Deposits of cyclosporin A (CyA), demonstrable by fine-needle aspiration biopsy and indirect immunofluorescence, are invariably seen in the transplant parenchymal cells in cases of CyA nephrotoxicity. Deposition of CyA is accompanied by concomitant changes in parenchymal-cell morphology but not by any significant inflammation. The degree of clinical nephrotoxicity is directly correlated with the amount of CyA in the graft but has no correlation with the dose of the drug and only a marginal correlation with the concentration of CyA in the recipient plasma. After reduction of dose, the deposits rapidly disappear from the transplant, with concomitant improvement of transplant function. It is concluded that demonstration of CyA in cytological specimens of a renal transplant is at present the best method of assessing CyA nephrotoxicity and of distinguishing nephrotoxicity from rejection.

Selenium levels in serum samples collected in 1973 from 111 subjects in whom cancer developed during the subsequent 5 years were compared with those in serum samples from 210 cancer-free subjects matched for age, race, sex, and smoking history. The mean selenium level of cases (0.129 +/- SEM 0.002 micrograms/ml) was significantly lower than that of controls (0.136 +/- 0.002 micrograms/ml). The risk of cancer for subjects in the lowest quintile of serum selenium was twice that of subjects in the highest. Multivariate adjustment for geographical area and serum levels of lipids, vitamins A and E, and carotene, did not alter this relation. The association between low selenium level and cancer was strongest for gastrointestinal and prostatic cancers. Serum levels of vitamins A and E compounded the effect of low selenium; relative risks for the lowest tertile of selenium were 2.4 and 3.9 in the lowest tertiles of vitamins E and A, respectively.

In a double-blind, dose-comparative trial, 32 patients with duodenal ulcer were assigned to receive either 20 mg/day or 60 mg/day omeprazole for 4 weeks. The 2-week healing frequency of 100% in the 60 mg/day group was significantly higher than that in the 20 mg/day group (63%). After 4 weeks all ulcers but one in the 20 mg/day group were healed (93% healing frequency). In both groups transient and mostly slight rises in serum alanine aminotransferase levels were observed (total 10 patients). One patient in the 20 mg/day group was withdrawn because of a pronounced rise in serum alanine aminotransferase on day 8. The reason for these liver reactions is not clear, but exclusion of a causal relation with omeprazole treatment must precede further clinical evaluation of this drug.

Single-dose ceftriaxone, 125 mg or 250 mg intramuscularly (IM), was compared with spectinomycin, 2 g IM, for treatment of men with uncomplicated urethral or anorectal infections due to penicillinase-negative Neisseria gonorrhoeae. Cure rates were 100% for 31 and 28 men treated with 125 mg and 250 mg ceftriaxone, respectively, and 97% for 58 men given spectinomycin. Among patients followed up for greater than or equal to 14 days, post-gonococcal urethritis occurred in 25% of 44 men treated with ceftriaxone and 19% of 47 given spectinomycin (p = NS). The geometric mean minimum inhibitory concentration of ceftriaxone for 79 pre-treatment isolates of N gonorrhoeae was 0.0058 microgram/ml, and all strains were inhibited by less than or equal to 0.063 micrograms/ml. Neither drug caused perceptible toxicity, but patient acceptance was greater for ceftriaxone than for spectinomycin. Ceftriaxone in a single dose of 125 mg is effective against uncomplicated urethral or anorectal gonorrhoea in men and may become a regimen of choice for this infection.

Antibody responses to poliovirus, diphtheria, pertussis, or tetanus vaccine were compared in five groups of infants. The 62 infants had been brought up on breast milk or on one of four types of artificial feed in the first five months of life. The types of artificial feed varied in quality and quantity of protein; they were high or low protein cow's milk, an adapted formula (with a casein/albumin ratio of 40/60), and a formula based on soy flour. After the age of 5 months, all infants were put on the same diet. The general pattern of antibody responses as determined by antibody levels when the infants were 5 and 8 months old was that those fed on breast milk or high-protein cow's milk had adequate and sustained antibody responses; those fed on the adapted formula had a high but temporary response; and those fed on low-protein cow's milk or the soy-based formula had poor responses.

