Tuberculosis (TB) is an infectious disease of international importance and ranks among the top 10 causes of death in the World. About one-third of the world's population is infected with Mycobacterium tuberculosis. Every year, approximately eight million people develop active disease and two million die of TB. The currently used BCG vaccines have shown variable protective efficacies against TB in different parts of the world. Moreover, being a live vaccine, BCG can be pathogenic in immunocompromised recipients. Therefore, there is an urgent need to develop new vaccines against TB. The comparative genome analysis has revealed the existence of several M. tuberculosis-specific regions that are deleted in BCG. The work carried out to determine the immunological reactivity of proteins encoded by genes located in these regions revealed several major antigens of M. tuberculosis, including the 6 kDa early secreted antigen target (ESAT6). Immunization with ESAT6 and its peptide (aa51-70) protects mice challenged with M. tuberculosis. The protective efficacy of immunization further improves when ESAT6 is recombinantly fused with M. tuberculosis antigen 85B. In addition, ESAT6 delivered as a DNA vaccine is also protective in mice. Whether these vaccines would be safe or not cannot be speculated. The answer regarding the safety and efficacy of these vaccines has to await human trials in different parts of the world.

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Currently we are in the midst of a chronic disease epidemic of congestive heart failure (CHF) worldwide. This epidemic is marked by a rapid rise in prevalent cases over the past decade that is due in part to the aging population and improved survival in patients with other cardiovascular conditions. At present there are 5 million Americans with congestive heart failure, with nearly 500000 new cases every year. To provide cost-effective treatment for patients with congestive heart failure, rapid and accurate differentiation of congestive heart failure from other causes of dyspnea must be accomplished. Although echocardiography is considered the gold standard for the detection of left ventricular dysfunction, it is expensive, is not always easily accessible, and may not always reflect an acute condition. B-type natriuretic peptide (BNP) is a cardiac neurohormone specifically secreted from the cardiac ventricles as a response to ventricular volume expansion, pressure overload, and resultant increased wall tension. BNP can be used in the diagnosis of CHF. However, the present American College of Cardiology/American Heart Association practice guidelines (2001) for the evaluation and management of CHF state that the role of blood BNP in the identification of patients with CHF remains to be fully clarified. We have discussed the role of BNP in the diagnosis and management of CHF.

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INTRODUCTION: The waiting times for elective surgery of Umbilical hernia (UH) in adults are unacceptably long in some cases. During this period, irreducibility and strangulation are possible. We operate on adult patients under local anaesthesia (LA) as day cases to avoid this delay and describe our experience in this paper. AIMS: The aims of our study were to look at the age and sex distribution, body weight, type and amount of local anaesthetic used, morbidity, admission and readmission rates, and waiting times of adult patients operated on for UH under LA. MATERIALS AND METHODS: It was a retrospective study covering a 4 year period from July 1996 to June 2000 including all adult patients undergoing the above procedure under the care of a single consultant general surgeon. A standard Mayo repair using non absorbable material was used without a mesh or a drain. RESULTS: 32 patients with UH were operated on under LA, 23 males and 9 females with a median age of 51 years (range 20 to 86 years). The body weight ranged from 63 to 120 (median 87) kg. The average duration of the procedure was 30 (range 22-40) minutes. Sedation was needed in 4 patients. Two patients developed wound infections, one superficial and one deep. There was no mortality. The median period of follow-up was 24 (range 4-48) months and there was no recurrence. The median waiting time for the operation was 6 weeks. CONCLUSIONS: Day case local anaesthetic repair of UH in adults seems to be safe and feasible with an acceptable morbidity. Suture repair in the right patient has excellent results and the waiting times are acceptable.

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Cutaneous metastasis from colon cancer is an uncommon event that usually occurs after identification of the primary tumour and generally indicates diffuse disease. Incisional metastasis occasionally occurs following laparoscopic or open colon cancer resection. However, to the authors' knowledge only one previous case of colon cancer presenting as a cutaneous metastasis in an old operative scar has been reported. We describe a case of colon cancer presenting as a cutaneous metastasis in an old cholecystectomy scar and discuss possible pathophysiological mechanisms.

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BACKGROUND: Enzyme replacement therapy (ERT) for Gaucher's disease with alglucerase or imiglucerase is efficacious, well-tolerated and safe. However, cost considerations, visits to medical facilities, potentially duration of theray for life, are issues of major concern to a proportion of treated patients and has, in some cases, led to the withdrawal of therapy. AIMS: To elucidate whether an extension of the interval between enzyme infusions to once every three weeks is as effective in maintaining the clinical responses achieved with the bi-monthly regimen. MATERIALS AND METHODS: Four patients with an optimal response to ERT (at 30 units/kg every two weeks for an average of 27 months), were subjected to enzyme dose/frequency changes that essentially constituted a reduction in cumulative dose over the treatment period. Patients were assessed every 6 months for alterations in haematological parameters, plasma chitotriosidase levels, liver and spleen size, and bone symptoms. RESULTS: All patients had to resume the previous infusion schedule of once every two weeks; one because of new bone marrow infiltrates, two because of visceral enlargement, and the fourth due to progressive anaemia. CONCLUSIONS: This limited experience suggests that a reduction in enzyme dose associated with an extended interval between infusions may lead to variable disease control, and underscores the need for individualization of enzyme therapy.

