MULTIDRUG RESISTANT TUBERCULOSIS – BIOMECHANISM,EPIDEMIOLOGY AND MANAGEMENT STRATEGIES

Muitidrug resistant tuberculosis has shown an alarming increase and this assumes added importance in view of the increasing number of HIV infected patients. This article reviews the biomechanism of resistance and discusses the present stategies that are available and recommended to tackle the rising incidence of tuberculosis due to resistant mycobacteria.KEYWORDS: Antitubereular drugs, Drug resistance, Mycobacterium tuberculosis     

Vitamin A intake and xerophthalmia among Indian children

OBJECTIVE: To estimate prevalence of xerophthalmia and to assess dietary intake of vitamin A in Indian children aged under 6 y. DESIGN: Cross sectional study. STUDY SETTING: Urban slums under Urban Health Centre affiliated to Department of Preventive and Social Medicine, Government Medical College, Nagpur, India. PARTICIPANTS: The study included 1094 all children under 6 y of age, from two randomly selected urban slums. METHODS: Xerophthalmia was diagnosed on the basis of ocular signs and symptoms (WHO recommendations). Dietary intake of vitamin A was assessed by using one year recall method recommended by International Vitamin A Consultative Group. RESULTS: Prevalence of xerophthalmia was estimated to be 8.7%. Nine hundred and ninety-five (90.9%) study subjects were identified as inhabitants consuming dietary vitamin A at below recommended levels. (UPF score < 210). Five hundred and ninety-three (54.2%) study subjects were consuming dietary vitamin A at approximately less than 200 RE/d (UPF score < 120) while 402 (36.2%) were consuming approximately 200-300 RE/d (UPF score 120-210). The prevalence of xerophthalmia was found to be decreasing as the score of usual pattern of food consumption (UPF) increased. CONCLUSIONS: Children with a dietary intake represented by a UPF score of less than 120 were at high risk of developing xerophthalmia, whereas, those consuming vitamin A equal to a UPF score greater than 120 were at comparatively less risk despite being below the recommended levels.     

Prevalence of antibodies to human immunodeficiency virus type 1 among blood donors prior to screening. The Transfusion Safety Study/NHLBI Donor Repository

The Transfusion Safety Study (TSS) and the National Heart, Lung, and Blood Institute (NHLBI) established a repository of approximately 200,000 sera from blood donors in late 1984 and early 1985. Collections were made in the four metropolitan areas with the highest prevalence of AIDS. Retrospective testing showed an overall anti-HIV-1 prevalence of 16 cases per 10,000 donations. In this study, the predictive value of a negative initial enzyme-linked immunoassay was estimated from both quality control specimens and the rescreening of 13,461 sera to be greater than 99.99 percent with respect to technical error. Among anti-HIV-1-positive persons, there was a 1.3- to 1.5-fold excess of first-time donors. The anti-HIV-1 prevalence among donors showed that infection was more common among young men than suggested by national reporting of AIDS cases. Anti-HIV-1 prevalence varied among the four metropolitan areas less than did reported AIDS cases, but, by 1987, the differences in the latter had decreased. Anti-HIV-1 prevalence in collection areas outside of the four major cities differed much more widely than that among the cities themselves. The TSS/NHLBI Donor Repository will remain available for the indefinite future for further evaluation of screening procedures for HIV-1 and other viruses for which transfusion is found to be an important route of transmission.     

Surgical management of multivalvular heart disease

Background This study of patients with multivalvular lesions was undertaken to assess optimal surgical management and identify risk factors for prognosis. Methods Five hundred and twenty one patients underwent valve repair or replacement surgery between January’90 and December’98. Mean age was 30.19±12.2 years and 342 were males. All patients had dyspnoea on exertion, 467 (89.6%) were in New York Heart Association (NYHA) Class III and 47 (9.0%) were in Class IV. Congestive Heart Failure in 67 (12.3%) and prior cardiac procedure in 66 (12.2%) were other risk factors. The valves affected were mitral and aortic in 483 (Group 1), mitral and tricuspid in 43 (Group II) and mitral, aortic and tricuspid in 40 (Group III) patients. Surgical procedures included, several different combinations using repair or replacement with prosthetic or biological substitutes. Results Operative mortality was 9.8% (51 patients). Follow up (1 to 108 months, mean 45 months) was 94% complete. Late mortality occurred in 48 patients (10.4%). Causes included, left ventricular dysfunction (n=21), valve thrombosis (n=10) and, endocarditis (n=8). Freedom from late events was 50.7±8.5% at 9 years. At their last visit 40 patients were in Class IV, 18 were in Class III, 59 in Class II and the remaining in Class I (NYHA). Conclusions Important predictors of early mortality were NYHA Class IV, congestive heart failure, tricuspid valve disease and prior cardiac surgery. Left ventricular dysfunction was an important determinant of late outcome.     

