72 Chinese patients who had been positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) for more than six months with stable serum hepatitis B virus DNA were randomised to receive recombinant alpha 2-interferon at doses of 2.5, 5, or 10 X 10(6) U/m2 intramuscularly thrice weekly for 12-24 weeks, or no treatment. 6 (11%) of 54 treated and 1 (6%) of 18 control patients became HBeAg-negative at the end of therapy or after 24 weeks of follow-up. 9 (17%) of treated but none of the control patients became HBeAg-negative between completion of therapy and 12 months. Reactivation of HBV replication subsequently occurred in 7 (13%) of the treated patients and in 1 control. Thus, sustained clearance of HBeAg was achieved only in 8 (15%) of treated patients at 12 months. Between 12 and 24 months 3 (9%) of treated patients and 1 control became negative for HBeAg. None of the patients became HBsAg-negative. alpha 2-interferon in the dose regimen used has little long-term effect in the suppression of HBV replication in Chinese patients with chronic HBV infection.

The effect of intravenous recombinant human tissue-type plasminogen activator (rt-PA) was compared with that of urokinase in 45 patients with angiographically documented pulmonary embolism (PE) in a randomised controlled trial. The two principal end-points were clot lysis at 2 h, as assessed by angiography, and pulmonary reperfusion at 24 h, as assessed by perfusion lung scanning. All patients received the full dose of rt-PA but urokinase infusions were terminated prematurely (on average after 18 h) in 9 patients because of allergy in 1 and uncontrollable bleeding in 8. By 2 h, 82% of rt-PA-treated patients showed clot lysis, compared with 48% of urokinase-treated patients (p = 0.008; 95% CI for the difference = 10-58%). Improvement in lung scan reperfusion at 24 h was identical in the two treatment groups. The reduction in fibrinogen did not differ significantly between the rt-PA and urokinase groups (45% vs 39% at 2 h and 34% vs 40% at 24 h). The results indicate that in the dose regimens employed, rt-PA acts more rapidly and is safer than urokinase in the treatment of acute PE.

To determine whether inhaled frusemide, a diuretic able to interfere with ion and water movement across airway epithelium, can modify exercise-induced bronchoconstriction, a three-part randomised, double-blind, placebo-controlled study was done in asthmatic patients who had a fall in FEV1 of at least 20% after running up and down a corridor. In the first part the effect of approximately 28 mg frusemide given as an aerosol was compared with that of a placebo. In the second part two doses of inhaled frusemide (approximately 14 mg and 28 mg) were examined. In the third part the effect of 20 mg oral frusemide was tested. Inhaled frusemide had a good and dose-related protective effect, whereas oral frusemide was ineffective. The mean (95% CI) maximum percentage falls in the FEV1 were: 11.5 (14.3-8.7) with frusemide and 33.8 (39.1-28.5) with placebo in the first part of the study; 13.6 (21.6-6.0) with 28 mg frusemide, 19.7 (28.2-11.3) with 14 mg frusemide, and 34.6 (39.4-30.0) with placebo in the second part of the study; and 15.2 (19.9-10.5) with inhaled frusemide, 38.2 (47.1-29.3) with oral frusemide, and 35.3 (45.9-24.7) with placebo in the last part of the study. The findings lend support to the hyperosmolarity hypothesis of exercise-induced asthma and may have therapeutic implications.

Two clinical trials of the phenanthrene methanol compound halofantrine in the treatment of Plasmodium falciparum were conducted in Malawi, in areas where the parasite was known to be chloroquine resistant. In the first trial all 46 patients had symptoms of malaria and parasite densities ranging from 2500/microliter to 212,000/microliter. They were given a single dose of halofantrine hydrochloride, 16 mg/kg body weight. The recrudescence rate on day 14 of follow up was unacceptably high (38%). In the second trial the dose given was 8 mg/kg 6 hourly for three doses. Of the 49 children followed up for 14 days, 47 became aparasitaemic--ie, the cure rate was 96%. In both trials the drug was very well tolerated. Halofantrine hydrochloride seems to be effective against P falciparum chloroquine sensitive and resistant strains in Africa.

Halofantrine hydrochloride given to 46 Kenyan children with falciparum malaria at 10 mg/kg for two doses, and to 60 other children at 8 mg/kg for three doses, resulted in rapid parasite clearance, mean parasite clearance times being 45.4 h and 54.8 h, respectively. In-vitro chemosensitivity tests showed that most infections were due to chloroquine-resistant parasites, and that parasite maturation was inhibited by considerably lower concentrations of halofantrine than of chloroquine.

Thromboxane and prostacyclin formation were monitored in twenty patients with acute myocardial infarction. Ten received 500 mg acetylsalicylic acid (ASA) orally starting 12 h after admission and then intermittently every third day for one month; the other ten did not receive ASA or any other drug known to interfere with the synthesis of prostanoids. In the ASA group thromboxane formation, initially raised, fell rapidly and remained low. In the control group thromboxane formation decreased very slowly and was not normal by the end of the study period. Prostacyclin formation seemed identical in the two groups. Thus intermittent ASA, in this dosage, efficiently inhibited the enhanced thromboxane formation in acute myocardial infarction without interfering with prostacyclin formation.