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This communication reports prenatal diagnosis of partial trisomy 21 resulting from balanced translocation (21q;22q) in a 36-year-old gravida 7, para 1 woman. The lady had only one living child and there was history of recurrent spontaneous first trimester abortions. Triple test was abnormal in the present conception. In addition, the woman had pericentric inversion of chromosome 9, a finding scarcely reported previously with carrier status in Indian literature. A few cytogeneticists consider this as a normal variant. However, many reports in the recent literature link pericentric inversion of chromosome 9 with infertility, recurrent abortions and a number of other abnormal conditions. A review of the relevant literature pertinent to the case is provided.

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BACKGROUND: In vitro results have shown that antimicrobial agents may induce the Gram-negative bacteria to release endotoxins (LPS), which in turn, could trigger the secretion of cytokines from monocytes. AIMS: To compare the effect of cefuroxime, netilmicin or ciprofloxacin on serum levels of LPS and tumour necrosis factor-alpha (TNFalpha). METHODS: Seventy-four patients with acute pyelonephritis caused by Gram-negative bacteria and signs of sepsis were randomly assigned to receive one of three intravenous regimens of cefuroxime, netilmicin or ciprofloxacin. Blood samples were collected before therapy and at specified time intervals for 96 hours after the initiation of treatment for the determination of serum levels of LPS and of TNFalpha. RESULTS: Patients treated with cefuroxime presented an early peak of LPS and of TNFalpha in serum two hours after the initiation of treatment compared to the other study groups. After that time interval, concentrations of LPS and TNFalpha were similar in all the study groups. Fever accompanied by endotoxaemia was still detected for 48 hours after the start of therapy in 36, 37.5 and 36% of patients treated with cefuroxime, netilmicin and ciprofloxacin respectively. The corresponding figures for these agents at 72 hours were 28, 12.5 and 24%, respective and 12, 4.2 and 4% at 96 hours (P value not significant). CONCLUSIONS: With the exception of an early peak in the serum levels of LPS and TNFalpha in patients treated with cefuroxime, no significant difference could be detected amongst the study groups as far as their effect on serum levels of LPS and TNFalpha were concerned. This suggests that these three antimicrobial agents may be administered safely at the early stages of sepsis.

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BACKGROUND: CD4+ T cells restrict parasitaemia during the first attack of falciparum malaria; humoral immunity, develops weeks later and protects against reinfection. HIV infection may affect severity of falciparum malaria and development of protective immunity. AIMS: To study the prevalence of HIV infection in Indian patients with severe falciparum malaria and its effect on severity of illness and recurrences of and mortality related to malarial infection. PATIENTS: Consecutive patients with severe falciparum malaria and voluntary blood donors. SETTING AND DESIGN: Prospective cohort study in a university hospital in Mumbai. RESULTS: Five (11.6%) of 43 patients and 521 (1.8%) of 28749 blood donors had HIV infection (OR 7.1, 95% CI = 2.8 to 18.2, p=0.001). Clinical features, APACHE II score, number of organs affected, parasite index and mortality in patients with and without HIV infection were comparable. CD4+ counts were < 500 cells/ microl in 2 patients and normal in 3. Opportunistic infections including pulmonary tuberculosis in one patient (CD4+ counts > 500 cells/ microl), and oral candidiasis in two (CD4+ counts 275 and 250 cells/ microl) were noted. One patient developed fatal Pneumocystis carinii pneumonia two weeks after recovering from malaria. P. falciparum infection recurred in 2 of the 4 HIV infected survivors and in none of 31 survivors without HIV infection (RR 38.8, 95% CI 2.2 to 671, p=0.01). CONCLUSIONS: HIV infection is associated with increased risk of severe malaria even with normal CD4+ counts; severity of disease and mortality are not increased. However, prior HIV infection impairs protective immune response to Plasmodium falciparum in residents of hypoendemic areas.

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CONTEXT: Researchers and investigators have argued that getting fully informed written consent may not be possible in the developing countries where illiteracy is widespread. AIMS: To determine the percentage of patients who agree to participate in a trial after receiving either complete or partial information regarding a trial and to find out whether there were gender or educational status-related differences. To assess reasons for consenting or refusing and their depth of understanding of informed consent. SETTINGS AND DESIGN: A simulated clinical trial in two tertiary health care facilities on in-patients. METHODS AND MATERIAL: An informed consent form for a mock clinical trial of a drug was prepared. The detailed / partial procedure was explained to a purposive sample of selected in-patients and their consent was asked for. Patients were asked to free list the reasons for giving or withholding consent. Their depth of understanding was assessed using a questionnaire. Chi-square test was used for statistical analyses. RESULTS: The percentages of those consenting after full disclosure 29/102 (30%) and after partial disclosure 15/50 (30%) were the same. There was a significant (p=0.043) gender difference with a lesser percentage of females (30%) consenting to participation in a trial. Educational status did not alter this percentage. Most patients withheld consent because they did not want to give blood or take a new drug. Understanding of informed consent was poor in those who consented. CONCLUSIONS: The fact that only one-third of subjects are likely to give consent to participate in a trial needs to be considered while planning clinical trials with a large sample size. Gender but not educational status influences the number of subjects consenting for a study. Poor understanding of the elements of informed consent in patients necessitates evolving better methods of implementing consent procedures in India.