20 525 patients from general practitioners' lists were randomly allocated into test and control groups. The 10 253 test subjects were invited to perform haemoccult faecal occult blood testing over 3 days. 3613 (36 . 8%) of the 9807 who received their invitations completed the test. Compliance was improved by direct invitation from the general practitioner and by prior health education by letter or interview. 77 people (2 . 1%) had a positive test result, and 50% of these on investigation had neoplastic disease--12 had invasive carcinomas (9 Dukes' stage A, 2 stage B, 1 stage C) and 27 had 40 adenomas (12 over 2 cm, 2 of which contained areas of severe dysplasia). In the year following the screening test 1 carcinoma (stage C) has presented in the group which accepted the test, and 10 carcinomas (4 stage B, 4 stage C, 2 stage D) have presented in the control group. This respresents a 3 . 6 times greater detection rate per 1000 persons in the test group than in the control group. Only 8 adenomas have presented in the control and non-responding groups. Fibreoptic sigmoidoscopy identified the 10 carcinomas within its range and 39 of the 40 adenomas. Double-contrast barium enema identified only 9 of the 12 carcinomas and 24 (62%) of the 40 adenomas. All 3 carcinomas not identified by barium enema were polypoid Dukes' stage-A lesions.

Dermatophagoîdes pteronyssinus allergen was instilled into the alveolar space of 7 allergic asthmatic patients during bronchoalveolar lavage. beta-glucuronidase concentration in the bronchoalveolar fluid from the challenged lung became significantly higher than that in the opposite control lung (3.90 +/- 1.88 nmol/h versus 0.86 +/- 0.55). The intracellular level of beta-glucuronidase in the alveolar macrophages in the challenged lung was 40.3% lower than that in the control lung. In 3 controls intracellular concentrations of beta-glucuronidase were similar before and after allergenic challenge and no enzyme activity could be detected in bronchoalveolar lavage fluid. These results suggest that alveolar instillation of an allergen in asthmatic patients rapidly stimulates alveolar macrophages, which may be involved in immediate hypersensitivity reactions in asthma.

41 outpatients who were long-term consumers of diazepam in therapeutic dosage were gradually withdrawn from the drug over 3 months by stepwise reduction. In a double-blind procedure half the patients began withdrawal immediately and half after 8 weeks. Of 36 patients who completed treatment, 16 (44.4%) experienced true withdrawal phenomena on reducing their drugs, but 8 other patients had pseudo-withdrawal reactions at a time when their drug treatment was unchanged. The pseudo-withdrawal reactions consisted of an increase in anxiety symptoms only, whereas true withdrawal symptoms also included perceptual changes and psychotic symptoms. Examination of pharmacological and clinical predictors of withdrawal phenomena and later relapse showed that personality factors were the most important, patients with passive-dependent traits having a significantly greater prevalence of withdrawal reactions.

Hypokalaemia is a common finding in acutely ill patients and may be related in part to increased sympathoadrenal activity. In an investigation to determine whether pretreatment with thiazide diuretics causes the serum potassium to fall to an even lower level during increased sympathoadrenal activity, adrenaline was infused into healthy subjects after pretreatment for 7 days with either bendrofluazide (5 mg) or placebo. Thiazide diuretic pretreatment had no effect on the adrenaline-induced changes in blood pressure and heart rate. However, not only was the baseline serum potassium lower after bendrofluazide (3 . 40 mmol/l vs 3 . 83 mmol/l) but the serum potassium also fell to a significantly lower level during adrenaline infusion after bendrofluazide (2 . 73 mmol/l vs 3 . 08 mmol/l). Transient profound hypokalaemia may increase the risk of ventricular arrhythmias in patients on diuretics, and routine monitoring of the resting serum potassium may underestimate this risk.

Dexamethasone was compared with placebo in a double-blind, crossover, randomised study of infants with severe bronchopulmonary dysplasia who had required mechanical ventilation for at least four weeks, despite treatment with diuretics, methylxanthines, bronchodilators, fluid restriction, nutritional supplementation, and ligation of the patent ductus arteriosus when indicated. Gestational age ranged from 27 to 33 weeks and birth weight from 800 to 1730 g. Patients received dexamethasone (0 . 5 mg/kg/day) or normal saline for the first 3 days, then treatment was crossed over for the next 3 days. The study was terminated when sequential analysis showed that all six patients had improved during dexamethasone therapy. Significant improvements were seen in ventilator-determined respiratory rate, peak inspiratory pressure, fractional inspired oxygen concentration, and alveolar arterial oxygen gradients (p less than 0 . 05). Although dexamethasone hastened weaning from mechanical ventilation, infection occurred in a substantial proportion of patients.