To evaluate the effects of a fibre-rich diet on blood glucose and serum lipoproteins, eight diabetic patients, four on insulin and four on oral hypoglycaemic drugs, were put on three different diets, a different one for each consecutive 10-day period: diet A (carbohydrate 53%, fibre 16 g), diet B (carbohydrate 53%, fibre 54 g), and diet C (carbohydrate 42%, fibre 20 g). All diets had identical polyunsaturated/saturated fat ratios. Both 2 h post-prandial glucose and mean daily glucose levels were significantly lower after diet B than after either of the two other diets, as were total and LDL cholesterol levels. Total and VLDL triglyceride levels after diet B were significantly lower than those after diet A but almost identical to those after diet C. HDL cholesterol concentration was not affected by dietary fibre but was significantly increased by the low-carbohydrate diet. A high-fibre, normal-carbohydrate diet (the fibre coming exclusively from foodstuffs with a naturally high content of fibre) improves blood glucose control and decreases the concentration of atherogenic lipoproteins in diabetic patients. This effect is independent of the amount of available carbohydrates in the diet.

97 patients with symptoms of early tetanus at the time of admission to hospital were treated with sedation, antibiotics, and human tetanus immune globulin (TIG). After intrathecal TIG 250 IU 3 patients out of 49 got worse but only 1 died while in a closely similar group of 48 patients in whom TIG was administered intramuscularly in dose of 1000 IU, the clinical features of the disease became severer in 15 (31%) and 10 (21%) died. The intrathecal use of TIG was devoid of side effects.

Human insulin synthesised by recombinant DNA technology was compared with highly purified porcine insulin in healthy men. Intracutaneous injection over a wide range of concentrations of both insulins into five subjects gave rise to no local reactions over a 48 h period. The glycaemic response to standard subcutaneous injection at high and low dose levels was measured with both insulins in each of six men. Plasma glucose decrement with the two insulins was similar but human insulin was perhaps slightly more potent than porcine insulin at the low dose, and slightly less so at the high. The glycaemic response to the isulins, each infused intravenously at high and low concentrations for 1 h in a further six subjects, showed a similar trend. Depression of glycaemia with human insulin slightly exceeded that with porcine insulin at the low concentration infusion and fell slightly short of it at the high. Genetically synthesised human insulin seems to be safe and effective in man. Its dose-response relationship may differ from that of porcine insulin.

One of the following treatments was randomly assigned to 101 consecutive patients with biopsy-proven chronic active hepatitis: prednisone 20 mg daily, azathioprine 100 mg daily, prednisone 20 mg and azathioprine 50 mg daily, or B vitamins 2 tablets daily (control group). Patients were observed at the beginning of the study, then at 2, 6, and 12 months after treatment. At each visit levels of HBsAg and Dane-particle-associated core-antigen (HBcAg) and their corresponding antibodies were determined. 42 patients were HBcAg positive at the beginning of the study. Of these 42 patients, the 34 who were under treatment remained HBcAg positive and showed a rise in HBcAg titre, while the 8 who were not treated had a fall in HBcAg titre (6 patients) or became HBcAg negative (2 patients) in 6 months. Among 59 patients who were HBcAg negative at the beginning of the study, this antigen became persistently detectable in 40% of the 42 patients who were treated, and was transiently present in 2 (12%) out of the 17 untreated patients (p < 0.05). Our data indicate that long-term prednisone and/or azathioprine treatments favour the replication of hepatitis-B virus in patients with HBsAg-positive chronic active hepatitis.

This is a further report on the mortality amongst men in the W.H.O. cooperative trial of the primary prevention of ischaemic heart disease (IHD) by clofibrate. Mean observation was 9.6 years, 5.3 in the trial and 4.3 afterwards; 911 deaths are recorded in 150 000 man-years. There were 25% more deaths in the clofibrate-treated group than in the comparable, high serum cholesterol, control group (p < 0.01), and there was an excess in the treated group in all the three participating centres. Mortality from all causes was higher in the treated group than in the high cholesterol controls during the trial, equal in the first two years after leaving the trial, but higher again after that. No particular disease accounted for the overall excess: the treated group had more deaths from IHD, stroke, cancer, and other major diseases though most of these differences were not individually significant. There was no excess in deaths due to accidents and violence. There was also a significant excess in the death rate from all causes, and from causes other than IHD, in the treated group compared with the second, low cholesterol, control group. No relationship could be shown between the excess mortality and cholesterol reduction, or the length of time on clofibrate. Explanation of the excess mortality is not apparent: a long term toxic effect of clofibrate, the possible consequences of reducing body cholesterol pools and, remotely, chance have all to be considered.

An evaluation of intra-operative B-mode ultrasound scanning of the extra-hepatic biliary tree and pancreas shows that it is a useful, noninvasive method of detecting bileduct calculi and assessing pancreatic disease. In 50 patients undergoing cholecystectomy for gallstones, ultrasound scanning was an accurate as per-operative cholangiography; the decision to explore the bileduct, made on ultrsound findings, was correct in 49/50 cases, and that made on X-ray findings was correct in 46/47 cases; there was 1 false-positive in each group. Scans of 5 patients with pancreatic disease were compared with 28 normal pancreatic scans. Infiltration of the portal vein by tumour was easily detected. Differentiation of carcinoma from chronic pancreatitis by ultrasound scanning might with more experience be possible, whilst identification of other pancreatic lesions, such as cysts, calculi, or endocrine tumours, will certainly be facilitated by this new technique.

