成人前B急性淋巴母细胞性白血病CD20表达与预后的关系

目的：探讨白细胞分化抗原CD20表达对成人前B急性淋巴细胞性白血病（Pre B-ALL）临床特征及治疗转归的影响。方法：回顾性分析我院2005-01／2008-01成人前B-ALL患者91例临床特征及治疗转归,比较CD20阳性患者及CD20阴性患者第1疗程诱导治疗完全缓解率、持续完全缓解率、髓外浸润率、复发率及2a生存率。结果：91例成人前B-ALL患者中CD20阳性患者43例（47％）,CD20阴性患者48例（53％）;CD20阳性与阴性患者经第1疗程诱导治疗后获完全缓解率分别为69.8％（30／43）,81.3％（39／48）（P〉0.05）,持续完全缓解率分别为11.6％（5／43）,41.7％（20／48）（P〈0.05）;髓外浸润率分别为46.5％（20／43）,22.9％（11／48）（P〈0.05）;复发率分别为65.1％（28／43）,39.6％（19／48）（P〈0.05）;2a总生存率分别为17.3％,47.2％（P〈0.05）。结论：成人Pre B-ALL瘤细胞表达CD20提示预后不良。     

B型流感病毒核衣壳蛋白ELISA捕获法的建立和临床应用2

目的 制备和鉴定B型流感病毒核衣壳（N）蛋白单克隆抗体（mAb）,建立双抗体夹心捕获抗原ELISA,用于B型流感病毒感染的早期诊断。方法 用重组B型流感病毒N蛋白和B型流感病毒抗原免疫BALB/c小鼠制备mAb,采用ELISA间接法、免疫荧光（IFA）和免疫印迹（WB）进行筛选和鉴定,通过竞争抑制试验分析抗体识别表位,并采用抗体配对试验建立双抗体夹心捕获抗原ELISA法检测B型流感病毒 N抗原。结果 获得12株特异性针对B型流感病毒 N蛋白的mAb,识别8个不同的抗原位点,根据mAb识别抗原表位,对mAb进行多种组合的配对试验,筛选出2株单抗BN4和BN8混合作为捕获抗体,辣根过氧化物酶标记的单抗BN1 和BN5混合作为测定抗体,建立了双抗体夹心ELISA法,测定新鲜的漱口液标本的灵敏度达100％,而对冻融的漱口液标本检测灵敏度为83.9％,与其他呼吸道病毒如A型流感病毒、副流感病毒等无交叉反应,特异度达100％。结论 获得特异性好的mAb,经过抗体的配对和优化,建立了一种灵敏度高、特异性强的B型流感病毒抗原的ELISA捕捉法,可用于B型流感病毒感染的早期实验室诊断及流行病学研究。     

Simian immunodeficiency virus-induced lymphatic tissue fibrosis is mediated by transforming growth factor beta 1-positive regulatory T cells and begins in early infection

In human immunodeficiency virus (HIV) infection, collagen deposition and fibrosis within the T cell zone disrupt the lymphatic tissue architecture, contributing to depletion of CD4(+) T cells and limiting immune reconstitution. We used relevant animal and in vitro models to investigate the kinetics and possible underlying mechanism(s) of this process. In the lymphatic tissue of simian immunodeficiency virus (SIV)-infected rhesus macaques, we observed parallel increases in immune activation, transforming growth factor (TGF) beta 1-positive regulatory T (T(reg)) cells, and collagen type I deposition by 7 days after inoculation, consistent with the hypothesis that early immune activation elicits a countering T(reg) cell response associated with TGF beta 1 expression and collagen deposition. In support of this hypothesis and the possible role of fibrosis in viral pathogenesis, we show (1) spatial colocalization and temporal concordance in levels of TGF beta 1(+) T(reg) cells and collagen deposition; (2) TGF beta 1(+) inducible T(reg) cell stimulation of primary lymphatic tissue fibroblasts to produce collagen type I in vitro; and (3) high levels of immune activation, TGF beta 1(+) T(reg) cells, and collagen deposition in pathogenic SIV infection of macaques, in contrast to apathogenic SIV infection in sooty mangabeys in which levels of immune activation, TGF beta 1(+) T(reg) cells, and collagen deposition were low. We thus conclude that the response of TGF beta 1(+) T(reg) cells to immune activation in early SIV/HIV infection is a double-edged sword: TGF beta 1(+) T(reg) cells normally have a positive effect by limiting immunopathological and autoreactive immune responses, but they also have a negative effect by dampening the antiviral immune response and, as we show here, causing deleterious effects on CD4(+) T cell homeostasis by inducing collagen deposition in lymphatic tissues.     

