and haplotypes with natural clearance of hepatitis C virus infection

The cytokine tumor necrosis factor alpha (TNF-alpha) is important in generating an immune response against a hepatitis C virus (HCV) infection. The functions of TNF-alpha may be altered by single-nucleotide polymorphisms (SNPs) in its gene, TNF. We hypothesized that SNPs in TNF may be important in determining the outcome of an HCV infection. To test this hypothesis, we typed nine TNF SNPs in a cohort of individuals with well-defined HCV outcomes. Three of these SNPs were typed in a second cohort. Data were analyzed using logistic regression stratifying by ethnicity, since rates of HCV clearance differ in black subjects versus white subjects. The SNP -863A was associated with viral clearance in black subjects (odds ratios (OR) 0.52, 95% confidence interval (CI) 0.29-0.93). Furthermore, the common wild-type haplotype -863C/-308G was associated with viral persistence in black subjects (OR 1.91, 95% CI 1.24-2.95). These findings were independent of linkage with human leukocyte antigen (HLA) alleles. Further study of this polymorphism and haplotype is needed to understand these associations and the role of TNF-alpha in determining outcomes of HCV infection.     

Pharmacokinetics of oral fumarates in healthy subjects

AIMS: To characterize the pharmacokinetics of fumarates in healthy subjects. METHODS: Ten subjects received a single fumarate tablet (containing 120 mg of dimethylfumarate and 95 mg of calcium-monoethylfumarate) in the fasted state and after a standardized breakfast in randomized order. Prior to and at fixed intervals after the dose, blood samples were drawn and the concentrations of monomethylfumarate, the biologically active metabolite, as well as dimethylfumarate and fumaric acid were measured using high-performance liquid chromatography. RESULTS: After a lag time, a transient increase in serum monomethylfumarate concentrations in the blood was observed, whereas dimethylfumarate and fumaric acid concentrations remained below the detection limit. The tlag was 240 min [range 60-603 min; 95% confidence interval (CI) 139, 471] shorter when the tablet was taken after an overnight fast (90 min; range 60-120 min; 95% CI 66, 107) than when taken with breakfast (300 min; range 180-723 min; 95% CI 0, 1002). The tmax was 241 min (range 60-1189 min, 95% CI 53, 781) shorter when the tablet was taken after an overnight fast (182 min; range 120-240 min; 95% CI 146, 211) than when taken with breakfast (361 min; range 240-1429 min; 95% CI 0, 1062). The mean Cmax for monomethylfumarate in the blood of fasting subjects was to 0.84 mg l(-1) (range 0.37-1.29 mg l(-1); 95% CI 0.52, 1.07) and did not differ from that in fed subjects (0.48 mg l(-1); range 0-1.22 mg l(-1); 95% CI 0, 5.55). CONCLUSIONS: The pharmacokinetics of monomethylfumarate in healthy subjects after a single tablet of fumarate are highly variable, particularly after food intake. Further experiments exploring the pharmacokinetics of oral fumarates are warranted in order to elucidate the mechanisms underlying variability in response in patients.     

红外光谱法和X-射线粉末衍射法研究棉酚的多晶型

棉酚是棉子中的一种色素,具有广泛生理活性。棉酚、醋酸棉酚、甲酸棉酚曾初步试用于男性节育,但有一定毒副作用,影响了临床进一步试用。目前国内外学者仍在进一步研究。棉酚的结构式如下:     

Hemolytic-uremic syndrome: intrarenal arterial Doppler patterns as a useful guide to therapy

Seventeen children with acute renal failure due to the hemolytic-uremic syndrome were examined with duplex Doppler ultrasound. Serial measurements of intrarenal arterial pulsatility were obtained by means of the Pourcelot index. These were compared with daily urine volume, both during the phase of renal failure (during which most of the children were undergoing peritoneal dialysis) and during recovery of renal function. During oliguria or anuria there was either no intrarenal arterial flow (ie, absent Doppler shifts), or absent, reversed, or markedly reduced diastolic flow. Within 24-48 hours after diastolic Doppler shifts returned to normal, diuresis occurred. The Doppler examination enabled prediction of recovery and allowed dialysis treatment to be abbreviated or, in some cases, canceled.     

