The effects of synvinolin (MK-733), a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, were investigated in 43 patients with heterozygous familial hypercholesterolaemia in a double-blind, placebo-controlled, dose-finding study. Synvinolin was given in doses ranging from 2.5 mg to 80 mg per day for 4 weeks. 8 patients received placebo. Low-density-lipoprotein cholesterol fell on average by 18% on 2.5 mg/day and 42% on 80 mg/day. The drug was as effective whether it was given once or twice daily. Serum high-density-lipoprotein cholesterol tended to increase and serum triglycerides to decrease on the higher doses. The drug was tolerated well. Except for a slight rise in alanine aminotransferase in 3 patients no objective side-effects were observed.

The hypothesis that homoeopathic potencies are placebos was tested in a randomised, double-blind, placebo-controlled trial. The study model chosen compared the effects of a homoeopathic preparation of mixed grass pollens with placebo in 144 patients with active hayfever. The homoeopathically treated patients showed a significant reduction in patient and doctor assessed symptom scores. The significance of this response was increased when results were corrected for pollen count and the response was associated with a halving of the need for antihistamines. An initial aggravation of symptoms was noted more often in patients receiving the potency and was followed by an improvement in that group. No evidence emerged to support the idea that placebo action fully explains the clinical responses to homoeopathic drugs.

In three double-blind placebo-controlled trials of pneumococcal capsular polysaccharide vaccines against death from acute lower-respiratory-tract infections (ALRI), children were vaccinated at 6 months to 5 years of age. The efficacy of the vaccines against ALRI as the sole cause of death was estimated at 59% in children vaccinated when younger than 5 years (p = 0.008) and 50% in children vaccinated when younger than 2 years (p = 0.043). Mortality from all causes was 19% less in the vaccinated group.

151 problem drinkers (105 men and 46 women) were recruited from the general medical and psychiatric services of a district general hospital and were allocated randomly to a community-based day centre (ACCEPT) or standard hospital inpatient and outpatient services. 115 patients (79%) were followed up at 12 months. The group as a whole showed improvement in all outcome indices at the 3-month follow-up, and this was maintained at 6 and 12 months. Patients assigned to ACCEPT services claimed to have reduced their alcohol intake (55%) more than their hospital counterparts (37%), and this was confirmed by their informants. Patients referred from the psychiatric services reduced their alcohol intake more than those from general medical services. It is concluded that treatment at a community day centre is at least as cost effective as hospital treatment of alcohol abuse.

Ten patients with moderate heart failure who still had symptoms despite 40 mg frusemide daily were treated with increased doses of frusemide and the addition of captopril in randomised order. Four different methods were used to assess the patients' response to treatment. Both treatments improved symptom-limited exercise tolerance, higher-dose frusemide having a more favourable effect. Perceived exertion during submaximal exercise was reduced by similar amounts by both treatments. The time taken to walk 100 m at a self-selected slow speed was reduced by both treatments; again higher-dose frusemide had a more beneficial effect. The higher dose of frusemide also had a more favourable effect on visual analogue scores for dyspnoea, fatigue, and general well-being.

In a double-blind trial 90 mildly hypertensive subjects aged 16-29 years were randomly assigned to 1 g calcium per day or placebo. Calcium supplementation did not affect systolic blood pressure, but at six and twelve weeks diastolic blood pressure had fallen by 3.1 (p = 0.04) and 2.4 (p = 0.11) mm Hg, respectively, more in the calcium group than it had in the placebo group. Subjects with a baseline plasma parathyroid hormone (PTH) higher than the median showed a 6.1 mm Hg (p = 0.01) greater fall in diastolic blood pressure after six weeks and 5.4 mm Hg (p = 0.01) after twelve than in the placebo group. The fall in diastolic blood pressure was greater in the calcium group than in the placebo group in subjects with a lower than median serum total calcium and in those with a large bodyweight. Calcium supplementation may lower blood pressure in young people with mildly raised blood pressure, particularly in those with high plasma PTH and/or low serum total calcium.

Eight patients with postprandial hypotension and orthostatic hypotension were treated with the somatostatin analogue SMS-201-995. Low doses of this drug (0.2-0.4 microgram/kg) raised the blood pressure after breakfast in all six patients with postprandial hypotension. 60 min after breakfast the mean sitting blood pressure was 35 +/- 10 (SEM) mm Hg higher after administration of SMS-201-995 0.4 microgram/kg than after placebo (p less than 0.001). Larger doses (up to 1.6 micrograms/kg) raised upright blood pressure during the postprandial period in five of seven patients. Before therapy three patients were unable to stand after eating; after an injection of SMS-201-995 0.8 microgram/kg at the beginning of breakfast they were able to walk for 35-100 min. The duration of therapeutic effect of each injection was 3-6 h. Treatment was followed by abdominal cramps and nausea in two patients with gastroparesis diabeticorum. SMS-201-995 holds promise as a treatment for postprandial hypotension and orthostatic hypotension.

