Prolonged clearance of microfilaraemia in patients with bancroftian filariasis after multiple high doses of ivermectin or diethylcarbamazine.

In a double-blind trial on 37 asymptomatic microfilaraemic subjects (minimum 400 microfilariae [mf] per mL) with Wuchereria bancrofti infection, the safety, tolerability and macrofilaricidal efficacy of 12 fortnightly doses of ivermectin, 400 micrograms/kg (ivermectin group), was compared with 12 fortnightly doses of diethylcarbamazine (DEC), 10 mg/kg (DEC group), over a period of 129 weeks after treatment. A control group (LDIC group) was treated with low dose ivermectin to clear microfilaraemia, for ethical reasons. Both ivermectin and DEC in high multiple doses were well tolerated and clinically safe. Macrofilaricidal efficacy was assessed by prolonged clearance of microfilaraemia, appearance of local lesions, and reduction of circulating W. bancrofti adult antigen detected by an antigen capture enzyme-linked immunoassay based on the monoclonal antibody AD12. Mf counts fell more rapidly after ivermectin than after DEC, but low residual mf levels were equivalent in these groups after week 4. Conversely, filarial antigen levels fell more rapidly after DEC than after ivermectin, but low residual antigen levels in these groups were statistically equivalent at all times beyond 12 weeks. Mild, self-limited systemic reactions to therapy were observed in all 3 treatment groups. Local reactions, such as development of scrotal nodules, were observed in several subjects in the DEC and ivermectin groups. These results suggested that high dose ivermectin and DEC both had significant macrofilaricidal activity against W. bancrofti, but neither of these intensive therapeutic regimens consistently produced complete cures. Thus, new drugs or dosing schedules are needed to achieve the goal of killing all filarial parasites in the majority of patients.

Efficacy of single dose combinations of albendazole, ivermectin and diethylcarbamazine for the treatment of bancroftian filariasis.

In a 'blind' trial on 50 male asymptomatic microfilaraemic subjects with Wuchereria bancrofti infection, the safety, tolerability and filaricidal efficacy of a single dose of albendazole (alb) 600 mg alone or in combination with ivermectin (iver) 400 micrograms/kg or diethylcarbamazine citrate (DEC) 6 mg/kg was compared with a single dose of the combination DEC 6 mg/kg and iver 400 micrograms/kg over a period of 15 months after treatment. All but one subject, with 67 microfilariae (mf)/mL, had pre-treatment counts > 100 mf/mL. All 4 treatments significantly reduced mf counts, but alb/iver was the most effective regimen for clearing mf from night blood: 9 of 13 subjects (69%) were amicrofilaraemic by membrane filtration 15 months after treatment compared to one of 12 (8%), 3 of 11 (27%), and 3 of 10 (30%) in the groups treated with alb, alb/DEC, and DEC/iver, respectively. Filarial antigen tests suggested that all 4 treatments had significant activity against adult W. bancrofti; alb/DEC had the greatest activity according to this test, with antigen levels decreasing by 77% 15 months after therapy. All 4 regimens were well tolerated and clinically safe, although mild, self-limited systemic reactions were observed in all treatment groups. These results suggest that alb/iver is a safe and effective single dose regimen for suppression of microfilaraemia in bancroftian filariasis that could be considered for control programmes. Additional benefits of this combination are its potent, broad spectrum activity against intestinal helminths and potential relative safety in areas of Africa where DEC cannot be used for filariasis control because of co-endemicity with onchocerciasis or loiasis.

Ethics of resource allocation in developing countries: the case of Sri Lanka.

The issues of prioritization of health care services and allocation of resources have recently received increasing attention and discussion. Several reports have been published by governments in different countries and the issues are discussed in many recent books and papers. In this paper the focus is on the problems faced by a developing country when allocation of health care resources is considered. We consider these issues under three headings and exemplify the situation in a developing country by taking Sri Lanka as an example. Firstly the evidence to formulate an ethical basis for the existing health care system in Sri Lanka is discussed, in particular the problem of defining a minimum quality of health care for the population. Secondly, we consider the issues which arise when we want to formulate the ethical basis for health sector reform. In particular, we examine current World Bank proposals. We shall argue that there are a number of important conceptual and ethical issues that have not been properly addressed in the various policy documents. Finally, we introduce our own alternative ethical framework for policy reform.

Effect of Momordica charantia on the glucose tolerance in maturity onset diabetes.

Investigations were carried out to evaluate the effect of Momordica charantia on the glucose tolerance of maturity onset diabetic patients. The fruit juice of M. charantia was found to significantly improve the glucose tolerance of 73% of the patients investigated while the other 27% failed to respond.

Effect of Momordica charantia on key hepatic enzymes.

