The efficacy and toxicity of bromocriptine, a drug which simulates dopamine, have been studied in twenty-eight patients with idiopathic parkinsonism. A double-blind, within-patient comparison between maximum tolerated doses of bromocriptine (mean 46-9 mg daily) and placebo revealed a substantial and statistically significant therapeutic response to the active drug. Adverse reactions were dose dependent, reversible, and similar to those encountered with levodopa. While taking bromocriptine fourteen patients were able to stop levodopa (with or without carbidopa); in five patients the dose of levodopa was reduced by 54% (mean). Eight patients could not tolerate bromocriptine; one patient failed to comply with prescribed adjustments of dosage.

Inhaled beclomethasone dipropionate and inhaled betamethasone valerate have been compared with oral prednisone in the treatment of 75 patients with asthma who were starting long-term corticosteroids for the first time. Both of the inhaled corticosteroids controlled asthma as well as did oral prednisone in those who had responded to therapy in the initial period of the trial. A daily dose of 400 mug of inhaled drug was approximately equivalent to 7-5 mg daily of prednisone. Prednisone suppressed the adrenal response to tetracosactrin, whereas the mean responses in the groups receiving inhaled corticosteroids did not change significantly from pre-trial values. The 30% incidence of other systemic unwanted effects of prednisone contrasted sharply with the low incidence (5%) of symptomatic oropharyngeal candidiasis in the patients receiving inhaled corticosteroids. In a sample of 19 patients no change in exfoliative cytology was detected over the period of the trial nor was there any evidence of fungal colonisation of the bronchial tree. There was no difference between the three treatment groups in the number of antibiotic courses prescribed. The persistent production of sputum made no difference to the response to inhaled corticosteroids. Patients not on sodium cromoglycate did as well in the trial as those receiving sodium cromoglycate. Both inhaled beclomethasone dipropionate and inhaled betamethasone valerate have advantages over oral prednisone in the maintenance treatment of patients with asthma, but in the management of exacerbations systemic corticosteroids will usually be needed as a supplement to inhaled therapy.

In a double-blind study, hepatitis-B immunoglobulin significantly protected patients in a haemodialysis unit against the development of HBs antigenaemia, compared to control patients receiving normal human immunoglobulin (p less than 0-01). Injections were given at the beginning and after 6 months, and observations extended over 16 months. Analysis of antiHBc and anti-HBs antibodies suggested that neutralisation of the virus inoculum, as well as modification of infection, may be implicated in the prevention of HBs antigenaemia.

A randomised clinical trial in 124 adult patients with typhoid fever, proved by blood culture, showed that amoxycillin in a dosage of 1 g. six-hourly for fourteen days is an alternative to chloramphenicol, which has hitherto been regarded as the drug of choice.

The results of 5-day cyclical combined chemotherapy for advanced breast cancer were compared in two trials with the less demanding 1-day and 2-day regimens. At all stages, except at 3 months, 5-day treatment was significantly more successful in providing regression and remission of tumours than the 1-day regimen. However, although the differences are not statistically significant, data from the second trial indicated that the 2-day regimen tended to be more effective than the 5-day regimen. The lower 95% confidence limit for the success of the 2-day treatment was 56.2% at 3 months.

A 95% ethanol solution containing 0-5% chlorhexidine digluconate caused a significantly greater mean reduction in skin bacteria (99-9% plus or minus 0-024) when rubbed by a gloved hand on to the skin of one hand for two minutes than when applied to the same area for the same time with the traditional gauze applicator for operation sites (90-7% plus or minus 2-12). The latter reduction, however, was greater than that reported in five previous experiments in which application of the same solution for the same time to two hands gave mean reductions varying from 79% to 84%. An aqueous solution and a 70% alcoholic solution of chlorhexidine also gave significantly greater reduction (and alcoholic povidone iodine almost significantly greater reduction) when applied by a gloved hand than on gauze. It is inferred that the effectiveness of skin disinfection depends both on the antiseptic used and on the manner of application, and varies with the amount of friction used in applying the antiseptic. Further studies on disinfection of the surgeon's hands with 0-5% chlorhexidine in 95% alcohol rubbed on and allowed to dry have supported its value and acceptability; the mean bacterial counts of washings from gloves of surgeons after operations were lower after the use of this method than after other preoperative preparations of the hands.

A prospective study was carried out of the frequency of thrombophlebitis and bacterial contamination of cannulas associated with four commonly used intravenous cannulas of differing length and chemical composition. For all cannulas the frequency of thrombophlebitis increased significantly with time. Long 'Teflon' cannulas were significantly more likely to be contaminated with bacteria and associated with thrombophlebitis than all other cannulas, while the low frequency of thrombophlebitis with butterfly stainless steel cannulas was shown to be due to their short duration of use. It is suggested that long teflon cannulas should be avoided and that infusion thrombophlebitis could be eliminated as a clinical problem by the use of intermittent short duration intravenous infusions.