Results of the European Working Party on High Blood Pressure in the Elderly (EWPHE) trial have been analysed in relation to age, sex, blood pressure, and previous cardiovascular disease. Cardiovascular mortality and the cardiovascular study-terminating events were significantly and independently related to treatment, age, cardiovascular complications at randomisation, and systolic but not diastolic blood pressure. The benefits of treatment observed in the trial seemed to be independent of entry blood pressure and the presence or absence of cardiovascular complications at entry. There was some evidence that treatment effect decreases with advancing age. Little or no benefit from treatment could be demonstrated in patients over the age of 80 years, the great majority of whom were women.

The long-term effect of exercise on blood-pressure (BP) was assessed in 13 untreated patients with essential hypertension. After a 6-week run-in period the levels of activity studied were sedentary, 45 min bicycling at 60-70% of maximum work capacity (Wmax) three times per week (3/week), and 45 min bicycling seven times per week (7/week), each for 4 weeks. The order differed between subjects in accordance with a Latin square. Supine BP, 48 h after each phase, averaged 148/99 mm Hg in the run-in and 143/96 mm Hg in the sedentary phase; it fell below values in the sedentary phase by 11/9 mm Hg with 3/week exercise, and by 16/11 mm Hg with 7/week exercise (both p less than 0.01). With increasing activity total peripheral resistance fell and the cardiac index rose. Plasma noradrenaline concentration fell below values in the sedentary phase by 21% and 33% after 3/week and 7/week exercise. Bodyweight and 24 h sodium excretion remained constant. Moderate regular exercise lowers BP and seems to be an important non-pharmacological method of treating hypertension.

The relation between tumour oestrogen and progesterone receptor status, menstrual status, relapse-free survival, and overall survival was analysed in 411 patients with early breast cancer randomised to receive either postoperative adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF) or no additional treatment (control). Prolongation of time to recurrence and survival was seen predominantly in premenopausal patients; these effects were seen only with tumours positive for steroid receptors, particularly progesterone. Chemotherapy led to permanent amenorrhoea in 61% of premenopausal patients. The therapeutic effects of chemotherapy were seen only when CMF induced permanent amenorrhoea in premenopausal patients. These findings support the hypothesis that the effect of adjuvant chemotherapy in early breast cancer may be mediated by ovarian suppression.

50 patients with chronic mucopurulent rhinosinusitis were randomly allocated to treatment with nasal sprays of dexamethasone, tramazoline, and neomycin, dexamethasone and tramazoline with no antibiotic, or matched placebo (propellant alone) four times daily to both nostrils for 2 weeks. The patients were assessed in a double-blind manner for symptomatic response and improvement in nasal mucociliary clearance, nasal airway resistance, sinus radiographs, and intranasal bacteriology and appearance. Both active preparations (with antibiotic 14 of 20 patients responded; without antibiotic 12 of 20 patients responded) were more effective than the placebo (2 of 10 patients responded). There was no significant difference in response between the active preparations with and without antibiotic. Thus, in treatment of chronic mucopurulent rhinosinusitis, reduction of the inflammatory response and decongestion make topical antibiotic unnecessary, probably by allowing host clearance mechanisms to recover.

In a double-blind trial in 21 patients with spasmodic torticollis botulinum-A toxin produced both subjective and objective improvement, including significant pain relief in 14 of the 16 patients presenting with pain. Side-effects were more frequently reported during placebo administration and no significant systemic adverse reactions were noted.

Platelet activating factor (PAF), a phospholipid inflammatory mediator, was given as an aerosol to eight normal subjects. PAF caused a dose-dependent bronchoconstriction in all subjects. This did not correlate well with responsiveness to methacholine. Some subjects showed tachyphylaxis to PAF-induced bronchoconstriction. No subject had a late bronchoconstriction response. Transient facial flushing and an increase in heart rate (mean 7 beats/min) occurred but there was no consistent change in blood pressure. Lyso-PAF, the inactive precursor and major metabolite of PAF, had no effect on pulmonary or cardiovascular responses. Six of the subjects took part in a double-blind, randomised, placebo-controlled, crossover study in which bronchial responsiveness to methacholine was measured over the 3 days after administration of PAF or lyso-PAF. PAF had a greater effect in raising responsiveness (p less than 0.01). Its maximum effect occurred at 3 days and returned to baseline in 1 to 4 weeks. PAF may contribute to the pathogenesis of bronchial hyperresponsiveness, which is the most characteristic abnormality in asthma.

The protective efficacy of oral B subunit killed whole-cell (BS-WC) and killed whole-cell (WC) cholera vaccines was assessed in 63 498 Bangladeshi children aged 2-15 years and women aged over 15 years. Each received three doses of BS-WC, WC, or placebo in a randomised, double-blinded fashion. Surveillance for cases seeking medical care up to six months after the third dose revealed 26 cases of confirmed cholera in the placebo group, 4 cases in the BS-WC group (protective efficacy 85%; p less than 0.0001), and 11 cases in the WC group (protective efficacy 58%; p less than 0.01). For each vaccine protective efficacy was consistent in different age-groups (2-10 years versus greater than 10 years) and for different severities of cholera.