210 psychiatric outpatients with generalised anxiety disorder (71), or panic disorder (74), or dysthymic disorder (65) diagnosed by an interview schedule for DSM-III were allocated by constrained randomisation to one of five treatments: diazepam (28), dothiepin (28), placebo (28), cognitive and behaviour therapy (84), and a self-help treatment programme (42). All treatments were given for 6 weeks and then withdrawn by 10 weeks. Ratings of psychopathology were made by psychiatric assessors blind to both treatment and diagnosis before treatment and at 2, 4, 6, and 10 weeks after randomisation. 18 patients had insufficient data for analysis because of early drop-out. There were no important differences in treatment response between the diagnostic groups, but diazepam was less effective than dothiepin, cognitive and behaviour therapy, or self-help, these three treatments being of similar efficacy. Significantly more patients in the placebo group took additional psychotropic drugs in the 10 week period, and those allocated to dothiepin and cognitive and behaviour therapy took the least.

The use of feverfew (Tanacetum parthenium) for migraine prophylaxis was assessed in a randomised, double-blind, placebo-controlled crossover study. After a one-month single-blind placebo run-in, 72 volunteers were randomly allocated to receive either one capsule of dried feverfew leaves a day or matching placebo for four months and then transferred to the other treatment limb for a further four months. Frequency and severity of attacks were determined from diary cards which were issued every two months; efficacy of each treatment was also assessed by visual analogue scores. 60 patients completed the study and full information was available in 59. Treatment with feverfew was associated with a reduction in the mean number and severity of attacks in each two-month period, and in the degree of vomiting; duration of individual attacks was unaltered. Visual analogue scores also indicated a significant improvement with feverfew. There were no serious side-effects.

354 patients with multiple sclerosis were randomised to receive either azathioprine 2.5 mg/kg daily or placebo in a double-masked trial. During follow-up of at least 3 years only small differences emerged between the groups. After 3 years the mean deterioration in Kurtzke disability score was 0.62 in the azathioprine group and 0.80 in the placebo group, a difference of 0.18 (95% confidence intervals [CI] -0.15 to +0.52) and in the ambulation index it was 0.84 and 1.25, respectively, difference 0.41 (95% CI 0.03 to 0.80). After 3 years there had been slightly fewer relapses in the azathioprine group (average 2.2) than in the placebo group (average 2.5) but the difference of 0.3 (95% CI -0.2 to +0.9) was not significant. Although the results favour a small beneficial effect from azathioprine the benefit is so small that the use of azathioprine cannot be generally recommended for most patients with multiple sclerosis. Analysis of subgroups (by sex, age, severity, rate of progression, HLA status, relapsing or progressive course) has not revealed any that have shown clear clinical benefit.

The Egyptian National Control of Diarrheal Diseases Project (NCDDP) started in 1983. A field trial done in Dakahlia Governorate in 1980 to promote oral rehydration therapy showed that the mortality rate for the under-fives during the diarrhoea season was 18.1/1000 in control villages and 10.5/1000 in "outreach" villages (p less than 0.001). In 1986 mortality rates had become similar in the two areas and lower than in 1980 (6.5/1000 and 6.0/1000, respectively), even though there were no significant changes in diarrhoea incidence. Virtually all the reduction in mortality was due to a decline in diarrhoea-associated deaths. The principal differences between 1986 and 1980 were better case-management by mothers and doctors, in both outreach and control villages, and far greater television ownership. Village civil registers showed only slight changes in under-five mortality from all causes after 1980, but an accelerating decline from 1983. Governorate-wide civil registration data showed slowly falling infant death rates from 1970 onward, accelerating after 1982, with most of the decline corresponding to the seasonal pattern of diarrhoea-associated mortality throughout the year. Thus NCDDP promotion of better treatment seems to have been responsible for the decline in mortality.

21 patients with severe persistent cyclical mastopathy of at least 5 years' duration were randomised to a control group who received general dietary advice or to an intervention group who were taught how to reduce the fat content of their diet to 15% of calories while increasing complex carbohydrate consumption to maintain caloric intake. Both groups were followed for 6 months with food records and measurement of plasma hormone and lipid levels. Severity of symptoms was recorded with daily diaries and patients were assessed at the beginning and end of the study by a physician who was unaware of their dietary regimen. After 6 months there was a significant reduction in the intervention group in the severity of premenstrual breast tenderness and swelling. Physical examination showed reduced breast swelling, tenderness, and nodularity in 6 of 10 patients in the intervention group and 2 of 9 patients in the control group.

Functional psychosis is conventionally subdivided into schizophrenia and manic depressive psychosis. Response to treatment is assumed to be a validating criterion for these diagnoses. The efficacy of pimozide (a dopamine antagonist neuroleptic), lithium, and a combination of the two was compared with that of placebo in a 4 week trial in 120 functionally psychotic patients each of whom was assessed for psychotic symptoms, manic symptoms, and depressive symptoms. The sample was subdivided into patients with predominantly elevated mood, predominantly depressed mood, and no consistent mood change. Pimozide reduced psychotic symptoms in all groups of patients. The only significant effect of lithium was to reduce elevated mood. Thus dopamine blockade seems relevant to the resolution of psychotic symptoms in all types of "functional" psychosis but the mode of action of lithium in psychotic patients concerns only mood. Application of standardised classifications of functional psychosis to these data did not change this conclusion.

48 patients over 6 years of age with strictly defined cerebral malaria were randomised to receive either a single intramuscular injection of phenobarbitone (3.5 mg/kg) or placebo in a double-blind, placebo-controlled study. Phenobarbitone significantly reduced the incidence of subsequent convulsions from 54% to 12.5%, without adverse effects. A single intramuscular injection of phenobarbitone is a simple, cheap, and effective method for prevention of convulsions in cerebral malaria.