包膜活性炭吸附血液灌流清除人血浆中毒鼠强的实验

目的:观察包膜活性炭对血浆中毒鼠强的清除率及吸附规律。方法:实验于2004-05/2006-04在军事医学科学院毒物药物研究所国家重点实验室完成。采用包膜活性炭灌流器对毒鼠强血浆样进行血液灌流吸附,在灌流的1,2,3h分别取样,经乙酸乙酯萃取后,用气相色谱氮磷检测器法(GC/NPD)测定其含量并计算清除率。结果:活性炭对毒鼠强的吸附作用在血液灌流1h最高,灌流2h后毒鼠强质量浓度无明显变化。400,200μg/L毒鼠强血液灌流1h清除率分别为(57.83±1.85)%,(48.18±1.81)%。结论:用包膜活性炭吸附剂进行血浆的灌流吸附,能清除大部分毒物,迅速降低血浆中毒鼠强的质量浓度。     

肾移植前后严重焦虑对肾功能衰竭患者病情的影响：1例报告

目的:观察焦虑情绪对肾功能衰竭患者肾移植前后病情转归的影响,并探讨其治疗对策。方法:患者为36岁男性,2005-11入华中科技大学同济医学院附属同济医院肾内科,入院诊断为慢性肾小球肾炎,慢性肾功能不全,失代偿期,患者知情同意。因严重焦虑引起肾功能迅速恶化,在1个多月内从代偿期迅速进展到尿毒症期,并经肾活检证实病情不可逆转,接受血液透析治疗,并行肾移植。观察其接受血液透析前后和肾移植前后的焦虑状态评分及肾功能。汉密顿焦虑量表包括14个项目,总评分超过29分,可能为严重焦虑;小于6分,患者没有焦虑症状。结果:①焦虑状态的评估结果:血液透析前患者的焦虑状态评分为31分,属于严重焦虑。血液透析后和肾移植前后多次评分,患者焦虑状态均完全解除。②随访结果:肾移植术后1个月,患者重新工作,随访至今,复查各项指标基本正常。结论:严重焦虑可使慢性肾小球肾炎患者肾功能在短期内迅速恶化,对病情的发展和转归有明显影响。在治疗过程中除了积极治疗原发疾病外,还应重视心理干预治疗。     

Discomfort and factual recollection in intensive care unit patients

Introduction

A stay in the intensive care unit (ICU), although potentially life-saving, may cause considerable discomfort to patients. However, retrospective assessment of discomfort is difficult because recollection of stressful events may be impaired by sedation and severe illness during the ICU stay. This study addresses the following questions. What is the incidence of discomfort reported by patients recently discharged from an ICU? What were the sources of discomfort reported? What was the degree of factual recollection during patients' stay in the ICU? Finally, was discomfort reported more often in patients with good factual recollection?

Methods

All ICU patients older than 18 years who had needed prolonged (>24 hour) admission with tracheal intubation and mechanical ventilation were consecutively included. Within three days after discharge from the ICU, a structured, in-person interview was conducted with each individual patient. All patients were asked to complete a questionnaire consisting of 14 questions specifically concerning the environment of the ICU they had stayed in. Furthermore, they were asked whether they remembered any discomfort during their stay; if they did then they were asked to specify which sources of discomfort they could recall. A reference group of surgical ward patients, matched by sex and age to the ICU group, was studied to validate the questionnaire.

