In a prospective controlled randomised trial, the prophylactic value of warfarin sodium (in doses aimed at maintaining a "Thrombotest" value of 10% and given from the day of admission until independent mobility had been achieved or for 3 mo, whichever was the sooner) was assessed in 160 elderly patients who had sustained a fracture of the femoral neck. Treatment significantly reduced the frequency of deep venous thrombosis (D.V.T.), whether indicated by the 125I-fibrinogen test during life or assessed by detailed post-mortem studies. Pulmonary embolism was eliminated in treated patients, but the difference in mortality between the treatment and control groups was not significant, indicating that causes of death other than pulmonary embolism are of major importance in these elderly patients. A case is made out for prophylactic anticoagulation on a selective basis.

242 women completed a controlled trial of methyldopa ('Aldomet') for moderate hypertension in pregnancy. Active treatment was associated with a significantly improved fetal outcome, due in part to a reduced number of mid-pregnancy abortions. There were 9 pregnancy losses in the control group, which included 4 mid-pregnancy abortions, and 1 fetal loss in the treated group. The birthweight and maturity of viable infants were similar in treated and control groups, and a detailed multivariate analysis confirmed that hypotensive treatment had no effect on fetal growth in utero. The better outcome associated with treatment was not due to the prevention of pre-eclampsia, and may be partly due to a direct or indirect effect of methyldopa on uterine activity. Methyldopa is safe to use for the treatment of hypertension in pregnancy in the context of close medical and obstetric supervision.

Two experiments designed to evaluate a programme for training medical students in history-taking skills were carried out. Results of the first indicate that students who underwent the programme reported almost three times as much relevant and accurate information after a test interview as those who received only traditional training. Results of the second experiment suggest that most of the programme's effect is attributable to discussion of a printed handout which presents the student with a detailed scheme for taking histories.

The effect on abnormal coagulation tests of infusions of fresh-frozen plasma (F.F.P), prothrombin complex concentrates, and a combination of these treatments was compared in 30 patients with chronic liver disease undergoing needle biopsy. A single dose of F.F.P. (12 ml/kg body-weight) was found to be the least effective therapeutic regimen. The concentrate containing factors II, IX, and X was also not adequate, but the additional administration of factor-VII concentrate corrected the prothrombin-time (P.T.) and "Normotest" (N.T.) in most patients. However, this regimen did not correct the prolonged kaolin activated partial thromboplastin-time (K.P.T.T.). The results of tests for exploring both the extrinsic (P.T. and N.T.) and intrinsic (K.P.T.T.) coagulation systems only became normal after the combined administration of a lower dose of F.F.P. (8 ml/kg body-weight) and of both concentrates (12 units/ml). There was no clinical or laboratory evidence of thrombotic complications. No patient developed acute hepatitis or hepatitis-B surface antigen in the twelve months after biopsy. These results indicate that prothrombin-complex concentrates in combination with F.F.P. may therefore be used to allow liver biopsy to be performed safely in patients presenting with severe coagulation defects.

A preliminary trial of oral zinc supplementation was conducted in twenty-four patients with chronic, refractory rheumatoid arthritis. Zinc sulphate (220 mg three times daily) or placebo capsules of identical appearance were added to pre-existing therapy for 12 wk. This double-blind trial was followed by an open 12-wk period when all subjects took zinc. During the double-blind phase, zinc-treated patients fared better than controls with regard to joint swelling, morning stiffness, walking time, and the patient's own impression of overall disease activity. The indices and joint tenderness also improved with zinc treatment in both groups of subjects during the second 12-wk period. These encouraging results indicate that oral zinc sulphate deserves futher study in patients with active rheumatoid arthritis.

Lithium therapy has been shown to have a therapeutic influence in reducing the drinking and incapacity by alcohol in depressive alcoholics in a prospective double-blind placebo-controlled trial conducted over one year, but it had no significant effect on non-depressed patients. Patients in the trial treated by placebo had significantly greater alcoholic morbidity if they were depressive than if they were non-depressive.

The therapeutic efficacy and side-effects of two preparations of levodopa with extracerebral decarboxylase inhibitors have been compared in 19 patients with idiopathic parkinsonism in a blind randomised crossover trial. The mean daily dose of levodopa was 658 +/- 64 mg/day (mean +/- S.E.M.) when given together with carbidopa 66 mg/day and 605 +/- 59 mg/day when levodopa was combined with benserazide 151 mg/day. There was no significant difference between the treatment regimens either in beneficial effects on parkinsonian symptoms and signs or in the adverse effects of levodopa assessed by a clinical observer unaware of the treatment given. Of the 19 patients studied, 9 preferred the carbidopa preparation, 8 preferred the benserazide preparation, and 2 had no preference. It is concluded that there is no significant difference in therapeutic effects or adverse reactions between the two commercially available decarboxylase inhibitor-containing preparations. Central-nervous-system actions and side-effects depend on the daily dose of levodopa, regardless of the different ratios of decarboxylase inhibitors to levodopa.

