A randomized controlled trial to evaluate the slow-acting symptom-modifying effects of colchicine in osteoarthritis of the knee: a preliminary report.

OBJECTIVE: To determine if colchicine added to nimesulide may have a beneficial effect on osteoarthritis (OA) of the knee. METHODS: Colchicine 0.5 mg twice daily or placebo was added to nimesulide (a nonsteroidal antiinflammatory drug) in 36 patients with OA of the knee in a randomized, double-blind, placebo-controlled trial over a 5-month period. RESULTS: The 30% improvement rate at 20 weeks was higher in the colchicine group than in the control group receiving placebo, as measured by total Western Ontario and McMaster University Osteoarthritis scores (57.9% versus 23.5%) and visual analog scale for index knee pain (52.6% versus 17.6%) (primary measures of response). The significance persisted on combined analysis by Mantel-Haenszel test (P = 0.062). Comparison of means also showed significant improvement in the colchicine group versus the control group in a multivariate analysis performed using T(2) test (P = 0.0115). CONCLUSION: Among patients with OA of the knee, the group receiving colchicine plus nimesulide exhibited significantly greater symptomatic benefit at 20 weeks than did the control group receiving nimesulide plus placebo.

A randomized controlled trial to evaluate the slow-acting symptom modifying effects of a regimen containing colchicine in a subset of patients with osteoarthritis of the knee.

OBJECTIVE: As crystals may contribute to inflammation in osteoarthritis (OA), it is hypothesized that colchicine may have symptom/disease modifying effects in OA. The objective of this study was to evaluate the symptomatic benefit of addition of colchicine to a regimen of intraarticular steroids and piroxicam in patients with knee OA with inflammation. DESIGN: 39 patients with OA of the knee with persisting inflammation, despite at least 2 weeks of piroxicam, were subjected to intraarticular steroid injection and randomly assigned to receive colchicine 0.5 mg twice daily or placebo in a randomized, double blind, placebo-controlled trial over 5 months. RESULTS: VAS for index knee pain (VAS-pain) and total KGMC score (a modified WOMAC index) at 16 and 20 weeks were significantly better in the colchicine group than the corresponding scores in controls. The benefit persisted on multivariate analysis at 16 weeks (Hotellings T(2)=18.6, F(5,33)=3.3154, P=0.015). The proportion of patients who had 30% or greater response at 16 weeks was significantly higher in the colchicine group in VAS-pain (69% vs 15%) and total KGMC scores (74% vs 45%) and the significance persisted on combined analysis using Mantel-Haenszel test (M-H Risk=5.9, 95% C.I.: 2.08 to 16.73). At 20 weeks, benefit of colchicine therapy was seen on pooled analysis only (M-H risk=3.71, 95% C.I.: 1.07=8.02). CONCLUSION: The addition of colchicine produced significantly greater symptomatic benefit at 16 and 20 weeks than intraarticular steroid and piroxicam alone in patients with knee OA with inflammation.

Response of Mycobacterium habana vaccine in patients with lepromatous leprosy and their household contacts. A pilot clinical study.

Single dose vaccination was carried out with Mycobacterium habana vaccine, 31 lepromatous leprosy cases receiving 1.5 mg (1.5 mg = 6.27 x 10(8) bacilli) and 36 household contacts randomly receiving 1.5, 2.0, 2.5 mg vaccine intradermally. Duration of study was 18 weeks. Vaccination induced lepromin conversion in 100% of lepromatous leprosy cases and lepromin negative household contacts and augmentation of lepromin reactivity in 100% of lepromin positive household contacts, which was stable for the 15 weeks duration of follow-up. The maximum augmentation in lepromin reactivity was obtained with 1.5 mg of vaccine, which is probably the supramaximal dose. Overall, post-vaccination, those without prior BCG vaccination scars showed higher mean values of lepromin augmentation. Local vaccination site changes included induration, ulceration, itching, pain and uncomplicated regional lymphadenopathy, all of which remitted spontaneously by 15 weeks. Systemic side-effects noted were pyrexia, ENL and jaundice, and were seen with no greater frequency than that reported in other vaccine trials. Overall, systemic side-effects were easily controlled and were not accompanied by clinically detectable nerve or ocular damage. The safety profile investigations revealed an increase in the mean values of Hb%, RBC count and PCV in household contacts and of PCV in lepromatous patients, post-vaccination. Alterations in the liver function tests were also observed in patients of lepromatous leprosy. Thus, M. habana vaccine appears to be useful in stimulating specific CMI against M. leprae as evidenced by increased lepromin reactivity.