Results

A total of 125 patients discharged from the ICU were included in this study. Data for 123 ICU patients and 48 surgical ward patients were analyzed. The prevalence of recollection of any type of discomfort in the ICU patients was 54% (n = 66). These 66 patients were asked to identify the sources of discomfort, and presence of an endotracheal tube, hallucinations and medical activities were identified as such sources. The median (min–max) score for factual recollection in the ICU patients was 15 (0–28). The median (min–max) score for factual recollection in the reference group was 25 (19–28). Analysis revealed that discomfort was positively related to factual recollection (odds ratio 1.1; P < 0.001), especially discomfort caused by the presence of an endotracheal tube, medical activities and noise. Hallucinations were reported more often with increasing age. Pain as a source of discomfort was predominantly reported by younger patients.

Conclusion

Among postdischarge ICU patients, 54% recalled discomfort. However, memory was often impaired: the median factual recollection score of ICU patients was significantly lower than that of matched control patients. The presence of an endotracheal tube, hallucinations and medical activities were most frequently reported as sources of discomfort. Patients with a higher factual recollection score were at greater risk for remembering the stressful presence of an endotracheal tube, medical activities and noise. Younger patients were more likely to report pain as a source of discomfort.

     

急性心肌梗死后外周血单个核细胞表面CD147与基质金属蛋白酶-9 mRNA表达的相关性

目的：基质金属蛋白酶在急性心肌梗死后的心室重构中起着重要作用，但其调节机制目前尚未明确。实验拟通过动物模型的建立及体外细胞培养，观察急性心肌梗死后单个核细胞表面CD147与心肌成纤维细胞基质金属蛋白酶-9 mRNA表达的关系。 方法：实验于2006—08／2007-06在河北省人民医院临床实验中心完成。实验材料：SD大鼠及SD仔鼠（出生1～3d）购自河北医科大学试验动物中心。实验过程中对动物处置符合动物伦理学标准。实验方法：①将30只大鼠随机分为急性心肌梗死组（n=15）和假手术组（n=15），假手术组只过线不结扎。流式细胞分析法检测大鼠术后24h外周血单个核细胞表面CD147表达。②选择SD仔鼠制备心肌成纤维细胞。将单个核细胞与心肌成纤维细胞以细胞数0．5：1，1：1，2：1混合培养24h后，半定量反转录一聚合酶联反应法检测基质金属蛋白酶-9 mRNA表达。当单核细胞与心肌成纤维细胞2：1混合时，加入CD147单克隆抗体1，2，4μL/L，培养24h后检测基质金属蛋白酶-9 mRNA表达。 结果：①急性心肌梗死后外周血单个核细胞表面CD147表达明显增加。②单个核细胞与心肌成纤维细胞混合培养，随着单个核细胞比例的增加，心肌成纤维细胞基质金属蛋白酶-9 mRNA表达增加。③在单个核细胞与心肌成纤维细胞2：1混合培养体系中，随着加入CD147单克隆抗体浓度的增加，基质金属蛋白酶-9 mRNA生成减少。 结论：急性心肌梗死后单个核细胞表面CD147表达明显增加，对心肌成纤维细胞基质金属蛋白酶-9生成起上游调节作用。     

应用遥测肌电技术实测分析人体助行带的生物力学作用

目的:人体助行带为一种随身佩带的动力装置,应用遥测肌电技术测定和分析自行研制的人体助行带的生物力学作用机制。方法:实验于2005-12/2006-06在天津体育大学运动生物力学实验室进行。选取天津市天津医院30名受试对象,均对本实验知情同意。按照生物力学的测试要求,首先对受试者进行5次以上行走状态下的遥测肌电测定,然后在同等条件下对受试者佩带助行带实施对照研究。实验采用的助行带为自行研制的,由腰至足以双层弹力带作为动力装置的弹性结构。结果:行走摆动相大腿肌肌电:佩带助行带后肌内侧肌、肌二头肌、半腱肌肌电高于佩带前(P<0.01)。支撑相小腿肌肌电:佩带助行带后胫前肌、腓骨长肌、腓肠肌肌电高于佩带前(P<0.01)。结论:通过弹力带施加于下肢的外部载荷,能够起到增强下肢肌电以及产生助行的生物力学功效。