To investigate the value of maintenance chemotherapy after early consolidation treatment, an attempt was made to induce remission in 162 previously untreated patients, age-range 7-65 years (median 43). The 74 patients who were still in remission after early consolidation treatment (given for 3-5 months) were assigned to either maintenance chemotherapy every 8 weeks for 2 years or to observation only. After a median observation period of 44 months there was no difference between the groups in duration of remission or survival. Surprisingly, patients above 40 survived longer after early consolidation (median 4 years) than did patients aged 40 and below (median 1.6 years, p = 0.0002).

108 children with standard-risk acute lymphocytic leukaemia (ALL) were randomised to a post-induction treatment protocol including 15 doses of intermediate-dose methotrexate (1000 mg/m2) in addition to conventional oral therapy of mercaptopurine and low-dose methotrexate. After median follow-up of 26 months, 22 patients have had relapses. Among the 108 patients, rates of methotrexate systemic clearance ranged from 44.7 to 132 ml/min/m2. When the group was divided into three subgroups according to the patients' rates of methotrexate clearance, statistical analysis of the Kaplan-Meier curves estimating the probability of complete remission showed significant differences (p = 0.016) among the subgroups, patients with faster clearance having higher probability of relapse. Multivariate Cox's regression analysis incorporating other potential prognostic variables identified three significant variables influencing the risk of relapse--methotrexate clearance and white-blood-cell count and haemoglobin level at diagnosis (p = 0.0015). This study has demonstrated the potential clinical importance of the rate of drug clearance in children with ALL.

Studies were conducted in Malindi, Kenya, to assess the response of Plasmodium falciparum to chloroquine and amodiaquine in vivo (by an extended 14-day test) and in vitro (with the Rieckmann micro test). In-vivo resistance was demonstrated in 19 of 69 (28%) infections treated with chloroquine, but in only 2 of 60 (3.3%) of those treated with amodiaquine (p less than 0.001). In-vitro resistance to chloroquine was demonstrated in 15 of 23 (65%) tests. In contrast, 22 of the same 23 isolates were sensitive to amodiaquine in vitro. Effective concentrations by probit analysis for 50% and 99% (EC50 and EC99) inhibition, respectively, were 180.7 and 4319.6 nmol/l for chloroquine and 12.2 and 147.0 nmol/l for amodiaquine. The results suggest that amodiaquine is effective for the treatment of chloroquine-resistant falciparum malaria in Kenya.

The efficacy of nortriptyline in the treatment of post-stroke depression was assessed by a double-blind study in thirty-four patients. Half of the patients had major depression. There was a significantly greater improvement in depression in patients treated with nortriptyline than in a similar group of placebo-treated patients. Depression was measured by the Hamilton depression scale, Zung depression scale, present state examination, and an overall depression scale. Successfully treated patients had serum nortriptyline levels in the therapeutic range. Post-stroke depressions are common, severe, and longstanding, and the demonstrated efficacy of nortriptyline provides an important addition to the treatments available for stroke patients.

Twenty-four patients with frequent drug-resistant seizures took part in a randomised double-blind placebo-controlled crossover trial of the GABA-transaminase inhibitor, gamma-vinyl GABA. It was added to their usual drug treatment in a dose of 3 g daily. The total number of seizures during the 9-week active treatment period was less than that in the placebo period (p less than 0.001, two-way analysis of variance). The greatest effect was on complex partial seizures. Mean weekly seizure frequency (complex partial and tonic-clonic) was 6.2 fits/week for the placebo period and 3.5 fits/week for the gamma-vinyl GABA period. Adverse effects, particularly drowsiness and mood changes, occurred more often during administration of active drug. Serum concentrations of phenytoin were lower during gamma-vinyl GABA treatment than during placebo (p less than 0.05), but the concentrations of other anticonvulsants given concomitantly did not change. These results suggest that gamma-vinyl GABA is an effective antiepileptic compound.

Antibodies against two physicochemically purified haemagglutinins (HAs) of Bordetella pertussis (filamentous HA and leucocytosis-promoting-factor HA) protect laboratory animals from pertussis. A vaccine containing these two HAs was prepared and tested in trials involving about 5000 children. Culture supernatant of Bordetella pertussis, phase I, was treated with ammonium sulphate, and a crude extract of the HAs was extracted from the precipitate by the use of concentrated sodium chloride. This crude extract was fractionated by sucrose density gradient centrifugation to obtain an HA preparation practically free of endotoxin. The HA preparation was treated with formalin to destroy its ability to induce leucocytosis and to cause histamine sensitisation. Aluminium hydroxide was added to the preparation as an adjuvant. The component vaccine is not only potent as judged by the mouse test but is also less than one-tenth as toxic as whole-cell vaccine as judged by leucocytosis promotion, histamine sensitisation, and endotoxicity tests. Field trials showed that component vaccine was as effective as and produced less side-effects than did conventional whole-cell vaccine. The vaccine has been used for mass immunisation in Japan since the autumn of 1981.

The effect of alcohol on blood-pressure was studied in 16 men with hypertension who regularly drank up to 80 g of alcohol daily. Antihypertensive treatment was stopped 2 weeks before the men were admitted to hospital for a 7-day study. Blood pressure remained high in 8 patients who continued their regular alcohol consumption up to the fourth day after admission. In the next 4 days no alcohol was taken and diastolic and systolic blood pressures fell significantly. 8 other patients had no alcohol for the first 3 days after admission, but they resumed alcohol consumption from day 4 to 7. In these patients, blood pressure fell slightly after admission. Reintroduction of alcohol produced statistically significant increases in both systolic and diastolic pressures. This study demonstrated a pressor effect of alcohol in patients with hypertension and confirms the link between alcohol and blood-pressure reported in population studies. The mechanism of alcohol-induced hypertension is uncertain and is more likely to be due to an effect of alcohol rather than to the pressor response produced by alcohol withdrawal.