Because of the high prevalence of hepatitis B virus (HBV) infection in The Gambia, HBV vaccination has been incorporated into the national expanded programme on immunisation. We have assessed the efficacy of the vaccine against HBV infection and chronic carriage by examining 720 3-4-year-old children who had received the vaccine in infancy and 816 who had not received it. The vaccine was 84% (95% CI 78-89%) effective against infection and 94% (84-98%) effective against chronic carriage. Vaccinated infants of mothers positive for hepatitis B surface and e antigens were at greater risk of breakthrough infection and chronic carriage than infants of uninfected mothers. The high vaccine efficacy against the HBV carrier state, the main risk factor for the development of chronic liver disease and liver cancer, offers hope that the prevalence of these diseases may be reduced in the future.

Brain natriuretic peptide (BNP) is a cardiac ventricular hormone that may be a sensitive and specific marker of changes in ventricular function. In a prospective, randomised open trial with 16 patients followed for 6 months after first Q wave anterior myocardial infarction we set out to determine: whether BNP concentrations are raised acutely, the effect on circulating BNP of angiotensin-converting enzyme (ACE) inhibition, how BNP and atrial natriuretic peptide (ANP) concentrations compared as correlates of left-ventricular ejection fraction, and whether plasma BNP concentrations could distinguish patients with low (< 40%) and relatively preserved (> 40%) ejection fractions. Plasma concentrations of BNP measured on days 2, 7, 8, 42, and 180 postinfarction were significantly raised in patients compared with normal controls and to a proportionately greater degree than ANP concentrations. Treatment with placebo (n = 8) or oral captopril (n = 8) from day 8 resulted in significantly lower BNP concentrations at days 42 (p = 0.05) and 180 (p < 0.05) in the captopril-treated group. Compared with ANP, BNP concentrations were much more strongly correlated with radionuclide-measured left-ventricular ejection fraction at days 2, 42, and 180. All 8 patients with baseline (day 2) ejection fractions of 40% or above had plasma BNP concentrations less than 10 pmol/L, whereas the 8 patients with ejection fractions less than 40% had BNP concentrations greater than 10 pmol/L. Our findings suggest that measurements of circulating BNP may identify those patients with significant left-ventricular dysfunction who have been highlighted by the Survival and Ventricular Enlargement study as likely to benefit from long-term ACE inhibition after myocardial infarction.

In a prospective electrocardiographic study of Karen patients with acute uncomplicated falciparum malaria, mefloquine (25 mg/kg) had no cardiac effects (n = 53), but halofantrine (72 mg/kg) induced consistent dose-related lengthening of the PR and QT intervals in all 61 patients treated. The likelihood of significant QTc prolongation (by more than 25% or a QTc of 0.55 s1/2 or more) was greater after halofantrine as retreatment following mefloquine failure than as primary treatment (7/10 vs 18/51; relative risk 2.0 [95% Cl 1.1-3.4], p = 0.04). More than 60% of the effect occurred with three doses of halofantrine (24 mg/kg). The arrhythmogenic potential of halofantrine should now be investigated.

High-dose chemotherapy and radiotherapy with autologous bone-marrow transplantation (ABMT) are increasingly used for the treatment of relapsed and resistant Hodgkin's disease, although there has been no randomised trial of this treatment. The British National Lymphoma Investigation therefore undertook a randomised comparison of high-dose chemotherapy (BEAM = carmustine, etoposide, cytarabine, and melphalan) plus ABMT with the same drugs at lower doses not requiring bone-marrow rescue (mini-BEAM) in patients with active Hodgkin's disease, for whom conventional therapy had failed. 20 patients were assigned treatment with BEAM plus ABMT and 20 mini-BEAM. All have been followed up for at least 12 months (median 34 months). 5 BEAM recipients have died (2 from causes related to ABMT and 3 from disease progression) compared with 9 mini-BEAM recipients (all disease progression). This difference was not significant (p = 0.318). However, both event-free survival and progression-free survival showed significant differences in favour of BEAM plus ABMT (p = 0.025 and p = 0.005, respectively). Recruitment to the trial became increasingly difficult because patients refused randomisation and requested ABMT. It was therefore closed early (40 patients rather than 66 intended). Nevertheless, we found a dose-response effect in these patients with relapsed and resistant Hodgkin's disease. High doses facilitated by ABMT can lead to better disease-free survival.