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Congenital long QT syndrome (LQTS) is a rare but life-threatening disorder affecting cardiac electrophysiology. It occurs due to mutation in genes encoding for the ion channels in ventricular cell membrane. Syncopal attacks and cardiac arrest are the main symptoms of the disease. Anti-adrenergic therapy with oral beta-blockers has been the mainstay of treatment for LQTS. However, up to 30% of patients fail to respond to medical therapy and remain symptomatic. An alarming 10% of patients still experience cardiac arrest or sudden cardiac death during the course of therapy. Left cardiac sympathetic denervation (LCSD) has been used as an alternative therapy in patients who are resistant to beta-blockers. Although LCSD appears effective in reducing the frequency of syncopal attacks and improving the survival rate in both the short and long-term, its use has not gained popularity. The recent advent of minimally invasive thoracoscopic sympathectomy may improve the acceptance of LCSD by physicians and patients in the future. The primary objective of this article was to review the current evidence of the clinical efficacy and safety of LCSD in the management of LQTS. The review was based on Medline search of articles published between 1966 and 2002.

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AIM: To compare the efficacy of ketoprofen and pethidine for peri-operative analgesia and post-operative nausea and vomiting in children undergoing vitreoretinal surgery and surgery for retinal detachment. MATERIAL AND METHODS: Children aged 7 to 16 years and ASA I status, undergoing vitreo-retinal surgery were randomly allocated to receive either ketoprofen 2mg/kg or pethidine 1mg/kg intravenously for peri-operative analgesia. In all patients, general anaesthesia was induced with thiopentone and intubation was facilitated with vecuronium bromide and maintained with 33% oxygen in nitrous oxide and isoflurane. Intra-operative and post-operative monitoring was done by an observer blinded to the technique. Intra-operative rescue analgesia was used if heart rate and/or blood pressure increased by 25% from pre-incision values. Post-operative pain and episodes of nausea and vomiting were evaluated at recovery (0 hour), 2, 6 and 24 hours intervals. Standard rescue analgesia and anti-emetic agents were administered if required. RESULTS: Eighty-six children were enrolled in the study. Forty-four received ketoprofen while 42 received pethidine. Intra-operative analgesia was comparable in both the groups and no significant difference was found in the requirement of intra-operative rescue analgesia, as well. Postoperatively 6/44 (13.6%) children in ketoprofen group had pain at recovery compared to 17/42 (40.4%) in pethidine group. Pain at 2, 6 and 24 hours, and postoperative analgesic requirement were not significantly different among the two groups. Post-operative nausea, vomiting, and antiemetic requirement were significantly less in the ketoprofen group at all time intervals. CONCLUSION: Ketoprofen is a satisfactory alternative analgesic to pethidine for vitreoretinal surgery and results in a lower incidence of postoperative nausea and vomiting.

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A 37-years-old female who was suffering from end-stage renal disease for about 6 years received allograft renal transplantation 4 years ago. She has been receiving 50mg of Cyclosporin A orally daily for immuno-suppression since then. Gross haematuria was noted and computerised tomography showed native left renal pelvic and ureteral multi-focal transitional cell carcinoma with severe hydronephrosis. Laparoscopic bilateral nephroureterectomy and bladder cuff excision were performed. In the past, history of previous operation was considered a relative contraindication for laparoscopic surgery. To our knowledge, we present the first case of laparoscopic treatment for native renal pelvic and ureteral transitional cell carcinoma after renal allograft transplantation without a hand-assisted device. This case shows the feasibility of laparoscopic bilateral nephroureterectomy in patients with transplanted kidneys.

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The Mitrofanoff procedure is a versatile technique that is successfully used in achieving continent urinary diversion for a wide variety of urological conditions. Appendix and usable segment of ureter are commonly employed for this purpose and provide desirable results. This communication describes a teenage girl with lumbosacral agenesis and neurogenic bladder in whom Meckel's diverticulum was successfully used for the Mitrofanoff procedure.

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Smallpox virus has gained considerable attention as a potential bioterrorism agent. Recommendations for smallpox (vaccinia) vaccination presume a low risk for use of smallpox as a terrorist biological agent and vaccination is currently recommended for selected groups of individuals such as health care workers, public health authorities, and emergency/rescue workers, among others. Information about adverse reactions to the smallpox vaccine is based upon studies completed during the 1950s and 1960s. The prevalence of various diseases has changed over the last four decades and new disease entities have been described during this period. The smallpox vaccination may be contra-indicated in many of these conditions. This has made pre-screening of potential vaccines necessary. It is believed that at present, the risks of vaccine-associated complications far outweigh the potential benefits of vaccination in the general population.

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