Nineteen unselected patients with mild to moderate essential hypertension, whose average supine blood pressure after two months' observation on no treatment was 156/98 mm Hg, were advised not to add salt to food and to avoid sodium-laden foods. After 2 weeks of sodium restriction patients were entered into an 8-week double-blind randomised crossover study of 'Slow Sodium' (Ciba) versus slow sodium placebo. The mean supine blood pressure was 7.1 mm Hg (6.1%) lower in the fourth week of placebo than that in the fourth week of slow sodium (p less than 0.001). Urinary sodium excretion in the fourth week of slow sodium was 162 +/- 9 mmol/24 h and that in the fourth week of placebo was 86 mmol +/- 9 mmol/24 h (p less than 0.001). There was no difference in potassium excretion. These results suggest that moderate sodium restriction achieved by not adding salt and avoiding sodium-laden foods should, if not already, become part of the management of essential hypertension.

Twelve asthmatic patients with nocturnal wheezing were given a single nocturnal oral dose of slow-release aminophylline or matched placebo in a double-blind crossover trial. A dose of slow-release aminophylline (mean 683 mg; 10.4 mg/kg) gave a therapeutic plasma-theophylline concentration 10 h later (mean 10.9 mg/l). This was not associated with any adverse effects. Mean peak expiratory flow on waking was significantly greater with aminophylline (332 +/- 31 l/min) than placebo (283 +/- 32 l/min), whereas evening values did not differ. There was a significant difference between morning and evening peak flow on placebo (mean 22%) but not on aminophylline (5%), indicating abolition of the morning fall in peak flow. This was not at the expense of response to beta-agonists, since the response to inhaled salbutamol was the same for both treatments. The use of extra metered doses of inhaled beta-agonist during the night was significantly less with aminophylline, and there was a subjective improvement in nocturnal symptoms in all patients. Slow-release aminophylline in adequate dosage appears to be the most effective treatment yet demonstrated for nocturnal asthma.

In a multicentre double-blind randomised study comparing the effects of sulphinpyrazone 400 mg twice daily with those of placebo in patients after myocardial infarction 727 patients (365 on sulphinpyrazone, 362 on placebo) were enrolled and followed up for 12-48 months (mean 19.2). Treatment began 15-25 days after infarction. There were 49 reinfarctions (9 fatal, 40 nonfatal)-34 occurred in the placebo group and 15 in the sulphinpyrazone group, a reduction of 56%. In addition, a significant reduction of thromboembolic events was noted. It is concluded that sulphinpyrazone is effective in the prevention of reinfarction in patients surviving a recent myocardial infarction.

In all subjects of the Australian therapeutic trial in mild hypertension, mean pressures for the two screening visits were within the range 95-109 mm Hg for diastolic blood-pressure phase V(DBP) and less than 200 mm Hg for systolic blood-pressure (SBP). In the 1943 control (placebo) subjects mean blood-pressures fell from 158/102 mm Hg at the first screening visit to 144/91 mm Hg 3 years later. At that time pressures remained within the mild hypertension range in 32%, ahd risen above it in 12%, and had fallen below in 48%. Trial end-points (ischaemic heart disease or cerebrovascular accident) occurred in 8%. The outcome was related to the level of initial pressure but not to other characteristics measured at entry. The mean initial pressures of 22 subjects who experienced a cerebrovascular event were higher than those of a matched group with no hypertensive complications, but the 88 subjects who experienced ischaemic-heart-disease events had initial pressures similar to those in a matched control group. The trial end-point rate was related to the average DBP of subjects throughout the trial in those with average DBP greater than or equal to 95 mm Hg, and at those levels subjects on active treatment had a higher incidence than subjects of the placebo group with the same DBP level. For those with average DBP below 95 mm Hg the incidence of trial end-points was not related to blood-pressure level or treatment. 16% of placebo subjects in this mild hypertensive population had a mean DBP of less than 95 mm Hg at the first three visits. If this were taken as an indication to withhold drug treatment, 3 years later one-quarter of them (4% of all subjects) would be found to be hypertensive or to have experienced a trial end-point, and thus inappropriately untreated, while the other 12% would have pressures below 95 mm Hg and have had no trial end-point.

