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.

41 outpatients who were long-term consumers of diazepam in therapeutic dosage were gradually withdrawn from the drug over 3 months by stepwise reduction.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.

A randomised study of 189 deliveries was conducted to compare performance in the conventional dorsal position with that in a birth chair. There was no significant difference in the length of the second stage of labour, the time spent bearing down, or the need for operative delivery. Overall blood-loss was greater among patients delivered in the chair but more of this group had either an intact perineum or only superficial damage. The condition of the neonates in the two delivery groups was similar.

Objective evidence of food hypersensitivity was sought by the use of exclusion diets and provocation tests in 23 patients who attributed a wide variety of symptoms to food allergy. Hypersensitivity to ingested substances was confirmed in 4, each of whom presented with typical atopic symptoms. None of these had psychological symptoms, but a high incidence of psychiatric disorder was found in patients whose belief that they had a food allergy could not be confirmed.

78 patients with bacterial meningitis were evaluated in a prospective, randomised study comparing twice-daily ceftriaxone as single-drug therapy with ampicillin and chloramphenicol given every 6 h. The groups were comparable in age, sex, days of illness before admission, and bacterial colony counts in cerebrospinal fluid (CSF). The pathogens were Haemophilus influenzae type b (54 cases), streptococci (9 cases), meningococci (9 cases), and unknown (6 cases). In 40 CSF specimens obtained 4-12 h after initiation of therapy, cultures were negative in 57% of the ceftriaxone patients and in 42% of the others. The mean falls in the CSF bacterial colony counts were 4.7 and 5.0 log10 colony-forming units/ml, respectively. Mean bactericidal activity in CSF was significantly greater in the ceftriaxone than in the conventional treatment group at the beginning and end of therapy. There were no significant differences in clinical responses or in frequency of complications, except for mild diarrhoea, which occurred in 16 ceftriaxone patients and in 8 in the other group (p less than 0.05).

28 patients who had a sustained diastolic blood pressure of 95 to 104 mm Hg and who had no treatment for it for at least 13 months before the trial, but who were otherwise unselected, took part in a randomised controlled trial in which the effect of a restricted sodium diet was compared with that of a general health package. The general health package did not include any specific hypotensive procedures. Changes in blood pressure were measured at predetermined intervals over the course of a year. Within each group both systolic and diastolic blood pressure fell to a highly significant extent after a year, but there was no significant difference between the groups. It would thus seem that the antihypertensive effect of a restricted sodium diet may be related to the increased consultation and monitoring activity of such intervention rather than to the dietary manipulation itself.

To determine whether advertising by infant formula companies shortens the duration of breast-feeding, we randomly assigned 448 breast-feeding new mothers to either receive or not receive a formula sample packet upon discharge from a maternity ward. These mother, unaware of the study, were then telephoned 3 months post partum by a research assistant blind to the randomisation status. "Sample" mothers were less likely to still be breast-feeding at 1 month (78% vs 84%, p = 0.07) and more likely to have introduced solid foods by 2 months (18% vs 10%, p = 0.01). These trends became more significant in three vulnerable subgroups: less educated mothers, primiparas, and mothers who had been ill post partum. Our results suggest that infant formula samples may shorten the duration of breast-feeding and hasten the age at which solids are introduced.

254 patients with serious gram-negative bacillary infections were enrolled into a multicentre, randomised, blind clinical trial and treated with tobramycin-ticarcillin or netilmicin-ticarcillin. The two treatment groups were similar as to sex, age, and weight. The mean daily dose of netilmicin (237 mg) was higher than that of tobramycin (211 mg), p less than 0.01, but the mean duration of therapy was longer with tobramycin (9.4 days versus 8.7 days), p less than 0.01. The netilmicin cohort also had more serious underlying diseases, p less than 0.028. Clinical (tobramycin, 93% and netilmicin, 91%) and bacteriological responses (tobramycin, 87% and netilmicin, 89%) were similar. 84 tobramycin and 73 netilmicin patients had serial audiograms. Eighth nerve deficits developed in 10 (12%) tobramycin and two (3%) netilmicin patients, p = 0.037. Drug-related renal dysfunction developed in 5 (4%) of 114 tobramycin patients whose renal function was monitored and in 1 (1%) of 116 netilmicin patients, p = 0.12.

Results are presented from the Belgian Heart Disease Prevention Project, part of the WHO European Collaborative Trial in the Multifactorial Prevention of Coronary Heart Disease (CHD). 19 409 men aged 40-59 yr took part; they were employed in thirty factories which formed the allocation units for a randomised controlled trial lasting 5-6 yr. The intervention package consisted largely of health education promoting a cholesterol-lowering diet, smoking cessation, weight control, physical activity, and treatment of arterial hypertension. A programme of information was supplemented by face-to-face counselling at the workplace by two physicians attached to the project. The coronary risk profile was reduced in the intervention group, compared with that in the control group, especially during the first 4 yr, by effects on serum cholesterol, number of cigarettes smoked daily, and arterial blood-pressure. Total mortality was 17.5% lower in the intervention group than in the control group (p = 0.038). Coronary mortality was reduced by a non-significant 20.8% whereas CHD incidence (non-fatal myocardial infarction plus fatal myocardial infarction plus sudden deaths) was reduced by 24.5% (p = 0.031). Non-fatal myocardial infarction (not a major end-point) was similarly reduced by 26.1% (p = 0.030).