Clinical evaluation of sibutramine in obese type 2 diabetic patients refractory to dietary management.

MATERIAL AND METHODS: An open, non-comparative study was carried out to assess the efficacy and toleration profile of sibutramine, a new antiobesity drug, in promoting weight loss in obese type 2 diabetes mellitus subject who failed to reduce weight after strict dietary control. Twenty seven patients completed the study. Sibutramine was started as a single morning dose of 10 mg and was subsequently increased to 15 mg daily if weight loss was not satisfactory. The total duration of the study was twelve weeks with followup at every four weeks. Effect of drug was monitored in terms of weight reduction, changes in body mass index, waist circumference, hip circumference, waist/hip ratio and other metabolic parameters. A fixed dietary prescription and concomitant therapy with drugs, if required and not likely to interfere with the trial therapy, was permitted but was not changed during the study period. RESULTS: At the end of 12 week, mean weight reduction in study subjects was 4.16 kg (p < 0.001), the corresponding BMI decreased by 1.6 (p < 0.0001) and hip circumference by 3.68 (p < 0.001). However, there was no significant change in fasting blood glucose and Hb(A1c) values. CONCLUSION: The study indicates sibutramine to be an effective and well tolerated agent leading to significant reduction in parameter of obesity in obese type 2 diabetic subjects.

Clinical profile of AIDS: a study at a referral hospital.

The present study describes the clinical and epidemiological features of 74 patients with human immunodeficiency virus (HIV) infection who presented to a referral hospital. Sixty two patients (83.7%) were diagnosed to have acquired immune deficiency syndrome (AIDS). Mean age of the patients was 34.9 +/- 12 years and male to female ratio was 3:1. Majority of patients (80%) were from lower socio-economic class. Multiple unprotected heterosexual contact with commercial sex workers in metropolitan cities of India, mainly Mumbai, was major risk factor in 82.1% male patients while most of the females (66.6%) had acquired infection from HIV positive husbands. Blood transfusion was the risk factor in 9(12.1%) patients. Sixty eight patients were infected with HIV 1, one with HIV 2, and five patients with both HIV 1 and HIV 2. Fever and weight loss were the commonest presenting symptoms. Tuberculosis, oropharyngeal candidiasis, and interstitial pneumonitis were present in 54.8%, 40.3% and 20.9% patients, respectively. Fourteen patients (22.5%) had generalised lymphadenopathy. Herpes zoster, cryptococcal meningitis, and peripheral neuropathy were infrequent. Response to standard antifungal and antitubercular treatment was satisfactory. Kaposi's sarcoma, lymphoma, and CNS toxoplasmosis were not found. The clinical manifestations of AIDS patients are strikingly different from that in the Western countries. It, thus, necessitates setting up of different guidelines for the clinical diagnosis and management of AIDS in India.

Oxy free radical system in heart failure and therapeutic role of oral vitamin E.