Although most strains of Campylobacter jejuni are susceptible in vitro to erythromycin and the drug has been recommended for treatment of campylobacter enteritis, prospective controlled trials have not been done. Erythromycin (250 mg 6-hourly for adults and 40 mg/kg daily for children) has been compared with placebo in a double-blind trial of 5-day therapy for acute campylobacter enteritis. The mean number of days of illness at onset of therapy was 5.6 for the treatment group (n = 15) and 6.5 for the placebo group (n = 14). There were no differences in temperature, symptoms, and stool characteristics between the two groups. The mean duration of unformed stools after treatment was 4.1 days in the erythromycin group and 3.5 days in the placebo group. Fever, when present, abated within 48 h in all but two patients in each group. Follow-up faecal cultures 2 days after completion of therapy, however, were negative in all 15 of the erythromycin-treated patients compared with 6 out of 14 controls. Thus erythromycin promptly eradicates C. jejuni from the faeces but does not alter the natural course of uncomplicated campylobacter enteritis when therapy begins 4 or more days after the onset of symptoms.

Analysis of 107 patients with cirrhosis and recent variceal haemorrhage included in a prospective randomised trial of endoscopic injection sclerotherapy showed that in the sclerotherapy group 22 (43%) of the 51 patients had episodes of haemorrhage during the period of treatment, but in only 4 did bleeding occur after the varices had been obliterated. This contrasts with episodes of bleeding in 42 (75%) of the 56 patients receiving standard medical management-a highly significant difference. The overall risk of bleeding per patient-month of follow-up was reduced threefold with sclerotherapy. Of 22 patients followed up for at least one year after obliteration of varices, 14 had no evidence of reappearance of varices within this period and, by means of cumulative life-analysis tables, survival was shown to be significantly improved in the sclerotherapy group.

The effect of 6 months of strict metabolic control upon eye and kidney function was studied in 32 insulin-dependent diabetics randomised either to unchanged conventional treatment (UCT) or to continuous subcutaneous insulin infusion (CSII). Retinal function was assessed by means of the macular recovery time (measured with nyctometry), the oscillatory potential (measured with electroretinography), and fluorophotometry. Renal function was assessed by the glomerular filtration rate (GFR) and the urinary albumin excretion rate. Individual median blood-glucose levels during the 6 months were 9.2 +/- 2.0 mmol/l (mean +/- SD) in the UCT group and 5.6 +/- 0.7 mmol/l in the CSII group. Haemoglobin Alc fell from 8.8 +/- 1.2 to 8.0 +/- 2% in the UCT group and from 9.6 +/- 1.7 to 6.7 +/- 1.0% in the CSII group. The UCT group showed a significant deterioration in all indices of retinal function (macular recovery -6%, oscillatory potential -5%, fluorophotometry +9%, whereas patients treated with CSII showed a distinct improvement (macular recovery +5%, oscillatory potential +7%, fluorophotometry -7%). GFR fell by 9% with CSII and rose 2% with UCT. Urinary albumin excretion fell by 12% with CSII and rose by 56% with UCT. This interim report of a one-year study supports the view that long-term control achieving near-normal blood-glucose levels may arrest or even reverse some of the features associated with diabetic microangiopathy.

In a comparative clinical trial to examine the influence of 10 days of preoperative parenteral nutrition (PPN) on the postoperative complication rate for gastrointestinal carcinoma 59 patients (controls) received the regular hospital diet and 66 received PPN. The two groups were similar in nutritional status and in distribution of site and stage of tumour and type of operation. The rates of postoperative wound infection, pneumonia, major complications, and mortality were generally lower in the PPN group, but the differences were significant only for major complications and mortality. The clinical results can be explained by the improvement in various indices of humoral and cellular immunocompetence and the protein status in the PPN group and their deterioration in the control group during the preoperative course.

