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.

In a blind crossover trial for 4 days, after at least 7 days on conventional treatment, 14 patients with postoperative small-bowel fistula were randomised to 2 days on a somatostatin analogue, octreotide (SMS 201-995), followed by 2 days on placebo (group 1) or vice versa (group 2), after which all patients were treated with octreotide until the fistula closed or reoperation was deemed necessary. In group 2 mean fistula output was reduced from 698 ml per 24 h pretreatment to 246 mg per 24 h after 2 days on octreotide; output increased from 228 ml per 24 h to 497 ml per 24 h when treatment with octreotide was interrupted by placebo. In 11 patients fistulae closed spontaneously in an average of 4.5 days after continous treatment with octreotide.

In a six month placebo-controlled cross-over trial twenty patients with hypertension and peripheral arterial disease were randomised to captopril 25 mg twice daily, atenolol 100 mg once daily, labetalol 200 mg twice daily, or pindolol 10 mg twice daily for one month. Although all treatments were equally effective at lowering blood pressure, pain-free and maximum walking distances on a treadmill were decreased by atenolol, labetalol, and pindolol, but not by captopril. Post-exercise calf blood flow availability was impaired by atenolol, labetalol, and pindolol, but not by captopril. Despite ancillary characteristics of cardioselectivity, intrinsic sympathomimetic activity, or combination with alpha-blockade, beta-blockers seem to impair the lower limb circulation in such patients, whereas captopril seems to preserve it, possibly by maintaining the collateral blood supply.