44 patients with endoscopically confirmed duodenal (36) or prepyloric (8) ulcers have received in a double-blind trial either the histamine H2-receptor antagonist cimetidine (30 patients) or placebo (14 patients) for six weeks. At three weeks 67% of patients treated with cimetidine and 17% of those receiving placebo had endoscopically healed ulcers (chi2 = 8.49; P less than 0.005). At six weeks all except 3 patients receiving cimetidine (90%) had healed ulcers compared with 36% receiving placebo (chi2 = 11.11; P less than 0.001). Those receiving cimetidine had less daytime and nocturnal pain than patients on placebo. The differences were statistically significant for daytime pain during four of six weeks. The cimetidine-treated patients consumed significantly less antacids than placebo-treated patients and these patients' overall assessments of their wellbeing were significantly better. All patients on cimetidine had a significant reduction (P less than 0.0005) of their basal and pentagastrin-stimulated acid secretion, but no reduction in acid secretion was measured in the group who received placebo.

55 patients with dendritic ulcer have been treated in a double-blind randomised manner by minimal wiping debridement of their ulcers followed by daily application of either partially purified human interferon (P.I.N.F.) or placebo. There were 6 recurrences of epithelial herpetic disease in 30 patients who received P.I.N.F. and 13 in 25 who received placebo. This provides the long-awaited data proving the antiviral effect of exogenous interferon in treatment of naturally occurring viral disease in man, and furnishes a sighting shot on the lower edge of the target of effective therapy.

The relation of perinatal mortality to plasma-urate concentrations and blood-pressure was studied in 332 pregnant patients with hypertension. Perinatal mortality was markedly increased when maternal plasma-urate concentrations were raised, generally in association with severe pre-eclampsia of early onset. Plasma-urate was a better indicator than blood-pressure of prognosis for the fetus. Maternal hypertension, even severe, without hyperuricaemia, was associated with an excellent prognosis for the fetus. Conversely, when maternal hypertension was mild and hyperuricaemia was severe, the prognosis for the fetus was poor. These findings suggest that, in terms of fetal health, changes in renal handling of urate may be a more important feature of pre-eclampsia than the hypertension.

38 hypertensive Canadian steelworkers who were neither compliant with medications nor at goal diastolic blood-pressure six months after starting treatment were allocated either to a control group or to an experimental group who were taught how to measure their own blood-pressures, asked to chart their home blood-pressures and pill taking, and taught how to tailor pill taking to their daily habits and rituals; these men were also seen fortnightly by a highschool graduate with no formal health professional training who reinforced the experimental manoeuvres and rewarded improvements in compliance and blood-pressure. Six months later, average compliance had fallen by 1.5% in the control group but rose 21.3% in the experimental group. Blood-pressures fell in 17 of 20 experimental patients (to goal in 6) and in 10 of 18 control patients (to goal in 2).

A controlled trial was undertaken to evaluate the practical consequences of screening in general practice. Of 2420 people aged 40-64 years examined in 1967-68, 191 (7.9%) had previously been told, at some time, that they had raised blood-pressure, other than during pregnancy. However, only 77 (3-2%) had any record of current antihypertensive treatment. Screening resulted in a further 50 persons (2-1%) being newly diagnosed as hypertensive in 1967-68 and a further 9 in 1969-70. Antihypertensive treatment was given to 21 of these immediately following diagnosis, while the treatment was adjusted in 23 of those already known to be hypertensive. In 1972-73 the blood-pressures of the screening population were directly compared with the control group. No significant differences in the distributions of their blood-pressure levels were observed. Over 95% of the new hypertensives discovered by the screening process in the control group in 1972-73 had visited their general practitioners for some reason during the previous five years. This suggests that "case-finding" by general practitioners would be more cost-effective than setting up separate blood-pressure screening clinics. However, the results of this study indicate that we need to know more about how raised blood-pressure can be successfully controlled over a long time, before any mass screening programmes can be actively encouraged.

A double-blind trial in twenty-nine patients with rosacea showed that, after 6 weeks' treatment, metronidazole was therapeutically superior to a placebo (P less than 0-02). It was particularly effective against papules and pustules. The mode of action of metronidazole and other antibiotics in rosacea is not known.

