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).

Changes in circulating triiodothyronine (T3), thyroxine (T4), binding of thyroid hormones to plasma proteins (resin-T3 test), cortisol, and glucose were evaluated in sixteen patients undergoing abdominal hysterectomy. In eight of the patients afferent neurogenic impulses from the surgical area were blocked during and after operation by epidural analgesia. These patients were pain-free, and the normal stress-induced increase in cortisol and glucose was abolished. During epidural analgesia and general anesthesia plasma-T3 fell rapidly and values in the hypothyroid range were found 6 hours after skin incision. Similarly, an increase in the resin-T3 test reflected decreased binding of T3 to plasma proteins. Plasma-T4 decreased slightly during surgery and epidural analgesia (as it does when other anaesthetics are given), but increased during general anaesthesia. These results indicated that the alterations in thyroid hormones and their binding to plasma proteins after surgery are not caused by a stress-induced increase in plasma-cortisol or by neurogenic afferent stimuli from the surgical area, factors which are both known to affect concentrations of other hormones.

The effects of intramuscular injection and subcutaneous infusion of desferrioxamine (D.F.) on urinary iron excretion were compared in eleven patients with thalassaemia major and one with congenital sideroblastic anaemia who were being maintained on regular blood-transfusions. Total (48-hour) urinary iron excretion ranged from 3-3 to 40-3 mg (mean 16-3 mg) in nine patients who received 750 mg D.F. intramuscularly before transfusion and from 3-9 to 32-3 mg (mean 11-9 mg) in ten patients who received D.F. by the same route after transfusion. In all 9 patients studied before transfusion, continuous subcutaneous infusion of 750 mg D.F. over 24 hours increased iron excretion by 61-5 to 135-8% (mean 101+/-25-4 S.D.%) compared with intramuscular injection of a similar dose. In the 10 patients studied after transfusion, the iron excretion produced by continuous subcutaneous infusion was from 18-9 to 213% (mean 128+/-74-3%) more than that produced by a single intramuscular injection of D.F. When the subcutaneous dose over 24 hours was increased to 1500 mg in six patients, 48-hour iron excretion ranged from 29-2 to 81-2 mg (mean 52-4 mg) and was increased by 80-2--794% (mean 429%) compared with the excretion when 750 mg was given by intramuscular injection. It is concluded that continuous subcutaneous infusion of D.F. produces more iron excretion in patients with iron overload than intramuscular injection. Providing a suitable portable pump can be carried by the patients, continuous subcutaneous infusion of desferrioxamine may prove a valuable means of preventing or treating iron overload in anaemic patients maintained on regular transfusions.

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.