Twenty patients of heart failure and ten matched healthy controls were included in the trial. Out of these 20 patients of heart failure, 12 patients were also studied prospectively. Plasma levels of superoxide anion and malonyldialdehyde were increased while the levels of superoxide dismutase, catalase and glutathione reductase were decreased in patients of heart failure as compared to control subjects. The alteration in oxidative stress and antioxidant system did not correlate with the age and sex of patients or the etiology of heart failure. With the increasing severity of heart failure the malonyldialdehyde and superoxide anion increased significantly and catalase, glutathione reductase and superoxide dismutase levels decreased. The group of heart failure patients with ejection fraction < 40% (n = 7) exhibited significantly higher levels of malonyldialdehyde than those with an ejection fraction > 40% (n = 13). The superoxide anion and malonyldialdehyde levels were significantly higher in patients of heart failure in the pre-treatment state as compared to those in post-treatment state. Conversely catalase, glutathione reductase and superoxide dismutase were higher in the post-treatment period as compared to their values before treatment. The addition of vitamin E in doses of 400 mg once a day orally for 4 weeks significantly reduced the malonyldialdehyde and superoxide anion levels and produced an elevation of the antioxidant enzymes. Thus, there is an apparent normalisation of the indices of oxidative stress following treatment of heart failure and a markedly improved response on vitamin E supplementation which may be more beneficial.

Dietary modulators of lipid metabolism in the Indian diet-heart study (I.D.H.S.).

Of the 621 adults (25 to 65 years of age, 531 males) with either risk factors or with coronary heart disease (CHD) 310 subjects were given a cardiovasoprotective (CVP) diet (group A) and 311 subjects a normal diet (group B) in a randomized, single blind and controlled fashion. Risk factors and incidence of CHD were comparable between the two groups. The intervention group received a significantly higher percentage of calories in relation to complex carbohydrates, vegetable proteins, polyunsaturated fatty acids and high P:S ratio diet as compared to the control group. The control group received higher saturated fat and cholesterol. Compliance was assessed by dietary questionnaire during the follow-up. After 8 weeks of dietary trial, there was a significant decrease in mean serum total cholesterol (8.2 vs 2.1%), low density lipoprotein (LDL) cholesterol (9.8 vs. 2.7%) and triglyceride (11.2 vs 5.8%) in the intervention group compared to baseline levels and changes in control subjects. Body weight and physical activity at the entry to study and during the trial were similar in both groups. The decrease in mean HDL cholesterol were insignificant both in the intervention (4.3%) and control group (5.0%). There were no adverse effects of diet during the 8 weeks of trial. It is possible that a diet with 27.5% energy from total fat including 10.1% energy from monounsaturated fatty acids, P:S ratio 1.38, 120 mg dietary cholesterol, 26.0 g dietary fibre per 1000 kcal would modulate the lipid metabolism resulting in a significant reduction in serum total cholesterol, LDL cholesterol and triglyceride with no reduction in HDL cholesterol. This diet may be capable of reducing CHD incidence and mortality in the long term Indian diet-heart study (IDHS).

Dietary strategies for risk-factor modification to prevent cardiovascular diseases.

To study the role of diet in cardiovascular risk-factor intervention, 458 high-risk individuals were asked to eat for either a cardiovasoprotective diet (group A, n = 228) or their usual diet (group B, n = 230) in a randomized single-blind fashion. Ages varied between 25 and 63 yr, and 414 were men. Group A received significantly more calories in relation to the amount of complex carbohydrates, vegetable proteins, polyunsaturated fats, fiber, potassium, magnesium, and vitamin C and fewer calories in saturated fat and cholesterol compared with group B. Age, risk factors, nutritional factors, complications, and laboratory data were similar at entry to the study. Dietary adherence was obtained by questionnaire. After 1 yr, there was a significant (P less than 0.02) decrease in total risk factors (32.0%) in group A compared with group B, and 1-yr mean serum cholesterol was significantly lower than the initial mean cholesterol in group A. There was a significant (P less than 0.02) decrease in total complications (38.3%) in group A compared with group B in association with a significant (P less than 0.02) decrease in cardiovascular end points (38.3%), including postexercise electrocardiographic changes, fatal and nonfatal myocardial infarction, and sudden death. Overall mortality and mortality due to ischemic heart disease was less in group A (8 and 3.5%) than group B (11 and 4.8%). However, because of the few cases, differences were insignificant. It is possible that diet causes a significant reduction in blood cholesterol and modification of other risk factors leading to a decrease in complications and cardiovascular end points in patients with risk factors of coronary heart disease.