The continuing spread of multidrug resistance in Plasmodium falciparum malaria makes the search for alternative treatments ever more urgent. We have investigated the relative efficacy of halofantrine and mefloquine in two paired randomised trials on the Thai-Burmese border, a multidrug-resistant area. In the first trial, 198 patients with acute uncomplicated falciparum malaria were randomly assigned either the standard halofantrine regimen (24 mg/kg) or mefloquine (25 mg/kg). The cumulative failure rates by day 28 were 35% with halofantrine and 10% with mefloquine (p = 0.0002). In the second study of 437 patients, a higher dose of halofantrine (8 mg/kg every 8 h for 3 days = 72 mg/kg) was both more effective and better tolerated than mefloquine 25 mg/kg; the failure rates were 3% and 8% (p = 0.03), respectively, or 1% vs 6% after adjustment for possible reinfections (p = 0.009). The rate of failure was higher after retreatment than after primary treatment in all study groups. Halofantrine 72 mg/kg was especially effective in the retreatment of these recrudescent infections; the failure rate was 44% with mefloquine and 15% with high-dose halofantrine (relative risk 3.0 [95% CI 1.2-7.3], p = 0.008). Thus, high-dose halofantrine is better tolerated and more effective than mefloquine for the treatment of uncomplicated falciparum malaria in this area. However, evidence of possible cardiotoxicity will need to be investigated fully before a role can be established for halofantrine in the treatment of multidrug-resistant malaria.

Sulphidopeptide leukotrienes are potent bronchoconstrictors and increase bronchial hyperreactivity, one of the hallmarks of asthma. We have demonstrated that leukotriene LTE4, the most stable of the sulphidopeptide leukotrienes, elicited an increase in the numbers of eosinophils and neutrophils in the lamina propria of the airway mucosa 4 h after inhalation in 4 asthmatic subjects. The numbers of eosinophils were, on average, 10-fold greater than those of neutrophils. There was no significant change in numbers of lymphocytes, plasma cells, mast cells, or macrophages. Since LTE4 recruits granulocytes, the potential of antisulphidopeptide leukotriene drugs as anti-inflammatory and "steroid-sparing" agents should be tested.

Despite encouraging results from screening trials the efficacy of mammography in reducing mortality remains somewhat controversial. Five studies have been done in Sweden. This overview, based on 282,777 women followed for 5-13 years in randomised trials in Malmö, Kopparberg, Ostergötland, Stockholm, and Gothenburg, reveals a 24% (95% confidence interval 13-34%) significant reduction of breast cancer mortality among those invited to mammography screening compared with those not invited. To avoid the potential risk of differential misclassification causes of death were assessed by an independent end-point committee after a blinded review of all fatal breast cancer cases. The mortality reduction was similar, irrespective of the end-point used for evaluation ("breast cancer as underlying cause of death" or "breast cancer present at death"). There was a consistent risk reduction associated with screening in all studies, although the point estimate of the relative risk for all ages varied non-significantly between 0.68 and 0.84. The cumulative breast cancer mortality by time since randomisation was estimated at 1.3 per 1000 within 6 years in the invited group compared with 1.6 in the control group. The corresponding figures after 9 years are 2.6 and 3.3 and after 12 years 3.9 and 5.1. The largest reduction of breast cancer mortality (29%) was observed among women aged 50-69 at randomisation. Among women 40-49 there was a non-significant 13% reduction. In this younger age group cumulative breast cancer mortality was similar in the invited and control group during the first 8 years of follow-up. After 8 years there was a difference in favour of the invited women. There was no evidence of any detrimental effect of screening in terms of breast cancer mortality in any age group. Among women aged 70-74 years screening seems to have had only a marginal impact.

Prevention of type I diabetes is now a practical goal thanks to the ability to define confidently a high-risk group and the success of preventive strategies in animal models. We describe here a pilot trial of low-dose insulin to prevent diabetes in relatives of patients with type I diabetes.

The spread of chloroquine-resistant Plasmodium falciparum malaria has led to increased use of mefloquine prophylaxis by US Peace Corps volunteers in sub-Saharan Africa. We compared long-term mefloquine with other drug regimens for effectiveness and tolerance. The incidence of Plasmodium falciparum infections and of adverse reactions was compared in Peace Corps volunteers who took chloroquine weekly, mefloquine weekly, mefloquine every other week, or weekly chloroquine plus daily proguanil. Weekly mefloquine was 94% more effective than chloroquine (95% CI 86% to 97%), 86% more effective than chloroquine plus proguanil (95% CI 67% to 94%), and 82% more effective than prophylaxis with mefloquine when taken every other week (95% CI 68% to 90%). No serious adverse reactions were observed. Mild adverse events were equally frequent in mefloquine users and chloroquine users, and the frequency of these events declined with increasing duration of prophylaxis. Mefloquine is an effective and well-tolerated drug for prophylaxis of malaria by short-term and long-term travellers.