The role of colonisation factor antigen (C.F.A.) in diarrhoea was studied in volunteers who ingested either E. coli H-10407, which possessed C.F.A., or H-10407-P, which lacked C.F.A. In the first study the dose given was 10(6) C.F.A.+ or C.F.A.- E. coli; in the second study the dose was 10(8) of the same organisms. Diarrhoea, with or without other symptoms, occurred only in those who ingested 10(8) C.F.A.+ E. coli. Those volunteers taking the C.F.A.- strain shed the test organism in the stool for only 2 or 3 days whereas those ingesting the C.F.A+ strain shed the organism until the end of the study (7 days). Antibody responses in those ingesting the C.F.A.+ strain were: anti-C.F.A., 7 of 12 volunteers; antitoxin, 6 of 13; and anti-O78 somatic antigen, 11 of 13. No volunteer ingesting the C.F.A. organism seroconverted to any of the antigens. The study showed the importance of C.F.A. in the pathogenesis of human disease due to toxigenic E. coli.

A double-blind cross-over trial was carried out to compare the effect of identical placebo with that of salbutamol inhalers used 30 min before inhalation of 100 microgram of beclomethasone dipropionate (B.D.P.) in 18 chronic asthmatics over two consecutive 4-week periods. The salbutamol and B.D.P. combination resulted in a significant improvement in the peak expiratory flow-rate and F.E.V.1, significantly less use of the rescue inhaler, and better control.

The early follow-up of patients treated by simple mastectomy alone or simple mastectomy combined with radical radiotherapy is presented. Both groups were well matched for age, menopausal status, duration of symptoms, size of tumour, and lymph-node involvement. There was no significant difference in survival of patients in the two groups at three years, but local recurrence was significantly more frequent (28%) in the mastectomy-alone patients. Early survival was not adversely affected by radiotherapy.

Forty-three oophorectomised patients were reviewed 8 years after their initial attendance at a research clinic investigating the aetiology and prevention of postmenopausal osteoporosis. Fifteen patients who had been treated with an oestrogen did not lose a significant amount of bone during the 8 years of therapy. Patients in the placebo-treated control group initially had bone loss of 2.6% per annum, which later fell to an average of 0.75% per annum. Fourteen patients who had been treated with oestrogen for the first 4 years lost no bone, but on withdrawal of oestrogen their bone mineral content fell over the next 4 years at an average rate of 2.5% per annum. 8 years after their initial attendance there was no significant difference between this group and patients who had received placebo for the full 8 years. The result of this study indicates that long-term prevention of bone loss by oestrogens has important medical, social, economic implications.

Normal human plasma contains not only active renin but also an inactive form of renin which, after exposure to low pH, can generate angiotensin I from renin substrate. When healthy volunteers were given first a diet containing 400 mmol sodium and then a diet containing 10 mmol sodium for 4 days the changes in salt intake stimulated large changes in active plasma-renin and smaller changes in inactive renin. Inactive renin comprises a larger fraction of total renin in plasma of salt-loaded healthy subjects than salt depleted subjects. When plasma of healthy men on a high-salt diet was applied to a column of 'Sephadex G-100', renin eluted in two peaks, corresponding to big renin (60 000 daltons) and normal renin of lower molecular weight (40 000 daltons). Active and inactive forms of renin were present in both peaks. Plasma from salt depleted healthy subjects showed a large single peak of renin activity with a maximum at 40 000 daltons. These studies demonstrate that both big and small renin can exist as inactive or active enzyme. Big renin, previously found in certain diseases and in pregnancy, is also present in normal human plasma. These observations suggest a possible physiological role for big renin.

Malnourished children have thymic atrophy which is reversed by zinc supplementation. To see if their defect in cell-mediated immunity was also associated with zinc deficiency ten children were skin-tested with Candida antigen on both arms. One test site was covered with local zinc sulphate and the other with placebo ointment. There was a highly significant increase in the typical delayed-hypersensitivity reaction at the site covered with zinc. The magnitude of the difference between the supplemented and unsupplemented arms correlated negatively with the plasma-zinc concentration. These data show that zinc deficiency is a cause of the immunoincompetence seen in malnutrition. The normal reactions of the zinc-supplemented side indicate that, of the many nutritional deficits of malnourished children, zinc deficiency specifically impairs the cell-mediated immune system. Local skin-testing with and without zinc may provide a measure of zinc status. Local application of zinc may enhance the reliability of tests to diagnose diseases such as tuberculosis in malnourished patients.