In a prospective trial, the prophylactic efficacy of low-dose heparin was investigated in 84 consecutive patients undergoing total-hip replacement. 52 of these were randomly allocated to receive heparin or a combination of heparin and dihydroergotamine (D.H.E.); the remaining 32 patients, who were operated on by one orthopaedic team and did not receive prophylaxis, acted as a control group. The frequency of deep-vein thrombosis (D.V.T.), determined by the 125I-fibrinogen test and venography, was 69% in the control group, 32% in the patients receiving heparin alone, and 16% in those receiving heparin and D.H.E. The difference between the control group and each group receiving prophylaxis was statistically significant. The frequency of femoral-vein thrombi, demonstrated by venography, was analysed separately because of its frequent association with major pulmonary embolism. Femoral-vein thrombi developed in 17 (53%) in the control group, while they developed in only 4 patients (8%) in the prophylaxis group (P less than 0.01). 1 patient in the control group died due to massive pulmonary embolism; in another patient, again in the control group, clinical features suggestive of major non-fatal pulmonary embolism developed. This complication was not observed in patients receiving prophylaxis. There was no difference in the amount of operative or postoperative blood-loss in the three groups. In 3 patients in the entire series wound haematomata developed; all 3 were controls and haematomata developed after the administration of streptokinase or large doses of heparin for the treatment of extensive femoral-vein thrombi. By use of a sensitive assay, heparin could be detected in the plasma in 67% of samples in patients in whom D.V.T. did not develop. In contrast, in those patients in whom D.V.T. developed, heparin could be detected in only 21% of blood-samples (P less than 0.01). It is concluded that in patients undergoing total-hip replacement, low-dose heparin prophylaxis is effective in reducing the frequency of life-threatening extensive thrombi in the femoral vein. Prophylaxis using a combination of heparin and D.H.E. requires further evaluation.

Three anaesthetic premedication regimens have been compared by double-blind controlled trial in 158 patients undergoing day-case surgery for varicose veins or hernia. Atropine plus droperidol was superior to atropine plus diazepam or atropine alone in lessening nausea and vomiting and in reducing the need for postoperative analgesia.

The clinical progress of 350 patients with early cancer of the breast was reviewed. In a five-year follow-up after simple mastectomy routine postoperative radiotherapy conferred no demonstrable benefit on those with histologically negative lymph-nodes. When the regional nodes were involved in the malignant process, radiotherapy led to an increased mortality in the early stages, but did reduce the incidence of local recurrence.

24 patients with chronic renal failure (glomerular filtration-rate (G.F.R.) 5-25 ml/min) participated in a double-blind placebo-controlled trial of the effects of 1 alpha-hydroxycholecalciferol (1alpha-H.C.C.) 1 mug daily for eleven weeks. This treatment induced significant increases in the intestinal absorption of calcium and in plasma-calcium which reached normal levels within two weeks. It also induced a significant reduction of the raised serum levels of parathyroid hormone. No significant changes were induced in plasma-phosphorus, plasma-alkaline-phosphatase, or in the degree of bone mineralisation as measured by the phosphorus/hydroxyproline ratio in bone. The bone mineral content in the forearm measured by photon absorptiometry decreased to the same extent in the 1alpha-H.C.C. groups and in the placebo group. The fall in G.F.R. over eleven weeks was 2-5 times greater in the 1alpha-H.C.C. group than in the placebo group, but this difference was not significant. It is concluded that 1alpha-H.C.C. treatment in chronic renal failure does not affect the progressive loss of calcium from bone despite normalisation of plasma-calcium.

36 patients who received a renal transplant and who subsequently underwent a rejection episode were randomised into two groups. The first group received a standard form of rejection therapy consisting in high doses of steroid drugs, and the second group received in addition 600 rads of radiotherapy to the graft. After three years (minimum follow-up twelve months) the groups were compared with respect to patient and graft survival and level of transplant function. No benefit was obtained by the group receiving radiotherapy.

