Outcomes of antiretroviral therapy in a northern Indian urban clinic

Problem

Antiretroviral therapy (ART) programmes have been successful in several countries. However, whether they would succeed as part of a national programme in a resource-constrained setting such as India is not clear. The outcomes and specific problems encountered in such a setting have not been adequately studied.

Approach

We assessed the efficacy and functioning of India’s national ART programme in a tertiary care centre in northern India. All ART-naive patients started on ART between May 2005 and October 2006 were included in the study and were followed until 31 April 2008. Periodic clinical and laboratory evaluations were carried out in accordance with national guidelines. Changes in CD4+ lymphocyte count, body weight and body mass index were assessed at follow-up, and the operational problems analysed.

Local setting

The setting was a tertiary care centre in northern India with a mixed population of patients, mostly of low socioeconomic status. The centre is reasonably well resourced but faces constraints in health-care delivery, such as lack of adequate human resources and a high patient load.

Relevant changes

The response to ART in the cohort studied was comparable to that reported from other countries. However, the programme had a high attrition rate, possibly due to patient-related factors and operational constraints.

Lessons learnt

A high rate of attrition can affect the overall efficacy and functioning of an ART programme. Addressing the issues causing attrition might improve patient outcomes in India and in other resource-constrained countries.     

Anti‐inflammatory effects of exendin‐4, a glucagon‐like peptide‐1 analog,on human peripheral lymphocytes in patients with type 2 diabetes

Aims/Introduction

Type 2 diabetes is characterized by dysregulation of immunity, oxidative stress and reduced incretin effects. Experimental studies suggest that glucagon‐like peptide (GLP‐1) might have immunomodulating effects. We hypothesize that GLP‐1 receptor agonist, exendin‐4, might reduce inflammatory response in type 2 diabetes.

Materials and Methods

Using peripheral blood mononuclear cells (PBMC) sampled from 10 type 2 diabetes and 10 sex‐ and age‐matched control subjects and supernatants from PBMC culture, the expression of phospho‐mitogen activated protein kinase (MAPK) signaling pathways in CD4+ T helper lymphocytes and monocytes was analyzed using flow cytometry. Cytokines/chemokines and superoxide anion before and after treatment with exendin‐4 were measured by cytometric bead array and chemiluminesence assay, respectively.

Results

Compared with control subjects, PBMC from type 2 diabetes patients showed activated MAPK (P38, c‐Jun NH2‐terminal protein kinase and extracellular signal‐regulated kinase) signaling pathway, elevated superoxide anion, increased pro‐inflammatory cytokines (tumor necrosis factor‐α, interleukin‐1β, interleukin‐6) and chemokines (CCL5/regulated on activation normal T‐cell expressed and secreted and CXCL10/interferon‐γ‐induced protein 10). These changes were attenuated by exendin‐4, possibly through the suppression of p38 MAPK.

Conclusions

These results suggest that exendin‐4 might downregulate pro‐inflammatory responses and reduce oxidative stress by suppressing MAPK signaling pathways in type 2 diabetes.     

糖化血红蛋白A1c浓度与心血管疾病及全因死亡率增加相关——糖化血红蛋白A1c浓度与冠心病事件、心血管事件、全因死亡率之间的相关性如何？

设计：队列研究（欧洲前瞻性癌症调查研究．诺福克地区组（EPIC—Norfolk）），平均随访时间为6年。     

中指和无名指伸肌腱疲劳性损伤19例

1一般资料 1.1对象1998-01/2004-06收集中指和无名指伸肌腱疲劳性损伤19(男10,女9)例,26指,年龄18～24岁,均为学员,且连续从事高强度军事训练2 wk. 累及中指5例、无名指7例、中指无名指均累及7例,食指和小指均未累及. 发病至就诊时间3 d～4 wk,由于指伸肌腱的疲劳性损伤目前缺乏统一的诊断标准,我们主要根据病史和临床表现做出诊断[1];但我们诊治的均在高强度的军事训练中发病,手指的伸展功能出现障碍,因此诊断不难.     