Cystic fibrosis and formes frustes of CFTR-related disease

Cystic fibrosis (CF) is the commonest genetic cause of bronchiectasis in the Caucasian population. Since identification of the putative gene in 1989, the molecular basis of the condition has become clearer with characterisation of the unique pathophysiology. The small airways are the primary site of lung disease, with an intense but localised inflammatory picture, dominated by neutrophils. The clinical heterogeneity is explained to some degree by the distinct molecular consequences of the many mutations that have been recognised to affect the CF transmembrane conductance regulator (CFTR) gene; however other genes appear to modify the phenotype as well as environmental exposure. It has become increasingly apparent that certain conditions may result from CFTR dysfunction without fulfilling diagnostic criteria for CF. In some cases this may result in single organ disease for which the term CF (or CFTR)-related disease has been advocated. Congenital bilateral absence of the vas deferens is the most clearly characterised of these. In other cases where a mild CF phenotype is apparent, atypical CF is probably a better term. It remains unclear whether carrier status predisposes to certain conditions such as chronic rhinosinusitis or pancreatitis.     

The beneficial effects of dichloroacetate in acute limb ischemia

OBJECTIVE: The purpose of this study was to determine the effects of dichloroacetate (DCA) in acute limb ischemia. METHODS: Anterior tibialis muscle samples of DCA-treated and control animals (Sprague Dawley rats) were collected and assayed for pyruvate dehydrogenase activity, lactate, adenosine triphosphate, and creatine phosphate using spectrophotometry. A physiograph was used to measure fatigability. In an ischemia/reperfusion model using New Zealand rabbits, serum lactate and end-tidal CO2 were compared. Skeletal muscle was evaluated microscopically for muscle necrosis. RESULTS: DCA administration resulted in a 50% increase in pyruvate dehydrogenase activity (p = 0.025), reversal of the increase in lactate levels seen during acute limb ischemia (p = 0.41), a significant increase in the time to skeletal muscle fatigue (p = 0.05), a trend toward increased adenosine triphosphate (p = 0.07), and a significant increase in creatine phosphate (p < 0.02). DCA treatment resulted in a decrease in serum lactate (p < 0.01) and end-tidal CO2 (p < 0.001). CONCLUSION: In acute limb ischemia and reperfusion, DCA administration provides metabolic protection to skeletal muscle.     

Airway ion transport impacts on disease presentation and severity in cystic fibrosis

ObjectivesAbnormal airway ion transport is a feature of cystic fibrosis. The aim of this study was to investigate whether distinct components of ion transport are associated with the clinical expression and severity of the disease.Design and methodsUnivariate and multivariate analyses were used to study interaction effects between nasal potential difference parameters and clinical status, recorded at stable conditions, in 75 F508del homozygous young adults.ResultsAll patients demonstrated increased sodium and reduced chloride conductances. Less sodium transport abnormalities were related to better respiratory function and nutrition. Presentation with digestive symptoms at diagnosis was associated with lower chloride conductance. With an accuracy of 85% good nutritional status was linked to more preserved lung function, increasing age and more preserved chloride conductance.ConclusionsIon transport abnormalities have distinct clinical outcomes. Sodium conductance relates to respiratory function and nutrition; chloride conductance to nutrition and presentation with digestive symptoms at diagnosis.     