34 hypertensive patients were assigned at random either to six weeks' treatment by yoga relaxation methods with bio-feedback or to placebo therapy (general relaxation). Both groups showed a reduction in blood-pressure (from 168/100 to 141/84 mm. Hg in the treated group and from 169/101 to 160/96 mm Hg in the control group). The difference was highly significant. The control group was then trained in yoga relaxation, and their blood-pressure fell to that of the other group (now used as controls).

In a double-blind randomised study, single intravenous doses of propranolol (0-1 mg. per kg.), practolol (1 mg. per kg.), acebutolol (1 mg. per kg.), or placebo were each administered at weekly intervals to six healthy volunteers. Forced expiratory volume in 1 second (F.E.V.1), resting and exercise heart-rate, and resting and exercise peak flow-rate (P.F.R.) were determined before and at 2, 3, 4, and 6 hours after each treatment. Venous blood-samples were also obtained at these times. Compared with placebo, resting heart-rate was reduced after all three drugs, but the corresponding differences in exercise heart-rate were much greater, more consistent, and of greater statistical significance. At 2, 3, and 4 hours when acebutolol and propranolol produced equivalent cardiac beta-blocking activity (judged by reductions in exercise heart-rate), their mean plasma concentratios were in the ratio of about 8/1; and at 2 hours when practolol and acebutolol gave rise to almost equivalent cardiac beta blockade, their mean plasma concentratio ration was 3/1. At times, reductions in F.E.V.1 and resting P.F.R. after propranolol (but not after practolol or acebutolol) were significantly greater than the corresponding changes after placebo. The reductions in exercies P.F.R. after propranolol (6 hours) and acebutolol (4 hours) (but not after practolol) were significantly greater than the changes after placebo. Changes in F.E.V.1, resting and exercise P.F.R. after propranolol, and the corresponding changes after practolol, were significantly different, all of which confirmed that practolol was more cardioselective than propranolo. In general, the reductions in F.E.V.1 and resting P.F.R. after acebutolol were slightly smaller than after propranolol, excepting at 6 hours when the difference between them was significant. The reductions in exercise P;F.R. after acebutolol and propranolol were of the same order, there being no significant differences between the two, whereas the reductions after acebutolol were clearly greater than the corresponding changes after practolol, the differences being significant at 2, 3, and 4 hours.

The efficacy of low-dose heparin in preventing fatal postoperative pulmonary embolism has been investigated in a multicentre prospective randomised trial. 4121 patients over the age of forty years undergoing a variety of elective major surgical procedures were included in the trial; 2076 of these were in the control group and 2045 patients received heparin. The two groups were well matched for age, sex, weight, blood-group, and other factors which could predispose to the development of venous thromboembolism. 180 (4-4 %) patients died during the postoperative period, 100 in the control and 80 in the heparin group: 72% of deaths in the control and 66% in the heparin group had necropsy examination. 16 patients in the control group and 2 in the heparin group were found at necropsy to have died due to acute massive pulmonary embolism (P smaller than 0-005). In addition, emboli found at necropsy in 6 patients in the control group and 3 in the heparin group were considered either contributory to death or an incidental finding since death in these patients was attributed to other causes. Taking all pulmonary emboli together, the findings were again significant (P smaller than 0-005). Of 1292 patients in whom the 125-I-fibrinogen test was performed to detect deep-vein thrombosis (D.V.T.) 667 were in the control group and 625 in the heparin group. The frequency of isotopic D.V.T. was reduced from 24-6% in the control group 7-7% in the heparin group (P smaller 0-005). In 30 patients D.V.T. was detected at necropsy; 24 in the control and 6 in the heparin group (P smaller 0-005). 32 patients in the control group and 11 in the heparin group developed clinically diagnosed D.V.T. which was confirmed by venography (P smaller than 0-005). In addition, 24 patients in the control and 8 in the heparin group were treated for clinically suspected pulmonary emoblism. The difference in the number of patients requiring treatment for D.V.T. and/or pulmonary embolism in the two groups was again significant (P smaller than 0-005). 9 patients were found at necropsy to have died from haemorrhage; 5 were in the control and 4 in the heparin group. A careful objective analysis of operative and postoperative bleeding in 1475 patients showed no statistically significant difference in the blood-transfusion requirements or in the fall in the postoperative haemoglobin level either in the individual operative groups or in the group as a whole. However, the difference in the number of patients who developed wound haematoma in the heparin and control groups was significant (P smaller 0-01). The results of the trial indicate that this form of prophylaxis can now be recommended for use on a large scale in "high-risk" patients undergoing major surgery.