Thirty-one, previously untreated, adult outpatients with idiopathic or focal grand-mal and/or focal minor seizures were treated initially with phenytoin. Serum-phenytoin concentrations were monitored to achieve an optimum range of 10-20 mug/ml if necessary. With a mean duration of follow-up of 14-7 months, only three (10%) patients have required the addition of a second drug, although without the guidance of serum concentrations sixteen (54%) might have been treated with a further drug. In the optimum serum-phenytoin range only 1 grand-mal attack occurred in this series, compared with a mean pre-treatment grand-mal seizure-rate of 1-1/month. Serum phenytoin declined slowly in fourteen (45%) patients. These observations suggest that many epileptic patients could be satisfactorily treated with one drug instead of the polypharmacy which they usually receive.

83 patients with colorectal carcinoma of the Dukes' C class were randomised to receive postoperative adjuvant therapy with B.C.G. alone or in combination with oral doses of 5-fluorouracil (5-F.U.), and have been followed for up to thirty months. Results were compared with carefully selected historical controls who were treated by surgery alone. A statistically significant prolongation of both disease-free interval and overall survival was observed in 50 patients receiving the combination of B.C.G. and 5-F.U. (P=0.03, P=0.01 respectively) as well as in 33 patients receiving B.C.G. alone (P=0.03, P=0.05 respectively). The efficacy of B.C.G.+5-F.U. was independent of the number of tumour-involved lymph-nodes in the surgical specimen. In contrast, B.C.G. given alone appears to be highly effective among 10 patients with 6 or more positive lymph-nodes (P less than 0.04) and ineffective (as yet) among 23 patients with 5 or less positive lymph-nodes. These results suggest that adjuvant immunotherapy, with or without chemotherapy, can improve the prognosis of surgically treated patients with colorectal carcinoma of the Dukes' C class.

The effects of intravenous glycerol and intravenous dextrose were compared using a double-blind trial in twenty-seven patients with acute stroke. Administration continued for up to 6 days. A standard scoring system was used for neurological evaluation. There was no difference in mortality or in improvement in neurological score between the two groups.

One cause of transplant rejection is curtailment of immunosuppressive therapy due to leucopenia. To determine those patients most apt to develop leucopenia due to azathiprine the granulocyte response to intravenous injections (i.v.) of hydrocortisone was evaluated in 10 patients who had rejected their grafts at least six month previously. 5 patients who had rejected their grafts with concomitant severe leucopenia had an inadequate response to hydrocortisone, while in the other 5, who had tolerated the drug, the response was similar to that of normal controls. Based on these observations, all the transplant candidates underwent the hydrocortisone stimulation test the results of which were correlated with their subsequent clinical course. All medical decisions were based on events other than the steroid test. 8 leucopenic patients underwent splenectomy. 6 improved their granulocyte response to hydrocortisone and tolerated azathioprine after transplantation. 2 patients who underwent splenectomy and an unoperated leucopenic man were unresponsive to the hydrocortisone test, did not tolerate azatioprine after transplantation and rejected their grafts. 4 candidates with normal responses to i.v. hydrocortisone received transplants uneventfully. In all 13 patients transplanted since the beginning of this study, the hydrocortisone test correctly predicted their tolerance to azathioprine.

In a prospective, randomized controlled study, 30 children who were receiving chemotherapy for malignant disease and who were anaemic and neutropenic, were randomized: 18 to receive transfusion to a Hb of 10-12 g/dl (group A) and 12 to receive moderate hypertransfusion to a Hb of 14-16 g/dl (group B). Children in group B had a significantly more rapid rise in polymorph count, lower incidence of infection, and lower incidence of interruption to chemotherapy. The findings of this study provide evidence for the existence of a common stem cell in human marrow, at least for erythroid and myeloid cell lines, and demonstrate that the concept of "stem-cell competition" derived from animal experiments has a human counterpart which is clinically significant.

In a study of the effect of somatostatin (growth-hormone release-inhibiting hormone) on plasma-renin in healthy volunteers, plasma-renin activity was measured by radioimmunoassay after the intravenous administration of somatostatin and also during frusemide-induced hyperreninaemia. While somatostatin was being given, basal values of renin were unchanged. Injection of frusemide alone produced hyperreninaemia; but, under somatostatin, renin release was inhibited by 45%. The results indicate that somatostatin is a potent inhibitor of renin and exerts its effect independent of sodium excretion, which was unchanged under somatostatin. Conceivably, somatostatin plays an important role in the regulation of endogenous renin release.