Validation of microsurgical models in microsurgery training and competence: a review

Microsurgery has expanded the scope of many surgical specialties and is evolving into an integral part of training programmes. The complexity of microsurgery requires considerable time and resources for adequate training and practice. This article reviews the validation of microsurgical models for microsurgery training and competence.     

医学催眠术治疗颞下颌紊乱

颞下颌紊乱的患者有咀嚼肌系统或颞下颌关节的功能障碍或二者兼有,典型症状为咀嚼肌疼痛,常伴有耳痛、头痛、面痛并向颈部或肩部放射,发病率约为5％左右。目前普遍认为心理压力是其主要原因,对该病的保守治疗方法主要包括对牙齿的治疗、理疗和抗炎治疗等。本研究目的是探讨医学催眠术对减轻颞下颌紊乱疼痛症状的作用。     

A survey of newborn screening for cystic fibrosis in Europe.

BACKGROUND: Cystic fibrosis (CF) is a recessively inherited condition caused by mutation of the CFTR gene. Newborn infants with CF have raised levels of immuno-reactive trypsinogen (IRT) in their serum. Measurement of IRT in the first week of life has enabled CF to be incorporated into existing newborn screening (NBS) blood spot protocols. However, IRT is not a specific test for CF and NBS therefore requires a further tier of tests to avoid unnecessary referral for diagnostic testing. Following identification of the CFTR gene, DNA analysis for common CF-associated mutations has been increasingly used as a second tier test. The aim of this study was to survey the current practice of CF NBS programmes in Europe. METHOD: A questionnaire was sent to 26 regional and national CF NBS programmes in Europe. RESULTS: All programmes responded. The programmes varied in number of infants screened and in the protocols employed, ranging from sweat testing all infants with a raised first IRT to protocols with up to four tiers of testing. Three different assays for IRT were used; in the majority (24) this was a commercially available kit (Delfia). A number of programmes employed a second IRT measurement in the 4th week of life (as the IRT is more specific at this point). Nineteen programmes used DNA analysis for common CFTR mutations on samples with a raised first IRT. Three programmes used a second IRT measurement on infants with just one recognised mutation to reduce the number of infants referred for sweat testing. Referral to clinical services was prompt and diagnosis was confirmed by sweat testing, even in infants with two recognised mutations in most programmes. Subsequent clinical pathways were less uniform. Multivariate analysis demonstrated a relationship between the age of diagnosis and the timing of the first IRT. More sweat tests were undertaken if the first IRT was earlier and the diagnosis was later. CONCLUSIONS: Annually these programmes screen approximately 1,600,000 newborns for CF and over 400 affected infants are recognised. The findings of this survey will guide the development of European evidence based guidelines and may help new regions or nations in the development and implementation of NBS for cystic fibrosis.     

Challenges and prospects for malaria elimination in the Southern Africa region

The burden of malaria has decreased dramatically within the past several years in parts of sub-Saharan Africa, including regions of Southern Africa. Important to effective regional malaria control in Southern Africa is the appreciation that the reductions in malaria have not been achieved uniformly, with some countries experiencing resurgence. Understanding the reasons for sustained low-level malaria transmission in the face of control efforts, why malaria control efforts have not been successful in particular epidemiological settings and the epidemiological and transmission patterns following resurgence are critical to improving further malaria control and possible elimination. The overall goal of the International Center of Excellence for Malaria Research in Southern Africa is to contribute to regional malaria control efforts that can be sustained beyond the duration of the project. This goal will be achieved through a combination of: (1) state-of-the-art research on malaria epidemiology, vector biology and the genetics of the malaria parasite in three different epidemiological settings; (2) collaborations with national malaria control programs to develop locally adapted and sustainable control strategies; and (3) training, career development and capacity building at research institutions throughout the region.