DL-dihydroxyphenylserine was given by mouth in a single-blind, placebo-controlled trial to two patients with orthostatic hypotension due to dopamine-beta-hydroxylase deficiency, in the hope of providing noradrenaline by endogenous decarboxylation. Dose-dependent increases in blood pressure were obtained over the range 150-600 mg. After 600 mg mean arterial pressure rose 33 and 19 mm Hg and these rises were tightly correlated with an increase in plasma noradrenaline (r = 0.995, p less than 0.001 and r = 0.88, p less than 0.05). Urinary noradrenaline increased from undetectable levels to 338 and 511 micrograms/24 h. Standing time (a correlate of functional capacity) also increased significantly in both patients. No side-effects were noted.

The protective efficacy against typhoid fever of a single intramuscular injection of 25 micrograms of the Vi capsular polysaccharide (CPS) was assessed in a randomised double-blind controlled trial. Vaccination of 11,384 children was followed by 21 months' surveillance. 47 blood-culture-proven cases of typhoid occurred in children who received meningococcal A + C CPS vaccine and 19 cases in those vaccinated with Vi CPS. Protective efficacy was 60% calculated from the day of vaccination and 64% from 6 weeks after vaccination. Surveillance also included 11,691 unvaccinated children; 173 cases occurred in this group. Protective efficacy in relation to the unvaccinated group was 77.4% and 81.0% after 21 months, calculated immediately and 6 weeks after vaccination, respectively. Vaccination was associated with minimum local side-effects, and an increase in anti-Vi antibodies occurred, as measured by radioimmunoassay and enzyme-linked immunosorbent assay. Antibody levels remained significantly raised at 6 and 12 months post vaccination. Vi CPS is thus a safe and effective means of typhoid vaccination.

The effect of inhibition of angiotensin-converting enzyme (ACE) on standard cough challenge was investigated in a double-blind, randomised study in sixteen normal volunteers. Captopril (25 mg) or matched placebo was given by mouth 2 h before inhalation of nebulised distilled water, citric acid, and incremental doses of capsaicin (0.5-20 mumol/l). Distilled water and citric acid challenge were not significantly changed by captopril pretreatment. However, captopril significantly shifted the dose-response curve to capsaicin inhalation. The geometric mean dose of capsaicin causing 20 coughs/min was 1.3 mumol/l for captopril and 2.8 mumol/l for placebo pretreatment (p = 0.04). Cough is a recognised side-effect of ACE inhibitors; the observation that cough challenge is changed by these drugs in normal subjects implies a role for ACE in the cough reflex, possibly by metabolism of substrates other than angiotensin I.

In 39 patients with endoscopically healed duodenal ulcers repeat endoscopy and two antral biopsies after 1 year showed a relapse rate of 59%. Only post-treatment Campylobacter pylori status was a significant predictor of endoscopic relapse. 79% of patients who remained culture positive had a relapse, compared with 27% of culture-negative patients. Relapse was more likely (66%) in patients with a recurrence of C pylori after apparent eradication of the organism than in those who remained negative for C pylori (10%). No patient who remained negative for C pylori had histological gastritis, whereas all with recurrence of C pylori showed histological gastritis. These findings suggest an important role for C pylori in duodenal ulcer relapse in the year after treatment.

131 patients with osteolytic metastases from breast cancer were randomised to receive long-term oral treatment with aminohydroxy-propylidene-bisphosphonate (APD), 300 mg daily (n = 70), or to act as controls (n = 61) in a multicentre trial. Specific antitumour therapy was at the discretion of the clinician and variable. An interim analysis was made after a median follow-up of 13 months in the APD group and 14 months in the controls. There was a significant reduction in pathological fractures and severe bone pain in the APD group, and hypercalcaemia was prevented. Consequently the necessity for radiotherapy for skeletal complications was more than halved; the number of systemic therapy changes was also reduced. Gastrointestinal side-effects of APD led to a drop-out of 8% of patients. Oral supportive APD therapy is simple and convenient, and significantly reduced skeletal morbidity in advanced breast cancer.

24 Chinese children aged 1.5-5 years and positive for hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), hepatitis B virus DNA polymerase (HBV DNAp), and HBV DNA on at least three occasions in the 6 months before the trial were randomised to receive either vitamin B complex or intramuscular recombinant alpha 2-interferon (r-IFN) ('Roferon') 10 X 10(6) IU/m2 thrice weekly for 12 weeks. In all 12 subjects receiving r-IFN, HBV DNAp and HBV DNA levels fell during the course of r-IFN injections. Within 4 weeks of cessation of r-IFN injection, the HBV DNAp and HBV DNA returned to pre-trial levels except in 2 subjects, in whom loss of HBV DNAp and HBV DNA was sustained for up to 18 months from onset of the trial. 1 child lost HBeAg at 18 months. 2 of the 12 children in the placebo group also had a sustained loss of HBV DNAp and HBV DNA during the 18 months, with 1 child losing HBeAg at 18 months. All 24 subjects remained positive for HBsAg. r-IFN produced very slight side-effects except for pyrexia and the "flu" syndrome, both of which showed rapid tachyphylaxis. In the dose given r-IFN was safe but had no long-term beneficial effects on HBsAg carriage in Chinese children.

Long-term follow-up of 98.3% of the 11,712 patients recruited in the GISSI trial of intravenous streptokinase (SK) in acute myocardial infarction has shown persistence of the beneficial effect observed during the hospital phase. At 12 months a significant difference in mortality was seen in the whole population (17.2% in SK group versus 19.0% in controls, p = 0.008, relative risk 0.90), and in the 0-3 and 3-6 h groups (relative risks 0.89 and 0.87, respectively). For most of the other strata according to which the trial population has been analysed, the magnitude and the direction of the effects were also substantially the same as those recorded in the hospital phase. SK thrombolysis should be considered among the recommended treatments of the acute phase, at least up to 6 h from onset of myocardial infarction.

Captopril alone as therapy for mild heart failure was compared with a combination of frusemide and amiloride in a double-blind randomised crossover trial in 14 patients who had previously been treated with diuretics. Although 10 patients remained stable on captopril alone, 4 patients deteriorated, with the development of pulmonary oedema of breathlessness. All 4 patients had had pulmonary oedema previously, unlike the patients who remained stable. Angiotensin converting enzyme inhibition alone is not sufficient treatment for patients with mild heart failure and a history of overt pulmonary oedema.