A double-blind clinical trial was carried out in 85 patients undergoing surgery to the upper shaft of the femur and to the hip-joint. In the control series, 27% developed pressure-sores before discharge from hospital. In the group in which 80 I.U. of corticotrophin (A.C.T.H.) in gelatin solvent was administered, only 12% developed pressure-sores. 19% of the patients with fractures to the upper shaft of the femur developed sores because accurate timing was not always possible. Prevention was complete in the case of total-hip replacement which is an elective procedure where A.C.T.H. can be administered at the right time to prevent disruptive damage to the microcirculation. It is suggested that the administration of A.C.T.H. should form part of the management of all high-risk surgical situations.

The effects of timolol (10 mg thrice daily) and hydrochlorothiazide (50 mg/day) have been compared in a double-blind factorial trial in 20 patients with essential hypertension. There were four randomised test phases of 8 weeks each during which patients received timolol alone, hydrochlorothiazide alone, timolol plus hydrochlorothiazide, and no treatment (placebo). Blood-pressure was measured weekly, alternately at the outpatient clinic and at the patient's home. Supine mean arterial pressure fell from 119 mm Hg in the placebo phase to 110 mm Hg in the hydrochlorothiazide phase, 106 mm Hg in the timolol phase, and 101 mm Hg in the combined timolol plus hydrochlorothiazide phase. Factorial analysis revealed that these effects of the two drugs were additive without any potentiation or antagonism. Mean plasma-renin activity (P.R.A.) was 5-02 ng/ml/3 h in the placebo phase falling to 1-79 in the timolol phase and rising to 9-54 in the diuretic phase, but remaining unchanged in the combined treatment phase (5-40 ng/ml/3 h). The data suggest that the hypotensive action of timolol is not dependent on the concomitant fall in P.R.A. The methods described provide a valuable tool for quantitating the effects of a given drug, and hence a valid basis for objective comparison.

A single intravenous dose of tobramycin and lincomycin, given at the start of gastrointestinal operations, significantly reduced the incidence of postoperative wound infection from 34% to 5%. The occurrence of both anaerobic and aerobic bacteria was reduced. Therapeutic concentrations of the antibiotics were maintained throughout the operative period in most cases. No toxic effects of the antibiotics were detected, no anaesthetic complication occurred, and resistant strains of bacteria normally sensitive to the antibiotics were not isolated from wounds.

22 patients complaining of primary menorrhagia or menorrhagia associated with an intrauterine device (I.U.C.D.) were studied in a double blind trial with crossover of ethamsylate and placebo. Acutal menstrual blood-losses were calculated from the iron content of used sanitary material during one pre-trail menstrual period and four trial menstrual periods, during which patients received ethamsylate ("Dicynene") treatment during two menstrual cycles and placebo during two cycles. During ethamsylate treatment the mean menstrual blood-loss was reduced by 50% in patients with primary menorrhagia and by 19% in patients with an I.U.C.D. This difference between the two groups is probably accounted for by the differing values of initial blood-loss which was significantly higher in the group with primary menorrhagia. Tampon usage and the duration of bleeding were not significantly altered by ethamsylate treatment. Reported side-effects, which were not serious, were equally common during ethamsylate and placebo treatment.

Bromocriptine, a dopamine receptor agonist, was administered to 20 patients with idiopathic parkinsonism taking levodopa (L-dopa) or "Sinemet" (levodopa combined with carbidopa in a 10/1 ratio) at optimum doses. In a double-blind randomised cross-over study lasting 6 months, the addition of bromocriptine (mean daily dose 79 mg) led to a significant (P less than 0.01) 74% reduction in the dose of sinemet and levodopa. "Total disability score" showed a significant (P less than 0.01) improvement at both low and high doses of bromocriptine. Tremor improved 50% (P less than 0.01), with significant improvements in gait, posture, writing, balance, rigidity, finger dexterity, and drooling. Adverse reactions were similar to those observed with sinemet and levodopa. Although both the cause and the cure of idiopathic parkinsonism remain elusive, bromocriptine appears to represent a therapeutic advance.

As part of a double-blind controlled clinical trial of cimetidine (1.6 g daily) in patients with endoscopically proven duodenal ulcer, repeat endoscopy has been carried out in 24 patients after two and/or six weeks' treatment. At six weeks, 9 out of 11 patients on cimetidine and 3 out of 12 patients on placebo had healed (P less than 0.025). A separate open pilot trial in 23 patients has shown no difference in ulcer healing at six weeks between patients taking 0.8 and 1.6 g daily. A total of 32 different patients received cimetidine in the two trials, and ulcer healing was observed in 21 (66%) at six weeks. No patients showed evidence of bone-marrow toxicity. A small but significant rise in mean S.G.O.T., S.G.P.T., and serum-creatinine occurred in 13 patients on cimetidine 1.6 g daily, but not in 13 patients on 0.8 g daily.

Two test meals were taken in random order on separate days by 8 non-insulin-requiring diabetic volunteers after 14-hour overnight fasts. Addition of 16 g guar and 10 g pectin to the control meal containing 106 g carbohydrate decreased markedly and significantly the rise in blood-glucose between 30 and 90 minutes and also resulted in significantly lower insulin levels between 30 and 120 minutes. When these meals were fed to 3 insulin-dependent diabetic subjects, a similar flattening of the post-prandial glucose rise ensued. This addition of certain forms of dietary fibre to the diet of diabetics significantly decreases post-prandial hyperglycaemia and would be expected to improve the control of blood-glucose concentration.