Results are presented for the UK centre of the WHO European Collaborative Trial in the Multifactorial Prevention of Coronary Heart Disease (CHD). 18 210 men took part, aged 40 to 59; they were employed in 24 factories, which formed the allocation units for a randomised controlled trial lasting 5-6 years. Intervention comprised advice on cholesterol-lowering diet, smoking cessation, weight control, exercise, and treatment of hypertension. Advice was given mainly through factory medical departments, the staff being supplemented a little by a visiting central team. Self-reported cigarette smoking was moderately reduced, but changes in other risk factors were small and not well sustained. There was no clear effect on hard CHD end-points (coronary deaths and myocardial infarction) or on all-causes mortality. However, there was a 36% reduction in the rate at which intervention subjects reported ill with other CHD (principally angina) during the study, and at the end fewer intervention men gave positive responses to a self-administered questionnaire on angina and chest pain. These apparent benefits were not substantiated by electrocardiographic evidence, suggesting that participation in a heart disease prevention campaign may bias reporting of symptoms. Experience in other centres of the Collaborative Trial, however, suggests that more effective risk factor control does reduce CHD incidence and mortality. This implies that for the UK the problem is to find means of enhancing the acceptance of health advice.

The value of adding chlorhexidine to urine drainage bags of male patients treated with indwelling catheters after prostatectomy and other transurethral operations was assessed in a randomised, prospective, controlled was assessed in a randomised, prospective, controlled study. Chlorhexidine kept the contents of all drainage bags sterile, but the frequency of urinary infection in the chlordexidine group (51%) did not differ significantly from that in the control group (45%). Most infections were endogenous, caused by organisms which probably came from the patient's own urethra. It was concluded that the method has no value in urology units where standards of catheter care and closed drainage are properly maintained. Controlled studies in other types of catheterised patients are needed, especially when the risks of cross-infection are high.

21 patients undergoing major abdominal surgery were randomly assigned to one of three groups. On the day of surgery and for the succeeding 4 days each group received a daily infusion of one of the following: 10 g glucose plus 70 mmol NaHCO3, 70 mmol leucine plus 70 mmol NaHCO3, or 70 mmol of sodium alpha-ketoisocaproate (KIC). No other calories were given. Leucine infusions had no significant effect on nitrogen (N) balance, 3-methylhistidine excretion, or plasma concentrations of pre-albumin or retinol-binding protein, but they increased blood acetoacetate concentration (p = 0.004). N balance was less negative (p = 0.002) and 3-methylhistidine excretion lower (p = 0.002) in the group receiving KIC than in those receiving glucose. Blood ketone bodies, plasma prealbumin, and plasma retinol-binding protein concentrations at the end of the study were significantly higher in the KIC group than in the others. These N-sparing effects of KIC may be related to the heightened ketosis that followed its administration, to suppression of protein degradation, or to an effect on liver protein turnover. KIC alone in small doses diminishes N wastage in postoperative but under the same conditions leucine does not.

A batch of lyophilised human diploid-cell-strain rabies vaccine was divided into three batches, which were exposed to different temperatures during their distribution to and storage at three centres in Pakistan. Vaccine potency after exposure to these temperatures was tested by measuring antibody response in those given the vaccine, and by three different laboratory tests. The results indicate that the vaccine retains its antigenicity for man and for laboratory tests despite continuous exposure to high ambient temperatures for up to 11 weeks. These findings, together with current developments in vaccine manufacture and treatment schedules, offer considerable hope to many countries with low budgets for health care and where rabies is poorly controlled.

A randomised controlled trial was conducted to assess whether bladder catheters with preconnected sealed junctions were associated with a lower risk of urinary-tract infection than were catheters without such junctions, and to determine whether prevention of catheter-associated infection would be accompanied by a reduction of mortality. Among those not taking systemic antibiotics, patients assigned sealed junction catheters had fewer infections and deaths. Before they received antibiotics, the risk of infection among those assigned unsealed catheters was 2.7 times that of patients assigned sealed catheters (95% confidence interval=1.3-5 . 4, p=0 . 007). Among the 220 patients who received no antibiotics, 14% (15/108) of those assigned unsealed catheters and 4% (4/112) of those assigned sealed catheters died. Stratification by important risk factors for mortality yielded an adjusted risk ratio for death of 3.4 (95% CI=1.1-10.7, p=0.03). Among patients who received systemic antibiotic the use of sealed catheters did not affect infection rates (RR=0.9, 95% CI=0.5-1.5, p=0.68) or deaths (RR=1.2, 95% CI=0.6-2.2, p=0.62). These data indicate how the rates of infection and mortality can be reduced in hospital. Since the degree of reduction in mortality corresponded with the degree of reduction of infection, measures to prevent catheter-associated nosocomial urinary tract infection should be implemented.

28 malnourished patients with Crohn's disease completed a controlled cross-over study to examine the effect of a low-residue liquid supplement on nutrition and disease activity. Patients spent two months on an ordinary diet (control period) and for two months took the nutritional supplement in addition (treatment period): the order of treatment and control periods was randomised. All anthropometric measurements, serum proteins, creatinine height index, and circulating T lymphocyte numbers increased significantly in the treatment period, while serum orosomucoid levels dropped significantly, suggesting that disease activity was reduced. The benefits were apparently due to the higher calorie intake with the enteral supplement. The results show that enteral supplementation can be managed successfully at home and may produce improvements in nutrition and disease activity.