Twenty-four-week safety and tolerability of nevirapine vs. abacavir in combination with zidovudine/lamivudine as first-line antiretroviral therapy: a randomized double-blind trial (NORA)

Objective To compare the safety/tolerability of abacavir and nevirapine in HIV‐infected adults starting antiretroviral (ARV) therapy in Uganda. Methods Twenty‐four‐week randomized double‐blind trial conducted with 600 symptomatic ARV‐naive adults with CD4 <200 cells/mm³ allocated to zidovudine/lamivudine plus 300 mg abacavir (A) and nevirapine placebo (n = 300) or 200 mg nevirapine (N) and abacavir placebo (n = 300) twice daily. The primary endpoint was any serious adverse event (SAE) definitely/probably or uncertain whether related to blinded nevirapine/abacavir. Secondary endpoints were adverse events leading to permanent discontinuation of blinded nevirapine/abacavir, and grade 4 events. Results Seventy‐two per cent participants were women; 19% had WHO stage 4 disease; the median age was 37 years (range 18–66); the median baseline CD4 count was 99 cells/mm³ (1–199). Ninety‐five per cent completed 24 weeks: 4% died and 1% were lost to follow‐up. Thirty‐seven SAEs occurred on blinded drug in 36 participants. Twenty events [6 (2.0%) abacavir, 14 (4.7%) nevirapine participants] were considered serious adverse reactions definitely/probably/uncertain whether related to blinded abacavir/nevirapine [HR = 0.42 (95% CI 0.16–1.09) P = 0.06]. Only 2.0% of abacavir participants [six patients (0.7–4.3%)] experienced a suspected hypersensitivity reaction (HSR). In total 14 (4.7%) abacavir and 30 (10.0%) nevirapine participants discontinued blinded abacavir/nevirapine (P = 0.02): because of toxicity (6A, 15N; P = 0.07, all rash/possible HSR and/or hepatotoxicity), anti‐tuberculosis therapy (6A, 13N), or for other reasons (2A, 2N). Conclusions There was a trend towards a lower rate of serious adverse reactions in Ugandan adults with low CD4 starting ARV regimens with abacavir than with nevirapine. This suggests that abacavir could be used more widely in resource‐limited settings without major safety concerns.     

Intratumoral injection of interferon-gamma gene-modified dendritic cells elicits potent antitumor effects: effective induction of tumor-specific CD8<Superscript>+</Superscript> CTL response

Purpose To examine the antitumor efficacy of intratumoral injection of interferon-gamma gene-modified dendritic cells (DC-IFN-) in a B16 melanoma model and to investigate its related immunological mechanisms.Methods C57BL/6 mice-derived DC were transfected with adenovirus encoding IFN- or -galactosidase (DC-LacZ). Secretion of IFN- and TNF- by DC was detected by ELISA. Nitric oxide (NO) production was measured by Griess reaction. Cytotoxicity of DC against tumor cell lines and activity of cytotoxic T lymphocytes (CTLs) were determined by ⁵¹Cr-release assay. TRP-2aa180–188-specific CD8⁺ CTLs in tumor-bearing mice with different treatment were determined by ELISPOT.Results DC-IFN- could secrete high levels of IFN-, NO and TNF-. DC-IFN- were cytolytic to B16 melanoma cells in vitro, but DC-LacZ and DC were not. Significant inhibition of tumor growth and prolonged survival were achieved in tumor-bearing mice intratumorally injected with DC-IFN- when compared with those in tumor-bearing mice intratumorally injected with DC, DC-LacZ, fibroblasts, IFN- gene-modified fibroblasts or PBS. After treatment with DC-IFN-, enhanced Th1 and decreased Th2 responses were observed, and B16 melanoma antigen TRP-2aa180–188-specific CD8⁺ CTLs were induced significantly in the tumor-bearing mice.Conclusions Intratumorally injected DC-IFN- can uptake tumor antigens in situ and cross-present tumor antigens to specific CD8⁺ T cells, hereby eliciting effective antitumor effects in murine model with preestablished B16 melanoma.     