The role of amino-terminal residues of the heavy chain of factor IXa in the binding of its cofactor, factor VIIIa

The purpose of this study is to determine which residues of the factor IXa heavy chain are important for interaction with the cofactor of factor IXa, factor VIIIa. Because the monoclonal antibody (MoAb) FXC008 inhibits interaction between factors IXa and VIIIa, and because it also reacts with residues 181-310 of the factor IXa heavy chain, we used the computer-modelled structure of the factor IXa heavy chain to select charged surface residues likely to interact with FXC008 and/or factor VIIIa. We made mutations in the region of residues 181-310 of the heavy chain of factor IX, and replaced these amino acids individually with those located at the same position in factor X. The mutated factor IX retained complete clotting activity and thus interacted normally with factor VIIIa. Five mutant proteins (factor IXK214F, factor IXK228R, factor IXE240Q, factor IXK247V, and factor IXN260K) reacted with heavy chain-specific MoAbs FXC008 and A-5. Neither factor IXD276K nor factor IXR248H bound to FXC008. Factor IXR252V had reduced affinity to FXC008. Our results suggest the following: (1) factor IXa residues 214, 228, 240, 247, 248, 252, 260, and 276 are not involved in specific interaction with factor VIIIa; and (2) the FXC008 and factor VIIIa binding sites may not share critical residues.     

非亲缘异基因外周血干细胞移植重建白血病幼儿造血功能：1例报告

目的:分析非亲缘异基因外周血干细胞移植治疗幼儿急性非淋巴性白血病的可行性。方法:患儿,男,3岁,于2005-07-18为行造血干细胞移植入本院血液科骨髓移植病房,入院诊断为急性非淋巴细胞性白血病-M5b。经抗肿瘤药物治疗病情获得完全缓解。患儿首先接受清髓性预处理,然后接受同性别非亲缘异基因外周血造血干细胞移植。①移植预处理包括马利兰、阿糖胞苷和环磷酰胺。移植前依次用药为马利兰3.2mg/(kg·d)×4d,口服,于移植前6,7,8,9d给药;阿糖胞苷3.2g/(m2·d)×2d,于移植前4,5d给药;环磷酰胺54mg/(kg·d),于移植前2,3d给药。②急性移植物抗宿主病的预防用药包括环孢菌素A和氨甲蝶呤、抗胸腺细胞球蛋白及吗替麦考酚酯。供者接受粒细胞集落刺激因子动员4d后采集外周血造血干细胞,供、受者间HLA全相合,患者血型A,供者血型B,主次要均不合。结果:①患儿移植后早期获得造血重建,中性粒细胞>0.5×109L-1和血小板>50×109L-1的天数分别是12d和11d。②移植后1个月经DNA短串联重复序列多态性分析证明为供者型完全植入,移植后3个月查骨髓象正常。③移植后3,6个月定期行淋巴细胞亚群检查表明除CD19 ,CD4 细胞未恢复外,自然杀伤细胞在移植后3个月恢复正常,T淋巴细胞CD3 与CD8 、体液免疫球蛋白在移植后6个月中均获得重建。④整个移植过程顺利,未出现明显感染和重度急性移植物抗宿主病。移植后96d时出现Ⅰ度皮肤移植物抗宿主病,经加用激素治疗,皮疹消失。移植术后已随访观察12个月,患儿正常生活。结论:如果患儿有HLA完全相合的供者,非亲缘异基因外周血干细胞移植治疗儿童高危白血病是一种有效和安全的方法,对国内独生子女家庭拓宽供者来源有重要的实用价值。     

Mapping of monoclonal antibodies to human factor IX

We used recombinant DNA techniques to map a panel of six monoclonal antibodies (MoAbs) to regions of the human factor IX molecule. A-2 maps to 17 amino acids at the amino terminus of the heavy chain of IXa; 2D5, an inhibitor of clotting, is defined to 36 amino acids of the first EGF- like domain of human factor IX. A-4, A-5, C10D, and FXC008 all map to a region of the heavy chain containing amino acids 180 through 310, suggesting an immunodominant site. FXC008 has been reported to interfere with binding of factor IXa to factor VIII:Ca.