43 patients undergoing treatment for acute leukaemia were randomised to receive either co-trimoxazole alone or co-trimoxazole with framycetin and colistin as antibacterial prophylaxis during periods of neutropenia. There were no significant differences between the two treatment groups in the time before the onset of the first fever, the number of episodes of fever or of septicaemia per patient, the number of neutropenic days during which patients remained afebrile or did not require systemic antibiotics, or the number of resistant organisms acquired. Co-trimoxazole alone is cheaper and easier to take than co-trimoxazole with framycetin and colistin, and it is therefore preferable to the three-drug combination for the prophylaxis of bacterial infection.

Treatment of hypertensive patients with dl-propranolol (640 mg/day) significantly inhibited thromboxane synthesis by their platelets and platelet aggregation induced by thrombin or arachidonic acid. The effects were dose-related and were also caused by the stereoisomer, d-propranolol (640 mg/day), which has very little beta-blocking activity. These findings suggest that the cardioprotective effects of propranolol may be due partly to this anti-platelet activity, to a reduction in thromboxane-induced coronary-artery vasoconstriction, or to both. d-Propranolol treatment may be particularly useful, since this isomer provides similar benefits without causing pronounced beta-adrenergic blockade.

The effect of placebo on blood-pressure levels in 20 hypertensive patients was examined as part of a double-blind randomised controlled trial with indoramin. Blood-pressure was measured by both standard sphygmomanometry and ambulant intra-arterial monitoring. Blood-pressure reduction during the placebo phase, as measured by sphygmomanometry in the outpatient clinic, was highly significant for both systolic and diastolic pressures. In the same subjects, concomitant assessment by ambulatory monitoring showed no significant effect of placebo on intra-arterial pressure. After indoramin treatment blood-pressures measured in the clinic showed a mean reduction of 6/8 mm Hg whereas intra-arterial monitoring showed mean reductions of 18/13 mm Hg. The placebo response, therefore, appears to be an artifact of clinic blood-pressure measurement and its use as a control value in pharmacological trials may lead to serious underestimation of the efficacy of the active drug.

The efficacy of argon laser photocoagulation in the endoscopic control of haemorrhage from peptic ulcers was tested in a controlled trial at two centres in London. Of 330 patients consecutively admitted with acute upper gastrointestinal tract haemorrhage, 76 were seen at endoscopy to have a peptic ulcer accessible to laser therapy and stigmata of recent haemorrhage. These patients were included in the trial. Identification of the exact source of haemorrhage within the ulcer crater was achieved by use of standard endoscopes with careful washing. Patients were stratified into three groups: ulcers with a visible vessel (52 total, 11 actively spurting); those without a vessel (17); and those with an overlying clot persisting after washing (7). Of the 52 patients with visible vessel, 8 of 24 treated with the laser and 17 of 28 control patients had a further haemorrhage. 7 control patients died after an episode of rebleeding, but no treated patients. Treated and control patients were well matched for other factors known to influence the case fatality rate. This is the first controlled trial to demonstrate a significant reduction in mortality by the use of a non operative treatment in patients with bleeding peptic ulcers.

To identify diets that are more effective than existing ones in reducing lipoprotein-mediated risk of atherosclerotic heart disease, the serum lipids and lipoprotein response to three modified diets was studied in twelve normal men living in an institution. The "Western" reference diet (40% energy from fat, P/S ratio 0.27) was compared in Latin square design with a fat-modified diet (diet B, 27% energy from fat, P/S 1.0, reduced cholesterol content); with a fat-modified diet supplemented with fruit, vegetable, and cereal fibre (diet C); and with a diet providing 40% energy from fat, having P/S ratio 1.0 and supplemented by fibre (diet D). The effects of fat modification and fibre-supplementation (diets C and D) were strongly additive-a fall serum cholesterol by 24-29%, in low-density-lipoprotein (LDL) cholesterol by 31-34%, and in serum triglyceride by 21-26%; and the reduction, by diet C, of the ratio of serum cholesterol to high-density-lipoprotein (HDL)-cholesterol by 21%, and that of LDL-cholesterol to HDL2-cholesterol by 26%. The additive effects of multiple changes in nutrient intake, each moderate in extent, permits the design of diets which are remarkably effective in reducing serum-cholesterol level.