The incidence of ventricular arrhythmias after myocardial infarction has been compared in a controlled study of procainamide, mexiletine, and placebo. Sixty male patients who has sustained a myocardial infarction and had received lignocaine for ventricular tachycardia or ventricular ectopic beats which were R-on-T, multiform, or close-coupled took part. The efficacy of the drugs was evaluated by continuous 24-hour recordings of the electrocardiogram on the 4th and 10th days after admission to the study. Procainamide was given as 500 mg. 4-hourly and mexiletine as 250 mg. 8-hourly with corresponding placebo regimens for 12 days. 77% of patients receiving placebo showed serious ventricular rhythm disorders compared with 33% receiving antiarrhythmic therapy (p smaller than 0.05). Although only 35% of patients receiving procainamide achieved accepted therapeutic plasma concentrations compared with 95% of those receiving mexiletine, both drugs were equally effective antiarrhythmically. The only major adverse effect of therapy noted was development of a positive antinuclear factor in a procainamide-treated patient. These results demonstrate the efficacy of oral antiarrhythmic agents in the management of ventricular arrhythmias after acute myocardial infarction. Mexiletine has the advantage of less frequent administration and lower toxicity.

230 Canadian steelworkers with hypertension took part in a randomised trial to see if compliance with antihypertensive drug regimens could be improved. For care and follow-up these men were randomly allocated to see either their own family doctors outside working-hours or industrial physicians during work shifts; the same men were randomly allocated to receive or not receive an educational programme aimed at instructing them about hypertension and its treatment. Surprisingly, the convenience of follow-up at work had no effect upon these men's compliance with antihypertensive drug regimens. Similarly, although men receiving health education learned a lot about hypertension, they were not more likely to take their medicine.

39 patients with carcinoma of the uterine cervix who were treated with radium and required repeated general anaesthetics were randomised to halothane and control groups. Their serum-alanine-aminotransferase (S.G.P.T.) levels were measured before each general anaesthetic, and those patients whose S.G.P.T. levels rose above 100 I.U. per litre were freed from the restriction determined by the initial allocation and treated as indicated clinically. None of the 21 patients in the control group had S.G.P.T. levels rising above 100 I.U. per litre. 4 out of 18 patients in the halothane group developed S.G.P.T. levels above 100 i.u. per litre before their third radium treatment. None of these had any symptoms or alteration in other liver-function tests, but liver biopsies in 2 of these patients showed changes characteristic of Hepatitis. Arbitrary selection of 18 out of the 39 patients would only give rise to the degree of abnormality observed in the halothane-treated group with a probability of about 0-02. In the patients studied who required repeated general anaesthetics at short time intervals, the monitoring of S.G.P.T. levels before each operation was useful screen for liver damage and may have reduced postoperative hepatic necrosis by preventing further anaesthetics with halothane when the liver was already damaged.

Patients who had received halothane within a periof of one year and who required another anaesthetic were allocated at random to be given halothane or a control anaesthetic, the control being fiben using halothane-free apparatus. There were 76 patients entries in each group. Serum-glutamic-oxaloacetic-transaminase (S.G.O.T.) levels were measured before the anaesthetics and serially postoperatively for two to three weeks. The S.G.O.T. levels in the halothane group were significantly higher than in the controls. High levels were confined to patients who had had less than four previous halothane anaesthetics, increases above normal in the remainder and in the controls being rate. 1 patient in the halothane group had an S.G.O.T. of 440 I.U. per litre and hepatocellular necrosis on liver biopsy. 2 patients in the halothane group whose S.G.O.T.s rose to more than twice normal showed a similar reaction to re-exposure to halothane, although they had not shown a reaction to an intervening control anaesthetic.

In a prospective, randomised trial, 111 obstetrically normal pregnant women, who had elective induction of labour performed between 39 and 40 weeks, were compared with 117 controls who were managed expectantly until 41 weeks. Compared with the controls, the patients who had elective induction of labour had significantly less meconium staining in labour and a smaller blood-loss after delivery. The mean length of labour, the amount of pethidine used, and the Apgar scores at 1 minute were similar in the two groups. In the electively induced group, the caesarean-section rate was lower and the use of epidural analgesia more common than in the controls, but the differences were mot statistically signficant. The hour of delivery was similar in the two groups, suggesting that convenience to medical and nursing staff would not be greatly changed by elective induction of labour. There was no evidence that the hazards to mother and child were increased by elective induction, and its use might improve perinatal mortality by reducing the number of unexplained mature stillbirths.