In a prospective trial 76 patients with venous thromboembolism have received intermittent constant-dosage heparin or continuously infused heparin with laboratory control. Frequencies of bleeding were similar in both groups. 32% of all patients bled, 13% severely. Retroperitoneal haemorrhage occurred in 5 patients. Major spontaneous bleeding was commoner in older patients and minor spontaneous bleeding in women. Bleeding was uncommon during the first 2 days of treatment, and its daily frequency was relatively constant thereafter. 21% of surgical wounds and 7% of arterial and venous puncture sites bled. These preliminary results illustrate the hazards of heparin therapy and suggest that bleeding complications are more closely related to duration of therapy, age, sex, and surgical trauma than to method of administration.

The results of using interrupted nylon skin sutures or subcuticular polyglycolic acid (P.G.A.) sutures after appendicectomy were compared in a prospective controlled trial in 127 patients. Wound infections were significantly more common when subcuticular skin closure was used.

Patients with inguinal hernia or haemorrhoids were randomly allocated to an experimental group expected to stay in hospital for only eight hours after surgery or a control group scheduled for discharge on the fifth or sixth day. There was no difference in clinical outcome between the two groups of hernia patients. However, complications were twice as common in haemorrhoid day-patients as in long-stay haemorhoid patients. The standard postoperative regimen for haemorrhoids has since been changed and the change has been accompanied by a fall in the complication-rate. Day-case surgery appears to have similar social effects on the patient and his family as traditional hospital care. There was no significant difference in either the additional expenditure incurred or patients' perceptions of the disruption associated with their operation and convalescence. In the hospital under study, day-case surgery was saving between 20 pounds and 29 pounds per patient. However, this conclusion should not be extrapolated to the N.H.S. as a whole without taking into account the use to which the resources released by day-case surgery will be put.

D-penicillamine, 900 mg daily, was used in a randomised controlled trial for treatment of patients with primary biliary cirrhosis. 19 patients received D-penicillamine and 13 received placebo. The two groups were similar in age, duration of illness, liver function tests, and liver histology. Before entry into the trial liver-copper concentration was raised in 25 of the 27 patients in whom it was measured. After three months patients taking D-penicillamine showed a significant reduction in serum-aspartate-transaminase concentrations compared with the placebo group, and this reduction seemed to be sustained. In the 4 patients on D-penicillamine for a year, a second liver biopsy showed that mean liver-copper concentration fell from 310 +/- 128 (S.E.M.) to 84 +/- 36 microng/g dry liver, compared with a reduction from 511 +/- 169 to 454 +/- 128 in the 7 patients in the placebo group in whom serial liver-copper measurements were available. Liver histology demonstrated a comparative improvement in cholestasis in patients on penicillamine, but the degree of inflammation, necrosis, and the histological stage of disease remained similar in both groups. In 5 of the 19 patients in the D-penicillamine group the drug was discontinued because of side-effects. D-penicillamine seems to be a promising treatment for patients with primary biliary cirrhosis. It may produce its effect by reducing liver-copper concentration.

The therapeutic value of increasing the daily dietary fibre intake was assessed over 3 months in a double-blind controlled trial of 18 patients. Significantly greater symptomatic relief was obtained by those on a high fibre regimen than by those in the control group, despite a marked initial placebo effect. The effectiveness of a high-fibre diet increased over the 3-month period.

In two controlled trials, involving 75 patients, on the prevention of bleeding from gastric erosions in fulminant hepatic failure, antacids given four-hourly had no significant effect. Only 35% of intragastric pH recordings taken at two-hourly intervals in the treated group were maintained above 5 with the doses used, whereas this could be consistently achieved with the histamine H2-receptor antagonists, metiamide and cimetidine. In the group receiving these drugs only 1 patient out of 26 bled, compared with 13 (54%) of the controls, a highly significant difference. Blood-transfusion requirements were significantly less in those treated with H2-receptor antagonists.

The results of a multicentre trial, designed to assess the efficacy of low-dose heparin in preventing fatal postoperative pulmonary embolism, were published in July 1975. In view of inconsistencies which have now become apparent in the data from one of the twenty-eight centres which took part in the trial, the results of the trial have been re-examined, excluding the data from this centre. Of 4031 patients remaining after exclusion of these data, 2033 were in the control group and 1998 in the heparin group. 170 (4-2%) patients died during the postoperative period, 94 in the control group and 76 in the heparin group; 70-2% of deaths in the control group and 65-7% in the heparin group had necropsy examination. 15 patients in the control group and none in the heparin group were found at necropsy to have died due to acute massive fatal pulmonary embolism (P less than 0-001). Exclusion of data from the one centre did not alter already published significant differences in the total incidence of deep-vein thrombosis, nor in the frequency of operative and post-operative bleeding complications observed in the control group and the heparin group.