药物洗脱支架的临床研究

目的:观察药物洗脱支架治疗冠状动脉(冠脉)病变的可行性和安全性.方法:对我院78例冠心病患者,置入药物洗脱支架(Cypher支架),治疗病变84处,A型病变4处,B型病变38处,C型病变42处.靶病变长度(19.89±10.61)mn,术前靶病变狭窄程度(86.00±10.01)%;目标血管直径(2.95±0.11)mm.其中长度＞20 mm的病变26处.68例支架在行球囊预扩张后置入,10例为支架直接置入.术前、术后常规使用抗血小板药物及治疗冠心病药物.观察药物洗脱支架置入的手术成功率、术中并发症、住院期间及短期临床随访期间的心脏事件.随访术后6个月时的再狭窄发生率.结果:78例患者84处病变共置入Cypher支架100枚,手术即刻成功率100%,术后冠脉造影提示病变残余狭窄(5.0±6.8)%.1例术后38小时因胸痛冠脉造影证实为支架内血栓形成.临床随访16～188天,平均(94.0±10.9)天,无一例心肌梗死或猝死发生.25例(32.05%)患者术后6个月随访冠脉造影未发现支架再狭窄.结论:药物洗脱支架置入时手术成功率高,未见术中并发症,部分病例短期随访效果令人鼓舞.     

The effects of HIV/AIDS on rural communities in East Africa: a 20‐year perspective

Much of the research on implications of the HIV epidemic for individual households and broader rural economies in the 1980s and early 1990s predicted progressive declines in agricultural production, with dire consequences for rural livelihoods. Restudies in Tanzania and Uganda show that from 1986 to the present, HIV and AIDS have sometimes thrown households into disarray and poverty, but more often have reduced development. The progressive and systematic decline predicted in earlier work has not come to pass. However, poverty remains, as does endemic HIV disease.     

Loss of the Y chromosome in Philadelphia-positive cells predicts a poor response of chronic myeloid leukemia patients to imatinib mesylate therapy

In chronic myeloid leukemia (CML), cytogenetic abnormalities found in addition to the t(9;22) translocation may impact the response to therapy. Loss of the Y chromosome is generally overlooked in this context, owing to its relatively frequent occurrence in healthy elderly patients. In this multicenter retrospective study, the outcome after imatinib treatment of 30 CML patients with karyotype showing Y chromosome loss (Y−) was compared to 30 Y+ control males diagnosed and treated at the same time in the same institutions. Y− patients had significantly delayed cytogenetic and molecular responses, lower event-free survival and shorter overall survival than Y+ patients. The negative impact of this abnormality was particularly marked when it occurred in a sub-clone (clonal evolution) rather than in all mitoses. These data indicate that loss of the Y chromosome should be taken into account in the prognostic evaluation of chronic myelogenous leukemia patients.     

醋酸铅对雄性小鼠附睾Y染色体基因Ddx3y蛋白表达的影响

[目的]通过观察亚慢性铅暴露对小鼠附睾组织Y染色体基因Ddx3y表达的影响,为探讨铅的雄性生殖毒作用机制提供依据。[方法]昆明种小鼠48只,按体重将小鼠随机分为对照组、0.5 g/L、1.0 g/L和1.5 g/L醋酸铅染毒组。通过自然饮用含不同浓度醋酸铅的方式使小鼠染铅,连续染毒60 d后取附睾组织。HE染色观察组织病理学变化,Western blotting和免疫组化方法检测附睾组织Ddx3y蛋白的表达及组织分布。[结果]与对照组比较,染铅组附睾管内精子数和分泌液均减少,尤其1.5 g/L染铅组最为明显。Western blotting检测结果显示,染铅组的小鼠附睾组织中Ddx3y蛋白表达明显低于对照组,且有剂量-反应关系。免疫组化结果显示,随着染铅剂量的增加,附睾组织中抗Ddx3y蛋白免疫反应明显降低。[结论]亚慢性铅暴露显著下调小鼠附睾组织Y染色体基因Ddx3y蛋白表达。     