The effect of Momordica charantia on certain key hepatic enzymes was investigated using male Sprague-Dawley rats as the animal model. Fruit juice and seed extract of Momordica charantia were administered orally at a daily dose of 1 ml/100 g body weight for 30 days under light ether anaesthesia while the control group received equivalent amounts of distilled water under identical conditions (n = 10 in each case). Serum gamma-glutamyl transferase (P < 0.001) and alkaline phosphatase (P < 0.01-0.001) concentrations were found to be significantly elevated following oral administration of both the fruit juice and the seed extract. Consistent significant histopathological changes in the liver were not observed in either treatment group although the prevalence of dilatation and/or congestion of the central vein sinusoidal system appeared to be twice as high following fruit juice treatment than in the other 2 groups. Thus, Momordica charantia may either contain hepatotoxins capable of causing cellular damage at the molecular level without causing significant histopathological changes or the plant may have an enzyme inducing effect.

Do nizatidine and cimetidine interact with ibuprofen?

The potential for interaction between ibuprofen and two histamine H2-receptor blocking drugs--nizatidine and cimetidine--was investigated in six healthy male volunteers aged 20 to 25 years. Each subject received placebo, nizatidine 300 mg and cimetidine 800 mg orally at 9.00 p.m. daily for six doses in three randomised treatment periods separated by eight days. On the third day of each treatment period ibuprofen 400 mg was administered at the same time and venous blood samples were taken at intervals throughout the night and subsequently up to 84 h after administration. There was no difference in the area under the plasma concentration-time curve, rate of absorption or half-life of elimination of ibuprofen between the three treatments. The elimination half-life of ibuprofen on placebo was 2.04 h. The elimination half-life of nizatidine on ibuprofen was 1.72 h and that of cimetidine was 3.54 h. The latter is higher than previously reported in normal subjects. It is concluded that neither H2-blocker affects the kinetics of ibuprofen in man.

A case of insulinoma with peripheral neuropathy.

A 25-year-old woman with chronic neuropsychiatric symptoms, peripheral neuropathy and hypoglycaemia was found to have an islet cell adenoma in the pancreas. Her neuropsychiatric symptoms disappeared following its removal and she partially recovered from her peripheral neuropathy.

Is biliary excretion of paracetamol significant in man?

The extent of biliary excretion of paracetamol and its principal metabolites was studied in 10 healthy adults. Duodenal intubation was performed approximately 12 h after an oral dose of 1 g paracetamol. Duodenal fluid was aspirated following intravenous cholecystokinin, and urine was collected for 12 h after dosing. The mean concentration of the cysteine and glucuronide conjugates in the bile was 253.7 +/- 39.0 micrograms ml-1 (s.e. mean) and 69.3 +/- 15.3 micrograms ml-1, respectively. The mean recoveries of the cysteine and glucuronide conjugates in the bile were 6.0 +/- 1.5 mg and 1.2 +/- 0.41 mg, respectively. The bile is an important route of elimination for the cysteine conjugate and accounts for 19.4 +/- 4.4% of the total excretion of the metabolite. The fate of the biliary excreted conjugates is not known, and needs further investigation.

Lipid profiles, anthropometry and dietary habits of adolescent school boys in Sri Lanka.

Serum lipid profiles, anthropometric parameters, dietary habits and smoking practice were determined in 637 adolescent school boys in the 10th to 13th year of school (mean age 16.7 ± 1.3 years), to determine the prevalence of risk factors for cardiovascular disease in later life. They all attended schools in Colombo, the capital city (n=416), and two other cities, Negombo and Kurunegala. Seven percent of the subjects had body mass index (BMI) values above a reference range (for age 14-16, > 23.5 kg/m2; older than 16 years > 24.5 kg/m2). The mean serum total cholesterol concentration was within the reference range (158.9± 27.2 mg/dL: 4.11± 0.70 mmol/L), but 16.5% had values >185 mg/dL. The percentages of subjects with high LDL (low density lipoprotein)cholesterol (>110 mg/dL) and apolipoprotein B (>85 mg/dL) concentrations were 21.9 % and 23.0% respectively, while low HDL (high density lipoprotein) cholesterol (<35 mg/dL) levels were noted in 27.3% of subjects. A significant (p<0.001) positive association was noted between serum total cholesterol concentration and BMI. There was no significant difference in the mean BMI or total cholesterol levels of subjects from the three areas in the age group 15-16.9 years. However, in the age group 17-18.9 years, subjects in the Kurunegala area had a lower prevalence of risk factors ie. significantly lower BMI and serum total cholesterol and apolipoprotein B concentrations than those in other areas. Overall, smoking prevalence was 4.5%, and higher in Colombo than in Negombo and Kurunegala. Further, the mean intake of cholesterol was significantly lower and the fibre intake was higher among subjects in Kurunegala, than those in other areas. Thirty two percent of subjects had a family history of coronary artery disease, hypertension or diabetes and these subjects had significantly higher BMI values than those who did not have a family history of the above diseases, but their lipid patterns were similar. Thus high BMI was a major factor leading to hypercholesterolaemi.

Medullary sponge kidney presenting with hypokalaemic paralysis.

Medullary sponge kidney associated with a defect in urine acidification is rare and usually of no clinical significance. We report a case presenting as hypokalaemic paralysis due to associated congenital distal renal tubular acidosis.