Dietary modulators of blood pressure in hypertension.

To study the role of diet, 197 patients of essential hypertension were randomized to either experimental diet (group A, 97 cases) or normal diet (group B, 100 cases) with diuretics given to both the groups. The age varied between 25 and 65 years and 154 were males. The study diet included a significantly higher content of potassium (K), magnesium (Mg), calcium (Ca), polyunsaturated fat, and complex carbohydrates compared to the normal diet. At entry to the study, age, sex, risk factors, mean blood pressures, mean serum Mg, K, Ca, and Na, and drug therapy were comparable in both groups. After 1 year of follow-up, there were significantly fewer patients with resistant hypertension in group A (5) than in group B (17). Mean systolic (148.22 +/- 10.1 mm Hg) and diastolic (90.2 +/- 4.84 mm Hg) pressures in group A were lowered compared to mean systolic (160 +/- 12.0 mm Hg) and diastolic (103.3 +/- 5.8 mm Hg) pressures in group B and initial mean systolic (152.2 +/- 12.8 mm Hg) and diastolic (99.8 +/- 7.2 mm Hg) pressures. Mean serum magnesium (1.86 +/- 9.22 mEq/l) and potassium (4.86 +/- 0.39 mEq/l) levels in group A were significantly higher compared to mean levels of 1.56 +/- 0.11 and 4.0 +/- 0.29 mEq/l, respectively, in group B. However compared to initial levels, K and Mg showed no significant changes in groups A and B. There was a significantly lower incidence of complications in group A (58) compared to group B (100). It is possible that a diet low in Na/K ratio and rich in complex carbohydrates, polyunsaturates, K and Mg may cause a significant reduction in blood pressure and its complications.

Magnesium and potassium administration in acute myocardial infarction.

This study included 264 patients with proven acute myocardial infarction who were randomized to either magnesium sulphate, potassium chloride, 10% glucose solution or a placebo containing 200 ml of 2% glucose solution given intravenously, slowly, daily for 3 days in a double-blind, placebo-controlled fashion. The ages varied between 30 and 65 years and 230 were males. Laboratory data such as enzymes, sodium, potassium, calcium and magnesium were obtained in all the patients before and after the therapy. Age, sex, risk factors and drug therapy were comparable between all the groups of patients. After 4 weeks of follow-up, there was a significant decrease in the total number of complications in group A (52%) and B (30%) patients, who were given magnesium and potassium compared to group C and D, who were administered only 10% glucose and placebo. There was a significant rise in mean serum magnesium and potassium levels in group A and B, respectively, after therapy compared to their mean concentrations before therapy. Although mortality was less in groups A and B, a firm statistical conclusion is not possible due to a lesser number of cases. However, it is possible that magnesium and potassium ions have beneficial effects on ischemia-induced alterations and myocardial metabolism resulting in less complications and mortality in group A and B patients.

Evaluation of filarial skin test with Brugia malayi larval antigen in the field.

To obtain comparable and reproducible results by filaria skin test with B. malayi larval antigen, standard procedure has been evolved. Antigen protein of 2 micrograms per test, injected intracutaneously, was found optimum for positive skin reaction. The reaction ratio based on increase of wheal area by 2 times or more was found to be statistically significant for interpreting positive results. However, in larger field trials, the simpler measurement of increase of wheal diameter by 1 1/2 times or more was found to be equally reliable. Patients treated with diethylcarbamazine citrate, antihistaminics and anti-inflammatory drugs are likely to be unresponsive to filarial antigen and will yield incorrect information.