C5a/C5aR通路对约氏疟原虫增殖和小鼠生存的影响

目的观察C5a/C5aR通路对约氏疟原虫17XL（P.y17XL）的增殖及其对BALB/c小鼠致死率的影响。结论将实验小鼠分为正常BALB/c组和C5aR-/-BALB/c组,每组5只,相同剂量的P.y17XL（2×105）分别感染正常BALB/c组小鼠和C5aR-/-BALB/c组小鼠,于感染后0、2、4和6d观察两组小鼠原虫血症和存活率的变化,并且采用ELISA检测感染P.y17XLBALB/c小鼠血清中C5a的水平。结果与正常组小鼠相比,C5aR-/-组小鼠生存期缩短,P.y17XL在C5aR-/-组小鼠的原虫血症较野生株小鼠高（P〈0.05）,而P.y17XL感染小鼠的血清中C5a含量低于未感染的小鼠。结论 C5a/C5aR能够抑制P.y17XL的增殖,并能延长感染小鼠的生存期。     

Sounding the 'citizen-patient': the politics of voice at the Hospice Des Quinze-vingts in post-revolutionary Paris

This essay explores new models of the citizen-patient by attending to the post-Revolutionary blind 'voice'. Voice, in both a literal and figurative sense, was central to the way in which members of the Hospice des Quinze-Vingts, an institution for the blind and partially sighted, interacted with those in the community. Musical voices had been used by members to collect alms and to project the particular spiritual principle of their institution since its foundation in the thirteenth century. At the time of the Revolution, the Quinze-Vingts voice was understood by some political authorities as an exemplary call of humanity. Yet many others perceived it as deeply threatening. After 1800, productive dialogue between those in political control and Quinze-Vingts blind members broke down. Authorities attempted to silence the voice of members through the control of blind musicians and institutional management. The Quinze-Vingts blind continued to reassert their voices until around 1850, providing a powerful form of resistance to political control. The blind 'voice' ultimately recognised the right of the citizen-patient to dialogue with their political carers.     

Programa de formación del residente de cirugía en un laboratorio experimental de cirugía minimamente invasiva (CENDOS)

Introduction

The rapid development of laparoscopic surgery makes resident training programmes necessary.

Objective

To analyse the results of a structured programme of laparoscopic training in an experimental laboratory.

Material and method

From 2003 until 2007, we trained 11 general surgery residents for 20 h every 3 months, for three years. The practice consisted of suture and anastomosis in Endo-Trainer with animal organs, as well as laparoscopic techniques in live animals. In the Endo-Trainer practice we evaluated the time and quality of anastomosis performance. In laparoscopic techniques (cholecystectomy and anti-reflux surgery) a task table was evaluated, from 0 (no errors) to 100 (severe lesion).

Results

In total, 314 anastomosis were performed by the 11 residents, with a median of 28.5 per resident (24-42). The mean time for the first gastro-jejunal anastomosis was 135 min (100-140) and 65 min (57.5-105) for the first jejunal-jejunal anastomosis. Maximum learning was achieved after 45 training hours. There wer no appreciable ifferences between both types of anastomosis. There was inadequate anastomosis quality due to leakage in 17.1% during the learning period and 13.7% during the consolidation period. In the animal, 172 procedures were performed. In cholecystectomy and anti-reflux surgery the mean scores were 2.4 and 5.6 points, respectively. In the remaining procedures, subjectively evaluated by the monitors, the quality was adequate in 65%, deficient in 22% and highly deficient in 13%.

Conclusions

This structured programme of laparoscopic skills based on intestinal anastomosis allows for quicker resident training.