Ten patients with excess body iron stores of different levels and with different diagnoses were given desferrioxamine inside osmotically lysed and resealed red blood cells (red cell ghosts). Red cell ghost entrapped desferrioxamine was given intravenously and, ten days later, an equal dose of desferrioxamine was administered via slow subcutaneous infusion over 10 h. Differences were apparent for these single dose challenges with respect to the pattern of urine iron excretion and the efficiency of iron chelation. The red cell ghost method consistently improved the efficiency of chelation, especially in patients with modestly increased body iron stores. This method of treatment may therefore prove to be of particular value in the patient with early siderosis who is embarking on a programme of regular transfusion for refractory anaemia.

214 patients were studied in a randomised trial to determine whether administraiton of intravenous atenolol within 12 hours of chest pain reduced eventual infarct size, as estimated by cumulative enzyme release and by ECG changes. 135 patients already had ECG evidence of infarction at entry; 72 received atenolol which significantly decreased subsequent enzyme release (atenolol and control means = 121 IU, SE +/- 10 and 177 IU, SE +/- 17; 2p < 0.005) and enhanced R-wave preservation (atenolol and control means = 46% +/- 3 and 36% +/- 3; 2p < 0.02). 79 patients had no evidence of infarction at entry; 44 did not receive atenolol and 27 of these subsequently developed infarction, whereas only 11 of 35 treated patients infarcted during their hospital stay (2p < 0.01). In hospital, fewer atenolol patients died (4 vs 9), had non-fatal cardiac arrests (2 vs 6), or required therapy for heart-failure (36 vs 47). Unlike many previous trials which had negative results, in this trial we gave the drug intravenously and promptly (median of 4 hours from onset of pain to injecton), thereby achieving early beta-blockade.

When prostacyclin (5 ng kg-1 min-1) was given during dialysis it enhanced the biological activity of heparin and prevented the activation and consumption of platelets. No adverse effects were observed. The reduction in heparin requirements produced by prostacyclin should make dialysis, safer, particularly for patients at risk of bleeding, while preserving the biocompatibility of the dialysis circuit. It remains to be established whether prevention of platelet activation will confer long-term benefit by inhibiting the prothrombotic state induced by haemodialysis, thereby reducing the risk of atherosclerosis in uraemic patients.

Continuous, oral administration of propranolol at doses which reduced the heart-rate by 25% produced a sustained decrease in portal venous pressure in cirrhotic patients with portal hypertension. This effect of propranolol might be useful in preventing recurrent bleeding due to ruptured oesophageal varices in patients with portal hypertension.

Adjuvant immunotherapy with polyadenylic-polyuridylic acid (PolyA.PolyU) was tested in a randomised trial on 300 patients with operable breast cancer, all of whom were treated by surgery with or without radiotherapy. They were randomly divided into an experimental group of 155 patients who were treated with 30 mg PolyA.PolyU intravenously per week for 6 weeks and a control group of 145 patients who received normal saline intravenously on the same schedule. The mean follow-up time was more than 50 months in both groups. The overall survival was significantly higher in the treated group (p less than or equal to 0.05), in whom the 5-year "relapse-free" surival was also increased. In node-positive patients, treatment increased the relapse-free survival (p less than or equal to 0.03) and overall survival (p less than or equal to 0.07). No side-effects were noted. Thus, immunotherapy with PolyA.PolyU appears to be a simple, non-toxic, and efficient adjuvant treatment in operable breast cancer.

Clinical metrologists have been employed in Leeds for the past seven years. They have come to assume increasing responsibility, particularly in the conduct and recording of clinical trials in the rheumatic diseases. Their work can be extended to the planning of trials, practical procedures, and other research activities. Analysis of 20 applications for a post that recently fell vacant at Leeds suggests that many married women, highly qualified professionally, who have completed their families, would welcome the opportunity to return to parttime nursing duties in "social hours". Increased responsibility and job satisfaction provided by the post compensate for a reduction in salary. Clinical metrology may be a new career grade in the National Health Service that allows for more careful monitoring of patients with constancy that cannot be achieved with rotating junior medical staff. Physicians can be released from the routine of follow-up, so that they have more time for diagnosis, management of complex problems, and research.

In the tenth year of follow-up of a multicentre trial of the management of operable breast cancer no significant difference in survival was found between patients treated with simple mastectomy alone (with radiotherapy later if the disease recurred) and those treated with simple mastectomy and routine immediate postoperative radiotherapy. There was a highly significant increased risk of local recurrence in the conservatively treated group, with a hazard ratio of 3.0. The biological and clinical relevance of these results is discussed.

In 23 hypertensive men, aged 47-55, propranolol reduced serum high-density-lipoprotein (HDL) cholesterol by 13% reduced the ratio of HDL to low-density-lipoprotein (LDL)+very-low-density-lipoprotein (VLDL) cholesterol by 15%, increased total triglycerides by 24%, and increased serum uric acid by 10%. Prazosin reduced total serum cholesterol by 9%, LDL+VLDL cholesterol by 10%, and total triglycerides by 16%. These changes are statistically highly significant. On combined treatment with propranolol and prazosin HDL cholesterol was still significantly reduced but changes in other blood lipids were small and insignificant. Uric acid remained elevated. When decisions about long-term therapy are made, such metabolic effects might be of special importance.

A new technique of axillary lymphoscintigraphy has been investigated in thirty patients with breast carcinoma. Intradermal injection of 100 muCi technetium-99m antimony sulphide colloid in 0.1 ml buffer produced satisfactory scans of axillary lymph-nodes in twenty-seven patients (90%). Ten patients with node metastases from breast cancer (9 confirmed histologically) had a defect in the lower axillary uptake on the side of the lesion. Three of the remaining seventeen patients with breast cancer and normal scans had nodal metastases seen histologically, but in two these were micro-metastases only. Axillary lymphoscintigraphy improved considerably the clinical assessment of node status, and corrected the clinical classification in five of six patients who had been misclassified by clinical examination.