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.

40 adult outpatients with active endoscopically proven duodenal ulceration, who would otherwise have merited elective ulcer surgery, entered a double-blind trial of either cimetidine (1g/day) or placebo. After twenty-eight days, 17 of 20 (85%) patients receiving cimetidine showed ulcer healing, compared with 5 of 20 patients receiving placebo (p less than 0.0005). Patients receiving cimetidine had significantly more pain-free days and pain-free nights than those receiving placebo. There was good correlation between ulcer healing and symptomatic relief (p less than 0.0005).

91 men with non-gonococcal urethritis (N.G.U.) were randomly treated with either sulphafurazole (sulfisoxazole), 500 mg orally q.i.d. for 10 days, or an aminocyclitol (streptomycin or spectinomycin), 2 g intramuscularity for 1 to 3 doses at 12 h intervals. Initial urethral cultures were positive for Chlamydia trachomatis (C) in 36 (40%). Ureaplasma urealyticum (U) was isolated from the urethra or urine from20 (95%) of 21 White men in a first episode of N.G.U. who had negative chlamydia cultures. Sulphafurazole, active against C. trachomatis but not U. urealyticum in vitro, produced a clinical response in 7 of 7 men with C+U- N.G.U. and 5 of 19 with C-U+ N.G.U. (P less than 0-01). Aminocyclitols, active against U. urealyticum but relatively inactive against C. trachomatis in vitro produced a clinical response in 0 of 6 men with C+U-N.G.U., 9 of 11 men with C-U+N.G.U. from whom ureaplasma was eradicated (P less than 0-01), and 0 of 8 with C-U+ N.G.U. from whom ureaplasma was not eradicated. C+U+ N.G.U. responded poorly to both antimicrobials alone. These results support the aetiological importance of both C. trachomatis and U. urealyticum in N.G.U.

Despite the presence of venostasis in the legs, intermittent compression of the arms during and after surgery reduced the incidence of deep venous thrombosis (D.V.T.) in the legs to half that in control patients and maintained blood fibrinolytic activity at preoperative values. It is suggested that the release of fibrinolytic activators is essential to the prophylactic action of pneumatic leggings.

68 patients were included in a prospective study of the treatment of borderline leprosy. 34 were treated with dapsone 5 mg daily, and 34 with 50 mg daily. Reversal reactions developed in 11 of those on 5 mg daily and in 3 of those on 50 mg daily. The statistically significant difference between the two treatment groups indicates that, contrary to previous teaching, dapsone given in higher dosage does not predispose patients to reversal reactions and indeed may prevent them.

Two clinical trials were conducted to compare the efficacy of 3 antimicrobial agents often recommended for the treatment of typhoid fever. Chloramphenicol was more effective than parenteral ampicillin or oral co-trimoxazole (trimethaprim/sulphamethoxazole) in reducing the duration of fever. Oral chloramphenicol was more effective than parenteral chloramphenicol probably because oral doses resulted in higher blood concentrations of the drug. However, parenteral chloramphenicol was given during the initial period of acute illness, without loss of efficacy.

Acute mountain sickness (A.M.S.) and its severe complications, high-altitude pulmonary oedema (H.A.P.O.) and cerebral oedema (C.O.), were studied in 278 unacclimatised hikers at 4243 m altitude at Pheriche in the Himalayas of Nepal. The overall incidence of A.M.S. was 53%, the incidence being increased in the young and in those who flew to 2800 m, climbed fast, and spent fewer nights acclimatising en route. It was unrelated to sex, to previous altitude experience, to the load carried, and to recent respiratory infections. The severity of A.M.S. was inversely related to age (independent of rate of ascent) and the highest altitude attained, and was highly ocrrelated with speed of ascent. There were 7 cases of H.A.P.O. and 5 with the more intractable C.O. and, of these 12, 11 had flown in, 9 had spent only one night at Pheriche, and none were on acetazolamide. 11 required evacuation. Acetazolamide, compared in a double-blind study with a placebo and also compared with no tablets at all, reduced both the incidence and the severity of A.M.S. in those who flew to 2800 m but not in those who hiked up to that altitude. Prevention consists in slow ascent, rapid recognition of warning signs, and prompt descent to avoid progression.

A rigimen of rifampicin plus isoniazid, supplemented in the first two months by ethambutol or streptomycin, was given for six, nine, twelve, or eighteen months in a controlled study of 696 patients with culture-positive pulmonary tuberculosis. The results obtained in the thirty-three months since the start of treatment when all the patients in the six-month and nine-month groups had completed at least two years and those in the twelve-month group had completed twenty-one months of post-chemotherapy follow-up revealed no relapses among patients receiving nine months chemotherapy and a 1% relapse-rate in the twelve-month group. The same regimen given for only six months resulted in a relapse-rate of 5% during the subsequent twenty-seven months. There were adverse effects with streptomycin but not with ethambutol. It is concluded that treatment with rifampicin plus isoniazid for nine months, supplemented by ethambutol in a dose of 25 mg/kg for the first two months, is now acceptable as standard chemotherapy for pulmonary tuberculosis in Britain.

117 patients with stage IIIA Hodgkin's disease were randomly allocated for treatment in a multicentre trial comparing the results of total nodal irradiation (T.N.I.) with those of combination chemotherapy. Staging procedures for most patients included laparotomy; a few patients whose staging did not include laparotomy were studied separately. Of the 81 patients staged by laparotomy, 40 out of 42 (95%) achieved complete remission (C.R.) after treatment by T.N.I. and 29 out of 39 (74%) achieved C.R. during treatment with mustine hydrochloride, vincristine ("Oncovin"), procarbazine, and prednisone (MOPP) (P=0.018). An analysis of the disease-free survival up to four years favoured the group of patients treated by T.N.I. (P less than 0.01) but differences in overall survival were not statistically significant. In the 36 patients with presumed IIIA disease whose staging did not include laparotomy no significant differences in the incidence of C.R. or rates of disease-free or overall survival were observed. It is concluded that T.N.I. is the optimum initial treatment for patients with IIIA disease whose staging includes laparotomy.

A double blind crossover trial of levamisole has been carried out in 47 patients with recurrent oral ulceration. Significant decreases in the number of ulcers and ulcer days were found after 2 months of intermittent administration of levamisole. About 64% of patients responded to the drug by a decrease in the number of ulcers of more than 50%, for two or more months. The remaining 36% of patients failed to respond to levamisole and 23% of these had an increased number of ulcers. The side-effects recorded in patients taking levamisole were comparable with those in patients on placebo, except for a flu-like syndrome in 1 patient and urticaria in another, necessitating withdrawal of the drug. The mechanism of action of levamisole in recurrent oral ulceration is not known, but it is suggested that levamisole may correct a deficiency of suppressor cells, or potentiate the cellular responses to crossreacting microbial agents.