Weight-gain in 35 slightly undernourished Australian Aboriginal infants was studied in hospital (49 admissions) during a blind controlled trial of a pre-hydrolysed low-lactose milk preparation and reconstituted full-cream milk powder. Infants fed the lactose hydrolysed milk gained 70% more weight than those receiving normal milk. Better weight-gains were achieved in those on the lactose hydrolysed milk irrespective of percentage standard weight for age, the presence of diarrhoea on admission to the trial, and stool sugar concentrations. The use of low-lactose milk should be considered in nutritional aid programmes for undernourished children throughout the world.

28 children with chronic asthma (15 in Denver and 13 in London) completed a 12 wk double-blind trial of treatment with sodium cromoglycate (cromolyn sodium), theophylline, and a combination of both. The three regimens were administered, each for 4 wk, in random sequence as part of a collaborative investigation of the relative efficacy of the two antiasthmatic agents. Cromoglycate was administered by inhalation in standard doses of 20 mg q.i.d. Theophylline dosage was individualized with the assistance of serum-theophylline measurements and averaged 6 mg/kg/dose q.i.d. (range 3-8--8-5 mg/kg/dose). Peak expiratory-flow rates measured twice daily on all patients averaged 75% of that predicted during cromoglycate administration, 79% during theophylline, and 81% during the combined-drug regimen (P less than 0.05). Patients had an average of 59% of days free of symptoms while on cromoglycate and 71% of days symptom-free when on both the theophylline and the combination regimens (P less than 0.025). None of the 13 patients whose asthmatic symptoms were previously controlled with cromoglycate was unable to complete the 4 wk trial with theophylline alone; 1 patient whose symptoms had been previously controlled with theophylline twice developed severe asthmatic symptoms while receiving cromoglycate, and he had to be withdrawn from that study period. No significant differences in adverse effects of the medication were observed during the 12 wk trial.

104 infants with symptomatic hypocalcaemia were randomly allocated to treatment with calcium gluconate, phenobarbitone, or magnesium sulphate. Infants treated with magnesium sulphate had higher plasma-calcium concentrations after 48 hours' treatment and fewer convulsions during and after the treatment period. Magnesium sulphate is recommended as the treatment of choice in symptomatic neonatal tetany whether or not there is hypomagnesaemia.

20 patients with severe essential hypertension (average blood-pressure 211/123 mm Hg) had an inadequate fall in blood-pressure with beta blockade alone. They were given in random order either 5 and then 10 mg of bendrofluazide a day or prazosin 2 mg three times daily rising to 5 mg if required. The trial was a within-patient comparison of the two drug regimens. 10 patients who did not achieve a satisfactory fall in pressure with either agent were then given all three drugs together. When bendrofluazide 5 or 10 mg was added to beta blockade there was an average fall in mean blood-pressure, standing, of 13%. When prazosin was added to beta blockade the average fall in mean blood-pressure, standing, was 16%. 18 patients who completed the trial had an average final blood-pressure, standing, of 139/93 mm Hg. In the prazosin period 8 patients continued to complain of dizziness after the first 24 h. With bendrofluazide serum-potassium levels fell below 3-6 mmol/l in half the patients within the first two weeks of treatment. It is concluded that patients with essential hypertension already treated with beta blockade who need an additional agent will get a further fall in blood-pressure with 5 mg of bendrofluazide. Prazosin appears to be a potent and appropriate third agent.

The efficacy of dextran-40 infusions or low-dose heparin or xantinol-nicotinate administration in preventing postoperative thromboembolic complications has been investigated in a prospective, controlled, randomised trial as part of an international multicentre trial. 382 patients over the age of forty years undergoing elective major general surgery were investigated; 100 had a complete protocol in the control, 94 in the heparin, 92 in the dextran, and 32 in the xantinol-nicotinate group. 31 patients died: 13 in the control group, 10 in the heparin group, 6 in the dextran group, and 2 in the xantinol-nicotinate group. In 4 controls, 6 in the heparin group, and 1 in the dextran group the cause of death was acute pulmonary embolism. 4 further controls, 1 in the heparin group, and 2 in the dextran group had emboli found at necropsy, which either contributed to the deaths or were incidental findings. The distribution of pulmonary emboli in this study did not show the difference between the control and the heparin group reported in the multicentre trial. The 125I-fibrinogen test was done in all patients. The frequency of isotopic deep-vein thrombosis was 36-0% in the controls, 12-8% in the heparin group, 21-7% in the dextran group, and 40-6% in the xantinol-nicotinate group. The difference between the controls and the heparin groups was highly significant and between the control and the dextran group, probably significant. There were significantly more side-effects in the heparin group than in the dextran group.

The effects of heparin and a semi-synthetic heparin analogue were compared in vivo and in vitro. The two drugs differed strikingly in their in-vitro behaviour: unlike heparin, the heparin analogue had little effect in a specific heparin assay or on overall clotting, as measured by the kaolin-cephalin clotting time (K.C.C.T.). When given by parenteral injection, the heparin analogue had almost the same potentiating effect on antithrombin III as mucous heparin, but without a comparable effect on the K.C.C.T. These observations suggest that the heparin analogue may have desirable characteristics for the prophylaxis of venous thrombosis, since it selectively potentiates antithrombin III in vivo while having little effect on overall clotting.