钙离子ATP酶2a基因修饰的骨髓干细胞移植治疗大鼠慢性心力衰竭

目的:观察肌浆网钙离子ATP酶2a基因修饰的骨髓干细胞移植对慢性心力衰竭大鼠心功能的影响。方法:实验于2004-07/2005-12在北京医科大学生物化学系实验室完成。选取4周龄清洁级雄性SD大鼠作为骨髓供体。雌性SD大鼠作为细胞移植、基因治疗受体,随机数字表法分为4组:肌浆网钙离子ATP酶2a基因治疗组(n=7)、骨髓干细胞移植治疗组(n=7)、肌浆网钙离子ATP酶2a基因修饰的骨髓干细胞移植组(n=8)、腺病毒空载体对照组(n=7)。结扎左冠状动脉制作急性心肌梗死后慢性心力衰竭大鼠模型,每组进行相应的基因治疗和细胞移植。治疗后21d,采用苏木精-伊红染色和MASSON染色评价心脏形态及结构变化,组织多普勒评价各组心功能。并检测肌浆网钙离子ATP酶2a基因和蛋白在宿主心脏的表达。结果:29只雌性大鼠均进入结果分析。①与腺病毒空载体对照组大鼠相比,骨髓干细胞移植治疗组和肌浆网钙离子ATP酶2a基因修饰的骨髓干细胞移植治疗组大鼠心室腔明显减小。MASSON染色显示,肌浆网钙离子ATP酶2a基因修饰的骨髓干细胞移植治疗组大鼠蓝色的胶原纤维染色区域减少,红色的肌纤维染色区域增多。②肌浆网钙离子ATP酶2a基因治疗组、骨髓干细胞移植治疗组和肌浆网钙离子ATP酶2a基因修饰的骨髓干细胞移植治疗组大鼠左室前壁、室间隔收缩及舒张期纵向峰值速度均较腺病毒空载体对照组显著升高[左室前壁:(0.58±0.03),(0.67±0.02),(0.78±0.05),(0.31±0.02)cm/s;(0.81±0.04),(1.26±0.04),(1.39±0.05),(0.40±0.01)cm/s;室间隔:(0.60±0.05),(1.00±0.08),(1.33±0.04),(0.40±0.01)cm/s;(0.70±0.04),(1.28±0.05),(1.57±0.03),(0.44±0.03)cm/s,P<0.001]。与肌浆网钙离子ATP酶2a基因治疗组相比,肌浆网钙离子ATP酶2a基因修饰的骨髓干细胞移植治疗组大鼠左室前壁、室间隔收缩及舒张期纵向峰值速度升高(P<0.001)。③肌浆网钙离子ATP酶2a基因治疗组和肌浆网钙离子ATP酶2a基因修饰的骨髓干细胞移植治疗组心肌内肌浆网钙离子ATP酶2amRNA表达强度明显高于骨髓干细胞移植治疗组和腺病毒空载体对照组。结论:肌浆网钙离子ATP酶2a基因修饰的骨髓干细胞移植能显著改善慢性缺血性心力衰竭大鼠心脏的收缩和舒张功能。     

Characterization of hyaluronan and TSG‐6 in skin scarring: differential distribution in keloid scars,normal scars and unscarred skin

Background Hyaluronan (HA) is a major component of the extracellular matrix (ECM) with increased synthesis during tissue repair. Tumour necrosis factor‐stimulated gene‐6 (TSG‐6) is known to catalyze the covalent transfer of heavy chains (HC1 and HC2) from inter‐α‐inhibitor (IαI) onto HA, and resultant HC?HA complexes have been implicated in physiological and pathological processes related to remodelling and inflammation. Objective The aims of this study were to determine the expression of HA, TSG‐6 and the IαI polypeptides in unscarred skin, normal scars and keloid scars. Methods Formalin‐fixed paraffin‐embedded sections of unscarred skin, normal scars and keloid scars were prepared from patient samples collected during scar revision surgery. Haematoxylin and eosin, as well as immunofluorescent staining for HA, TSG‐6 and the three polypeptide chains of IαI (i.e. HC1, HC2 and bikunin) were performed. Results All skin types stained positive for TSG‐6, HC1, HC2 and bikunin, associated with keratinocytes, fibroblasts and skin appendages all in close proximity to HA. Keloid lesions showed altered HA organization patterns compared with unscarred skin and normal scars. TSG‐6 staining was significantly more intense in the epidermis compared with the dermis of all sample types. There was a significant reduction in TSG‐6 levels within keloid lesions compared with the dermis of unscarred skin (P = 0.017). Conclusion TSG‐6 is expressed in unscarred skin, where its close association with HA and IαI could give rise to TSG‐6‐mediated HC?HA formation within this tissue. A reduction in the beneficial effects of TSG‐6, caused by diminished protein levels in keloid lesions, could contribute to this abnormal scarring process.